Comparação entre o Disease Activity Score-28 e o Juvenile Arthritis Disease Activity Score na artrite idiopática juvenil

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Renata Campos Capela

2015-02-01

Full Text Available Introdução A avaliação de atividade da artrite reumatoide e da artrite idiopática juvenil é feita por meio de instrumentos distintos, respectivamente pelo DAS-28 e pelo JADAS. Objetivo Comparar o DAS-28 e o JADAS com a pontuação de 71, 27 e 10 articulações, na artrite idiopática juvenil. Método Foram avaliadas 178 visitas em oito pacientes com artrite idiopática juvenil, participantes de um ensaio clínico controlado de fase III, testando eficácia e segurança do abatacepte. Pontuaram-se as articulações ativas e limitadas, a avaliação global pelo médico e pelos pais em escala analógica visual de 0-10 cm e a velocidade de hemossedimentação convertida em escala de 0-10, em todas as visitas. A comparação entre os índices de atividade entre diferentes observações foi por Anova ou modelo ajustado Gama. As observações pareadas entre o DAS-28 e o JADAS 71, 27 e 10, respectivamente, foram analisadas por meio de regressão linear. Resultados Houve diferença significativa entre as medidas individuais, exceto a VHS, nos primeiros quatro meses de tratamento com biológico, quando cinco entre os oito pacientes atingiram a resposta ACR-Pedi 30, com melhora. Os índices DAS-28, JADAS 71, 27 e 10 também apresentaram diferença relevante durante o período de observação. O ajustamento por meio de regressão linear entre o DAS-28 e o JADAS resultou em fórmulas matemáticas para conversão: [DAS-28 = 0,0709 (JADAS 71 + 1,267] (R2 = 0,49; [DAS-28 = 0,084 (JADAS 27 + 1,7404] (R2 = 0,47 e [DAS-28 = 0,1129 (JADAS-10 + 1,5748] (R2 = 0,50. Conclusão A conversão da pontuação do DAS-28 e do JADAS 71, 27 e 10 por esse modelo matemático permitiria a aplicação equivalente de ambos em adolescentes com artrite.

Mental health status can reflect disease activity in rheumatoid arthritis.

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Sokolovic, Sekib; Dervisevic, Vedina; Fisekovic, Saida

2014-06-01

A significant number of patients with rheumatoid arthritis (RA) link the start of illness with psychological trauma or severe stress. Impaired mental health (IMH), defined as depression and anxiety with psychoneuroimmunological factors, can play a significant role in RA. The main objective of this research was to investigate the mutual correlation of IMH and RA activity, estimated by the laboratory and clinical parameters in RA patients. An open clinical prospective study that lasted for 6 months was designed. There were 72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for mental health status. The study population was randomized following the Brief Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no symptoms) to 4 (severe). This mental test was done only once during the study. Following the results from the BSI scale, RA patients were divided into mentally stable and mentally unstable patients to investigate the influence of RA activity on mental health. The following laboratory and clinical parameters were analyzed: sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody, and disease activity score (DAS28). All RA patients did not express extra-articular manifestations or Sjögren's syndrome. The chi-square test, ANOVA, Pearson's coefficient, and IBM Statistics - SPSS v19 were used. From a total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable patients. All patients had either moderate or severe active disease. The only significant correlation of IMH and activity of RA was found in CRP and DAS28, but no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with unstable mental health compared to stable mental health patients, where RA was associated with a moderate DAS average value of 4.35 and

There Is No Further Gain from Calculating Disease Activity Score in 28 Joints with High Sensitivity Assays of C-Reactive Protein Because of High Intraindividual Variability of CRP: A Cross Sectional Study and Theoretical Consideration

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Jensen Hansen, Inger Marie; Asmussen Andreasen, Rikke; Antonsen, Steen

Background/Purpose: The threshold for reporting of C-reactive protein (CRP) differs from laboratory to laboratory. Moreover, CRP values are affected by the intra individual biological variability.[1] With respect to disease activity score in 28 joints (DAS28) and Rheumatoid Arthritis (RA), precise...... threshold for reporting CRP is important due to the direct effects of CRP on calculating DAS28, patient classification and subsequent treatment decisions[2] Methods: This study consists of two sections: a theoretical consideration discussing the performance of CRP in calculating DAS28 with regard...... to the biological variation and reporting limit for CRP and a cross sectional study of all RA patients from our department (n=876) applying our theoretical results. In the second section, we calculate DAS28 twice with actual CRP and CRP=9, the latter to elucidate the positive consequences of changing the lower...

The association of body mass index with disease activity and clinical response to combination therapy in patients with rheumatoid arthritis

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Maryam Mirpourian

2014-01-01

Full Text Available Background: The role of obesity in clinical curse of rheumatoid arthritis (RA is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. Materials and Methods: Active RA patients with the disease activity score using 28 joint counts (DAS28 > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week plus hydroxychloroquine (200 to 400 mg/day and prednisolone (2.5 to 10 mg/day and were followed by DAS28 for up to 24 weeks. Results: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001 after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = -0.415, P = 0.005 and waist circumference (r = -0.296, P = 0.05 were correlated with baseline DAS28. Although BMI (r = -0.337, P = 0.025 and waist circumference (r = -0.315, P = 0.038 were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. Conclusion: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients.

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

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Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Disease activity score in rheumatoid arthritis with or without secondary fibromyalgia

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Zammurrad, S.; Munir, W.; Farooqi, A.

2013-01-01

Objective: To correlate disease activity score (DAS-28) in the patients with rheumatoid arthritis (RA) with and without secondary fibromyalgia. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, from November 2011 to April 2012. Methodology: Patients aged above 16 years diagnosed to have rheumatoid arthritis according to ACR/EULAR criteria 2010 were included in the study. Fibromyalgia (FM) was diagnosed by ACR 1990 criteria. Patients of other autoimmune diseases or psychiatric illnesses were excluded. DAS was determined and compared using t-test with significance at p < 0.05. Results: The mean age of study subjects was 42.9 years. Thirty one out of total 138 patients had fibromyalgia (22.4%). Female gender was predominant (92.0%); being 96.8% in patients with and in 88.2% without fibromyalgia. The average DAS score was high (5.3 + 1.5) in fibromyalgia patients compared to those without fibromyalgia (3.9 + 1.2); this difference in mean value was statistically significant (p = < 0.001). Conclusion: DAS-28 is a useful tool for assessing rheumatoid arthritis disease status in outpatient setting, however, increased disease activity must be assessed for possible co-existence of fibromyalgia which can spuriously give high DAS value and adversely affect treatment decision. (author)

Impact of hepatitis C virus infection on disease activity, functional status and ultrasonography findings in Egyptian rheumatoid arthritis patients

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Nabila Abd EI-Hamid Gohar

2018-04-01

Full Text Available Background: Hepatitis C virus (HCV infection is one of the most frequently encountered public health problems in Egypt. It is associated with many autoimmune diseases such as rheumatoid arthritis. Aim of the work: To assess the impact of HCV infection in rheumatoid arthritis (RA Egyptian patients; its relation to disease activity, functional status and ultrasonography findings. Patients and methods: The study included 155 RA patients further classified according to the presence of concomitant HCV infection into 2 groups; rheumatoid arthritis (RA and rheumatoid arthritis/hepatitis C virus (RA/HCV groups. All patients were subjected to full history taking, thorough clinical examination, laboratory investigations, assessment of disease activity using the disease activity score 28 (DAS28 and assessment of functional status using the modified health assessment questionnaire (MHAQ. Ultrasonography (US assessment was done using the German US7 score. Results: Both DAS28 and MHAQ scores showed significant differences between both the RA and the RA/HCV groups (p < 0.001, with higher mean values observed in the RA/HCV group (5.4 ± 1.1 and 1.05 ± 0.79 respectively. Significantly higher US7 synovitis scores were found in the RA/HCV group compared to the RA group (p = 0.03. US7 synovitis tenosynovitis scores revealed significant correlations with DAS28 and US7 synovitis scores correlated with MHAQ in both groups. Conclusion: Concomitant HCV infection in RA patients had an impact on disease activity. RA patients with concomitant HCV infection (RA/HCV had higher DAS28 and MHAQ scores, with higher US7 synovitis scores compared to RA patients. US7 score is a valuable objective tool for the assessment of RA disease activity. Keywords: Rheumatoid arthritis, HCV infection, Ultrasonography, DAS28, MHAQ

Blood Monocyte Subsets and Selected Cardiovascular Risk Markers in Rheumatoid Arthritis of Short Duration in relation to Disease Activity

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Ewa Klimek

2014-01-01

Full Text Available Objectives. To evaluate blood monocyte subsets and functional monocyte properties in patients with rheumatoid arthritis (RA of short duration in the context of cardiovascular (CV risk and disease activity. Methods. We studied conventional markers of CV risk, intima media thickness (IMT, and blood monocyte subsets in 27 patients aged 41 ± 10 years with RA of short duration (median 12 months and 22 healthy controls. The RA subjects were divided into low (DAS28: 2.6–5.1 and high (DAS28 > 5.1 disease activity. Results. RA patients exhibited increased levels of intermediate (CD14++CD16+ monocytes with decreased CD45RA expression compared to controls, increased counts of classical (CD14++CD16− monocytes, and decreased percentages of nonclassical (CD14+CD16++ monocytes. Patients with high disease activity had lower HLA DR expression on classical monocytes compared to low disease activity patients. There were no differences in monocyte subsets between subjects with DAS > 5.1 and DAS ≤ 5.1. There were no significant intergroup differences in IMT and the majority of classical CV risk factors. Conclusions. Patients with RA of short duration show alteration in peripheral blood monocyte subsets despite the fact that there is no evidence of subclinical atherosclerosis. Disease activity assessed with DAS28 was associated with impaired functional properties but not with a shift in monocyte subpopulations.

Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis

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Wallman, Johan K; Eriksson, Jonas K; Nilsson, Jan-Åke

2016-01-01

between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs. RESULTS: Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work......OBJECTIVE: To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA). METHODS: Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005-2010. Health Assessment...... Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register-derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare...

Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between self-rated clinimetric evaluation and clinical evaluation with activity indexes: DAS28, CDAI and SDAI.

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Horta-Baas, Gabriel; Pérez Bolde-Hernández, Arturo; Hernández-Cabrera, María Fernanda; Vergara-Sánchez, Imelda; Romero-Figueroa, María Del Socorro

2017-10-11

To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis.

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Kuusela, Elina; Kouri, Vesa-Petteri; Olkkonen, Juri; Koivuniemi, Riitta; Äyräväinen, Leena; Rajamäki, Kristiina; Valleala, Heikki; Nordström, Dan; Leirisalo-Repo, Marjatta; Ainola, Mari; Eklund, Kari K

2018-03-20

To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity. The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28). At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA. Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

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Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

2017-08-01

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

Rheumatoid arthritis disease activity and vitamin D deficiency in an Asian resident population.

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Quraishi, Mohammed K; Badsha, Humeira

2016-04-01

We aimed to assess the prevalence of vitamin D deficiency and its association with rheumatoid arthritis (RA) disease activity in a UAE population. Forty-five consecutive subjects were prospectively recruited during the early summer with their clinical examination and Health Assessment Questionnaire (HAQ) being recorded at a clinic appointment, along with their blood sample being taken for the 25-hydroxyvitamin D (25(OH)D) total test. Thirty-five (76%) patients claimed to be exposed to sunlight for Disease Activity Score (DAS28) or HAQ scores. A direct relationship was observed between HAQ scores and DAS28 scores (P culture. No association was observed between vitamin D and disease activity. However, the high prevalence of vitamin D deficiency may negatively impact on bone health of these patients in the future. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

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Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

2016-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity.

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Sakthiswary, Rajalingham; Rajalingam, Shamala; Hussein, Heselynn; Sridharan, Radhika; Asrul, Abdul Wahab

2017-12-01

The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.

Development and validation of modified disease activity scores in rheumatoid arthritis

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Baker, Joshua F; Conaghan, Philip G; Smolen, Josef S

2014-01-01

-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear......OBJECTIVE: To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures.......15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

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El-Rabbat M, Sarah; Mahmoud, Nermeen K; Gheita, Tamer A

2017-04-11

To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in patients with rheumatoid arthritis treated with synthetic drugs, in clinical remission by DAS28.

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Ventura-Ríos, Lucio; Sánchez Bringas, Guadalupe; Hernández-Díaz, Cristina; Cruz-Arenas, Esteban; Burgos-Vargas, Rubén

2017-11-29

To identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). This is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. Patients' mean age was 49.1±13.7 years; 83% were women. The mean disease duration was 8±7 years and remission lasted for 27.5±31.8 months. The mean DAS28 score was 1.9±0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI 95%, 0.34-0.81) and 0.81, p<0.0001 (CI 95%, 0.27-0.83) respectively. Low percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Thyroid disorders in patients with newly diagnosed rheumatoid arthritis is associated with poor initial treatment response evaluated by disease activity score in 28 joints-C-reactive protein (DAS28-CRP)

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Emamifar, Amir; Hangaard, Jørgen; Jensen Hansen, Inger Marie

2017-01-01

peptide antibody (anti-CCP), and antinuclear antibody (ANA), and also disease activity score in 28 joints-C-reactive protein at the time of diagnosis and after 4 months (±1–2 months) of treatment initiation were extracted from Danish Danbio Registry. Patients’ electronic hospital records for the past 10...... years were reviewed to reveal if they had been diagnosed with thyroid disorders or they had abnormal thyroid test.In all, 439 patients were included, female 60.1%, mean age 64.6 ± 15.0 years and disease duration 2.6 ± 1.7 years. Prevalence of thyroid disorders was 69/439 (15.7%) and hypothyroidism...... treatment compared with patients with isolated RA after 4 months of treatment (P = .02). There were no associations between thyroid disorders and age, disease duration, and also IgM RF positivity.Presence of thyroid disorders in RA patients is suggestive of a more aggressive disease and poor outcome...

STAT4 rs7574865 G/T polymorphism is associated with rheumatoid arthritis and disease activity, but not with anti-CCP antibody levels in a Mexican population.

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Durán-Avelar, Ma de Jesús; Vibanco-Pérez, Norberto; Hernández-Pacheco, Raquel Rocío; Castro-Zambrano, América Del Carmen; Ortiz-Martínez, Liliana; Zambrano-Zaragoza, José Francisco

2016-12-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the Taqman® system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 ≥ 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.

Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

LENUS (Irish Health Repository)

Pontifex, Eliza K

2011-01-27

Abstract Introduction With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Methods Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman\\'s rho test) were calculated. Results Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in

Dynamic contrast-enhanced 3-T magnetic resonance imaging: a method for quantifying disease activity in early polyarthritis

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Navalho, Marcio [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital da Luz, Radiology Department, Lisbon (Portugal); Hospital da Luz, Centro de Imagiologia, Lisbon (Portugal); Resende, Catarina [Hospital da Luz, Rheumatology Department, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Rodrigues, Ana Maria; Fonseca, Joao Eurico; Canhao, Helena [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Gaspar, Augusto [Hospital da Luz, Radiology Department, Lisbon (Portugal); Campos, Jorge [Hospital de Santa Maria, Radiology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal)

2012-01-15

To determine whether measurement of synovial enhancement and thickness quantification parameters with 3.0-Tesla magnetic resonance imaging (3-T MRI) can reliably quantify disease activity in patients with early polyarthritis. Eighteen patients (16 women, 2 men; mean age 46 years) with early polyarthritis with less than 12 months of symptoms were included. MRI examination using 3-T device was performed by a new approach including both wrists and hands simultaneously in the examination field-of-view. MRI scoring of disease activity included quantification of synovial enhancement with simple measurements such as rate of early enhancement (REE; REE{sub 57} = S{sub 57}/S{sub 200}, where S{sub 57} and S{sub 200} are the signal intensities 57 s and 200 s after gadolinium injection) and rate of relative enhancement (RE; RE = S{sub 200} - S{sub 0}). Both wrists and hands were scored according to the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for synovitis. Disease activity was clinically assessed by the 28-joint Disease Activity Score (DAS28). DAS28 score was strongly correlated with RE (r = 0.8331, p < 0.0001), REE (r = 0.8112, p < 0.0001), and RAMRIS score for synovitis (r = 0.7659, p < 0.0002). An REE score above 0.778 accurately identified patients with clinically active disease (sensitivity 92%; specificity 67%; p < 0.05). A statistically significant difference was observed in the RE, REE, and RAMRIS scores for synovitis between patients with active and inactive disease (p < 0.05). Our findings support the use of 3-T dynamic contrast-enhanced MRI for precise quantification of disease activity and for discriminating active disease from inactive disease in early polyarthritis. (orig.)

Vitamin D is not useful as a biomarker for disease activity in rheumatoid arthritis.

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de la Torre Lossa, Paola; Moreno Álvarez, Mario; González Guzmán, María Del Carmen; López Martínez, Rafael; Ríos Acosta, Carlos

2018-05-17

To determine whether there is an association between serum vitamin D levels and the Disease Activity Index in patients with rheumatoid arthritis (RA). An analytical, retrospective, cross-sectional study was performed at the Hospital Luis Vernaza and Center for Rheumatology and Rehabilitation. We included 18 to 75-year-old patients with a diagnosis of RA according to the 2010 classification criteria, and with a 25-hydroxyvitamin D (25 [OH] D) test within the last 3 months. The activity of the disease was assessed with the 28-joint Disease Activity Score (DAS28) and C-reactive protein (CRP) as an acute-phase reactant. Spearman's rank correlation coefficient was used to establish association between the variables. A total of 100 RA patients were studied. The mean vitamin D levels were 32.9 ± 11.5 ng/mL. In all, 45% showed insufficient 25 (OH) D and 55% had normal levels; no deficient vitamin D values were found. According to the DAS28-CRP, patients with low, moderate and high activity had an average vitamin D level of 30.4 ± 10.7, 31.9 ± 10.7, and 31.8 ± 12.1 ng/mL, respectively. There were no significant correlations between the disease activity and the serum vitamin D level (P=.60). In our group of RA patients, there was no statistically significant correlation between the levels of vitamin D and the activity of the disease, nor were other determining variables associated with vitamin D levels. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis.

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Salaffi, Fausto; Di Carlo, Marco; Vojinovic, Jelena; Tincani, Angela; Sulli, Alberto; Soldano, Stefano; Andreoli, Laura; Dall'Ara, Francesca; Ionescu, Ruxandra; Simić Pašalić, Katarina; Balčune, Ineta; Ferraz-Amaro, Iván; Tlustochowicz, Malgorzata; Butrimienė, Irena; Punceviciene, Egle; Toroptsova, Natalia; Grazio, Simeon; Morović-Vergles, Jadranka; Masaryk, Pavol; Otsa, Kati; Bernardes, Miguel; Boyadzhieva, Vladimira; Cutolo, Maurizio

2017-05-24

To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states. A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score. The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; Pdisease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; Pdisease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001). The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

The impact of patients reported flares on functional impairment in rheumatoid arthritis patients with low-disease activity

DEFF Research Database (Denmark)

Küttel, Dorota Paulina; Christensen, R.; Primdahl, J.

2015-01-01

-term outcomes. Objectives: To investigate whether transient patient reported flares can influence functional disability in patients with established low active RA. Methods: Out of 287 patients from the AMBRA trial (1), 268 RA patients with low disease activity (DAS28CRP MCID of 0.22) was compared across three...

Serum Leptin levels do not correlate with disease activity in Rheumatoid Arthritis

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Sibel Yilmaz Oner

2015-01-01

Full Text Available Objectives Leptin, is a fat tissue hormone which effects energy expenditure , food intake , hematopoiesis, osteogenesis, angiogenesis, reproductive and immune systems. We aimed to determine serum leptin levels and investigate the association between disease activity and other parameters in RA patients. Methods Patients with RA (n=106 as the study group, healthy controls (n=52 and osteoarthritis (OA patients (n=37 as a control group were enrolled to the study. RA patients were categorized in four different groups according to DAS28 scores: remission ,low (LDA, moderate (MDA or high (HDA disease activity . Results No differences were present between the body mass indices of the three groups. Mean leptin levels in RA patients, OA group and healthy individuals were 25,60±13,41, 23,03±11,51 and 23,81±12,85 ng/ml, respectively and no significant difference was present between the groups. Nine of (8,5% RA patients were in remission, 16 (15,1% were in LDA, 40 (37,7% in MDA and 41 (38,7% were in HDA. Leptin levels did not correlate with DAS28 scores of RA patients (r=-0,12, p=0,11. Mean leptin levels in RA patients with remission was 32,65±7, 28 in LDA 23,94±10,94 in MDA 26,73±14,92 and in HDA 23,59±13,50 ng/ml (p=NS. No associations were observed between leptin levels and CRP, ESR, RF positivity and disease duration. Conclusions Our study revealed no correlation of disease activity and serum leptin levels. Therefore leptin does not seem to be an appropriate biomarker to monitorize inflammation in RA.

Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

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Lucie Andrés Cerezo

2015-01-01

Full Text Available Objective. Progranulin (PGRN is implicated in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n=47 and OA (n=42 and healthy controls (n=41. Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP, disease activity score (DAS28-CRP, and health assessment questionnaire (HAQ was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1±100.2 and 221.5±102.5 versus 128.1±34.7 ng/mL; P<0.001. Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5±275.3 versus 241.4±165.2 ng/mL; P=0.002. PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r=0.327, P=0.049 and HAQ score (r=0.323, P=0.032, while synovial fluid PGRN correlated only with HAQ (r=0.310, P=0.043 in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.

Reevaluation of the role of duration of morning stiffness in the assessment of rheumatoid arthritis activity.

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Khan, Nasim A; Yazici, Yusuf; Calvo-Alen, Jaime; Dadoniene, Jolanta; Gossec, Laure; Hansen, Troels M; Huisman, Margriet; Kallikorm, Riina; Muller, Raili; Liveborn, Margareth; Oding, Rolf; Luchikhina, Elena; Naranjo, Antonio; Rexhepi, Sylejman; Taylor, Peter; Tlustochowich, Witold; Tsirogianni, Afrodite; Sokka, Tuulikki

2009-11-01

To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy--a single centre, open-label study.

LENUS (Irish Health Repository)

Pontifex, Eliza K

2011-01-01

With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent.

The association of immunoglobulin A, immunoglobulin G and anti-cyclic citrullinated peptide antibodies with disease activity in seronegative rheumatoid arthritis patients

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Mansoor Karimifar

2014-01-01

Full Text Available Background: Rheumatoid arthritis (RA is a common autoimmune disease that is associated with progressive disability, systemic complications, and early death. The present study was aimed to investigate the level of immunoglobulin G (IgG and IgA isotypes and anti-cyclic citrullinated peptide (CCP antibody and to assess their association with disease severity based on disease activity score (DAS-28 in patients with IgM rheumatoid factor (IgM-RF negative RA. Materials and Methods: In this cross-sectional study, 62 RA patients with IgM-RF negative were assessed. Radiographs were obtained for all RA patients. The RF (IgG, and IgA and anti-CCP were measured by using the enzyme-linked immunosorbent assay. Values of cut-off points over 15 UI/mL for IgA IgA-RF, 20 UI/mL for IgG-RF and over 20 units for anti-CCP were considered positive. DAS-28 score was compared in regard to the IgA-RF and IgG-RF and anti-CCP positivity using Mann-Whitney test. Results: DAS-28 score in IgA-RF positive was significantly higher than IgA-RF negative (mean score, 6.03 ± 0.33 vs. 5.44 ± 0.76 respectively, P = 0.035. In IgG-RF positive patients, DAS-28 score was similar to patients with IgG-RF negative (5.64 ± 0.59 vs. 5.46 ± 0.78 respectively, P = 0.396. Furthermore, in patients with anti-CCP positive DAS-28 score was significantly higher than patients with anti-CCP negative (5.72 ± 0.61 vs. 5.38 ± 0.79 respectively, P = 0.049. Conclusion: Findings indicated that there was a significant association between the amounts of IgA and anti-CCP with severity of disease in RF negative RA patients while there was no significant association between the amounts of IgG and severity of RA disease.

Fibromyalgia Complicating Disease Management in Rheumatoid Arthritis

International Nuclear Information System (INIS)

Abbasi, L.; Haidri, F. R.

2014-01-01

Objective: To evaluate frequency of fibromyalgia in rheumatoid arthritis and its effect on disease activity score. Study Design: Cross-sectional study. Place and Duration of Study: The Indus Hospital, Karachi, from December 2010 to May 2011. Methodology: All adult patients of either gender diagnosed as rheumatoid arthritis on the basis of clinical, laboratory and X-ray criteria were included in the study. The sample data was separated into two groups depending on presence or absence of fibromyalgia and 28 joint disease activity score (DAS-28) value was evaluated. Results: There were 31 (25.83%) patients with rheumatoid arthritis and fibromyalgia (RAFM) out of the total 120. The median (IQR) age of patients was 40 (32 - 51) years. All were females. The overall female frequency was 79 (88.8%). The median (IQR) DAS-28 score in RA group was 4.9 (3.66 - 5.71), while the median (IQR) DAS-28 score in RAFM was 7.04 (6.62 - 7.64) [p < 0.0001]. The number of patient getting combination therapy of DMARD in RAFM group was 61.3% while in RA group was 42.7%. Conclusion: DAS-28 was found to be significantly higher in RAFM patients probably because of higher perception of pain. (author)

CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic 'window of opportunity'

DEFF Research Database (Denmark)

Greisen, Stinne Ravn; Schelde, Karen Kræmmer; Rasmussen, Tue Kruse

2014-01-01

placebo (DMARD) (n¿=¿37) or methotrexate plus adalimumab (DMARD¿+¿ADA) (n¿=¿39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n¿=¿38) were also examined.ResultsBaseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients...... in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho¿=¿0.34) and 40 (rho¿=¿0.39), visual analogue score (rho¿=¿0.38) and simplified disease activity index (rho¿=¿0.25) (all P¿... a significantly 2-fold more in the DMARD¿+¿ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho¿=¿0.58, p¿

Dyslipidemia Pattern in Rheumatoid Arthritis Patients with Correlation of Disease Activity

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Prakash Joshi

2017-06-01

Full Text Available Rheumatoid arthritis (RA is a multi-factorial disease which affects the immune system and ultimately various tissues in the body that typically affects middle-aged individuals. Our objectives were to evaluate prevalence of dyslipidemias and its pattern in RA patients in Central India and correlate dyslipidemia with disease activity. This cross-sectional study was conducted on RA patients at Sri Aurobindo Institute of Medical Sciences and Post Graduate Institute, Indore (M.P. between January 2014 and December 2015. Lipid profiles were determined following 12-hour overnight fasting, and the association of lipid profiles with and disease activity was determined. The maximum number of cases presented in the age group was 41-50(36%. Disease is more prevalent in female population. Maximum number of pateints (34 patients had duration of illness ranged between 1 to 10 years. Most of the patients presented with high disease activity (90%. Total cholesterol levels were significantly higher in female cases as compared to controls. Similar to total cholesterol, LDL cholesterol was significantly higher in female cases as compared to controls. There was no significant difference of HDL, VLDL and TG between cases and controls. Mean lipid profile values were similar in male cases and controls. Positive correlation of DAS-28 (ESR was observed with total cholesterol and LDL levels in female patients only. No correlation of HDL, LDL and triglyceride were observed with DAS- 28 (ESR in both male and female patients. Lipid profiles were similar in both treatment naive and on treatment patients. No significant difference in mean lipid profile values expect HDL was observed in two groups created on the basis of RA factor. A lipid profile value has no positive or negative correlation with duration of illness. [J Contemp Med 2017; 7(2.000: 132-137

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

Science.gov (United States)

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

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Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Correlations between fatigue and disease duration, disease activity, and pain in patients with rheumatoid arthritis: a systematic review

DEFF Research Database (Denmark)

Groth Madsen, S.; Danneskiold-Samsøe, B.; Stockmarr, Anders

2016-01-01

of correlation measures between fatigue and the covariates. RESULTS: A total of 121 studies were included in the analyses, including > 100 000 RA patients. A high level of fatigue was seen even in well-treated patients, demonstrating fatigue as a major problem in RA. Fatigue was found to be positively correlated...... in MEDLINE and EMBASE, followed by selection of studies according to set criteria, data extraction, and statistical analyses of the relationships in RA between fatigue and the following covariates: disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the 28-joint Disease Activity...... Score (DAS28), swollen to tender joint count ratio (STR), and pain. Linear regression analyses of fatigue regressed on each of the six covariates, and a multiple regression analysis where fatigue was regressed on the six covariates through a forward selection procedure was carried out with construction...

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

Science.gov (United States)

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-01-01

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

Urological comorbidities in Egyptian rheumatoid arthritis patients: Risk factors and relation to disease activity and functional status

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Marwa Niazy

2017-10-01

Full Text Available Aim of the work: To assess the urological disorders in rheumatoid arthritis (RA patients, analyse the risk factors and to find their relation to disease activity and functional status. Patients and methods: 291 RA patients (253 females and 38 males; F:M 6.7:1 and 242 matched controls were included. Urological disorders in the form of urinary tract infections (UTI, urolithiasis and acute urine retention (AUR were assessed, risk factors were analysed. Disease activity score (DAS-28 and modified health assessment questionnaire (mHAQ were calculated. Results: RA patients had more frequent urological disorders (38.14% than controls (20.66%, more UTI (p < 0.001 and this difference persisted in females (p < 0.001. Urolithiasis tended to be more frequent in RA patients (p = 0.3; the difference was significant between the female patients and controls (p = 0.04. Urinary stones were comparable between the male patients and controls (p = 0.2. RA patients had more AUR (4.8% than the controls (2.1% (p = 0.07. Asthmatic patients particularly the females had more UTI (p = 0.001 and p < 0.001 respectively. UTIs were observed with higher steroid doses (p = 0.04 and urolithiasis were noticed more in hypertensive female patients (p = 0.03. Patients with higher DAS-28 and mHAQ developed more urological comorbidities (p0.49 and p = 0.82 respectively. UTI and urolithiasis were detected in patients with higher DAS 28 (p = 0.1 and p = 0.4 respectively. Conclusion: RA patients were found to have more urological disorders. Bronchial asthma, hypertension and higher steroid doses may increase risk for urinary comorbidities in RA. Patients with higher DAS28 and mHAQ had more urological comorbidities, however without statistically significant difference.

AN ASSOCIATION OF CYTOKINE LEVELS WITH DISEASE ACTIVITY, AUTOANTIBODY LEVELS, AND JOINT DESTRUCTIVE CHANGES IN EARLY RHEUMATOID ARTHRITIS

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A. S. Avdeeva

2015-01-01

Full Text Available Objective: to assess the association of cytokine profile measures with disease activity, autoantibody levels, and joint destructive changes in patients with early rheumatoid arthritis (RA.Subjects and methods. Forty-five patients, including 35 women, with early RA were examined. Their median age was 53.5 [46; 59.5] years; the duration of the disease – 7.0 [4.0; 11.5] months; DAS28 – 5.8 [4.9; 6.4]; 91 and 96% of the patents were positive for rheumatoid factor (RF and anticyclic citrullinated peptide antibodies, respectively. Serum cytokine concentrations were estimated using the xMAP multiplex technology. The modified Sharp method was employed to quantify radiographic changes.Results and discussion. A group of 30 patients with high disease activity (DAS28 >5.1 had higher levels of interleukin (IL-6 (62.3 [36.1; 127.5] pg/ml and IP-10 (6367.8 [3682.7; 10691.3] pg/ml than 15 patients with moderate/low disease activity (DAS28 ≤5.1 (35.8 [13.4; 64.2] and 3222.6 [1881.0; 5671.9] pg/ml, respectively, p < 0.05. The patients highly positive for IgM RF had higher levels (pg/ml of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-12, IL-15, interferon-γ, and tumor necrosis factor-α; the chemokine monocyte chemotactic protein-1 and the growth factors IL-7 and vascular endothelial growth factor (4.8 [2.8; 19.3], 23.0 [7.1; 55.8], 64.2 [41.6; 170.5], 52.2 [30.9; 126.9], 2.4 [0.2; 11.2], 210.8 [119.9; 584.2], 90.7 [42.7; 307/9], 57.5 [26.1; 93.8], 54.9 [37.1; 123.7], and 143.3 [70.6; 249.6] pg/ml than those who were negative/lowly positive for IgM RF (2.3 [1.9; 3.1], 4.9 [2.9; 16.8], 24.9 [20.4; 45.4], 25.6 [19.9; 57.1], 0.2 [0.01; 1.65], 94.4 [86.3; 138.9], 37.3 [23.6; 47.7], 20.9 [12.3; 33.9], 32.6 [28.1; 37.8], 74.2 [53.5; 147.6], respectively (p < 0.05.Conclusion. There are significant differences in cytokine profile measures in patients with early RA in relation to disease activity and serum autoantibody levels.

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

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Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Shared care or nursing consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis outpatients with low disease activity--patient outcomes from a 2-year, randomised controlled trial

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Primdahl, Jette; Sørensen, Jan; Horn, Hans Christian

2014-01-01

were randomised to 2-year follow-up by either: (1) planned rheumatologist consultations, (2) shared care without planned consultations or (3) planned nursing consultations. The primary outcome was change in disease activity. DAS28-CRP, Health Assessment Questionnaire, visual analogue scale (VAS......)-pain, fatigue, global health, confidence and satisfaction, quality-of-life by the Short Form 12 and self-efficacy measured by the RA Self-Efficacy questionnaire and the Arthritis Self-Efficacy Scale, were recorded annually and safety measures were recorded. x-Rays of hands and feet were taken at baseline...... and at 2-year follow-up. Mixed effect models were used to explore differences between the three groups over time. RESULTS: At 2-year follow-up, the group allocated to nursing consultations had lower disease activity than the group that underwent rheumatologist consultations (DAS28-CRP -0.3, p=0...

Use of exploratory factor analysis to ascertain the correlation between the activities of rheumatoid arthritis and infection by human parvovirus B19.

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Kakurina, Natalja; Kadisa, Anda; Lejnieks, Aivars; Mikazane, Helena; Kozireva, Svetlana; Murovska, Modra

2015-01-01

We evaluated a possible correlation between the clinical activities of rheumatoid arthritis (RA) and human parvovirus B19 (B19) infection using exploratory factor analysis (EFA). RA patients were organized into two groups: 100 patients in the main group and 97 in the RA(DAS28) group. Four subgroups were defined from the main group according to the presence or absence of certain infection-specific markers: group I comprised 43 patients who had IgG antibodies against B19; group II, 25 patients with active B19 infection (B19-specific IgM antibodies and/or plasma viremia); group III, 19 patients with latent/persistent B19 infection (virus-specific sequences in peripheral blood leukocytes' DNA with or without B19-specific IgG antibodies), and group IV, 13 patients without infection markers. The RA(DAS28) group was divided into four subgroups similarly to the main group: group I, 35; group II, 31; group III, 19; and group IV, 12 patients. Disease-specific clinical values in both groups were analyzed employing EFA, and the RA(DAS28) group was additionally assessed using Disease Activity Score (DAS)28. RA activity was higher in patients who had markers of B19 infection. The highest activity of RA in both study groups was in patients with latent/persistent infection. In the RA(DAS28) group, according to DAS28, the highest activity of RA was in patients with active B19 infection. Using EFA and DAS28, a correlation between the clinical activity of RA and B19 infection was confirmed. These data suggest that EFA is applicable for medico-biological studies. Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Korean Red Ginseng exhibits no significant adverse effect on disease activity in patients with rheumatoid arthritis: a randomized, double-blind, crossover study

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Soo-Kyung Cho

2018-04-01

Full Text Available Background: Panax ginseng is a well-known immune modulator, and there is concern that its immune-enhancing effects may negatively affect patients with rheumatoid arthritis (RA by worsening symptoms or increasing the risk of adverse effects from other drugs. In this randomized, crossover clinical trial, we evaluated the impact of Korean Red Ginseng (KRG on disease activity and safety in RA patients. Methods: A total of 80 female RA patients were randomly assigned to either the KRG (2 g/d, n = 40 treatment or placebo (n = 40 groups for 8 wk, followed by crossover to the other treatment group for an additional 8 wk. The primary outcome was the disease flare rate, defined as worsening disease activity according to the disease activity score 28 joints-erythrocyte sedimentation rate (DAS28-ESR. The secondary outcomes were development of adverse events (AEs and patient reported outcomes. Outcomes were evaluated at baseline and 8 wk and 16 wk. The outcomes were compared using the Chi-square test. Results: Of the 80 patients, 70 completed the full study. Their mean age was 51.9 yr, and most exhibited low disease activity (mean DAS28-ESR 3.5 ± 1.0 at enrollment. After intervention, the flare rate was 3.7% in each group. During KRG treatment, 10 AEs were reported, while five AEs were developed with placebo; however, this difference was not statistically significant (p = 0.16. Gastrointestinal- and nervous system-related symptoms were frequent in the KRG group. Conclusion: KRG is not significantly associated with either disease flare rate or the rate of AE development in RA patients. Keywords: effect, Korean Red Ginseng, rheumatoid arthritis, safety

Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

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Jacobsen, Søren; Garred, Peter; Madsen, Hans Ole

2009-01-01

OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease...... modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease...... activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2...

Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA

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Sørensen, Jan; Primdahl, J; Horn, Hc

2014-01-01

per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Conclusions: Shared care and nurse care seem to cost less but provide broadly similar......Objectives: To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). Method: In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse...... consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient...

Sarcopenia in rheumatoid arthritis: prevalence, influence of disease activity and associated factors.

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Ngeuleu, Ange; Allali, F; Medrare, L; Madhi, A; Rkain, H; Hajjaj-Hassouni, N

2017-06-01

Evaluate the prevalence of sarcopenia on patients with rheumatoid arthritis (RA), the influence of sarcopenia on disease activity and factors associated with sarcopenia. One hundred and twenty-three patients aged over 18 years with RA based on the 1987 ACR/EULAR classification criteria were enrolled. We performed a whole body DXA scan using a dual-energy X-ray absorptiometry (DXA) scanner lunar prodigy to measure fat mass, lean mass, and bone mass in the whole body and body parts. According to the anthropometric equation by Baumgartner et al., sarcopenia was defined as Relative skeletal mass index (RSMI) sarcopenia with the r of Pearson and Spearman. Factors associated and related to sarcopenia were assessed using multiple regression analysis and t independent test. We included 123 patients (107 women). 49 subjects (39.8%) where suffering from sarcopenia, of which 40 women. Most of the sarcopenic patients were between 41 and 50 years old. Sarcopenia on female subjects was not related to parameters of disease activity evaluated by DAS 28, CDAI and SDAI. Most of the sarcopenic patients had normal BMI and abnormal waist circumference. In simple regression analysis sarcopenia was related to BMI, DAS 28 ESR, bone erosion, waist circumference and HAQ. In multiple regression analysis, sarcopenia was positively related to an increase cardiometabolic risk [p = 0.025, OR 0.176, CI (0.038-0.980)], normal BMI [p = 0.004, OR 12.3, CI (2.27-67.6)], over fat BMI [p = 0.004, OR 12.3, CI (2.27-67.6)] and bone erosion [p = 0.012, OR 0.057 CI (0.006-0.532)]. No statistical difference was found according to disease duration and steroids use between sarcopenic and non sarcopenic patients. Sarcopenia is prevalent and related to age, bone erosion, normal/over fat BMI and high cardiometabolic risk according to waist circumference but not with disease activity.

Comorbidities in Turkish patients with rheumatoid arthritis: association with the health-related quality of life in terms of disease activity, functional and radiological status, severity of pain, and social and emotional functioning

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Yesim Garip

2016-10-01

Full Text Available Aims: The aim of our study was to investigate the comorbidities in Turkish RA patients and evaluate the impact of comorbidities on health-related quality of life (HRQoL in terms of disease activity, functional and radiological status, severity of pain, and social and emotional functioning. Methods: In a cross-sectional setting, a total of 160 RA patients who were admitted to our outpatient clinic between December 2013 and February 2014 were consecutively enrolled in the study. Comorbidities were recorded. Disease activity was measured by using Disease Activity Score-28 (DAS28. Stanford Health Assessment Questionnaire (HAQ was used for determining functional status, Nottingham Health Profile (NHP for HRQoL, and modified Sharp Score for radiological damage. Major results: Comorbidities were reported in 107 patients (66.88 %. The most common was peptic ulcer (31.25%. This was followed by osteoporosis (21.25%, dyslipidemia (15.63%, depression (15%, hypertension (13.75%, diabetes mellitus (13.13%, thyroid disorders (%8.13, lung diseases (%6.88, cardiovascular diseases (6.25%, and cancers [(1 breast cancer, 1 malign melanoma, 3 lung carcinoma, 3.13%], respectively. Patients with comorbidities scored significantly higher in DAS28, HAQ, pain, energy and physical mobility subgroups of NHP (p0.05. Conclusions: Comorbid conditions of RA are common and associated with more active and severe disease and functional impairment. Comorbidities should be detected and treated earlier to reduce its negative impact on outcome in RA.

Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity

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F. Ragni Alunni

2011-09-01

Full Text Available Background: There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. Objectives: To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. Methods: Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score £3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. Results: Patients had higher intima-media thickness than controls of all the sites evaluated at carodit artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. Conclusions: Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

Relationship between leptin concentrations and disease activity in patients with rheumatoid arthritis.

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Batún-Garrido, José Antonio de Jesús; Salas-Magaña, Marisol; Juárez-Rojop, Isela Esther; Hernández-Núñez, Eúfrates; Olán, Francisco

2018-05-11

Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). The data suggest that serum leptin is elevated in patients with active RA. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis

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Christensen, Anton Wulf; Rifbjerg-Madsen, Signe; Christensen, Robin

2014-01-01

activity score DAS28 can classify some patients with active RA solely based on a high tender joint count and poor patient global health score. In such cases, intensified treatment with anti-inflammatory drugs would be expected to yield poorer results than in cases with DAS28 elevation due to a high score...... (ie, degree of central sensitisation). The main objective of this study was to examine the prognostic values of pressure pain-induced temporal summation, ultrasound Doppler activity and the interaction between them in relation to treatment response (DAS28-CRP change) in patients with RA initiating any...... anti-inflammatory therapy. METHOD AND ANALYSIS: 120 participants ≥18 years of age will be recruited. Furthermore, they must be either (1) diagnosed with RA, untreated with disease-modifying antirheumatic drugs for at least 6 months and about to initiate disease-modifying antirheumatic drug treatment...

Expression of K2P5.1 potassium channels on CD4+ T lymphocytes correlates with disease activity in rheumatoid arthritis patients.

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Bittner, Stefan; Bobak, Nicole; Feuchtenberger, Martin; Herrmann, Alexander M; Göbel, Kerstin; Kinne, Raimund W; Hansen, Anker J; Budde, Thomas; Kleinschnitz, Christoph; Frey, Oliver; Tony, Hans-Peter; Wiendl, Heinz; Meuth, Sven G

2011-02-11

CD4+ T cells express K(2P)5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K(2P)5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K(2P)5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Expression levels of K(2P)5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K(2P)5.1. K(2P)5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K(2P)5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K(2P)5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Disease activity in RA patients correlates strongly with K(2P)5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K(2P)5.1 as a potential biomarker for disease activity and differential diagnosis.

Influence of anti-cyclic citrullinated peptide on disease activity, structural severity, and bone loss in Moroccan women with rheumatoid arthritis

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Imad Ghozlani

2018-04-01

Full Text Available Aim of the work: The aim of this study was to assess the influence of anti-cyclic citrullinated peptide (anti-CCP on disease activity, radiological severity, functional disability and bone loss in Moroccan women with rheumatoid arthritis (RA. Patients and methods: One hundred and thirty-six women with RA were recruited. Age, weight, height, disease duration and steroids cumulative dose were identified. Anti-CCP and Rheumatoid factor (RF were determined. Disease activity score (DAS28 was assessed and functional repercussion measured by the Health Assessment Questionnaire-disability index (HAQ-DI. Radiological status was assessed by the Sharp/van der Heijde (SvH erosion and narrowing score. Bone mineral density was determined by a Lunar Prodigy Vision Dual-energy X-ray absorptiometry and vertebral fracture assessment was classified using a combination of Genant semi-quantitative approach and morphometry. Results: Patients mean age was 49.6 ± 7.4 years and disease duration 7.7 ± 5 years. 109 (80.1% patients were anti-CCP positive. There was no significant difference in DAS28 between patients with and without anti-CCP. Nevertheless, weight, erythrocyte sedimentation rate (ESR, rheumatoid factor titer and positivity, SvH narrowing and erosion score and osteoporosis were significantly higher in patients with positive anti-CCP. Stepwise regression analysis showed that the presence of anti-CCP was independently associated with osteoporosis and SvH erosion score. Conclusions: Anti-CCP antibodies are strongly predictive for the development of osteoporosis and erosions in Moroccan RA patients. They not only have a valuable role in the disease prognosis prediction but also may be a relevant determinant of bone loss in RA. The presence of these antibodies warrants special attention. Keywords: Rheumatoid arthritis, Anti-cyclic citrullinated peptide, Disease activity, Joint damage, Bone loss

Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis

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Dirven Linda

2012-07-01

Full Text Available Abstract Objective To determine the prevalence of vertebral fractures (VFs after 5 years of disease activity score (DAS-steered treatment in patients with early rheumatoid arthritis (RA and to investigate the association of VFs with disease activity, functional ability and bone mineral density (BMD over time. Methods Five-year radiographs of the spine of 275 patients in the BeSt study, a randomized trial comparing four treatment strategies, were used. Treatment was DAS-steered (DAS ≤ 2.4. A height reduction >20% in one vertebra was defined a vertebral fracture. With linear mixed models, DAS and Health Assessment Questionnaire (HAQ scores over 5 years were compared for patients with and without VFs. With generalized estimating equations the association between BMD and VFs was determined. Results VFs were observed in 41/275 patients (15%. No difference in prevalence was found when stratified for gender, prednisone use and menopausal status. Disease activity over time was higher in patients with VFs, mean difference 0.20 (95% CI: 0.05-0.36, and also HAQ scores were higher, independent of disease activity, with a mean difference of 0.12 (95% CI: 0.02-0.2. Age was associated with VFs (OR 1.06, 95% CI: 1.02-1.09, mean BMD in spine and hip over time were not (OR 95% CI, 0.99: 0.78-1.25 and 0.94: 0.65-1.36, respectively. Conclusion After 5 years of DAS-steered treatment, 15% of these RA patients had VFs. Higher age was associated with the presence of VFs, mean BMD in hip and spine were not. Patients with VFs have greater functional disability over time and a higher disease activity, suggesting that VFs may be prevented by optimal disease activity suppression.

THE RELATIONSHIP OF FoxP3+ T REGULATORY CELLS TO DISEASE ACTIVITY AND ANTIBODY LEVELS IN EARLY RHEUMATOID ARTHRITIS

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A. S. Avdeeva

2017-01-01

Full Text Available Objective: to analyze the relationship of the count of FoxP3+ T regulatory cells (Tregs to the clinical and laboratory parameters of disease activity and the levels of antibodies in a group of patients with early rheumatoid arthritis (RA.Subjects and methods. The investigation enrolled 45 patients with early RA (2010 ACR/EULAR criteria who had not previously received treatment with methotrexate, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28 5.01 [4.18; 5.8]; 71.1% of the patients were rheumatoid factor (RF positive and 88.9% were anti-cyclic citrullinated peptide positive. The relative and absolute counts of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+ were measured by immunofluorescence staining and multicolor flow cytometry. A control group consisted of 20 healthy donors who were matched for sex and age with the examined patients.Results and discussion. DАS28 was high, moderate, and low in 22 (48.9%, 20 (44.4%, and 3 (6.7% patients, respectively. As compared with the healthy donors, the patients with early RA were observed to have lower values in the percentage of FoxP3+CD25+ cells, in the percentage and absolute count of FoxP3+ICOS+ cells, in the percentage and absolute count of FoxP3+CD154+ and FoxP3+ CD274+ T cells; p<0.05 in all cases. Negative correlation was recorded between the percentage of FoxP3+CD25+ and C-reactive protein (CRP (r=-0.4; that of CD152+intracellular and DAS28 (r=-0.35, ESR (r=-0.46, CRP (r=-0.54; that of FoxP3+CD127 and CRP (r=-0.42; that of CD25+CD127 and DAS28 (r=-0.38, SDAI (r=-0.41, CDAI (r=-0.36, ESR (r=-0.39, CRP (r=-0.47; p<0.05 in all cases.The patients who were seronegative for RF were found to have higher values in the percentage of CD25+CD127, in the percentage and absolute count of Foxp3+CD154+ and Foxp3+CD274+ T lymphocytes.Conclusion. The given data may indicate that the

Severe deficiency of 25-hydroxyvitamin D3 (25-OH-D3) is associated with high disease activity of rheumatoid arthritis

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Haga, Hans-Jacob; Schmedes, Anne; Naderi, Yusuf

2013-01-01

This study aims to measure the serum level of 25-hydroxyvitamin D₃ (25-OH-D₃) in 302 patients with rheumatoid arthritis (RA), studying the association to disease activity. Three hundred two RA patients underwent clinical examination and serological analysis. 25-Hydroxyvitamin D₃ was determined...... by high-performance liquid chromatography-tandem mass spectrometry. Vitamin D₃ deficiency defined as serum levels of 25-hydroxyvitamin D₃ below 50 nmol/l was detected in 101 RA patients (33.4 %). There was no significant correlation between the serum level of 25-hydroxyvitamin D₃ and Disease Activity...... Score 28 (DAS28) (3w) score. In a subpopulation of RA patients with very low serum level of 25-OH-D₃ (≤15 nmol/l) (n = 15), there were significant differences compared to patients with normal 25-OH-D3 (n = 200): higher percentage of patients with positive rheumatoid factor (100.0 versus 77.5 %; p = 0...

Trends towards an improved disease state in rheumatoid arthritis over time: influence of new therapies and changes in management approach: analysis of the EMECAR cohort.

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González-Alvaro, Isidoro; Descalzo, Miguel Angel; Carmona, Loreto

2008-01-01

The disease activity in patients with rheumatoid arthritis has improved during the past decade. The availability of new drugs and also a better assessment of the disease have been proposed to be responsible for this improvement. In the present work we estimate the effect of these factors on disease activity and function in patients with rheumatoid arthritis at the beginning of the new century. The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled in 2000 from the random sampling of rheumatoid arthritis patients registered in 34 centers. The cohort was composed of 789 patients who underwent a baseline assessment plus four annual follow-up visits in which functional ability (Health Assessment Questionnaire score), the disease activity score obtained from 28-joint count with three parameters (DAS28-3) and radiological progression (Larsen score) were recorded. The effect of the calendar year on the DAS28-3, the Health Assessment Questionnaire score, and the Larsen score was obtained from adjusted models in which all treatments were included as dummy variables. The effect of time as the beta coefficient (95% confidence interval) for 2004, taking 2000 as a reference year, was -0.43 (-0.58 to -0.28) for the DAS28-3, 0.15 (0.07 to 0.22) for the Health Assessment Questionnaire score, and 4.4 (2.68 to 6.12) for the Larsen score. Treatment with new therapies, either leflunomide or TNF antagonists, increased in frequency from 1.1% (n = 8) in 2000 to 30.9% (n = 144) in 2004. Treatment with TNF antagonists (-0.28 (-0.5 to -0.05)) and with gold salts (-0.21 (-0.38 to -0.04)) was independently associated with a decrease in the DAS28-3 over time, whereas cyclosporin A treatment (0.45 (0.13 to 0.76)) was associated with an increase in disease activity. The mean disease activity of rheumatoid arthritis has improved from 2000 to 2004. An explanation is the introduction of new therapies, but not solely. Other factors related to the

The effect of an intensive smoking cessation intervention on disease activity in patients with rheumatoid arthritis

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Roelsgaard, Ida Kristiane; Thomsen, Thordis; Østergaard, Mikkel

2017-01-01

in patients with RA. Methods: This will be a multicentre, open label, two arm, parallel group, RCT, including 150 daily smokers with RA, being in remission or having low-moderate disease activity (DAS28 ≤ 5.1). The intervention group (n = 75) will receive five counselling sessions with a trained smoking...... cessation counsellor based on the principles of motivational counselling. Furthermore, intervention patients will be offered nicotine replacement therapy tailored to individual needs. Participants randomised to the control group will receive standard care. The co-primary outcome is a hierarchical endpoint...... intervention (motivational counselling combined with tailored nicotine replacement therapy) versus standard care on smoking cessation, and consequently on disease activity. Secondary objectives are to explore the effect on flare, risk factors for CVD, lung function, physical function, HR-QoL, pain and fatigue...

Power of national economy, disease control and employment status in patients with RA-an analytical multi-site ecological study.

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Pieringer, Herwig; Puchner, Rudolf; Pohanka, Erich; Danninger, Kathrin

2016-02-01

In rheumatology, sufficient disease control is a central part of the treatment concept. However, modern treatment strategies are associated with a substantial economic burden for health care systems. Ecological studies offer the unique opportunity to analyse differences between groups as well as group level effects. In the present analytical multi-site ecological study, we investigated whether more powerful national economies as measured by the gross domestic product per capita (GDPpc) are associated with better disease control in RA patients as measured by the disease activity score 28 (DAS28). We used aggregated data on RA patients from the recently published COMORA study as well as the World Health Organization database. There was a strong negative correlation between DAS28 and GDPpc (r = -0.815; p = 0.0002). Adjustment for sex, smoking status, disease duration or current employment status did not significantly change this association. There was a strong, negative correlation between DAS28 and age (r = -0.870; p < 0.001) and a strong, positive correlation between GDPpc and age (r = 0.737; p = 0.002). Adjustment for age reduced the regression coefficient (DAS28/GDPpc) to -0.000018 (p = 0.054). There was a negative correlation between DAS28 and current employment status (r = -0.642; p = 0.008) and a positive correlation between GDPpc and employment status (r = 0.722; p = 0.002). In conclusion, there is evidence of an association between disease control and GDPpc. This association is alleviated after adjustment for age. Of note, in countries with higher GDPpc, a higher proportion of RA patients are currently employed. This is true despite the fact that RA patients in countries with higher GDPpc are also older.

Influence of balneophysical therapy on activity, functional capacity, and quality of life in patients with rheumatoid arthritis

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Stojanović Sonja

2009-01-01

Full Text Available Introduction It has been well known that balneophysical therapy has a therapeutic effect on clinical and biological parameters of disease activity in the patients with rheumatoid arthritis (RA. Objective. To determine the influence of balneophysical therapy on functional capacity, activity and quality of life of the patients with RA primarily treated with some of disease modifying antirheumatic drugs. Methods. The study enrolled 73 patients with RA treated with some of disease modifying antirheumatic drugs (Methotrexate in 85% of patients. During hospitalization at the Clinical Rheumatologic Department of the Institute 'Niska Banja', the patients were treated, beside the medicamentous therapy, by hydrotherapy (oligomineral, homeothermic, low radioactive water, mineral peloid therapy, electrotherapy and kinesiotherapy. Before and after balneotherapy, the patients filled in the Health Assessment Questionnaire (HAQ and the Quality of Life Rheumatoid Arthritis (QOL-RA scale. The Disease Activity Score (DAS 28 was used to measure the disease activity before and after balneotherapy. A possible value of HAQ was from 0 to 3, and QOL-RA from 0 to 10. Results. The mean value of the duration of balneophysical therapy was 14.7±4.8 days. We found significant improvement of functional capacity in the patients with RA. The average HAQ score before balneotherapy was 1.07±0.61, and 0.86±0.55 after balneotherapy, which was statistically significantly lower (p<0.05. DAS 28 after balneotherapy was also statistically significantly lower than DAS 28 before balneotherapy: the mean value of DAS 28 before therapy was 6.30±0.81 and after therapy 5.48±0.75 (p<0.001. The quality of life significantly improved after balneophysical therapy: the mean value of QOL-RA scale before therapy was 5.38±1.62 and after therapy 7.35±1.81 (p<0.05. Conclusion. Balneophysical therapy, when properly dosed, is an effective, adjuvant therapy in the patients with RA of mild disease

A K Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. A K Das. Articles written in Bulletin of Materials Science. Volume 28 Issue 2 April 2005 pp 131-136 Fly Ash. Some studies on the reaction between fly ash and lime · A Basumajumdar A K Das N Bandyopadhyay S Maitra · More Details Abstract Fulltext PDF. The reaction between ...

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

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Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Cut-Offs and Response Criteria for the Hospital Universitario La Princesa Index (HUPI and Their Comparison to Widely-Used Indices of Disease Activity in Rheumatoid Arthritis.

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Isidoro González-Álvaro

Full Text Available To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI in patients with chronic polyarthritis.Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal [PEARL] study and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide [EMECAR] including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC analysis. The areas under ROC (AUC were compared to those of validated indexes (SDAI, CDAI, DAS28. ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI.The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if ≤2, low disease activity if >2 and ≤5, moderate if >5 and <9 and high if ≥9. HUPI's AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28's AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756 and CDAI (AUCs: 0.789 and 0.728. HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values.The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis.

Cut-Offs and Response Criteria for the Hospital Universitario La Princesa Index (HUPI) and Their Comparison to Widely-Used Indices of Disease Activity in Rheumatoid Arthritis.

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González-Álvaro, Isidoro; Castrejón, Isabel; Ortiz, Ana M; Toledano, Esther; Castañeda, Santos; García-Vadillo, Alberto; Carmona, Loreto

2016-01-01

To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal [PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide [EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if ≤2, low disease activity if >2 and ≤5), moderate if >5 and <9 and high if ≥9. HUPI's AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28's AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis.

Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.

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Smolen, Josef S; Aletaha, Daniel; Gruben, David; Zwillich, Samuel H; Krishnaswami, Sriram; Mebus, Charles

2017-04-01

Tofacitinib is an oral JAK inhibitor that is used for the treatment of rheumatoid arthritis (RA). In previous clinical trials of tofacitinib, a Disease Activity Score in 28 joints (DAS28)-based analysis was used to assess outcomes. In this study, remission rates according to various remission criteria were evaluated across 5 phase III randomized controlled studies. In all 5 studies, tofacitinib was administered at a dosage of 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs. One of the studies included adalimumab 40 mg once every 2 weeks. In addition to the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]), a primary efficacy variable used in the phase III studies, disease activity was assessed post hoc by the 4-variable DAS28 using the C-reactive protein level (DAS28-4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean-based assessment. A total of 3,306 patients were analyzed (1,213 of these patients received tofacitinib 5 mg twice daily, 1,212 received tofacitinib 10 mg twice daily, 679 received placebo, and 202 received adalimumab 40 mg every 2 weeks). Remission rates varied according to the criteria used, with higher rates in the active-treatment groups for the DAS28-4(CRP) than for other scores. At month 3, remission rates with tofacitinib 5 mg twice daily were 18-22% using the DAS28-4(CRP), 5-10% using the DAS28-4(ESR), 4-7% using the SDAI, 5-6% using the CDAI, and 2-7% using the Boolean-based method. In contrast, the remission rates with placebo varied from 0% to 7%, with small differences between the DAS28-4(ESR) and the DAS28-4(CRP). Although tofacitinib at dosages of 5 mg twice daily and 10 mg twice daily was effective compared with placebo in achieving disease remission, regardless of the disease activity measure, remission rates were substantially higher when

The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study

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Emamifar, Amir; Jensen Hansen, Inger Marie

2018-01-01

To investigate the impact of comorbid diseases on rheumatoid arthritis (RA) outcome. All patients diagnosed with RA since 2006, who were registered in our local Danbio registry, were included in this cohort study. Patients’ demographics, serology results, and Disease Activity Score in 28 joints......-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months of treatment initiation were collected. Patients’ electronic hospital records were evaluated for a positive history of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency, and the presence of other...... diagnosed autoimmune diseases. 1035 RA patients were included. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid...

Enhancement of soluble CD28 levels in the serum of Graves' disease.

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Sun, Zhongwen; Yi, Lixian; Tao, Hong; Huang, Jingfang; Jin, Zhenghong; Xiao, Yang; Feng, Caiyun; Sun, Jing

2014-01-01

Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

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Lang Yi

2016-01-01

Full Text Available The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA patients, and healthy controls (HC in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28. In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

MiDAS: the field guide to the microbes of activated sludge.

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McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads; Nierychlo, Marta; McIlroy, Bianca; Hansen, Aviaja Anna; Karst, Søren Michael; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

2015-01-01

The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes--knowledge that will be an invaluable resource for the optimal design and operation of these systems. © The Author(s) 2015. Published by Oxford University Press.

Changing clinical patterns in rheumatoid arthritis management over two decades: sequential observational studies.

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Mian, Aneela N; Ibrahim, Fowzia; Scott, Ian C; Bahadur, Sardar; Filkova, Maria; Pollard, Louise; Steer, Sophia; Kingsley, Gabrielle H; Scott, David L; Galloway, James

2016-01-27

Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ). Four cross-sectional surveys between 1996 and 2014 in two adjacent secondary care rheumatology departments in London evaluated changes in drug therapy, DAS28 and its component parts and HAQ scores (in three surveys). Descriptive statistics used means and standard deviations (SD) or medians and interquartile ranges (IQR) to summarise changes. Spearman's correlations assessed relationships between assessments. 1324 patients were studied. Gender ratios, age and mean disease duration were similar across all cohorts. There were temporal increases in the use of any DMARDs (rising from 61% to 87% of patients from 1996-2014), combination DMARDs (1% to 41%) and biologic (0 to 32%). Mean DAS28 fell (5.2 to 3.7), active disease (DAS28 > 5.1) declined (50% to 18%) and DAS28 remission (DAS28 disability measured by HAQ. As a consequence the relationship between DAS28 and HAQ has become weaker over time. Although the reasons for this divergence between disease activity and disability are uncertain, focussing treatment entirely in suppressing synovitis may be insufficient.

Percentages of CD4+CD161+ and CD4−CD8−CD161+ T Cells in the Synovial Fluid Are Correlated with Disease Activity in Rheumatoid Arthritis

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Jinlin Miao

2015-01-01

Full Text Available Objective. CD161 has been identified as a marker of human IL-17-producing T cells that are implicated in the pathogenesis of rheumatoid arthritis (RA. This study aimed to investigate the potential link between the percentage of CD161+ T cells and disease activity in RA patients. Methods. Peripheral blood (PB from 54 RA patients and 21 healthy controls was evaluated. Paired synovial fluid (SF (n = 17 was analyzed. CD161 expression levels on CD4+, CD8+, and CD4−CD8− T cells were assessed by flow cytometry. Results. The percentage of CD4+CD161+ T cells in RA SF was higher than RA PB, and it was positively correlated with DAS28, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP. CD4−CD8−CD161+ T cell percentage was decreased in RA PB and was further reduced in RA SF, and its level in SF was inversely correlated with DAS28, ESR, and CRP. However, CD8+CD161+ T cell percentage was neither changed in RA PB and SF nor correlated with disease activity indices. Conclusion. An increased CD4+CD161+ T cell percentage and a decreased CD4−CD8−CD161+ T cell percentage are present in RA SF and are associated with disease activity, and the accumulation of CD4+CD161+ T cells in SF may contribute to the local inflammation of RA.

Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.

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van Herwaarden, Noortje; den Broeder, Alfons A; Jacobs, Wilco; van der Maas, Aatke; Bijlsma, Johannes W J; van Vollenhoven, Ronald F; van den Bemt, Bart J F

2014-09-29

-guided anti-TNF dose tapering (137 participants). These studies include only adalimumab and etanercept; controlled data on other anti-TNF agents are absent. Two studies were available in full text; one was assessed as having low risk of bias and the other high risk. Five studies were available only as one or more abstracts. Because data provided in these abstracts were limited, risk of bias was unclear. Clinical heterogeneity between the trials was high.Dose reduction of anti-TNF (etanercept data only) showed no statistically significant or clinical relevant difference in disease activity score in 28 joints (DAS28) (mean difference (MD) 0.10, 95% confidence interval (CI) -0.11 to 0.31) (scale 0.9 to 8; higher score indicates worse disease activity). The proportion of participants who maintained low disease activity was slightly lower among participants given reduced doses of the anti-TNF agent (risk ratio (RR) 0.87, 95% CI 0.78 to 0.98, absolute risk difference (ARD) 9%). Radiographic outcome was slightly worse, but this was not clinically meaningful, compared with continuation of anti-TNF (MD 0.11, 95% CI 0.08 to 0.14) (scale 0 to 448; higher score indicates greater joint damage). Function was not statistically different between anti-TNF dose reduction and continuation (MD 0.10, 95% CI 0.00 to 0.20) (scale 0 to 3; higher score indicates worse functioning). Reinstalment of anti-TNF after failure of dose reduction showed a 5% risk of persistent flare. Data on numbers of serious adverse events (SAEs) (RR 0.58, 95% CI 0.23 to 1.45, ARD -2%) and withdrawals due to adverse events (AEs) (RR 0.57, 95% CI 0.17 to 1,92, ARD -1%) were inconclusive. Most outcomes were based on moderate quality evidence.Participants who discontinued anti-TNF (adalimumab and etanercept data) had higher mean DAS28 (DAS28-erythrocyte sedimentation rate (ESR): MD 1.10, 95% CI 0.86 to 1.34) and DAS28-C-reactive protein (CRP): MD 0.57 95% CI -0.09 to 1.23) and were less likely to maintain a low disease

Interleukin-23 in early disease development in rheumatoid arthritis

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Andersen, Thomas; Hvid, M; Johansen, C

2015-01-01

randomized to methotrexate (MTX) plus adalimumab (ADA; n = 75) or MTX plus placebo-ADA (PLA; n = 76). Plasma samples were obtained at baseline and at months 3, 6, and 12 together with values for C-reactive protein (CRP), the 28-joint Disease Activity Score based on CRP (DAS28CRP), scores on the Clinical......OBJECTIVES: To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis (eRA) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels. METHOD: Treatment-naïve eRA patients from the OPERA cohort were included (n = 151). Patients were...... Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI), visual analogue scale (VAS) for pain/fatigue/physician global and total Sharp/van der Heijde score (TSS). IL-23 was measured at each time point. RESULTS: IL-23 levels decreased significantly in the ADA group from 20.6 pg...

Rheumatic Disease among Oklahoma Tribal Populations: A Cross-Sectional Study

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Gaddy, Jasmine R.; Vista, Evan S.; Robertson, Julie M.; Dedeke, Amy B.; Roberts, Virginia C.; Klein, Wendy S.; Levin, Jeremy H.; Mota, Fabio H.; Cooper, Tina M.; Grim, Gloria A.; Khan, Sohail; James, Judith A.

2012-01-01

Objectives Rheumatic diseases cause significant morbidity within American Indian populations. Clinical disease presentations, as well as historically associated autoantibodies, are not always useful in making a rapid diagnosis or assessing prognosis. The purpose of this study is to identify autoantibody associations among Oklahoma tribal populations with rheumatic disease. Methods Oklahoma tribal members (110 rheumatic disease patients and 110 controls) were enrolled at tribal-based clinics. Rheumatic disease patients (suspected or confirmed diagnosis) were assessed by a rheumatologist for clinical features, disease criteria, and activity measures. Blood samples were collected and tested for common rheumatic disease autoantibodies (ANA, anti-CCP, anti-RF, anti-Ro, anti-La, anti-Sm, anti-nRNP, anti-Ribosomal P, anti-dsDNA, and anti-cardiolipins). Results In patients with suspected systemic rheumatic diseases, 72% satisfied ACR classification: 40 (36%) rheumatoid arthritis, 16 (15%) systemic lupus erythematosus, 8 (7%) scleroderma, 8 (7%) osteoarthritis, 4 (4%) fibromyalgia, 2 (2%) seronegative spondyloarthropathy, 1 Sjogrens syndrome, and 1 sarcoidosis. When compared to controls, RA patient sera were more likely to contain anti-CCP (55% vs 2%, pdisease activity scores (DAS28 5.6 vs 4.45, p=0.021) while anti-RF positivity did not (DAS28 5.36 vs 4.64, p=0.15). Anticardiolipin antibodies (25% or rheumatic disease paitents vs 10% of contros,; p=0.0022) and ANA (63% vs 21%, prheumatic disease patients. Conclusion Anti-CCP may serve as a better RA biomarker in AI patients, while the clinical significance of increased frequency of aCLs needs further evaluation. PMID:22896022

Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE).

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Sugihara, Takahiko; Ishizaki, Tatsuro; Hosoya, Tadashi; Iga, Shoko; Yokoyama, Waka; Hirano, Fumio; Miyasaka, Nobuyuki; Harigai, Masayoshi

2015-05-01

The aim of this study was to evaluate structural damage and physical disability in patients with elderly-onset RA (EORA) who were treated in clinical practice with a therapeutic strategy targeting low disease activity (LDA). Data from 151 MTX-naive patients (mean age 74.9 years) with EORA from a prospective, monocentric registry were analysed. Treatment was adjusted every 3 months targeting LDA [28-joint DAS using ESR (DAS28-ESR) target strategy was observed in 83.4% of the 151 patients at week 24 and in 75.5% at week 52. At week 52, 67.6% of the patients were receiving a nbDMARD alone, 31.0% a TNFi with or without MTX and 1.4% tocilizumab. At week 52, structural remission (ΔmTSS/yr ≤0.5) was achieved in 49.7% of the patients, functional remission (HAQ-DI ≤0.5) in 63.4% and LDA in 51.0%. Clinical responses at weeks 12 and 24 were significant independent predictors of CRRP. Cumulative disease activity during the first 12 weeks predicted CRRP with a C-statistic of 0.888. Achieving structural remission, functional remission and LDA in clinical practice in EORA patients are realistic goals. Our results indicate significant benefits for a therapeutic strategy targeting LDA for EORA patients in clinical practice. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of non-surgical periodontal therapy on periodontal laboratory and clinical data as well as on disease activity in patients with rheumatoid arthritis.

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Cosgarea, Raluca; Tristiu, Roxana; Dumitru, Raluca Bianca; Arweiler, Nicole Birgit; Rednic, Simona; Sirbu, Cristina Ioana; Lascu, Liana; Sculean, Anton; Eick, Sigrun

2018-03-27

To compare the effect of non-surgical periodontal therapy on clinical and inflammatory parameters in patients with moderate to severe chronic periodontitis (CP) and rheumatoid arthritis (RA) (RA-CP) with that in CP patients without RA. Eighteen patients with RA-CP and 18 systemically healthy patients with CP were treated with scaling and root planing (SRP) within 24 h. At baseline, and at 3 and 6 months after SRP, clinical periodontal parameters, inflammatory markers, and microorganisms in subgingival biofilm were assessed. In addition, disease activity markers of RA (DAS28, CRP, ESR) and specific antibodies (RF) were monitored in the RA-CP group. In both groups, non-surgical therapy yielded to statistically significant improvements in all investigated clinical periodontal variables; in RA patients, a statistically significant decrease in serum-CRP was seen at 3 months. At all time-points, levels of inflammatory markers in GCF were higher in RA-CP than in CP patients. Counts of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola decreased statistically significantly in CP but not in the RA-CP group. Changes of DAS28 correlated positively with those of P. gingivalis and negatively with the plaque index. Within their limits, the present data suggest that (a) non-surgical periodontal therapy improves periodontal conditions in CP patients with and without RA and (b) in patients with RA, eradication of P. gingivalis in conjunction with a high level oral hygiene may transiently decrease disease activity of RA. In patients with RA and CP, non-surgical periodontal therapy is a relevant modality not only to improve the periodontal condition but also to decrease RA activity.

SAT0125 The impact of selected comorbidities on treatment outcome in patients with rheumatoid arthritis: an exploratory cohort study

DEFF Research Database (Denmark)

Emamifar, Amir; Jensen Hansen, Inger Marie

2018-01-01

diagnosed rheumatoid arthritis is associated with poor initial treatment response evaluated by disease activity score in 28 joints-C-reactive protein (DAS28- CRP): An observational cohort study. Medicine (Baltimore) 2017;96:e8357. [2] Emamifar A, et al. Patients with newly diagnosed Rheumatoid Arthritis......Background: Patients with Rheumatoid Arthritis (RA) may present with various comorbidities resulting in worse treatment response.[1-2] Objectives: To investigate the impact of selected comorbid diseases on RA outcome with the aim of Disease Activity Score in 28 joints-C-Reactive Protein (DAS28-CRP......). Methods: All our RA patients were included in this study. Patients’ demographics, serology results and DAS28-CRP at the time of diagnosis and after 4 months of treatment initiation were collected. Patients’ electronic hospital records were evaluated for a positive history of thyroid diseases, Diabetes...

Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.

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Behrens, Frank; Meier, Lothar; Prinz, Jörg C; Jobst, Jürgen; Lippe, Ralph; Löschmann, Peter-Andreas; Lorenz, Hanns-Martin

2018-04-01

To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

INTERLEUKIN 28 RECEPTOR GENE ALPHA IL28RA AND PSORIASIS: ASSOCIATION WITH DISEASE SEVERITY AND AGE AT ONSET

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E. S. Galimova

2015-01-01

Full Text Available Molecular basis still remains unclear for psoriasis, a chronic inflammatory skin disease. It biological features are presented by abnormal differentiation of epidermal keratinocytes, overgrowth and dilation of blood vessels, and leukocyte infiltration of dermal and epidermal skin layers. These events appear to be driven, mainly, by various cytokines and chemokines released by activated T cell populations. The aim of this replication study was to determine, whether the rs4649203 SNP of IL28RA gene is associated with susceptibility to psoriasis. A total of 341 patients with psoriasis and 407 matched healthy controls were enrolled to carry out a case control study. Genotyping was performed using a Real-Time PCR assay. Our preliminary data suggest that the polymorphism located in IL28RA gene, known to be related to inflammatory and immunity processes, showed an association with patients’ age at onset and the disease severity. The results of this study are promising, with respect to development of a personalized approach to psoriasis treatment.

Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: Results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry

DEFF Research Database (Denmark)

Hetland, Merete Lund; Christensen, Ib Jarle; Tarp, Ulrik

2010-01-01

response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number...... versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1...

HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population.

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Konda Mohan, Vasanth; Ganesan, Nalini; Gopalakrishnan, Rajasekhar; Venkatesan, Vettriselvi

2017-10-01

To investigate the presence of the 'shared epitope' (SE) in the HLA-DRB1 alleles in patients with RA and to ascertain the frequency of the HLA-DRB1 alleles with autoantibodies (anti-cyclic citrullinated peptide [anti-CCP] rheumatoid factor [RF]) and disease severity. A total of 200 RA patients and 200 apparently healthy subjects participated in the study. HLA-DRB1 were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP and RF in serum were determined by in vitro quantitative enzyme-linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score-28 (DAS-28). Chi-square test and Student's t-test were used in the statistical analysis. A significant increase in the frequency of HLA-DRB1*01, *04, *10 and *14 were identified in RA patients and showed a strong association with the disease susceptibility. While the frequencies of HLA-DRB1*03, *07, *11 and *13 were significantly lower in RA patients than in controls. The other HLA-DRB1 alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti-CCP and RF antibodies did not showed significant difference in SE-positive patients compared with SE-negative patients. DAS-28 values of RA patients showed no significant difference between SE-positive and SE-negative groups. Our results indicate that HLA-DRB1*01, *04, *10 and *14 alleles are related with RA, while HLA-DRB1*03, *07, *11 and *13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with disease activity and diagnostic capacity

DEFF Research Database (Denmark)

Gudmann, N. S.; Siebuhr, A. S.; Christensen, A. F.

2017-01-01

originate from soft connective tissues, were significantly higher in axSpA and PsA as compared with healthy control subjects. CIM and C3M correlated with ASDAS and DAS28. Overall, ICTP, which arises from bone degradation, did not differ between disease versus healthy. However, ICTP was lower in HLA-B27...

MiDAS Field Guide – a Comprehensive Online Source of Information About the Microbes of Activated Sludge

DEFF Research Database (Denmark)

Nierychlo, Marta; McIlroy, Simon Jon; Saunders, Aaron Marc

this information in MiDAS field guide (www.midasfieldguide.org). MiDAS taxonomy gives a solid foundation for the study of microbial ecology of the wastewater treatment processes. The online MiDAS field guide links the identity of genera that are important for the wastewater treatment process to details about...... guide to the microbes of activated sludge by comparing microbial community composition in 32 WWTPs located worldwide. This will facilitate a better understanding of the ecology of the ecosystem of activated sludge. Reference: McIlroy et al. MiDAS: the field guide to the microbes of activated sludge...... on a survey of 25 full-scale Danish wastewater treatment plants over 6 years and using MiDAS taxonomy, we have collected more than 150 key organisms in activated sludge wastewater treatment systems, linked their identity with available information on their function and distribution and included...

28 CFR 549.15 - Infectious disease training and preventive measures.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Infectious disease training and... INSTITUTIONAL MANAGEMENT MEDICAL SERVICES Infectious Disease Management § 549.15 Infectious disease training and..., incorporating a question-and-answer session, about infectious diseases to all newly committed inmates, during...

A comparison of disease burden in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis.

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Brigitte Michelsen

Full Text Available The main objective of this study was to compare disease burden in rheumatoid arthritis (RA, psoriatic arthritis (PsA and axial spondyloarthritis (ax-SpA.In this cross-sectional study, all the RA (1093, PsA (365 and ax-SpA (333 patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman's rho.The reported pain, joint pain, patient's global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28 (0.3±0.1, p = 0.003, Clinical Disease Activity Index (CDAI (1.0±0.4, p = 0.028 and Routine Assessment of Patient Index Data 3 (RAPID3 (0.4±0.1, p = 0.004 were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001 and CDAI (rho = 0.768, p<0.001 in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI (rho = 0.902, p<0.001 and Bath Ankylosing Spondylitis Functional Index (BASFI (0.865, p<0.001 in ax-SpA and PsA.In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of clinical significance. Our study indicates that

Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

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Tomohiro Koga

Full Text Available To determine prognostic factors of clinically relevant radiographic progression (CRRP in patients with rheumatoid arthritis (RA achieving remission or low disease activity (LDA in clinical practice.Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs. CRRP was defined as the yearly progression of modified total Sharp score (mTSS >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC curve to estimate the performance of relevant variables for predicting CRRP.The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA positivity at baseline (OR = 15.2, 95%CI 2.64-299, time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45, and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42.ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

DEFF Research Database (Denmark)

Ammitzbøll, Christian Gytz; Steffensen, Rudi; Bøgsted, Martin

2014-01-01

investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. RESULTS: The minor allele of rs1205 C > T was associated......INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision...

The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis

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Kermani, TA; Cuthbertson, D; Carette, S; Hoffman, GS; Khalidi, NA; Koening, CL; Langford, CA; McKinnon-Maksimowicz, K; McAlear, CA; Monach, PA; Seo, P; Warrington, KJ; Ytterberg, SR; Merkel, PA; Matteson, EL

2016-01-01

Objective To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA). Methods Patients with GCA enrolled in a prospective, multicenter, longitudinal study with symptoms of active vasculitis during any visit were included. Spearman’s rank correlation was used to explore the association of the BVAS with other measures of disease activity. Results During a mean (SD) follow-up of 2.3 (1.6) years, symptoms of active GCA were present in 236 visits in 136 subjects (100 female, 74%). Median (range) BVAS1 (new/worse symptoms) was 1 (0–10) and median (range) BVAS2 (persistent symptoms) was 0 (0–5). Median (range) physician global assessment (PGA) was 4 (0–9) for disease activity in the past 28 days and 2 (0–9) for activity on the day of the visit. Important ischemic manifestations of active vasculitis not captured by the BVAS included tongue/jaw claudication (27%), upper extremity claudication (15%), lower extremity claudication (5%), carotidynia (7%), ischemic retinopathy (5%). During 25 visits (11%) with active disease, all symptoms of active vasculitis were captured in the “Other” category yet still resulted in a BVAS 1 and BVAS 2 of 0. BVAS1 moderately correlated with PGA for the past 28 days (Spearman’s correlation 0.50) and physician-rated disease activity for the past 28 days (Spearman’s correlation 0.46). Conclusions The BVAS has limited utility in GCA. Patients with active GCA can have a BVAS of 0. Many important ischemic symptoms attributable to active vasculitis are not captured in the composite score. PMID:27036388

MiDAS

DEFF Research Database (Denmark)

McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

2015-01-01

The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties...... of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge...... communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...

easyDAS: Automatic creation of DAS servers

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Jimenez Rafael C

2011-01-01

Full Text Available Abstract Background The Distributed Annotation System (DAS has proven to be a successful way to publish and share biological data. Although there are more than 750 active registered servers from around 50 organizations, setting up a DAS server comprises a fair amount of work, making it difficult for many research groups to share their biological annotations. Given the clear advantage that the generalized sharing of relevant biological data is for the research community it would be desirable to facilitate the sharing process. Results Here we present easyDAS, a web-based system enabling anyone to publish biological annotations with just some clicks. The system, available at http://www.ebi.ac.uk/panda-srv/easydas is capable of reading different standard data file formats, process the data and create a new publicly available DAS source in a completely automated way. The created sources are hosted on the EBI systems and can take advantage of its high storage capacity and network connection, freeing the data provider from any network management work. easyDAS is an open source project under the GNU LGPL license. Conclusions easyDAS is an automated DAS source creation system which can help many researchers in sharing their biological data, potentially increasing the amount of relevant biological data available to the scientific community.

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

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Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

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Tam, Lydia Ho-Pui; Shang, Qing; Li, Edmund Kwok-Ming; Wong, Priscilla Ching-Han; Kwok, Kitty Yan; Kun, Emily Wai-Lin; Yim, Isaac Cheuk-Wan; Lee, Violet Ka-Lai; Yip, Ronald Man-Lung; Pang, Steve Hin-Ting; Lao, Virginia Weng-Nga; Mak, Queenie Wah-Yan; Cheng, Isaac Tsz-Ho; Lau, Xerox Sze-Lok; Li, Tena Ka-Yan; Zhu, Tracy Yaner; Lee, Alex Pui-Wai; Tam, Lai-Shan

2018-05-15

To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].

CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves' disease and modulates clinical phenotype of disease.

Science.gov (United States)

Pawlak-Adamska, Edyta; Frydecka, Irena; Bolanowski, Marek; Tomkiewicz, Anna; Jonkisz, Anna; Karabon, Lidia; Partyka, Anna; Nowak, Oskar; Szalinski, Marek; Daroszewski, Jacek

2017-01-01

Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR-RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)-PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT 16-21 )/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT 16-21 )GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT >21 )GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT >21 ]/[AT >21 ] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a

Disease activity, obesity, functional disability, and depression in patients with rheumatoid arthritis : Impact on lipid status, glycoregulation, and risk for coronary heart disease.

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Ostojic, P; Bartolovic, D

2016-09-01

This study aims to estimate the impact of disease activity, obesity, functional disability, and depression on lipid status, glycoregulation, and risk for coronary heart disease (CHD) in patients with rheumatoid arthritis (RA). A total of 36 patients with RA (30 women and 6 men, mean age 54.9 years, mean disease duration 7.9 years) were included in this study. We estimated the impact of age, body mass index, disease activity [assessed by DAS28 index and C-reactive protein (CRP) value], functional ability (estimated using the HAQ disability index), and depression [assessed using the Beck Depression Inventory (BDI)] on glycoregulation, lipid status, and risk for CHD in our patients. Glycoregulation was assessed by measuring insulin resistance, insulin, and glucose in blood. Lipids tested in blood included total cholesterol, HDL and LDL cholesterol, and triglycerides (TG). The 10-year risk for CHD was estimated using the Framingham risk score. Of 36 patients, 11 (30.6 %) fulfilled the criteria for metabolic syndrome (MS). Ten of 11 patients (90.1 %) with MS have a 10-year risk for CHD greater than 10 % compared to only 3 of 25 patients (12 %) without MS (p = 0.0001). Patients with high disease activity had lower HDL values than patients with mild or moderate disease activity (1.4 vs. 1.7 mmol/l, p = 0.04). Significant correlations were observed between CRP level and insulinemia (ρ = 0.57, p = 0.003), as well as CRP level and the HOMA index (ρ = 0.59, p = 0.002). The body mass index (BMI) correlated significantly with total cholesterol (r = 0.46, p = 0.02), LDL (ρ = 0.41, p = 0.04), and TG (ρ = 0.65, p Obesity was found to be an independent risk factor for increased total cholesterol, LDL cholesterol, and TG. Depressed patients with RA tend to be overweight or obese and, therefore, have an unfavorable lipid profile.

Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

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Kyler B Pallister

Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

Reactor neutron activation analysis for aluminium in the presence of phosphorus and silicon. Contributions of /sup 28/Al activities from /sup 31/P (n,. cap alpha. ) /sup 28/Al and /sup 28/Si (n,p) /sup 28/Al reactions

Energy Technology Data Exchange (ETDEWEB)

Mizumoto, Yoshihiko (Kinki Univ., Higashi-Osaka, Osaka (Japan). Faculty of Science and Technology); Iwata, Shiro; Sasajima, Kazuhisa; Yoshimasu, Fumio; Yase, Yoshiro

1984-01-01

Reactor neutron activation analysis for aluminium in samples containing phosphorus and silicon was studied. The experiments were performed by using pneumatic tube of the Kyoto University Reactor (KUR). At first, the ratios of the /sup 28/Al activity produced from /sup 27/Al(n, ..gamma..) /sup 28/Al reaction by thermal neutrons to that from /sup 31/P(n, ..cap alpha..)/sup 28/Al reaction by fast neutrons, and to that from /sup 28/Si(n, p)/sup 28/Al reaction were measured by ..gamma..-ray spectrometry. With a ratio of about 5 for the thermal to fast neutron flux of KUR, the ratio of the /sup 28/Al activity from aluminium to that from phosphorus was to be 812 +- 7, and to that from silicon 282 +- 3. Secondly, the contributions of /sup 28/Al activities from phosphorus and silicon and the determination limit of aluminium were calculated for various parameters, such as fast neutron flux, thermal to fast neutron flux ratio, amounts of phosphorus and silicon, etc. Thirdly, on the basis of these results, aluminium contents in spinal cords and brains of amyotrophic lateral sclerosis, Parkinsonism-dementia complex and control cases were determined.

Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.

Science.gov (United States)

Kaeley, Gurjit S; Nishio, Midori J; Goyal, Janak R; MacCarter, Daryl K; Wells, Alvin F; Chen, Su; Kupper, Hartmut; Kalabic, Jasmina

2016-11-01

To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX). Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient. After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP ( 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1. PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial.

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Kremer, Joel M; Rigby, William; Singer, Nora G; Birchwood, Christine; Gill, Darcy; Reiss, William; Pei, Jinglan; Michalska, Margaret

2018-03-25

To evaluate whether tocilizumab (TCZ) monotherapy is non-inferior to TCZ + methotrexate (MTX) in maintaining clinical response in patients with rheumatoid arthritis (RA) who achieve low disease activity with TCZ+MTX. Patients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneous. At 24 weeks, patients who achieved Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) ≤3.2 were randomized to receive TCZ monotherapy or continue TCZ+MTX until week 52. The primary outcome was the comparison of mean change in DAS28-ESR from weeks 24 to 40 between the TCZ monotherapy and TCZ+MTX arms (non-inferiority margin of 0.6). Secondary outcomes included DAS28-ESR worsening ≥1.2, achievement of DAS28-ESR <2.6 and ≤3.2 and safety and immunogenicity. Of 718 patients enrolled, 294 were randomized at week 24 (TCZ monotherapy, n = 147; TCZ+MTX, n = 147). The mean changes in DAS28-ESR from weeks 24 to 40 were 0.46 and 0.14 in the TCZ monotherapy and TCZ+MTX arms, respectively (weighted difference between the groups, 0.318 [95% CI 0.045, 0.592]); discontinuing MTX in TCZ responders was non-inferior to continuing MTX. Safety events were broadly similar between the randomized treatment groups; the most common serious adverse event was infection, occurring in 2.1% of patients in the TCZ monotherapy group and 2.2% in the TCZ+MTX group. Patients with RA receiving TCZ+MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity in the 16 weeks following MTX discontinuation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Predictive Factors Related to the Efficacy of Golimumab in Patients with Rheumatoid Arthritis

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Katsuaki Kanbe

2015-01-01

Full Text Available In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF-α and interleukin (IL-6 including baseline characteristics in patients with rheumatoid arthritis (RA treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP and Simplified Disease Activity Index (SDAI scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

Antimicrobial activity of plants used as medicinals on an indigenous reserve in Rio das Cobras, Paraná, Brazil.

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Moura-Costa, Gislaine F; Nocchi, Samara R; Ceole, Ligia F; de Mello, João Carlos P; Nakamura, Celso Vataru; Dias Filho, Benedito Prado; Temponi, Livia G; Ueda-Nakamura, Tania

2012-09-28

A considerable percentage of global biodiversity is located in Brazil, a country that also has rich cultural and ethnic diversity. In the community of Rio das Cobras, Paraná, plants are still widely used in the health care not only by indigenous people but also by the non-indigenous population that inhabits the region. The investigation of the efficacy and safety of these plants in the treatment of infectious diseases provides insights for future studies of these species allowing the appropriated use by the indigenous people, since few or none study has been conducted so far. Evaluate the antimicrobial activity and cytotoxicity of some plants used as medicinal on an indigenous reserve in Rio das Cobras, Paraná, Brazil. The aqueous extracts were obtained by decoction and the 50% and 70% hydroalcoholic extracts by turbo extraction. The extracts were tested against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Candida parapsilosis, Candida tropicalis, Leishmania amazonensis, Poliovirus and HSV-1. Cytotoxicity assay using VERO cells were also performed. None of the extracts had a selectivity index (SI)>1 for any of the tested bacteria. Only Campomanesia eugenioides and Schinus terebinthifolius had an SI>1.0 for all of the tested Candida species. The best anti-Leishmania activity was obtained with Zanthoxylum rhoifolium and Schinus terebinthifolius. Extracts of Cordia americana were the most effective against herpes simplex virus type 1. Zanthoxylum rhoifolium was the most effective against Poliovirus, and Ocimum gratissimum was effective against both Poliovirus and Herpes Simplex virus. Among the plants investigated in the present study, Zanthoxylum rhoifolium had the fewest cytotoxic effect. The plants investigated in the present study exhibited potential for future pharmacological uses, but additional studies, especially with regard to in vivo toxicity, must be conducted. The results of this

Prevalence of Asymptomatic Arterial Hypertension and Its Correlation with Inflammatory Activity in Early Rheumatoid Arthritis.

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Bajraktari, Ismet H; Rexhepi, Sylejman; Berisha, Idriz; Lahu, Ali; Kryeziu, Avni; Durmishi, Bastri; Bajraktari, Halit; Bahtiri, Elton

2017-08-15

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation. One hundred and seventy-nine early RA patients diagnosed in agreement with ACR/EULAR (American College of Rheumatology/ European League against Rheumatism) 2010 criteria were consecutively included in the study. CRP (C-reactive protein) and anti CCP (Antibodies to cyclic citrullinated peptides) serum levels, WBC (white blood cells) count and ESR (Erythrocyte sedimentation rate), likewise DAS-28 (28-joint disease activity score) were determined in all included patients. Parametric tests were used to compare the characteristics of the groups and to test the correlation of the variables. Statistical data analysis revealed that a majority of the patients were females (n = 141; 78.7%); the mean age at RA onset was 49.13 ± 12.13 years. Overall prevalence of hypertension was 44.13 % (n = 79). In comparison with the normotensive patients, the hypertensive patients were older and had significantly higher values of CRP, ESR, anti-CCP and DAS-28. A highly significant positive correlation between all the study parameters and systolic and diastolic blood pressure was observed. Presence of significantly higher values of CRP, ESR, anti-CCP and DAS-28 in hypertensive patients indicate that inflammation is associated with an increased risk of hypertension. In this context, early screening for arterial hypertension and adequate therapeutic measures should be considered in early RA patients.

An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

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Martin-Martin LS

2017-03-01

Full Text Available LS Martin-Martin,1 F Giovannangeli,2 E Bizzi,2 U Massafra,2 E Ballanti,2 M Cassol,3 A Migliore2 1Department of Internal Medicine, Regina Apostolorum Hospital, 2Operative Unit of Rheumatology, 3Department of Internal Medicine, San Pietro Fatebenefratelli Hospital, Rome, Italy Background: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA. One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA. The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28, clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

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Fonseca, João Eurico; Canhão, Helena; Reis, Paulo; Santos, Maria José; Branco, Jaime; Quintal, Alberto; Malcata, Armando; Araújo, Domingos; Ventura, Francisco; Figueiredo, Guilherme; da Silva, José Canas; Patto, José Vaz; de Queiroz, Mário Viana; Santos, Rui André; Neto, Adriano José; de Matos, Alves de; Rodrigues, Ana; Mourão, Ana Filipa; Ribeiro, Ana Sofia; Cravo, Ana Rita; Barcelos, Anabela; Cardoso, Anabela; Vilar, António; Braña, Arecili; Faustino, Augusto; Silva, Candida; Godinho, Fátima; Cunha, Inês; Costa, José António; Gomes, José António Melo; Pinto, José António Araújo; da Silva, J A Pereira; Miranda, Luís Cunha; Inês, Luís; Santos, Luís Maurício; Cruz, Margarida; Salvador, Maria João; Ferreira, Maria Júlia; Rial, Maria; Bernardes, Miguel; Bogas, Mónica; Araújo, Paula; Machado, Pedro; Pinto, Patrícia; de Melo, Rui Gomes; Cortes, Sara; Alcino, Sérgio; Capela, Susana

2010-01-01

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

O conceito de espaço na epidemiologia das doenças infecciosas The concept of space in infectious disease epidemiology

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Luiz Jacintho da Silva

1997-10-01

Full Text Available Análise teórica da utilização do conceito de espaço na epidemiologia das doenças infecciosas. Faz-se uma breve retrospectiva do uso de diferentes conceituações de espaço e de suas implicações. Ênfase é dada à teoria dos focos naturais de Pavlovsky e às interações entre a epidemiologia e a geografia. O problema atual das infecções emergentes é visto como determinante da necessidade de se intensificarem as discussões sobre este conceito na epidemiologia das doenças infecciosas.This article analyzes how space is employed in infectious disease epidemiology, with a brief retrospective of the various definitions of space and its implications. Emphasis is given to the theory of natural foci of infectious diseases formulated by Pavlovsky and the interactions of epidemiology and geography.The current problem posed by emerging infections is seen as a determinant of the need for further discussion on the concept of space in infectious disease epidemiology.

Das, Prof. Gobardhan

Indian Academy of Sciences (India)

Das, Prof. Gobardhan Ph.D. (Imtech), FNASc. Date of birth: 10 December 1966. Specialization: Immunology, Infectious Diseases, Cell Biology Address: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110 067, U.T.. Contact: Office: (011) 2670 4559, 2673 8824. Residence: (0124) 424 2351

USE OF MULTIPARAMETER ANALYSIS OF LABORATORY BIOMARKERS TO ASSESS RHEUMATOID ARTHRITIS ACTIVITY

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A. A. Novikov

2015-01-01

Full Text Available The key component in the management of patients with rheumatoid arthritis (RA is regular control of RA activity. The quantitative assessment of a patient’s status allows the development of standardized indications for anti-rheumatic therapy.Objective: to identify the laboratory biomarkers able to reflect RA activity.Subjects and methods. Fifty-eight patients with RA and 30 age- and sex-matched healthy donors were examined. The patients were divided into high/moderate and mild disease activity groups according to DAS28. The serum concentrations of 30 biomarkers were measured using immunonephelometric assay, enzyme immunoassay, and xMAP technology.Results and discussion. Multivariate analysis could identify the factors mostly related to high/moderate RA activity according to DAS28, such as fibroblast growth factor-2, monocyte chemoattractant protein-1, interleukins (IL 1α, 6, and 15, and tumor necrosis factor-α and could create a prognostic model for RA activity assessment. ROC analysis has shown that this model has excellent diagnostic efficiency in differentiating high/moderate versus low RA activity.Conclusion. To create a subjective assessment-independent immunological multiparameter index of greater diagnostic accuracy than the laboratory parameters routinely used in clinical practice may be a qualitatively new step in assessing and monitoring RA activity.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

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Amalia Lamana

Full Text Available BACKGROUND: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS: We studied 640 patients with early arthritis (76% women; median age, 52 years, recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28 as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044. Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162. After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

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Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F; Lopez-Nevot, Miguel A; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

2012-01-01

The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

Estimativa do vigor das sementes e das plântulas de Bixa orellana L.

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Roberta Leopoldo Ferreira

Full Text Available RESUMO A multiplicação de espécies como as da planta de urucum tem limitações em função do conhecimento limitado das características morfológicas e fisiológicas das sementes e das plântulas e da restrição de métodos para determinar a qualidade dessas sementes. Nessa pesquisa, o objetivo foi estudar a adequação do teste de envelhecimento acelerado para estimar o vigor das sementes de urucum (Bixa orellana L., relacionando os resultados desse teste com a formação das plântulas e as diferenças de genótipo dos acessos genéticos. As sementes de urucum, representadas por quatro acessos genéticos, e por três lotes, foram avaliadas pelos testes de germinação, primeira contagem da germinação, classificação do vigor das plântulas e emergência das plântulas (total e índice de velocidade. No teste de envelhecimento acelerado foram avaliados a temperatura, de 41 ºC, e os períodos, de 48; 72 e 96 horas, de exposição das sementes às umidades relativas de 100% (água e de 76% (solução saturada de NaCl. A solução saturada reduz a quantidade de água absorvida pelas sementes de urucum, expostas às condições do teste de envelhecimento acelerado, reduzindo a deterioração das sementes, favorecendo a uniformidade dos resultados e a redução da proliferação de fungos, comuns na germinação das sementes de urucum. O teste de envelhecimento acelerado, com água ou solução salina, por 72 horas ou 96 horas, é eficiente para classificar as sementes de urucum quanto à qualidade. Assim, as variações dos teores de água das sementes de urucum devem ser entre 23;6 e 28;9% (72 horas e 29;7 e 32;9% (96 horas para a utilização da água e entre 7,3 e 9,5% para a utilização da solução salina de NaCl.

[An example of partnership cooperation. Cantonal League against Tuberculosis and Lung Diseases/Association "Das Band"].

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Michaelis, E

1984-01-01

Together with the Cantonal League against Tuberculosis and Lung Diseases of Zurich, the Association "Das Band" has organized a first course for parents of children with asthma. The course is a component of the associations new "Prophylaxis Program for Children with Asthma and Their Parents". By exchanging ideas, the parents should become able to reflect their situation, characterized by excessive protectionism, aggressiveness, and guiltiness, and they also should learn to accept the disease as a part of their daily life. The first course, which meanwhile is followed by a second one, provided a first base for the solution of the many problems.

Comparison of Disease Activity Score in 28 joints with ESR (DAS28, Clinical Disease Activity Index (CDAI, Health Assessment Questionnaire Disability Index (HAQ-DI & Routine Assessment of Patient Index Data with 3 measures (RAPID3 for assessing disease activity in patients with rheumatoid arthritis at initial presentation

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B Siddhartha Kumar

2017-01-01

Interpretation & conclusions: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation.

Atividades biológicas das lectinas PHA, WGA, jacalina e artocarpina Biological activities of PHA, WGA, jacalin and artocarpin lectins

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Ana Maria Sell

2000-05-01

Full Text Available As lectinas são (glicoproteínas que se ligam a açúcares. O interesse destas moléculas na investigação científica se deve às diversas atividades biológicas a elas atribuídas. Além da identificação de grupos sangüíneos, da caracterização de microorganismos e da estimulação mitogênica de células imunes, as lectinas estão envolvidas nos processos de reconhecimento e das interações celulares. No presente trabalho, revisamos algumas atividades biológicas das lectinas PHA (fitohemaglutinina de Phaseolus vulgaris, WGA (aglutinina de germe de trigo, jacalina e artocarpina (lectinas de Artocarpus integrifolia. PHA, jacalina e artocarpina são mitogênicas para os linfócitos, estimulam a produção de citocinas endógenas, a atração e a ativação de leucócitos. WGA é uma lectina não-mitogênica, no entanto, modula a resposta de defesa estimulando a liberação de superóxido pelos neutrófilos. O entendimento das atividades biológicas permitirá o uso destas moléculas como uma ferramenta útil no diagnóstico e tratamento de muitas doenças.Lectins are ubiquitous (glycoproteins, which exhibit a specific and reversibly carbohydrate binding activity. Because of their structural complexity and variability, they can participate in many physiological functions. Besides the blood groups identification, microorganism characterization and mitogenic immune cell proliferation, they are involved in the cell recognition and cell-cell interaction. In the present work we revised some biological activities of the PHA (Phaseolus vulgaris phytohemagglutinin, WGA (wheat germ agglutinin, jacalin and artocarpin (Artocarpus integrifolia lectins. PHA, jacalin and artocarpin may stimulate lymphocyte proliferation, attract and activate mononuclear cells and stimulate endogenous citokines production. WGA is a nonmitogenic lectin, however it may stimulate neutrophil superoxide production. The understanding of the lectin biological activities may

Characteristics of patients with rheumatoid arthritis in Qatar: a cross-sectional study.

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Lutf, Abdo; Poil, Abdul R; Hammoudeh, Mohammed

2014-01-01

To describe the clinical characteristics, serologic, radiological and clinical disease activity, and modality of therapy in patients with rheumatoid arthritis (RA) at tertiary outpatient care in Qatar. The study design was cross-sectional where 100 consecutive cases who met 1987 American College of Rheumatology criteria for diagnosis of RA were enrolled in this study. Demographic data (sex, nationality and age) numbers of swollen and tender joints, X-rays and current medications were collected during outpatients visits to Hamad General Hospital. Disease Activity Score of 28 joints (DAS28) and Health Assessment Questionnaires (HAQ) scores were calculated. All patients with RA who were seen as rheumatology outpatients were invited to participate in the study. One hundred patients were seen and examined during their follow-up at the outpatient clinic; data were collected and analyzed. Females represented 67% of all patients, 6% had more than six swollen joints, 9% had more than six tender joints. DAS28 and erythrocyte sedimentation rate (DAS28) calculation revealed 49% of patients were in remission (DAS28  3.2.Mean HAQ score was 1.02. Rheumatoid factor (RF) was positive in 63%, while anti-cyclic citrullinated protein antibody (anti-CCP) was positive in 71%, and 49% were positive for both. Radiography of hands and feet during the previous year was done in 65% of patients: 11% of them had erosions. Sixty-six percent were on one synthetic disease-modifying anti-rheumatic drug (DMARD) and 27% where on more than one synthetic DMARD and 7% where on no DMRD. Glucocorticoids were used in 51% and 29% were on biologics. Sixty-four percent of rheumatoid arthritis patients in Qatar were in remission or had low disease activity while the remaining 36% had active disease and among these patients 29% were on biologics. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - October 2011 update.

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Fonseca, João Eurico; Bernardes, Miguel; Canhão, Helena; Santos, Maria José; Quintal, Alberto; Malcata, Armando; Neto, Adriano; Cordeiro, Ana; Rodrigues, Ana; Mourão, Ana Filipa; Ribeiro, Ana Sofia; Cravo, Ana Rita; Barcelos, Anabela; Cardoso, Anabela; Vilar, António; Braña, Arecili; Faustino, Augusto; Silva, Candida; Duarte, Cátia; Araújo, Domingos; Nour, Dolores; Sousa, Elsa; Simões, Eugénia; Godinho, Fátima; Brandão, Filipe; Ventura, Francisco; Sequeira, Graça; Figueiredo, Guilherme; Cunha, Inês; Matos, J Alves; Branco, Jaime; Ramos, João; Costa, José António; Gomes, José António; Pinto, José; Silva, José Canas; Silva, J A; Patto, José Vaz; Costa, Lúcia; Miranda, Luís Cunha; Inês, Luís; Santos, Luís Maurício; Cruz, Margarida; Salvador, Maria João; Ferreira, Maria Júlia; Rial, Maria; Queiroz, Mário Viana; Bogas, Mónica; Araújo, Paula; Reis, Paulo; Abreu, Pedro; Machado, Pedro; Pinto, Patrícia; André, Rui; Melo, Rui; Garcês, Sandra; Cortes, Sara; Alcino, Sérgio; Ramiro, Sofia; Capela, Susana

2011-01-01

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of nonresponders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 despite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res­ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist’s clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Registry of Biologic Therapies improves quality of life especially in young patients with better baseline functional status.

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Boubouchairopoulou, Nadia; Flouri, Irini; Drosos, Alexandros A; Boki, Kyriaki; Settas, Loukas; Zisopoulos, Dimitrios; Skopouli, Fotini N; Papadopoulos, Ioannis; Iliopoulos, Alexios; Kyriopoulos, John; Boumpas, Dimitrios T; Athanasakis, Konstantinos; Sidiropoulos, Prodromos

2016-01-01

To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.

Joint involvement in patients affected by systemic lupus erythematosus: application of the swollen to tender joint count ratio

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E. Cipriano

2015-09-01

Full Text Available Joint involvement is a common manifestation in systemic lupus erythematosus (SLE. According to the SLE disease activity index 2000 (SLEDAI-2K, joint involvement is present in case of ≥2 joints with pain and signs of inflammation. However this definition could fail to catch all the various features of joint involvement. Alternatively the Swollen to Tender joint Ratio (STR could be used. This new index, which was originally proposed for rheumatoid arthritis (RA patients, is based on the count of 28 swollen and tender joints. Our study is, therefore, aimed to assess joint involvement in a SLE cohort using the STR. SLE patients with joint symptoms (≥1 tender joint were enrolled over a period of one month. Disease activity was assessed by SLEDAI-2K. We performed the swollen and tender joint count (0-28 and calculated the STR. Depending on the STR, SLE patients were grouped into three categories of disease activity: low (STR1.0. We also calculated the disease activity score based on a 28-joint count and the erythrocyte sedimentation rate (DAS28-ESR. We enrolled 100 SLE patients [F/M 95/5, mean±standard deviation (SD age 46.3±10.6 years, mean±SD disease duration 147.1±103.8 months]. The median of tender and swollen joints was 4 (IQR 7 and 1 (IQR 2.5, respectively. The median STR value was 0.03 (IQR 0.6. According to the STR, disease activity was low in 70 patients, moderate in 23 and high in 7. A significant correlation was identified between STR values and DAS28 (r=0.33, p=0.001. The present study suggests a correlation between STR and DAS28, allowing an easier and faster assessment of joint involvement with the former index.

Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

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Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

2017-01-01

Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

Thrombus scintigraphy with Ga-67 DFO-DAS-Fibrinogen, 2

International Nuclear Information System (INIS)

Kawasaki, Yukiko

1987-01-01

In our previous in vivo study 67 Ga DFO-DAS-Fibrinogen was assessed for its usefulness as a radiopharmaceutical for the detection of thrombin in experimental animals (Report 1). The present study was undertaken to appraise the diagnostic value of 67 Ga DFO-DAS-Fibrinogen in human disease, especially in relation to blood coagulability as well as to thrombolytic drug regimen being given, in an effort to investigate its clinical applicability. Involved in this study were 48 patients with thrombosis proven by X-ray CT and other examinations. Of these 48, 42 had arterial thrombosis (20 with aortic aneurysm including the dissecting form, 11 in postoperative condition following vascular surgery with a prosthesis, 9 with intracardiac thrombosis accompanying heart disease, and 1 each with occlusive arteriosclerosis and cerebral infarction) and 6 had venous thrombosis. The 67 Ga DFO-DAS-Fibrinogen test proved to be positive in 55 % of arterial thrombin and in 50 % of venous thrombin. It is interesting to note that as high a positivity rate as 80 % was obtained for aortic aneurysm, although the positivity rate was disappointingly low for left atrial thrombin. No distinct correlation was noted to exist between the degree of accumulation of the tracer in thrombotic lesions and any of factors conceivably of clinical releavance, i.e. time elapsing from onset till testing, thrombolytic medication being given, and hematological factors. 67 Ga DFO-DAS-Fibrinogen appeared to be a radiodiagnostic agent that could possibly indicate the existing activity status of thrombosis. (author)

Most patients who reach disease remission following anti-TNF therapy continue to report fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Science.gov (United States)

Druce, Katie L; Bhattacharya, Yagnaseni; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

2016-10-01

RA-related fatigue is common and debilitating, but does not always respond to immunotherapy. In the context of anti-TNF therapy, we aimed to examine whether patients achieving disease remission experienced remission of fatigue. Data from the British Society for Rheumatology Biologics Register for RA were used. In participants with severe baseline fatigue [36-item Short Form Health Survey (SF-36) vitality score ⩽12.5], we identified those in disease remission [28-joint DAS (DAS28) 12.5) and complete remission (SF-36 vitality score >50) at follow-up. Demographic (e.g. sex, age), clinical (e.g. inflammation, joint erosion and co-morbidities) and psychosocial (e.g. SF-36 domains and HAQ) characteristics were compared between responder and non-responder groups. Severe baseline fatigue was reported by 2652 participants, of whom 271 (10%) achieved a DAS28 <2.6 by 6 months. In total, 225 participants (83%) reported partial remission and were distinguished from those who did not by better health status on all psychosocial domains. Far fewer [n = 101 (37.3%)] reported full fatigue remission. In addition to reporting clinically poorer health status, they were distinguished on the basis of a history of hypertension, depression and stroke as well as baseline treatment use of steroids and antidepressants. Despite achieving clinical remission, many RA patients do not achieve complete remission of their fatigue. Therefore, despite being important in overall disease control, reductions in disease activity are not always sufficient to ameliorate fatigue, so other symptom-specific management approaches must be considered for those for whom fatigue does not resolve. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevalência das manifestações clínicas iniciais da granulomatose de Wegener no Brasil: relato de seis casos e revisão da literatura Wegener's granulomatosis: prevalence of the initial clinical manifestations - report of six cases and review of the literature

Directory of Open Access Journals (Sweden)

Carlos Ewerton Maia Rodrigues

2010-04-01

Full Text Available OBJETIVOS: Descrever as manifestações clínicas iniciais da Granulomatose de Wegener (GW diagnosticada no Brasil. PACIENTES E MÉTODOS: Análise retrospectiva de seis prontuários do Serviço de Reumatologia do Hospital Geral de Fortaleza (HGF, assim como a realização de um levantamento bibliográfico dos casos de GW descritos no Brasil obtidos dos bancos de dados LILACS, SciELO e MEDLINE. RESULTADOS: O estudo identificou 49 pacientes; 15 (31% do sexo masculino e 34 (69% do sexo feminino. A forma sistêmica ocorreu em 35 pacientes (73%: 28 adultos, cinco crianças e dois adolescentes. A doença limitada ocorreu em 13 adultos e uma criança. A média da idade adulta no início da doença foi de 42,2 anos (18 a 65 anos. O quadro clínico agudo, com sintomas há menos de três meses do diagnóstico, ocorreu em 41% (20/49 da casuística e a forma insidiosa, em 59% (29/49 dos pacientes. A prevalência das manifestações clínicas iniciais nos adultos com doença sistêmica (n = 28 foi 64% (18/28 das vias aéreas superiores (VAS, 36% (10/28 pulmonares, 18% (5/28 renais, 25% (7/28 oculares, 11% (3/28 cutâneas, 25% (7/28 musculoesqueléticas e 7% (2/28 neurológicas. Na forma limitada do adulto (n = 13, os sintomas prevalentes foram 84% (11/13 VAS, 23% (3/13 oculares e 15% (2/13 pulmonares. CONCLUSÃO: No Brasil, a prevalência das manifestações clínicas iniciais da GW foi semelhante aos resultados da literatura. A falta de especificidade dos sintomas pode retardar o diagnóstico na forma insidiosa da doença e aumentar a morbimortalidade das formas agudas.OBJECTIVES: To describe the initial clinical manifestations of Wegener's Granulomatosis (WG in Brazil. PATIENTS AND METHODS: Retrospective analysis of six medical records of WG patients followed-up at the Rheumatology Department of Hospital Geral of Fortaleza (HGF, as well as a bibliographic survey of cases of WG in Brazil on LILACS, SciELO, and MEDLINE databases. RESULTS: The study

Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study.

Science.gov (United States)

Detert, Jacqueline; Bastian, Hans; Listing, Joachim; Weiß, Anja; Wassenberg, Siegfried; Liebhaber, Anke; Rockwitz, Karin; Alten, Rieke; Krüger, Klaus; Rau, Rolf; Simon, Christina; Gremmelsbacher, Eva; Braun, Tanja; Marsmann, Bettina; Höhne-Zimmer, Vera; Egerer, Karl; Buttgereit, Frank; Burmester, Gerd-R

2013-06-01

To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28Health Assessment Questionnaire (HAQ) score and radiographic progression. 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01). A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).

Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

Science.gov (United States)

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2017-09-01

To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy

DEFF Research Database (Denmark)

Rask Lage-Hansen, Philip; Chrysidis, S; Lage-Hansen, M

2016-01-01

identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2......OBJECTIVES: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. METHOD: Questionnaires developed to diagnose FM were...... applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. RESULTS: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were...

Determinação das curvas de secagem das sementes de andiroba em secador solar

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Andreza P. Mendonça

2015-04-01

Full Text Available Comumente, o óleo de andiroba é extraído na Amazônia pelo método tradicional ou ainda por prensa. A eficiência na extração está relacionada ao aquecimento e ao teor de água das sementes. Desta forma, a determinação de um modelo de secagem que represente satisfatoriamente os dados experimentais é de suma importância para minimizar as alterações promovidas pelo processo obtendo-se, consequentemente, produto de qualidade. O objetivo do trabalho foi descrever a cinética de secagem das sementes de andiroba, tal como ajustar os modelos matemáticos aos dados experimentais usando-se secador solar. Foi utilizado, como critério do ajuste dos modelos matemáticos, o coeficiente de determinação, a magnitude do erro médio relativo e o desvio-padrão da estimativa. A secagem em menor tempo (14 dias da Carapa surinamensis para atingir o teor de água de equilíbrio (12,28% se deve, possivelmente, ao menor tamanho das sementes e à maior quantidade de óleo em relação à Carapa guianensis. O modelo Logarítmico e o de Midilli et al. foram os que melhor se ajustaram aos dados experimentais para as sementes das duas espécies de andiroba.

Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

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Tchetina, Elena V; Demidova, Natalia V; Markova, Galina A; Taskina, Elena A; Glukhova, Svetlana I; Karateev, Dmitry E

2017-10-01

To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

Science.gov (United States)

Alemao, Evo; Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J; Allison, Paul D; Rutten-van Mölken, Maureen P M H; Frits, Michelle L; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E

2016-03-01

To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M-HAQ), the EuroQol 5-domain (EQ-5D; a quality-of-life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM-HAQ -0.047; P = 0.0100) and CDAI ≤2.8 (-0.073; P = 0.0003) but not DAS28-CRP measures was associated with enhanced physical functioning and health-related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Rastreamento e diagnóstico ecocardiográfico das arritmias e cardiopatias congênitas fetais Screening and echocardiographic diagnosis of arrhythmias and congenital heart diseases in the fetus

Directory of Open Access Journals (Sweden)

Sandra Regina Marques Carvalho

2006-05-01

Full Text Available OBJETIVO: analisar os resultados obtidos em programa de rastreamento e diagnóstico de arritmias e cardiopatias congênitas centrado em uma unidade terciária e determinar a importância do diagnóstico precoce na evolução fetal e neonatal. MÉTODOS: foram analisados os resultados da avaliação cardíaca fetal efetuada em 1159 gestantes em dois níveis diferentes. Nível I: uso da ultra-sonografia morfológica com o objetivo de rastrear a presença de alteração cardíaca, sem estabelecer um diagnóstico diferencial. Nível II: por ecocardiograma fetal com o objetivo de diagnosticar as cardiopatias fetais existentes. Os resultados da detecção de arritmias bem como da avaliação das alterações estruturais foram comparados, sendo estabelecidas a sensibilidade e a especificidade para ambos os níveis no pré-natal, ao exame pós-natal ou à necropsia. A concordância entre ambos os níveis foi calculada pelo índice kappa. RESULTADOS: as arritmias detectadas no nível I foram confirmadas em todos os casos e não houve falso-negativos, sendo que em cinco pacientes houve necessidade de tratamento intra-útero. A detecção das alterações estruturais obtidas no nível I teve sensibilidade de 72% e especificidade de 98%, com 28% de falso-positivos. No nível II estes parâmetros foram, respectivamente, de 100 e 99%. De acordo com o coeficiente kappa de 57%, um grau de concordância de categoria moderada foi observado entre ambos os níveis. Das cardiopatias congênitas da nossa série 51% necessitaram intervenção farmacológica ou invasiva no período neonatal. CONCLUSÃO: o estudo ultra-sonográfico obstétrico é fundamental no rastreamento das alterações cardíacas fetais. O ecocardiograma fetal apresentou alto índice de sensibilidade e especificidade no diagnóstico das arritmias e cardiopatias congênitas, possibilitando o tratamento precoce das alterações graves.PURPOSE: to analyze the results of a screening and diagnostic

Understanding the relationship between the EQ-5D, SF-6D, HAQ and disease activity in inflammatory arthritis.

LENUS (Irish Health Repository)

Adams, Roisin

2012-02-01

BACKGROUND: The growth of economic analyses and in particular cost-utility analyses (CUA), which use the QALY as a measure of outcome, has heightened the interest in the methodologies used to calculate the QALY. The EQ-5D has produced quite different utility values from that of the SF-6D. This article seeks to understand these differences using a cohort of patients with inflammatory arthritis. OBJECTIVE: To examine the relationship between the disease-specific measure, Health Assessment Questionnaire (HAQ) disability index (DI) and the preference-based measures, SF-6D, EQ-5D and European League Against Arthritis (EULAR) Disease Activity Score (DAS) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Patients with RA and PsA (n = 504) attending a tertiary rheumatology referral centre completed the HAQ, SF-6D and the EQ-5D before starting biological therapy and again 12 months later. The SF-36 was converted into a utility using the preference-based SF-6D. Clinical outcomes such as the DAS, joint counts and laboratory measures were also recorded. We calculated single index utility scores from the preference-based instruments using UK population norms. We used regression analysis to derive a mapping function and calculated utility scores from the HAQDI and the DAS 28. RESULTS: The mean utility observed at baseline for RA was 0.43 for the EQ-5D and 0.54 for the SF-6D and for PsA was 0.49 for the EQ-5D and 0.57 for the SF-6D. The utility gain demonstrated by the EQ-5D was over twice that of the SF-6D. The EQ-5D scored 17% of the RA group as less than 0 (state defined as worse than death); 7% of this group remained less than 0 at follow-up. The distribution of the utility estimates was similar for both RA and PsA. CONCLUSIONS: Our findings draw attention to the impact of states worse than death on the overall distribution for the EQ-5D derived utilities and how these impact on its use in practice. EQ-5D-derived QALY changes are over twice

Proteasome Activators, PA28α and PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy

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Saeed Yadranji Aghdam

2016-01-01

Full Text Available Diabetic nephropathy (DN and diabetic retinopathy (DR are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN and Monocyte Chemoattractant Protein-1 (MCP-1 in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR.

The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

Science.gov (United States)

McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

2017-07-07

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Nonergot dopamine-receptor agonists for treating Parkinson's disease – a network meta-analysis

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Thorlund K

2014-05-01

Full Text Available Kristian Thorlund,1,2,4 Ping Wu,3,4 Eric Druyts,3,4 Shawn Eapen,3,4 Edward J Mills2–4 1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 2Stanford Prevention Research Center, Stanford University, Stanford, CA, USA; 3Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 4Redwood Outcomes, Vancouver, BC, Canada Objective: To compare the efficacy of the three nonergot dopamine-receptor agonists (DAs pramipexole, ropinirole, and rotigotine for the treatment of early and advanced Parkinson's disease (PD. Materials and methods: Bayesian network meta-analyses were performed separately for early and advanced PD, and at time points 11–16 and 24–28 weeks. Outcomes for early PD included improvement on the Unified Parkinson's Disease Rating Scale (UPDRS activities in daily life (UPDRS-II, motor function (UPDRS-III, and their subtotal (UPDRS-II + III. Outcomes for advanced PD also included daily “off time” (hours, but not UPDRS-II + III. Results: Totals of 23 and 24 trials informed early and advanced PD analyses. For early PD UPDRS-II at 11–16 weeks, pramipexole and rotigotine were statistically significantly superior to placebo, but ropinirole was not. For UPDRS-III and UPDRS-II + III, all DAs were statistically significantly better than placebo and exhibited similar improvements. At 24–28 weeks, results were also statistically significant for all DAs versus placebo, and the magnitudes of improvements were similar for pramipexole, ropinirole and rotigotine. Advanced PD improvements on UPDRS-II, UPRDS-III, and off time were statistically significant for pramipexole, ropinirole, and rotigotine versus placebo. At 11–16 weeks, rotigotine yielded slightly smaller effects than ropinirole and pramipexole, but credible intervals on differences were wide. For off time, results were near identical. At 24–28 weeks, results were similar for all three outcomes. Ropinirole yielded a

Comparison of Photo Optical Imaging with Musculoskeletal Ultrasound and Clinical Examination in the Assessment of Inflammatory Activity in Proximal Interphalangeal Joints in Rheumatoid Arthritis and Osteoarthritis.

Science.gov (United States)

Amitai, Isabella; Werner, Stephanie; Schicke, Bernd; Burmester, Gerd-Rüdiger; Minet, Olaf; Zabaryło, Urszula; Backhaus, Marina; Ohrndorf, Sarah

2015-09-01

Lightscan is a novel, rapid, low-cost, easily operated and noninvasive imaging technology used to assess inflammatory activity in proximal interphalangeal (PIP) joints. The results are calculated automatically. To our knowledge, this is the first comparative study of photo optical imaging (POI), with clinical examination (CE), disease activity score at 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and musculoskeletal ultrasonography (US) in healthy subjects and patients with rheumatoid arthritis (RA) or osteoarthritis (OA). There were 688 PIP joints of both hands examined in 87 subjects (38 RA, 21 OA, 28 healthy) by Lightscan and compared with CE for clinically swollen and tender joints, DAS28-ESR (only RA), and US. With US as reference, POI had a sensitivity of 74% and a specificity of 93%. In the receiver-operating curve (ROC) analysis, the Lightscan showed a higher sensitivity and specificity [area under the curve (AUC) 0.879] for the distinction of healthy subjects versus patients (OA, RA) than US in greyscale (GSUS; AUC 0.797) and power Doppler (PDUS; AUC 0.67). POI correlated significantly with GSUS (r 0.473, p POI and GSUS were up to 79%, between POI and PDUS up to 92%, and between POI and CE up to 66%. POI did not correlate with DAS28-ESR. The Lightscan is a new technology offering sensitive imaging detection of inflammatory changes in subjects with RA and OA with PIP arthritis. POI was more sensitive than CE and correlated significantly to GSUS and PDUS, while presenting a higher sensitivity and specificity for the detection of healthy subjects versus patients (RA, OA) based on the ROC analysis.

Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA: cost-effectiveness based on a 2-year randomized trial.

Science.gov (United States)

Sørensen, J; Primdahl, J; Horn, H C; Hørslev-Petersen, K

2015-01-01

To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.

MiDAS Field Guide – a Comprehensive Online Source of Information About the Microbes of Activated Sludge

DEFF Research Database (Denmark)

Nierychlo, Marta; McIlroy, Simon Jon; Saunders, Aaron Marc

activated sludge wastewater treatment systems, linking their identity with available information on their function and distribution. The guide includes the approx. 100 abundant genera that are present in most treatment plants (based on a survey of 25 full-scale Danish wastewater treatment plants...... are provided. The MiDAS Field Guide is a continuously developing resource where all working in the field are invited to contribute....... that would be otherwise excluded from analyses. The MiDAS database importantly provides a common taxonomy for the field that gives a solid foundation for the study of microbial ecology of the activated sludge process and related wastewater treatment processes, such as biofilms and granular sludge. Each genus...

Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia.

Science.gov (United States)

Lee, Yvonne C; Hackett, James; Frits, Michelle; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E; Segurado, Oscar G; Sasso, Eric H

2016-04-01

To examine the association between a multibiomarker disease activity (MBDA) score, CRP and clinical disease activity measures among RA patients with and without concomitant FM. In an observational cohort of patients with established RA, we performed a cross-sectional analysis comparing MBDA scores with CRP by rank correlation and cross-classification. MBDA scores, CRP and clinical measures of disease activity were compared between patients with RA alone and RA with concomitant FM (RA and FM) by univariate and multivariate analyses. CRP was ⩽1.0 mg/dl for 184 of 198 patients (93%). MBDA scores correlated with CRP (r = 0.755, P < 0.001), but were often discordant, being moderate or high for 19%, 55% and 87% of patients with CRP ⩽0.1, 0.1 to ⩽0.3, or 0.3 to ⩽1.0 mg/dl, respectively. Among patients with CRP ⩽1.0 mg/dl, swollen joint count (SJC) increased linearly across levels of MBDA score, both with (P = 0.021) and without (P = 0.004) adjustment for CRP, whereas CRP was not associated with SJC. The 28-joint-DAS-CRP, other composite measures, and their non-joint-count component measures were significantly greater for patients with RA and FM (n = 25) versus RA alone (n = 173) (all P ⩽ 0.005). MBDA scores and CRP were similar between groups. MBDA scores frequently indicated RA disease activity when CRP did not. Neither one was significantly greater among patients with RA and FM versus RA alone. Thus, MBDA score may be a useful objective measure for identifying RA patients with active inflammation when CRP is low (⩽1.0 mg/dl), including RA patients with concomitant FM. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis.

Science.gov (United States)

Syngle, Ashit; Vohra, Kanchan; Garg, Nidhi; Kaur, Ladbans; Chand, Prem

2012-02-01

Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 μg, Vonder(®) (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). Twenty-four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire-Disability Index [HAQ-DI] scores, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. After treatment, flow-mediated vasodilation improved from 9.64 ± 0.65% to 15.82 ± 1.02% (P < 0.01), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 ± 0.13 to 5.1 ± 0.14 μmol/L (P = 0.004), ESR from 63.00 ± 3.5 to 28.08 ± 1.5 mm in the first h (P < 0.01) and CRP levels from 16.7 ± 4.1 to 10.74 ± 2.9 mg/dL (P < 0.01). DAS28 and HAQ-DI scores were significantly reduced, from 5.9 ± 0.17 to 3.9 ± 0.17 (P < 0.01) and 4.6 ± 0.17 to 1.7 ± 0.22 (P < 0.01), respectively. Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs-induced inflammation. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and

Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.

Science.gov (United States)

Chen, Jiaxi; Li, Shuang; Shi, Jianfeng; Zhang, Lili; Li, Jun; Chen, Shiyong; Wu, Chunlong; Shen, Bo

2016-03-01

Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

MENYOAL KESENJANGAN ANTARA DAS SOLLEN ISLAM DENGAN DAS SEIN PRAKSIS KEHIDUPAN KAUM MUSLIMIN

Directory of Open Access Journals (Sweden)

Yusuf Suyono

2016-03-01

Full Text Available Abstract:This paper embarks from the question why the valuable Islamic ethics cannot be ethos grounded in the nation-state Muslim majority country-including in Indonesia? Phenomena such as the majlis taklim, majlis dhikr, interest pilgrimage exceeds the quota, the Islamic banking activity is equally excited, is real. However, it is not enough. Muslims should master the science, economics, and the strategic role of national politics. Islamic ethics is Dassollen, the Muslims condition is DasSein. ProphetMuḥammad has abled to unite Das sein andDassollenin his life, because Islam hasbecomehis bloodso that he is a mirror and store front of Islampar excellence. Muslims, as his follower, not been able todo like him. Al-Amir ArsalanSyākib, Muḥammad ‘Abduh, MohammadIqbal, Muḥammadal-Ghazālī, Ḥassan Ḥanafihavetried to formulatehow tobridge the gapbetween Das sollenandDasSein forMuslims. Theyhave adeep concern about thewide gapbetweenDasSeinpraxis in life of Muslims with DassollenIslamicteachings in slogan ya’lu walā yu’la ‘alaih. Whileatthe same timetheyseehowthe berufethos of Calvinismcouldencouragethe ethos ofmoderncapitalismto its adherentsin Western Europe, a Zen Buddhistethoscouldpushthe Japaneseintothe Asiantigers, andspirit Confucius encouragethe Korean peopleintothe Asiandragon. Abstrak:Tulisan ini berangkat dari pertanyaan mengapa etika Islam yang adiluhung itu tidak bisa membumi menjadi etos bangsa di negara-negara yang mayoritas penduduknya Muslim–termasuk di Indonesia. Fenomena seperti majlis taklim, majlis zikir, minat menunaikan ibadah haji melebihi kuota, aktivitas perbankan syariah tak kalah bersemangat, adalah nyata. Namun, itu tidak cukup. Umat Islam seharusnya lebih dari itu dalam penguasaan ilmu pengetahuan, ekonomi, dan peran strategis politik kebangsaan. Etika Islam itulah Das Sollen, keadaan kaum Muslimin itulah Das Sein. Muhammad Rasulullah telah mampu menyatukan Das Sein dan Das Sollen dalam hidupnya. Hal

Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: A systematic review and meta-analysis.

Science.gov (United States)

Franco, André Silva; Freitas, Thiago Quadrante; Bernardo, Wanderley M; Pereira, Rosa Maria R

2017-06-01

Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

Ultrasound resistive index, power Doppler, and clinical parameters in established rheumatoid arthritis.

Science.gov (United States)

Bisi, Melissa Cláudia; do Prado, Aline Defaveri; Piovesan, Deise Marcela; Bredemeier, Markus; da Silveira, Inês Guimarães; Mendonça, José Alexandre; Staub, Henrique Luiz

2017-04-01

Ultrasonography (US) is a useful tool for the evaluation of sinovial vascularization and proliferation in rheumatoid arthritis (RA). Accordingly, resistive index (RI) on spectral Doppler (sD) US provides a quantitative analysis of vascular inflammation, but its utility in the evaluation of RA activity has not been established. Our objective was to determine the association of RI with other US parameters of synovitis and with clinical disease activity in established RA. Patients with positive power Doppler (pD) were included in a prospective cross-sectional study. Disease activity and disability were evaluated using the Disease Activity Score in 28-joints (DAS28) and Health Assessment Questionnaire (HAQ), respectively. Gray scale (GS) synovitis, pD, and sD analyses were performed by one of two examiners in wrists and the second and third metacarpophalangeal and proximal interphalangeal joints. The 10-joint GS and 10-joint pD scores and mean RI were then calculated. Weighted kappa (WK) values were employed to assess interobserver reability, and correlations were tested using the Spearman coefficient. Ninety-five RA patients (median duration of disease of 7 years and mean DAS28 of 4.32 ± 1.66) were included. WK values in real-time US were 0.77 for synovitis, 0.87 for pD, and 0.68 for RI. There were no significant correlations of RI with 10-joint GS, 10-joint pD, DAS28, joint counts, or HAQ (P > 0.10 for all tests). Patients in remission had a mean RI similar to those with high disease activity (0.62 ± 0.10, n = 15 versus 0.63 ± 0.13, n = 34, respectively). The addition of the RI score did not seem to improve US performance in patients with established RA.

Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs in rheumatoid arthritis: results of the GO-MORE study in Spain.

Science.gov (United States)

Alonso, Alberto; González, Carlos M; Ballina, Javier; García Vivar, María L; Gómez-Reino, Juan J; Marenco, Jose Luis; Fernández-Nebro, Antonio; Ordás, Carmen; Cea-Calvo, Luis; Arteaga, María J; Sanmartí, Raimon

2015-01-01

To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). The patients received subcutaneous golimumab 50mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR>5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

49 CFR 28.152-28.159 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.152-28.159 Section 28.152-28.159 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.152-28.159 [Reserved] ...

49 CFR 28.171-28.999 - [Reserved

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2010-10-01

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49 CFR 28.132-28.139 - [Reserved

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2010-10-01

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49 CFR 28.161-28.169 - [Reserved

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2010-10-01

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49 CFR 28.141-28.148 - [Reserved

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2010-10-01

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49 CFR 28.104-28.109 - [Reserved

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2010-10-01

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49 CFR 28.112-28.129 - [Reserved

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2010-10-01

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Tracking of leisure time physical activity during 28 yr in adults: the Tromsø study.

Science.gov (United States)

Morseth, Bente; Jørgensen, Lone; Emaus, Nina; Jacobsen, Bjarne K; Wilsgaard, Tom

2011-07-01

Physical activity plays an important role in the prevention of many serious diseases. To develop targeted strategies that encourage physical activity, knowledge of stability of physical activity levels over time is essential. The aim of this study was to examine tracking of leisure time physical activity in adults in Northern Norway during three decades. We followed 5432 women and men who attended the Tromsø Study in 1979-1980, as well as repeated examinations after 7 and 28 yr. Baseline age was 20-54 yr (mean age=35.8 yr). Physical activity was assessed by self-administered questionnaires. Tracking of physical activity, defined as maintenance of relative rank of physical activity level, was estimated by Spearman correlation coefficient and by weighted κ statistics. Tracking in terms of predictability of later values from earlier measurements was analyzed by generalized estimating equations. A higher-than-expected proportion of subjects maintained their physical activity level from examination 1 to 2 (58%) and 3 (53%). κ statistics showed agreement of 0.41 and 0.29, respectively. Belonging to a specific physical activity level at baseline increased the odds of belonging to the same category at later examinations (sedentary odds ratio (OR)=3.9 (95% confidence interval (CI)=3.5-4.4), moderately active OR=2.2 (95% CI=2.0-2.4), active OR=2.9 (95% CI=2.6-3.3), and highly active OR=14.0 (95% CI=8.7-22.5)). Being physically active in young adulthood increased the odds of being physically active later in life (moderately active OR=3.4 (95% CI=3.0-3.9), active OR=5.4 (95% CI=4.6-6.4), and highly active OR=13.0 (95% CI=7.4-22.8)). This study showed tracking of leisure time physical activity during 28 yr in a cohort of adults.

The Structural Basis of Exopolygalacturonase Activity in a Family 28 Glycoside Hydrolase

Energy Technology Data Exchange (ETDEWEB)

Abbott,D.; Boraston, A.

2007-01-01

Family 28 glycoside hydrolases (polygalacturonases) are found in organisms across the plant, fungal and bacterial kingdoms, where they are central to diverse biological functions such as fruit ripening, biomass recycling and plant pathogenesis. The structures of several polygalacturonases have been reported; however, all of these enzymes utilize an endo-mode of digestion, which generates a spectrum of oligosaccharide products with varying degrees of polymerization. The structure of a complementary exo-acting polygalacturonase and an accompanying explanation of the molecular determinants for its specialized activity have been noticeably lacking. We present the structure of an exopolygalacturonase from Yersinia enterocolitica, YeGH28 in a native form (solved to 2.19 {angstrom} resolution) and a digalacturonic acid product complex (solved to 2.10 {angstrom} resolution). The activity of YeGH28 is due to inserted stretches of amino acid residues that transform the active site from the open-ended channel observed in the endopolygalacturonases to a closed pocket that restricts the enzyme to the exclusive attack of the non-reducing end of oligogalacturonide substrates. In addition, YeGH28 possesses a fused FN3 domain with unknown function, the first such structure described in pectin active enzymes.

Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial.

Science.gov (United States)

Bechman, Katie; Sin, Fang En; Ibrahim, Fowzia; Norton, Sam; Matcham, Faith; Scott, David Lloyd; Cope, Andrew; Galloway, James

2018-01-01

Tapering of anti-tumour necrosis factor (TNF) therapy appears feasible, safe and effective in selected patients with rheumatoid arthritis (RA). Depression is highly prevalent in RA and may impact on flare incidence through various mechanisms. This study aims to investigate if psychological states predict flare in patients' dose tapering their anti-TNF therapy. This study is a post-hoc analysis of the Optimizing TNF Tapering in RA trial, a multicentre, randomised, open-label study investigating anti-TNF tapering in RA patients with sustained low disease activity. Patient-reported outcomes (Health Assessment Questionnaire, EuroQol 5-dimension scale, Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F), 36-Item Short Form Survey (SF-36)) were collected at baseline. The primary outcome was flare, defined as an increase in 28-joint count Disease Activity Score (DAS28) ≥0.6 and ≥1 swollen joint. Discrete-time survival models were used to identify patient-reported outcomes that predict flare. Ninety-seven patients were randomised to taper their anti-TNF dose by either 33% or 66%. Forty-one patients flared. Higher baseline DAS28 score was associated with flare (adjusted HR 1.96 (95% CI 1.18 to 3.24), p=0.01). Disability (SF-36 physical component score), fatigue (FACIT-F) and mental health (SF-36 mental health subscale (MH)) predicted flare in unadjusted models. In multivariate analyses, only SF-36 MH remained a statistically significant predictor of flare (adjusted HR per 10 units 0.74 (95% CI 0.60 to 0.93), p=0.01). Baseline DAS28 and mental health status are independently associated with flare in patients who taper their anti-TNF therapy. Fatigue and function also associate with flare but the effect disappears when adjusting for confounders. Given these findings, mental health and functional status should be considered in anti-TNF tapering decisions in order to optimise the likelihood of success. EudraCT Number: 2010-020738-24; ISRCTN: 28955701

Maintenance of Remission with Etanercept-DMARD Combination Therapy Compared with DMARDs Alone in African and Middle Eastern Patients with Active Rheumatoid Arthritis.

Science.gov (United States)

Bassiouni, Hassan; Spargo, Catherine Elizabeth; Vlahos, Bonnie; Jones, Heather E; Pedersen, Ron; Shirazy, Khalid

2018-06-01

To compare etanercept (ETN) and placebo (PBO) for maintaining low disease activity (LDA) achieved with ETN in patients with rheumatoid arthritis (RA) from Africa and the Middle East. In this subset analysis of the Treat-to-Target trial (ClinicalTrials.gov identifier NCT01981473), 53 adult patients with moderate-to-severe RA nonresponsive to methotrexate were treated with 50 mg ETN/week for 24 weeks (Period 1). Patients achieving LDA were randomized to continue ETN treatment or switched to PBO for an additional 28 weeks (Period 2). The proportion of patients maintaining LDA or remission in each arm at the end of Period 2 was determined. Additional efficacy and patient-reported outcomes (PROs) were also evaluated. During Period 1, 51 patients achieved LDA according to the disease activity score-28 joints-erythrocyte sedimentation rate (DAS28-ESR LDA) and 30 achieved remission. At week 52, nine of 22 and eight of 29 in the ETN and PBO groups, respectively, remained in DAS28-ESR LDA without experiencing a flare. Additionally, six of 14 and five of 16 in the ETN and PBO groups, respectively, remained in remission. Among patients experiencing a flare during Period 2, 13 of 22 and 21 of 29 received ETN or PBO, respectively. The median time to flare was 193 and 87 days in the ETN and PBO groups, respectively. At week 52, consistently more patients in the ETN group than in the PBO group achieved predetermined efficacy and PRO endpoints. These data suggest continuing ETN maintenance therapy is beneficial to patients after they have achieved their treatment target. However, this subset analysis is limited by the small patient population and must be interpreted with caution. Pfizer. ClinicalTrials.gov identifier, NCT0198147.

[Trachoma epidemiological school survey in the city of Embu das Artes--SP].

Science.gov (United States)

Caninéo, Paulo Antonio; Nishimura, Shizuko; Medina, Norma Helen; Koizumi, Inês Kazue; Cardoso, Maria Regina Alves

2012-01-01

To estimate the trachoma prevalence in school children in Embu das Artes - SP, aiming the implementation of the disease epidemiological surveillance. The city of Embu das Artes - SP, is 25 km far from the capital of the State. In the years of 2003-2004, a trachoma survey was conducted in a cluster sample of school children with the same methodology of the national trachoma student's survey of the Ministry of Health. Previously to the trachoma active search, activities of health education were performed in all schools. External ocular examinations were done in all students to detect trachoma according to the WHO criteria. All cases of trachoma were notified and their families were submitted to an external ocular examination. The cases were treated with 1% tetracycline ointment or systemic azithromycin. 2,374 students from nine sampled selected public schools were examined. The prevalence of follicular inflammatory trachoma (TF) was 3.1% (IC 95%: 2.4-3.9), varying from 0.5% to 4.2% in the examined schools. The prevalence for males was 3.2% and for females was 3.0%. The greater prevalence (8.6%) was found in 6 year-old children. The disease showed a mild behavior in this city, because no cases of intense inflammatory trachoma or cicatricial trachoma were detected. However, the prevalence was greater than the one found in the city of São Paulo. Epidemiological surveillance activities of trachoma must be continuous, mainly in places where the greater prevalence had been found.

A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.

Science.gov (United States)

Chandran, Binu; Goel, Ajay

2012-11-01

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis.

Science.gov (United States)

George, Michael D; Østergaard, Mikkel; Conaghan, Philip G; Emery, Paul; Baker, Daniel G; Baker, Joshua F

2017-10-01

Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. NCT00361335 and NCT00264550; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial

NARCIS (Netherlands)

Levitsky, Adrian; Brismar, Kerstin; Hafström, Ingiäld; Hambardzumyan, Karen; Lourdudoss, Cecilia; van Vollenhoven, Ronald F.; Saevarsdottir, Saedis

2017-01-01

The aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA). Body mass index (BMI) was available in 260 patients from the Swedish pharmacotherapy trial (SWEFOT). Differences in disease activity (DAS28), functional

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis.

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Iwamoto, Naoki; Tsuji, Sosuke; Takatani, Ayuko; Shimizu, Toshimasa; Fukui, Shoichi; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-Ya; Aramaki, Toshiyuki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Terada, Kaoru; Origuchi, Tomoki; Eguchi, Katsumi; Ueki, Yukitaka; Kawakami, Atsushi

2017-01-01

We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (Ptofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs.

Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes.

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Piantoni, S; Regola, F; Zanola, A; Andreoli, L; Dall'Ara, F; Tincani, A; Airo', P

2018-01-01

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p adj ). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p adj  = .005) as well as those with an effector memory ( p adj  = .004) and TDEM ( p adj  = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with

Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal

DEFF Research Database (Denmark)

Einarsson, Jon Thorkell; Geborek, Pierre; Saxne, Tore

2016-01-01

of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)]. METHODS: Patients with RA...... treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) achieved...... SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit. RESULTS: Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI...

Instrumental Neutron Activation Analysis- INAA: environmental studies in Das Velhas Basin, Minas Gerais, Brazil

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Rabelo V, M.A.; Andrade Q, M.T.; Araujo M, R.; Albernaz A, I.; Oliveira, A.H. de

2006-01-01

The Instrumental Neutron Activation Analysis - INAA was applied to determine concentrations of several elements in unpolluted areas and in the mining and farming region of the Das Velhas Basin, Minas Gerais State, Brazil. INAA was applied using the TRIGA Mark I IPR - R1 reactor at the Nuclear Technology Development Center of the National Committee of Nuclear Energy (CDTN/CNEN), in Belo Horizonte city, Minas Gerais State. At 100 kW of potency the flux of neutrons is 6.6 10 11 n.cm -2 .s -1 . The samples analyzed were: water; sediment; gravel of gold mine and forage. The obtained results for the Das Velhas Basin in water and sediment samples - mining companies region - show a high level (μg/g) of contamination with the analyzed elements, mainly in the sediment samples. During the period of floods, in farming region hundreds of kilometers away, contamination is found in fish and forage, reaching and harming both people and animals that live in the marginal region. (Author)

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

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Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

2018-05-20

This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

Heat Shock Proteins 60 and 70 Specific Proinflammatory and Cytotoxic Response of CD4+CD28null Cells in Chronic Kidney Disease

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Ashok K. Yadav

2013-01-01

Full Text Available Background. CD4+CD28null T cells are expanded in peripheral blood of patients with chronic kidney disease and associated with subclinical atherosclerosis. However, triggers for the oligoclonal expansion and activation of these cells are not clear. Methods. We investigated twenty-five stage V-IV chronic kidney disease (CKD patients and eight healthy subjects (HC. Peripheral mononuclear cells were isolated and incubated with heat shock protein- (HSP 60 and 70. CD4+CD28null and CD4+CD28+ cells were sorted by flowcytometry and antigen specific response was assessed by the mRNA and protein expression of interferon (IFN-γ, perforin, and granzyme B using qRT-PCR and Elispot. Results. The basal mRNA expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was higher in subjects with CKD compared to that in HC (P<0.0001. Subjects with CKD also showed expression of IFN-γ, perforin, and granzyme B in the CD4+CD28+ subset, but this was much weaker than that seen in the CD4+CD28null population (P<0.0001. We did not note the expression of these molecules at mRNA or protein level in either subset of CD4 cells in HC. After incubation with HSP60 and HSP70, CD4+CD28null cells showed increased expression at mRNA (P<0.001 and protein level (P<0.001. CD4+CD28+ cells also showed a weak increase in expression. No antigen-specific response was noted in HC. Conclusion. These data show that CD4+CD28null cells in subjects with CKD react with HSP60 and HSP70 by upregulating the expression of IFN-γ, perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might play a role in initiation and/or progression of atherosclerosis in CKD subjects through perturbation of CD4+CD28null cells.

Use of tofacitinib in real clinical practice to treat patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs: Results of a multicenter observational study

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D. E. Karateev

2016-01-01

Full Text Available Tofacitinib (TOFA, a member of a new class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs, is a promising medication for the treatment of rheumatoid arthritis (RA and other immunoinflammatory diseases. The paper describes the Russian experi-ence with TOFA used to treat severe RA.Patients and methods. 101 RA patients (18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months who were positive for rheumatoid factor (89.1% and anti-cyclic citrullinated peptide antibodies (74.7% and resistant to therapy with synthetic DMARDs (sDMARDs (80.2% and biological agents (19.8% were given TOFA at a dose of 5 mg twice daily, which could be doubled if necessary. TOFA was used alone (n=9 or in combination with methotrexate (MT (n=75 or other sDMARDs (n=17. The achievement of low disease activity (LDA and clinical remission at 3 and 6 months of treatment by DAS28-ESR SDAI, and CDAI scores, and the indices of safety and tolerability were assessed.Results. A total of 93 (92.1% of the 101 patients completed a 24-week period of the investigation. 8 (7.9% patients prematurely discontinued TOFA after an average of 2.75±0.71 months. At the end of the study, the patients achieved the primary endpoint (LDA including remission in terms of DAS28-ESR ≤3.2 (34.7%, SDAI ≤11 (47.5%, and CDAI ≤10 (48.5% and the secondary endpoints (clinical remission in terms of DAS28-ESR ≤2.6 (17.8%, SDAI ≤3.3 (8.9%, and CDAI ≤2.8 (6.9%. When TOFA was combined with MT, the discontinuation rate for the former was significantly lower (2.7% than when TOFA was used in combination with other sDMARDs (29.4% or alone (11.1%; p<0.01. At 3 and 6 months of follow-up, LDA was achieved more frequently when TOFA was combined with MT than when other treatment regimens were used. Fatal outcomes and serious adverse events (AEs, as AEs previously undescribed in the literature, were not seen during a follow-up within

Structural and biochemical analysis of atypically low dephosphorylating activity of human dual-specificity phosphatase 28.

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Bonsu Ku

Full Text Available Dual-specificity phosphatases (DUSPs constitute a subfamily of protein tyrosine phosphatases, and are intimately involved in the regulation of diverse parameters of cellular signaling and essential biological processes. DUSP28 is one of the DUSP subfamily members that is known to be implicated in the progression of hepatocellular and pancreatic cancers, and its biological functions and enzymatic characteristics are mostly unknown. Herein, we present the crystal structure of human DUSP28 determined to 2.1 Å resolution. DUSP28 adopts a typical DUSP fold, which is composed of a central β-sheet covered by α-helices on both sides and contains a well-ordered activation loop, as do other enzymatically active DUSP proteins. The catalytic pocket of DUSP28, however, appears hardly accessible to a substrate because of the presence of nonconserved bulky residues in the protein tyrosine phosphatase signature motif. Accordingly, DUSP28 showed an atypically low phosphatase activity in the biochemical assay, which was remarkably improved by mutations of two nonconserved residues in the activation loop. Overall, this work reports the structural and biochemical basis for understanding a putative oncological therapeutic target, DUSP28, and also provides a unique mechanism for the regulation of enzymatic activity in the DUSP subfamily proteins.

The efficacy of the traditional Chinese medicine Juanbi pill combined with methotrexate in active rheumatoid arthritis: study protocol for a randomized controlled trial.

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Wang, Qiong; Wang, Yi-Ru; Jia, Qing-Yun; Liu, Li; Xu, Chong-Qing; Wang, Xiao-Yun; Yao, Min; Cui, Xue-Jun; Shi, Qi; Wang, Yong-Jun; Liang, Qian-Qian

2018-03-20

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling and painful joints, eventually leading to joint destruction. There is still a lack of effective therapy to treat RA. The Juanbi pill is a Chinese medicine that has been widely used to treat active RA in China for hundreds of years, relieving pain and protecting the affected joints from malformation. However, there is no solid evidence to show the effect of the Juanbi pill on the management of active RA. We will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether the traditional Chinese medicine Juanbi pill could relieve joint pain in RA and protect the joints. A total of 120 patients with active RA will be enrolled and treated with the Juanbi pill or a placebo for 3 months. The primary outcome measures are as follows: rate of in the American College of Rheumatology (ACR)50, change in the 28-joint Disease Activity Score (DAS28) from baseline at beginning of therapy to 3 months, and a change in the van der Heijde modified Sharp score measured from baseline to 12 months. The secondary outcome measures are as follows: rate of change in ACR20, ACR70, Health Assessment Questionnaire-Disability Index (HAQ-DI), and change in score in the Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens Insomnia Scale (AIS) from baseline to 2-week, 1-month, 2-month, 3-month, 6-month, and 12-month follow up. In addition, the rate of change (score) in the ACR50 and DAS28 from the baseline to 2-week, 1-month, 2-month, 6-month, and 12-month follow up are also the secondary outcome measures. Although the Juanbi pill has been used in China for many years to treat RA, there is a lack of consensus about its effectiveness. This trial will provide convincing evidence about the effect of Juanbi pill on active RA. ClinicalTrials.gov, NCT02885597 . Registered on 30 August 2016.

Factors influencing spinal sagittal balance, bone mineral density, and Oswestry Disability Index outcome measures in patients with rheumatoid arthritis.

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Masamoto, Kazutaka; Otsuki, Bungo; Fujibayashi, Shunsuke; Shima, Koichiro; Ito, Hiromu; Furu, Moritoshi; Hashimoto, Motomu; Tanaka, Masao; Lyman, Stephen; Yoshitomi, Hiroyuki; Tanida, Shimei; Mimori, Tsuneyo; Matsuda, Shuichi

2018-02-01

To identify the factors influencing spinal sagittal alignment, bone mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in patients with rheumatoid arthritis (RA). We enrolled 272 RA patients to identify the factors influencing sagittal vertical axis (SVA). Out of this, 220 had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the sagittal plane; 183 completed the ODI questionnaire. We collected data regarding RA-associated clinical parameters and standing lateral X-ray images via an ODI questionnaire from April to December 2012 at a single center. Patients with a history of spinal surgery or any missing clinical data were excluded. Clinical parameters included age, sex, body mass index, RA disease duration, disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic citrullinated peptide antibody, serum rheumatoid factor, serum matrix metalloproteinase-3, BMD and treatment type at survey, such as methotrexate (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We measured radiological parameters including pelvic incidence (PI), lumbar lordosis (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD, and ODI using multivariate regression analysis. Multivariate regression analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX nonuse, and glucocorticoid use. Lower BMD was associated with female, older age, higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and glucocorticoid use. In managing low back pain and spinal sagittal alignment in RA patients, RA-related clinical factors and the treatment type should be taken into consideration.

Changing clinical patterns in rheumatoid arthritis management over two decades:Sequential observational studies

OpenAIRE

Mian, Aneela N; Ibrahim, Fowzia; Scott, Ian C; Bahadur, Sardar; Filkova, Maria; Pollard, Louise; Steer, Sophia; Kingsley, Gabrielle H; Scott, David L; Galloway, James

2016-01-01

BACKGROUND: Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ).METHODS: Four cross...

Reliability And Validity Of Turkish Version Of Motor Activity Log-28

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Burcu Ersöz Hüseyinsinoğlu

2011-06-01

Full Text Available OBJECTIVE: The aim of this study was to adapt the Motor Activity Log-28 (MAL-28 into Turkish and probe the reliability and validity of this questionnaire in stroke patients. METHODS: Following the translation of the MAL-28 into Turkish, its reliability and construct validity was examined in 30 stroke patients. For the reliability study, patients were interviewed twice within a three day period, during which no rehabilitative activities were undertaken. The test-retest reliability was determined by using intra-class correlation coefficient (ICC and Spearman correlation coefficient (r; internal consistency was determined by Cronbach's alpha (α. The construct validity was examined by comparing MAL-28 Quality Of Movement (QOM scale and Amount Of Use (AOU scale with Wolf Motor Function Test (WMFT-Performance Time (PT and Functional Ability (FA scores. Furthermore, item-to-scale correlations of AOU and QOM scales were determined and correlation between totol scores of two scales was examined. RESULTS: Turkish version of MAL-28 AOU and QOM scales were reliable (ICC scores were 0.97 and 0.96, respectively and internally consistent (Cronbach’s α value was 0.96 for both scales. Test-retest reliability was supported (AOU, r=0.94; QOM, r=0.93. WMFT FA scores was correlated with both scales (r=0.63. Correlation between WMFT PT and AOU and QOM scales were -0.56 and -0.55. AOU and QOM scales were highly correlated (r=0.95. CONCLUSION: The findings indicate that Turkish version of MAL-28 is reliable and valid in individuals with stroke. Further investigation about its responsiveness is needed before using that version as a primary measurement in clinical trials

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

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de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

2014-01-01

To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

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Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

2015-01-01

Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis.

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Naoki Iwamoto

Full Text Available We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA in a real-world setting.Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks.Fifty-eight patients (82.9% continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline. 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX or patients whose treatment with tocilizumab (TCZ failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs previously used was independently associated with achievement of DAS-low disease activity.Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs.

Factors associated with sustained remission in patients with rheumatoid arthritis.

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Martire, María Victoria; Marino Claverie, Lucila; Duarte, Vanesa; Secco, Anastasia; Mammani, Marta

2015-01-01

To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital.

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Wick, M C; Ernestam, S; Lindblad, S; Bratt, J; Klareskog, L; van Vollenhoven, R F

2005-01-01

To determine whether the tumour necrosis factor-alpha (TNF-alpha) antagonist adalimumab (Humira) can be efficacious after secondary loss of efficacy (i.e. loss of clinical response in patients who had initially demonstrated clinical response) to infliximab (Remicade) or etanercept (Enbrel). We studied 36 patients from the Stockholm TNF-alpha follow-up registry (STURE) who received adalimumab after secondary loss of efficacy to infliximab (group A, n = 27) or etanercept (group B, n = 9), and 26 patients who were started on adalimumab as the first TNF-alpha antagonist (group C). In group A, the baseline disease activity score 28 (DAS28) at infliximab institution was 5.5+/-0.2. During infliximab treatment, the mean best DAS28 was 3.7+/-0.2 (p<0.001), but increased to 5.2+/-0.3 when infliximab was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.5+/-0.3 (p<0.003), and then to 4.2+/-0.2 at 6 months (p<0.001). In group B, the baseline DAS28 at etanercept institution was 6.6+/-0.5. During etanercept treatment, the mean best DAS28 was 4.6+/-0.5 (p<0.01), but increased to 5.7+/-0.4 by the time etanercept was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.8+/-0.3 (p<0.005), and to 4.1+/-0.2 at 6 months (p<0.001). In group C, the mean baseline DAS28 was 5.6+/-0.3. After 6 months of adalimumab therapy, the DAS28 decreased to 3.5+/-0.4 (p<0.001). ACR20 responses with adalimumab in groups A, B, and C were similar (70-78%). For patients with secondary loss of efficacy from infliximab or etanercept, switching to adalimumab can restore a good clinical response.

Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, EQ-5D [corrected] RAQoL, and HAQ in patients with rheumatoid arthritis

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Linde, Louise; Sørensen, Jan; Ostergaard, Mikkel

2008-01-01

.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82). Validity: all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC > 0.95) and internal consistency (Cronbach's alpha > 0.90). Responsiveness: SF-36 bodily pain scale......, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. Validity (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated...... questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline. RESULTS: The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1...

MiDAS

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McIlroy, Simon Jon; Kirkegaard, Rasmus Hansen; McIlroy, Bianca

A deep understanding of the microbial communities and dynamics in wastewater treatment systems is a powerful tool for process optimization and design (Rittmann et al., 2006). With the advent of amplicon sequencing of the 16S rRNA gene, the diversity within the microbial communities can now...... web platform about the microbes in activated sludge and their associated ADs. The MiDAS taxonomy proposes putative names for each genus-level-taxon that can be used as a common vocabulary for all researchers in the field....

Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice.

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Anderson, Jaclyn; Caplan, Liron; Yazdany, Jinoos; Robbins, Mark L; Neogi, Tuhina; Michaud, Kaleb; Saag, Kenneth G; O'Dell, James R; Kazi, Salahuddin

2012-05-01

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice. The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations. Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures. We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings. Copyright © 2012 by the American College of Rheumatology.

Th1-Th17 Ratio as a New Insight in Rheumatoid Arthritis Disease.

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Bazzazi, Hadi; Aghaei, Mehrdad; Memarian, Ali; Asgarian-Omran, Hossein; Behnampour, Nasser; Yazdani, Yaghoub

2018-02-01

The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (pTh1 cells in RA patients were less than healthy group (pTh17/Th1 cell only in new cases of RA were more than healthy control groups (pTh1/Th17 ratio in RA patients is statistically different with healthy control group (pTh1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease.

The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.

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van Vollenhoven, Ronald F; Houbiers, Jos G A; Buttgereit, Frank; In 't Hout, Joanna; Boers, Maarten; Leij, Susanne; Kvien, Tore K; Dijkmans, Ben A C; Szczepański, Leszek; Szombati, Istvan; Sierakowski, Stanislaw; Miltenburg, André M M

2010-02-01

Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. The observed lack of clinical benefit in RA patients treated with an ERalpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERalpha-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.

Validity and responsiveness of a self-administered foot evaluation questionnaire in rheumatoid arthritis.

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Yano, Koichiro; Ikari, Katsunori; Ochi, Kensuke; Ishida, Osamu; Sakuma, Yu; Yoshida, Shinji; Koyama, Takuma; Koenuma, Naoko; Momohara, Shigeki

2015-05-01

A self-administered foot evaluation questionnaire (SAFE-Q) was developed by the Japanese Society for Surgery of the Foot (JSSF). The aim of this study is to evaluate the validity and responsiveness of the SAFE-Q in patients with rheumatoid arthritis (RA). In total, 180 patients with RA answered the SAFE-Q. Of 180 patients, 34 answered the SAFE-Q twice, preoperatively and postoperatively, to assess responsiveness. Construct validity was tested by comparing the 5 SAFE-Q subscales and the JSSF standard rating system for the RA foot and ankle scale (JSSF-RA), a Japanese version of the Health Assessment Questionnaire (JHAQ), disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). Responsiveness was examined by calculating the standardized response mean (SRM) and effect size (ES) 3 months after surgery. There were moderate correlations between the SAFE-Q and the JSSF-RA and JHAQ. Conversely, a low correlation was observed between the SAFE-Q and DAS28, SDAI, and CDAI. The responsiveness was high, with an SRM of 0.9 and ES of 0.7 for pain subscales. SAFE-Q is a useful tool for assessing the foot and ankle in RA patients.

Kalyan Das

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. Kalyan Das. Articles written in Resonance – Journal of Science Education. Volume 5 Issue 12 December 2000 pp 76-76 Book Review. Linear Algebra and Linear Models · Kalyan Das · More Details Fulltext PDF ...

Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.

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Ceara E Walsh

Full Text Available TNF inhibitors (TNFi have revolutionised the treatment of rheumatoid arthritis (RA. Natural killer (NK cells and Natural Killer Cell Receptor+ T (NKT cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs. Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.Patients with RA were recruited for this study, (i RA patients in clinical remission following a minimum of one year of TNFi therapy (n = -15; (2 Active RA patients, not currently or ever receiving TNFi (n = 18; and healthy control volunteers (n = 15. Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b expression on T-(CD3+CD56-, NK-(CD3-CD56+ and NKT-(CD3+CD56+ cells was determined by flow cytometry.Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05. CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05, with no differences observed for CD161 and CD57. CD3+CD56- cell expression of NKG2A was inversely related to DAS28 (r = -0.612, p<0.005.High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with

Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE).

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Nash, Peter; Ohson, Kamal; Walsh, Jessica; Delev, Nikolay; Nguyen, Dianne; Teng, Lichen; Gómez-Reino, Juan J; Aelion, Jacob A

2018-05-01

Evaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA. Patients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52. Among 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast's safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0-24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo). In biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports. NCT01925768; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.

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Gheita, Tamer A; Sayed, Safaa; Gheita, Heba A; Kenawy, Sanaa A

2016-03-01

To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001). Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Eletroforese em acetato de celulose das proteínas do líquido cefalorraqueano: valores normais

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Izelino Caldas Filho

1977-09-01

Full Text Available Foi feita eletroforese das proteinas de LCR colhido por via lombar de 19 pacientes neurologicamente normais entre 10 e 54 anos. A proteinorraquia total variou entre 10 e 28 mg% (método de Meulemans. Sete pacientes eram normais e 12 apresentavam neuroses. As médias das frações separadas pela eletroforese foram: pré-albumina 4.3%; albumina 54.8%; globulina alfa-1 5.9%; globulina alfa-2 8.3%; globulinas beta 15.5%; globulinas gama 11.2%.

Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

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Harris, Nathaniel; Eudy, Amanda; Clowse, Megan

2018-06-15

While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this activity is typically assessed by the physician. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. Univariate and multivariable regression models were used to assess the relationship between patient and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with lupus or rheumatoid arthritis (RA) enrolled in a prospective registry at a single academic center from 2008-2016. In women with RA, patient-reported disease activity is associated with preterm birth (OR 5.9 (1.5-23.9)), and gestational age (beta -1.5 weeks (-2.6, -0.4 weeks)). The physician assessment of disease activity also predicted preterm (OR 2.1 (1.2-3.5)), small for gestational age births (OR 1.8 (1.03-3.1), and gestational age in weeks (beta -0.6 weeks (-0.9, -0.02 weeks)). On the other hand, SLE patient-reported disease activity measures, including the HAQ, pain or global health measures, are not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 (1.-6.3)), cesarean delivery (OR 2.3 (1.0-5.3)), and preeclampsia (OR 2.8 (1.3-6.3)). The results do not appear to be driven by lupus nephritis or antiphospholipid syndrome. For women with RA, patient-reported measures of disease activity may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, no patient-reported measures were associated with adverse outcomes while physician measures of disease activity helped predict several adverse pregnancy outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical and ultrasound evaluation of the response to tocilizumab treatment in patients with rheumatoid arthritis: a case series.

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Epis, Oscar; Filippucci, Emilio; Delle Sedie, Andrea; De Matthaeis, Anna; Bruschi, Eleonora

2014-05-01

This case series evaluates the clinical and ultrasound response to tocilizumab treatment in patients with rheumatoid arthritis (RA). Six patients with active RA (DAS28 ≥ 3.2) for ≥6 months, refractory to conventional DMARDs or anti-TNF agents, received tocilizumab 8 mg/kg every 4 weeks, as monotherapy or in combination with DMARDs, for 6 months. The following clinical parameters were assessed monthly: number of tender joints (28 and 44 joints), number of swollen joints (28 and 44 joints), DAS28-ESR, DAS28-CRP, VAS score, global health status, health assessment questionnaire, patient global assessment of disease activity, physician global assessment of disease activity, functional assessment of chronic illness therapy (FACIT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients also underwent a gray-scale ultrasonography (US) assessment with power Doppler evaluation at each visit. All clinical parameters improved during the study, versus baseline. This improvement was statistically significant for most parameters 2 months following tocilizumab initiation and was sustained to the end of the observation period. The number of tender joints (44-joint evaluation), the FACIT score, and ESR and CRP concentrations were significantly improved versus baseline values after the first month of tocilizumab treatment. The course of US evaluations mirrored that of clinical parameters; a faster and more evident response was observed for foot joints, with respect to hand joints. This case series suggested the rapid clinical benefit of tocilizumab. Ultrasound assessment showed that the onset of this effect was faster in the foot joints than in the hand joints.

S Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. S Das. Articles written in Bulletin of Materials Science. Volume 25 Issue 6 November 2002 pp 557-560. 3-D mapping with ellipsometrically determined physical thickness/refractive index of spin coated sol–gel silica layer · S Das P Pal S Roy S Chakraboarty P K Biswas.

Habitual physical activity in mitochondrial disease.

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Apabhai, Shehnaz; Gorman, Grainne S; Sutton, Laura; Elson, Joanna L; Plötz, Thomas; Turnbull, Douglass M; Trenell, Michael I

2011-01-01

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype. Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001). 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001) and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001). After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s) = -0.49; 95% CI -0.33, -0.63, Pphysical activity between different genotypes mitochondrial disease. These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.

Prevalence of Coxitis and its Correlation with Inflammatory Activity in Rheumatoid Arthritis.

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Bajraktari, Ismet H; Krasniqi, Blerim; Rexhepi, Sylejman; Bexheti, Sadi; Bahtiri, Elton; Bajraktari, Halit; Luri, Besim

2018-02-15

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterised by intra-articular and extra-articular manifestations but very rarely with coxitis. This study aimed to investigate the prevalence of coxitis, clinical changes, and its correlation with the parameters of inflammatory activity. A cohort of 951 patients diagnosed with ACR/EULAR (American College of Rheumatology/European League against Rheumatism) 2010 criteria was enrolled in this prospective, observational and analytic research study. The CBC (Complete Blood Count), ESR (Erythrocyte sedimentation rate), CRP(C - reactive protein), Anti CCP (Antibodies to cyclic citrullinated peptides), X-ray examination of palms and pelvis, and the activity of the disease as measured by DAS - 28 (28 - joint disease activity score) were carried out in all subjects. Independent samples t-test was used to compare the group's characteristics, whereas Pearson correlation test was used to analyse the correlation between study variables. Of the total number of the subjects, 730 (76.8 %) were females, whereas 221 (23.2%) were males. The average age was 51.3, y/o while the most of them were between 40 - 49 y/o (32.6%). The prevalence of coxitis was 14.2%, mostly found in males (19.46%). The echosonografic prevalence of changes was 21.45%, while the radiological changes were 16.3%; in both cases, the changes were more expressed in males. The analysis showed that inflammatory parameters were significantly higher in patients with coxitis. Coxitis has high economic cost because it ends up with a mandatory need for a total hip joint prosthesis. Thus the results of this study can serve to plan and initiate early preventive measures.

Habitual physical activity in mitochondrial disease.

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Shehnaz Apabhai

Full Text Available Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI.Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001. 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001 and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001. After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s = -0.49; 95% CI -0.33, -0.63, P<0.01. There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.

Work productivity in rheumatoid arthritis: relationship with clinical and radiological features.

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Chaparro Del Moral, Rafael; Rillo, Oscar Luis; Casalla, Luciana; Morón, Carolina Bru; Citera, Gustavo; Cocco, José A Maldonado; Correa, María de Los Ángeles; Buschiazzo, Emilio; Tamborenea, Natalia; Mysler, Eduardo; Tate, Guillermo; Baños, Andrea; Herscovich, Natalia

2012-01-01

Objective. To assess the relationship between work productivity with disease activity, functional capacity, life quality and radiological damage in patients with rheumatoid arthritis (RA). Methods. The study included consecutive employed patients with RA (ACR'87), aged over 18. Demographic, disease-related, and work-related variables were determined. The reduction of work productivity was assessed by WPAI-RA. Results. 90 patients were evaluated, 71% women. Age average is 50 years old, DAS28 4, and RAQoL 12. Median SENS is 18 and HAQ-A 0.87. Mean absenteeism was of 14%, presenting an average of 6.30 work hours wasted weekly. The reduction in performance at work or assistance was of 38.4% and the waste of productivity was of 45%. Assistance correlated with DAS28 (r = 0.446; P productivity was noticed in higher levels of activity and functional disability. Patients with SENS > 18 showed lower work productivity than those with SENS work productivity were HAQ-A and RAQoL. Conclusion. RA patients with higher disease severity showed higher work productivity compromise.

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

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ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Combination of Mangifera indica L. extract supplementation plus methotrexate in rheumatoid arthritis patients: a pilot study.

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López Mantecón, Ana M; Garrido, Gabino; Delgado-Hernández, René; Garrido-Suárez, Bárbara B

2014-08-01

The purpose of the present study was to evaluate the possible therapeutic effects and the safety of Mangifera indica extract (Vimang tablets, 300 mg) combined with methotrexate (MTX) on reducing disease activity in rheumatoid arthritis (RA). Twenty patients with active RA underwent a year of treatment with MTX (12.5 mg/week) associated to non-steroidal anti-inflammatory drugs (NSAIDs) and/or prednisone (5-10 mg/day) were randomly allocated to the experimental group (n=10), that received the extract supplementation (900 mg/day) or preceding usual treatment (n=10) during 180 days. RA activity was evaluated using the tender and swollen joint counts, erythrocyte sedimentation rate, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment's efficacy was demonstrated with ACR criteria. Only the patients of MTX-Vimang group revealed statistically significant improvement in DAS 28 parameters with respect baseline data but no differences were observed between groups. ACR improvements amounted 80% only in MTX-Vimang group at the 90 days (pVimang group, 100% of patients decreased NSAIDs administration (p<0.01) and 70% of those eradicated gastrointestinal side effects (p<0.01) ensuing of the preceding treatment. Other adverse effects were not reported. Copyright © 2013 John Wiley & Sons, Ltd.

CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter

International Nuclear Information System (INIS)

Drela, Nadzieja; Zesko, Izabela; Jakubowska, Martyna; Biernacka, Marzena

2006-01-01

The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4 + and CD8 + T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28 low/high thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population. The increase of the percentage of CD28 low and the decrease of CD28 high thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation

The Microbial Database for Danish wastewater treatment plants with nutrient removal (MiDas-DK) – a tool for understanding activated sludge population dynamics and community stability

DEFF Research Database (Denmark)

Mielczarek, Artur Tomasz; Saunders, Aaron Marc; Larsen, Poul

2013-01-01

Since 2006 more than 50 Danish full-scale wastewater treatment plants with nutrient removal have been investigated in a project called ‘The Microbial Database for Danish Activated Sludge Wastewater Treatment Plants with Nutrient Removal (MiDas-DK)’. Comprehensive sets of samples have been collected......, analyzed and associated with extensive operational data from the plants. The community composition was analyzed by quantitative fluorescence in situ hybridization (FISH) supported by 16S rRNA amplicon sequencing and deep metagenomics. MiDas-DK has been a powerful tool to study the complex activated sludge...

T helper-independent activation of human CD8+ cells: the role of CD28 costimulation.

Science.gov (United States)

Van Gool, S W; Zhang, Y; Kasran, A; de Boer, M; Ceuppens, J L

1996-07-01

The concept that activation of MHC class I-restricted CD8+ cells entirely depends on help from MHC class II-restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ cells can directly be activated by MHC class I-expressing professional antigen-presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28-mediated costimulation for T helper cell-independent activation of purified human CD8+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting Fc gamma R+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ cells by allogeneic MHC class I on EBV-transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti-CD80 and anti-CD86 MoAb or CTLA-4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T-cell activation. CsA and CD80/CD86-blocking agents were synergistic in completely inhibiting activation of CD8+ cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance.

Work Productivity and Costs Related to Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis.

Science.gov (United States)

Kruntorádová, Klára; Klimeš, Jiří; Šedová, Liliana; Štolfa, Jiří; Doležal, Tomáš; Petříková, Alena

2014-09-01

To determine and compare the impact of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis on work productivity, to calculate the productivity costs (PC), and to map out factors that influence (functional status and disease activity) work productivity. The Work Productivity and Activity Impairment questionnaire was used to evaluate productivity losses of patients with RA (n = 77), AS (n = 230), and psoriasis (n = 93). Demographic data, patient-reported outcomes (PROs) (Health Assessment Questionnaire [HAQ] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and clinical parameters (Disease Activity Score in 28 joints [DAS28], body surface area [BSA], and Psoriasis Area and Severity Index [PASI]) were collected. The correlations among PROs, clinical parameters, and overall productivity loss were examined, and multiple regression models were used to examine relationships among parameters and productivity loss. PC were calculated using the friction cost approach. Mean patient age and disease duration were 47.1 and 15.7 years, respectively. The mean HAQ and DAS28 in patients with RA were 1.22 and 5.6, respectively. The mean BASDAI score in patients with AS was 4.43. The mean BSA and PASI score in patients with psoriasis were 21.1% and 12.9, respectively. The percentage of patients with psoriatic arthritis (in those with psoriasis) was 24.7%. We did not find significant differences in Work Productivity and Activity Impairment domains among various diagnoses. Patients with AS, RA, and psoriasis reported overall work productivity losses of 40.9%, 42.9%, and 42.8%, respectively. Daily activity impairments were approximately 50.0%. Overall work productivity loss strongly correlated with PROs, whereas correlations with clinical parameters were weak. The HAQ and BASDAI were identified as major predictors of productivity impairment. The greatest loss in productivity was in those with psoriatic arthritis; however, it was not significant. In

DAS performance analysis

International Nuclear Information System (INIS)

Bates, G.; Bodine, S.; Carroll, T.; Keller, M.

1984-02-01

This report begins with an overview of the Data Acquisition System (DAS), which supports several of PPPL's experimental devices. Performance measurements which were taken on DAS and the tools used to make them are then described

Reconhecimento das marcas patrocinadoras dos times de Futebol Brasileiro

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Giovani Blasi Martino Lanna

2017-01-01

Full Text Available Resumo O futebol é uma das maiores paixões dos brasileiros e os fatos que cercam esse esporte são constantemente propagados nos diversos meios de comunicação. A vasta divulgação do esporte desperta o interesse de muitas empresas a querer vincular a sua marca a determinado time de futebol com vistas a maximizar seus retornos de exposição, imagem e vendas. O presente estudo objetivou verificar o reconhecimento das marcas patrocinadoras dos times de futebol brasileiro na percepção dos torcedores. O público alvo do estudo foi composto por estudantes universitários selecionados por amostragem não probabilística por conveniência, totalizando 126 estudantes. A coleta de dados foi realizada por meio de questionário, no mês de junho de 2015, que foi respondido através de entrevista pessoal e individual. Os resultados demonstraram que 28,3% dos respondentes não torcem por nenhum time e 71,7% torcem por algum time. Considerando apenas a parcela dos respondentes que torcem por algum time, 28,9% não reconhecem nenhuma marca patrocinadora do time que torce e 71,1% reconhecem. Observa-se que a maior parcela dos torcedores reconhece as marcas patrocinadoras do time de futebol. Conclui-se que quando o indivíduo torce por algum time de futebol há um reconhecimento considerável das marcas patrocinadoras. ABSTRACT Recognition of sponsoring brands of Brazilian Football teams Football is one of the greatest passions of Brazilians and the facts surrounding this sport are constantly propagated in the media. The wide dissemination of the sport awakens the interest of many companies that want to link their brand to a certain football team in order to maximize your exposure returns, image and sales. This study aimed to verify he recognition of the sponsoring brands of Brazilian football teams in the perception of the fans. The study was composed of college students selected as target for non-probabilistic sampling for convenience, totaling 126

Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients.

Science.gov (United States)

Mateen, Somaiya; Moin, Shagufta; Khan, Abdul Q; Zafar, Atif; Fatima, Naureen; Shahzad, Sumayya

2017-06-14

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients. Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment. RA patients showed a significant change in the oxidative stress biomarkers (ROS, P hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx). Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

Science.gov (United States)

Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

2016-04-01

Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Being active when you have heart disease

Science.gov (United States)

Heart disease - activity; CAD - activity; Coronary artery disease - activity; Angina - activity ... Getting regular exercise when you have heart disease is ... It may also help you be more active without chest pain or other ...

Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices

Directory of Open Access Journals (Sweden)

F.M. Perrotta

2013-07-01

Full Text Available The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range 43.5/28-69 years; disease duration (median/range 9.7/1-36 years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy. Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR, ASDAS-C-reactive protein (CRP, bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03. FMD did not statistically differ between patients and controls (12.5% vs 15%; P>0.05. We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04. No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls.

Saarland and Rheinland-Pfalz Mines Inspectorate. Annual report 1996. Economic and technical aspects, industrial safety and environmental protection, statistics, activities of the mining authorities; Oberbergamt fuer das Saarland und das Land Rheinland-Pfalz. Jahresbericht 1996. Bergwirtschaft, Bergtechnik, Arbeitsschutz, Umweltschutz, Statistiken, Taetigkeiten der Bergbehoerden

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-04-01

The annual report of the Saarland and Rheinland-Pfalz Mines Inspectorate outlines the economic and technical developments in mining in these two German states as well as the activities of the mining authorities in all fields of mining. (orig.) [Deutsch] Der Jahresbericht des Oberbergamtes fuer das Saarland und das Land Rheinland-Pfalz gibt einen Ueberblick zur bergwirtschaftlichen und bergtechnischen Entwicklung in beiden Bundeslaendern und vermittelt einen umfassenden Einblick in die Taetigkeiten der Bergbehoerden in den vielfaeltigen Bergbauzweigen. (orig.)

Plantas medicinais e seus usos pelos sitiantes da Reserva Rio das Pedras, Mangaratiba, RJ, Brasil Medicinal plants and its uses by the ranchers from the Rio das Pedras Reserve, Mangaratiba, RJ, Brazil

Directory of Open Access Journals (Sweden)

Maria Franco Trindade Medeiros

2004-06-01

Full Text Available Os sitiantes que residem na Reserva Rio das Pedras, localizada no município de Mangaratiba, Estado do Rio de Janeiro, têm origem nos meeiros que trabalhavam nas plantações de banana da antiga fazenda Goiabal. Atualmente, esta fazenda corresponde ao Club Méditerranée, na cota próxima ao oceano Atlântico e à Reserva Rio das Pedras, acima da Rodovia Rio/Santos (BR-101, sendo um remanescente de Floresta Ombrófila Densa no Estado. O objetivo deste estudo foi resgatar informações sobre o uso de plantas medicinais pelos sitiantes que ainda residem nesta Reserva. Através de entrevistas estruturadas e semi-estruturadas aplicadas junto à comunidade, pôde-se fazer um levantamento das plantas presentes ao redor das casas dos mesmos. Ao todo foram citadas 36 espécies medicinais, distribuídas em 34 gêneros e 25 famílias. Estas espécies estão relacionadas a 28 usos medicinais, organizados em sete categorias. Predominaram espécies de plantas herbáceas (21 spp. seguidas das arbustivas (oito spp. e arbóreas (cinco spp.. Constatou-se que a folha foi a parte mais utilizada e o modo de preparo do remédio foi o decocto. Quantificou-se o número de citações por informante para cada táxon, possibilitando a indicação das espécies mais utilizadas na área, como a erva-de-santa-maria (Chenopodium ambrosioides L. e a pitanga (Eugenia uniflora L..The ranchers who live in Rio das Pedras Reserve, which lies in Mangaratiba County, State of Rio da Janeiro, came from sharecroppers who worked at the banana plantation of the farmer Goiabal farm. Nowadays, that farm corresponds to the Méditerranée Club in the area next to the Atlantic Ocean and to Rio das Pedras Reservation, above the Rio/Santos highway (BR-101, it is a remainder of the Dense Ombrophylous Forest in the State. The aim of this study was to collect information about the use of medicinal plants by the ranchers who still live in that Reservation. A survey of the plants, which could be

Impact of Falls on Physical Activity in People with Parkinson's Disease.

Science.gov (United States)

Hiorth, Ylva Hivand; Larsen, Jan Petter; Lode, Kirsten; Tysnes, Ole-Bjørn; Godfrey, Alan; Lord, Sue; Rochester, Lynn; Pedersen, Kenn Freddy

2016-01-01

A complex relationship exists between motor impairment, physical activity (sedentary behavior, standing and ambulatory activity) and falls in people with Parkinson's disease (PD). To explore associations between recent fall history and the ability to retain an active lifestyle as determined by the volume, pattern and variability of physical activity in people with PD. Forty-eight participants with PD were recruited from the Norwegian ParkWest study. Body posture and ambulatory activity were monitored objectively over 7 days using the activPAL3 accelerometer. Clinical assessments included the Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale motor section and Falls Efficacy Scale-International. Structured interviews were performed to obtain information about demographics, fall history last 6 months, mobility and dementia. Participants with a fall history (n = 20) spent more time sedentary and less time standing than non-falling participants (n = 28). There were no significant differences regarding pattern or variability of sedentary behavior, standing or ambulatory activity in falling versus non-falling participants. Confidence in being able to get up from floor contributed significantly to time spent in sedentary behavior and ambulatory activity in participants with fall history, whereas motor impairment was significantly associated with time spent in all facets of physical activity for non-falling participants. Fall history in our PD cohort was associated with a more sedentary lifestyle, but not less ambulatory activity. More emphasis on improving the capacity to safely complete activities of daily living and increase confidence in getting up from floor may reduce sedentary behavior in people with PD.

A regulação judicial das responsabilidades parentais: Direito e ciência em (inter)ação

OpenAIRE

Casaleiro, Paula

2013-01-01

As transformações do regime de regulação das responsabilidades parentais, como a adoção de critérios legais indeterminados, e a entrada em vigor da Lei n.º 133/99, de 28 de agosto, que introduziu a assessoria técnica complementar, estreitaram a relação do direito e da justiça de família e das crianças com outros saberes, como o serviço social, a medicina ou a psicologia. No presente artigo analisar-se-á o regime de regulação judicial das responsabilidades parentais e a sua aplicação prática, ...

Effect of nonsurgical periodontal treatment in patients with periodontitis and rheumatoid arthritis: A systematic review

Science.gov (United States)

Silvestre-Rangil, Javier; Bagan, Leticia; Bagan, Jose V.

2016-01-01

Background Periodontitis has been regarded as a potential risk factor for rheumatoid arthritis (RA). A systematic review is made to determine whether nonsurgical periodontal treatment in patients with RA offers benefits in terms of the clinical activity and inflammatory markers of the disease. Material and Methods A search was made of the Medline-PubMed, Cochrane, Embase and Scopus databases to identify studies on the relationship between the two disease processes, and especially on the effects of nonsurgical treatment in patients of this kind. The search was based on the following keywords: rheumatoid arthritis AND periodontitis (MeSH), rheumatoid arthritis AND periodontal treatment. Results Eight articles on the nonsurgical treatment of patients with periodontitis and RA were finally included in the study. All of them evaluated clinical (DAS28) and laboratory test activity (ESR, CRP, IL-6, TNFα) before and after treatment. A clear decrease in DAS28 score and ESR was recorded, while other parameters such as CRP, IL-6 and TNFα showed a non significant tendency to decrease as a result of treatment. Conclusions Nonsurgical treatment improved the periodontal condition of patients with periodontitis and RA, with beneficial effects upon the clinical and laboratory test parameters (DAS28 and ESR), while other inflammatory markers showed a marked tendency to decrease. However, all the studies included in the review involved small samples sizes and follow-up periods of no more than 6 months. Larger and particularly longitudinal studies are therefore needed to more firmly establish possible significant relations between the two disease processes. Key words:Periodontitis, rheumatoid arthritis, periodontal treatment. PMID:26946202

Early impairment of cognitive functions in Parkinson's disease Comprometimento precoce das funções cognitivas na doença de Parkinson

Directory of Open Access Journals (Sweden)

Florindo Stella

2007-06-01

Full Text Available BACKGROUND: Impairment in non-motor functions such as disturbances of some executive functions are also common events in Parkinson's disease patients. OBJECTIVE: To verify the performance of Parkinson's disease patients in activities requiring visuoconstructive and visuospatial skills. METHOD: Thirty elderly patients with mild or moderate stages of Parkinson's disease were studied. The assessment of the clinical condition was based on the unified Parkinson's disease rating scale (56.28; SD=33.48, Hoehn and Yahr (2.2; SD=0.83, Schwab and England (78.93%, clock drawing test (7.36; SD=2.51, and mini-mental state examination (26.48; SD=10.11. Pearson's correlation and stepwise multiple regression were used for statistical analyses. RESULTS: The patients presented deterioration in visuospatial and visuoconstructive skills. CONCLUSION: The clock drawing test proved to be a useful predictive tool for identifying early cognitive impairment in thesbe individuals.CONTEXTO: Comprometimento em funções não-motoras como perturbações em algumas funções executivas são também eventos comuns em pacientes com doença de Parkinson. OBJETIVO: Verificar as performances de pacientes com doença de Parkinson em atividades que requerem habilidades visuo-construtivas e visuo-espaciais. MÉTODO: Pacientes idosos (n=30 nos estágios leve ou moderado da doença de Parkinson foram estudados. O diagnóstico da condição clínica foi realizado por meio de: unified Parkinson's disease rating scale (56,28; SD=33,48, Hoehn e Yahr (2,2; SD=0,83, Schwab e England (78,93%, teste do desenho do relógio (7,36; SD=2,51, e mini-exame do estado mental (26,48; SD=10,11. A correlação de Pearson e a análise de regressão múltipla foram empregadas na análise estatística. RESULTADOS: Os pacientes apresentaram deterioração nas habilidades vísuo-espaciais e visuoconstrutivas. CONCLUSÃO: O teste do desenho do relógio provou ser uma ferramenta útil e preditiva para

Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy.

Science.gov (United States)

Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

2016-04-01

To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

Science.gov (United States)

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

Spatial arrangement and functional role of α subunits of proteasome activator PA28 in hetero-oligomeric form

Energy Technology Data Exchange (ETDEWEB)

Sugiyama, Masaaki, E-mail: sugiyama@rri.kyoto-u.ac.jp [Research Reactor Institute, Kyoto University, Osaka 590-0494 (Japan); Sahashi, Hiroki [Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Kurimoto, Eiji [Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Faculty of Pharmacy, Meijo University, Nagoya 468-8503 (Japan); Takata, Shin-ichi [J-PARC Center, Japan Atomic Energy Agency, Ibaraki 319-1195 (Japan); Yagi, Hirokazu; Kanai, Keita; Sakata, Eri [Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Minami, Yasufumi [Department of Biotechnology, Maebashi Institute of Technology, Gunma 371-0816 (Japan); Tanaka, Keiji [Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Kato, Koichi, E-mail: kkatonmr@ims.ac.jp [Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787 (Japan); Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787 (Japan)

2013-03-01

Highlights: ► Homologous α and β subunits are alternatively arranged in the PA28 heptameric ring. ► The flexible loops of the three α subunits surround the site of substrate entry. ► The loops serve as gatekeepers that selectively hinder passage of longer peptides. - Abstract: A major form of proteasome activator PA28 is a heteroheptamer composed of interferon-γ-inducible α and β subunits, which share approximately 50% amino acid identity and possess distinct insert loops. This activator forms a complex with the 20S proteasome and thereby stimulates proteasomal degradation of peptides in an ATP-independent manner, giving rise to smaller antigenic peptides presented by major histocompatibility complex class I molecules. In this study, we performed biophysical and biochemical characterization of the structure and function of the PA28 hetero-oligomer. Deuteration-assisted small-angle neutron scattering demonstrated three α and four β subunits are alternately arranged in the heptameric ring. In this arrangement, PA28 loops surround the central pore of the heptameric ring (site for peptide entry). Activating the 20S proteasome with a PA28 mutant that lacked the α subunit loops cleaved model substrates longer than a nonapeptide with better efficiency when compared to wild-type PA28. Based on these data, we hypothesize that the flexible PA28 loops act as gatekeepers, which function to select the length of peptide substrates to be transported between the proteolytic chamber and the extra-proteasomal medium.

Atividades antioxidante, antinociceptiva e anti-inflamatória das folhas de Mucuna pruriens (L. DC Antioxidant, antinociceptive and anti-inflammatory activity of Mucuna pruriens (L. DC. leaves

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E.V.S. Motta

2013-01-01

Full Text Available A espécie Mucuna pruriens (L. DC. (Fabaceae é popularmente conhecida no Brasil como "café berão" e "pó de mico". Suas sementes são bastante estudadas sendo empregadas na medicina popular para o tratamento de desordens nervosas e do aparelho reprodutor, porém poucas informações sobre a composição química e atividade farmacológica das folhas dessa espécie são descritas na literatura. Assim, os objetivos desse estudo foram: a determinação do perfil fitoquímico, a avaliação da atividade antioxidante in vitro, e a avaliação das atividades anti-inflamatória e antinociceptiva in vivo do extrato metanólico das folhas de M. pruriens nas concentrações de 100 e 300 mg/kg. O estudo fitoquímico foi realizado por meio da pesquisa qualitativa dos constituintes químicos e determinação quantitativa do teor de fenóis totais e flavonoides. O potencial antioxidante foi avaliado pelos métodos do DPPH e poder de redução. As atividades anti-inflamatória e antinociceptiva foram a ante foi promissor, com CI50 de 13,2∝g/mL pelo método do DPPH, e CE50 de 47,9∝g/mL pelo método que avalia o poder de redução. Em relação à atividade anti-inflamatória, o extrato foi capaz de inibir o edema de orelha em 63% (100mg/kg e 28% (300mg/kg. Quanto à atividade antinociceptiva, houve redução do número de contorções abdominais de 64% (100 mg/kg e 69% (300 mg/kg. Estes resultados indicam que M. pruriens apresenta um potencial farmacológico promissor e reforçam o conceito de que a pesquisa de plantas com usos etnofarmacológicos pode revelar um número substancial de respostas em ensaios in vitro e in vivo.The species Mucuna pruriens (L. DC. (Fabaceae is popularly known in Brazil as "café berão" and "pó de mico". Its seeds have been widely studied and used in folk medicine for the treatment of nervous and reproductive system disorders; however, few studies are related to the chemical composition and pharmacological activity of its

P K Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. P K Das. Articles written in Bulletin of Materials Science. Volume 23 Issue 4 August 2000 pp 249-253 Nitride Ceramics. Optimization of time–temperature schedule for nitridation of silicon compact on the basis of silicon and nitrogen reaction kinetics · J Rakshit P K Das.

The role of 18F-FDG PET in characterising disease activity in Takayasu arteritis

International Nuclear Information System (INIS)

Webb, Myles; Chambers, Anthony; AL-Nahhas, Adil; Maudlin, Lucy; Rahman, Lucy; Frank, John; Mason, Justin C.

2004-01-01

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 18 F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists' criteria for TA. 18 F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that 18 F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment. (orig.)

Effect of infliximab dose increase in rheumatoid arthritis at different trough concentrations: a cohort study in clinical practice conditions

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Chamaida ePlasencia

2015-10-01

Full Text Available BackgroundEvidence supporting treatment intensification in rheumatoid arthritis is limited and controversial. We explored outcomes of infliximab dose increases and accounted for pre-existing trough levels in patients with active rheumatoid arthritis (RA.MethodsThis study was a retrospective study of 42 RA patients who received increased infliximab following an insufficient response (DAS28 > 3.2. Serum concentrations of infliximab and antibodies to infliximab (ATI and DAS28 and EULAR clinical response parameters were recorded for one year. Analyses were performed in three patient groups that were defined by infliximab serum concentration prior to treatment enhancement: No detectable, Low (< 1.1 µg/mL or High (≥ 1.1 µg/mL drug levels. Results No circulating infliximab was detected in 20 patients (47.6 %, but 13 (30.9 % and 9 (21.4 % patients exhibited Low and High levels, respectively. ATI were only detected in patients with No detectable drug levels because the drug interferes with ELISA. DAS28 disease activity globally showed a modest improvement after dose escalation, but this improvement did not persist after 6 and 12 months. Infliximab serum levels increased significantly in the High group (p=0.016, but no increase was achieved in the Low and No detectable groups. The three study groups exhibited similar disease activity over time, and no improvement was observed in the non-responder EULAR rates. ConclusionsThese results suggest that the efficacy of an infliximab dose increase is limited, and the response is independent of the infliximab trough serum concentration that is achieved prior to escalation.

Signaling signatures and functional properties of anti-human CD28 superagonistic antibodies.

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Zoe Waibler

Full Text Available Superagonistic CD28 antibodies (CD28SAs activate T lymphocytes without concomitant perturbation of the TCR/CD3-complex. In rodents these reagents induce the preferential expansion of regulatory T cells and can be used for the treatment of autoimmune diseases. Unexpectedly, the humanized CD28 superagonist TGN1412 caused severe and life threatening adverse effects during a recently conducted phase I clinical trail. The underlying molecular mechanisms are as yet unclear. We show that TGN1412 as well as the commercially available CD28 superagonist ANC28.1 induce a delayed but extremely sustained calcium response in human naïve and memory CD4+ T cells but not in cynomolgus T lymphocytes. The sustained Ca++-signal was associated with the activation of multiple intracellular signaling pathways and together these events culminated in the rapid de novo synthesis of high amounts of pro-inflammatory cytokines, most notably IFN-gamma and TNF-alpha. Importantly, sustained transmembranous calcium flux, activation of Src-kinases as well as activation of PI3K were found to be absolutely required for CD28SA-mediated production of IFN-gamma and IL-2. Collectively, our data suggest a molecular basis for the severe side effects caused by TGN1412 and impinge upon the relevance of non-human primates as preclinical models for reagents that are supposed to modify the function of human T cells.

P Chaitanya Das

Indian Academy of Sciences (India)

P Chaitanya Das G Srinivasa Murthy C P Gopalakrishnan P C Deshmukh · More Details Fulltext PDF. Volume 9 Issue 7 July 2004 pp 77-85 Classroom. Motion of Charged Particles in Electromagnetic Fields and Special Theory of Relativity · P Chaitanya Das G Srinivasa Murthy P C Deshmukh K Satish Kumar T A Venkatesh.

S K Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. S K Das. Articles written in Bulletin of Materials Science. Volume 24 Issue 4 August 2001 pp 373-378 Metals and Alloys. Evaluation of solid–liquid interface profile during continuous casting by a spline based formalism · S K Das · More Details Abstract Fulltext PDF. A numerical ...

Determining Pathways to Improvements in Fatigue in Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

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Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

2015-09-01

There is debate as to the role of inflammatory disease activity in the etiology of rheumatoid arthritis (RA)-related fatigue. We undertook this study to determine the relationship of fatigue to disease activity by examining pathways associated with change in fatigue in subjects starting anti-tumor necrosis factor (anti-TNF) therapy for the first time. Participants who had been recruited to the British Society for Rheumatology Biologics Register for RA provided information on fatigue (Short Form 36 [SF-36] vitality scale) and other health status variables at the start of anti-TNF therapy and 6 months later. The Disease Activity Score in 28 joints (DAS28) and inflammation (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP] level) were also reported. A path analysis model comprising changes in fatigue, pain, disease activity, disability, and mental health, along with effects of sex and a history of depression, was used to examine those with high levels of fatigue at baseline (score of ≤12.5 units on the SF-36 vitality scale). The DAS28 was substituted for ESR/CRP to delineate the specific role of inflammation. With a total of 2,652 participants, we identified a well-fitting model (χ2  = 0.18, P = 0.98) accounting for 40% of the variance in fatigue change. There was no direct pathway from change in inflammation to change in fatigue; instead, significant pathways to change in fatigue were observed from changes in disease activity, pain, mental health, and disability, along with effects of sex and a history of depression. A total of 82% of the effect of change in disease activity was indirect, of which ∼50% was mediated through a change in pain. Improvements in fatigue do not appear to be driven by inflammatory disease activity; instead, they appear to result indirectly from improvements in pain. Additional significant pathways through disability and mental health suggest potentially modifiable factors that could be targeted to improve clinically

The relationship between disease activity, quality of life, and personality types in rheumatoid arthritis and ankylosing spondylitis patients.

Science.gov (United States)

Donisan, T; Bojincă, V C; Dobrin, M A; Bălănescu, D V; Predețeanu, D; Bojincă, M; Berghea, F; Opriș, D; Groșeanu, L; Borangiu, A; Constantinescu, C L; Ionescu, R; Bălănescu, A R

2017-07-01

We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.

B P Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. B P Das. Articles written in Bulletin of Materials Science. Volume 25 Issue 6 November 2002 pp 517-519. Structural, dielectric and electrical properties of Sm-modified Pb(SnTi)O3 ferroelectric system · B P Das R N P Choudhary P K Mahapatra · More Details Abstract Fulltext ...

Simultaneous Treatment with Subcutaneous Injection of Golimumab and Intra-articular Injection of Triamcinolone Acetonide (K-Method in Patients with Rheumatoid Arthritis Undergoing Switching of Biologics: Retrospective Case–Control Study

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Katsuaki Kanbe

2016-01-01

Full Text Available Background Tight control of severe rheumatoid arthritis (RA in patients with high disease activity, even when using biologics, is sometimes difficult using a treat-to-target strategy. Switching from one biologic to another is associated with lower efficacy than that in treatment-naive cases. We developed the K-method that involves simultaneous treatment with golimumab and intra-articular joint injection of triamcinolone acetonide (TA in patients undergoing switching of biologics. We performed this retrospective case–control study to investigate the efficacy of achieving an immediate treatment response using the K-method. Methods This study involved 20 patients with RA (control group, 10 patients; K-method group, 10 patients. Patients in the control group were switched to golimumab from other biologics without intra-articular injection of TA. The K-method involved injection of 1 mL of TA (40 mg/mL and 2 mL of 1% lidocaine hydrochloride into swollen or painful joints on the same day as golimumab treatment. A quick response one day after treatment was compared between the two groups according to the disease activity score 28 based on C-reactive protein (DAS28 CRP, clinical disease activity index (CDAI, simplified disease activity index (SDAI, European League Against Rheumatism (EULAR response, and remission rate. These parameters were investigated for 24 weeks. Results The K-method group showed significant improvements in DAS28 CRP, CDAI, and SDAI at one day, 12 weeks, and 24 weeks compared with the control group. The number of swollen and tender joints and the patient and doctor global visual analog scale scores were also significantly different between the two groups. The remission rates based on DAS28 CRP were 30% at one day, 50% at 12 weeks, and 60% at 24 weeks in the K-method group. The EULAR good/moderate response rates were 80% at one day, 90% at 12 weeks, and 90% at 24 weeks in the K-method group; however, these rates were only 10%, 40

Descrição das lesões microscópicas das pregas vestibulares de adultos autopsiados e sua relação com as causas de óbito e doença de base Description of microscopic lesions of vestibular folds of autopsied adults and their relationship with cause of death and underlying disease

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Renata C. Rossi

2005-04-01

Full Text Available Com o aumento dos métodos invasivos que são utilizados para o diagnóstico de doenças do trato respiratório é de se esperar que as alterações das pregas vestibulares (PV sejam mais freqüentes. Além disso, recentemente tem sido discutida a importância das PV na proteção do organismo contra agentes infecciosos e pouco se sabe sobre as lesões microscópicas em pacientes autopsiados, pois o estudo das cordas vocais não é rotina no exame post mortem. OBJETIVO: O objetivo deste estudo foi descrever as alterações microscópicas das pregas vestibulares e realizar a sua relação com as causas de óbito e doença de base de adultos autopsiados. FORMA DE ESTUDO: coorte transversal. MATERIAIS E MÉTODOS: Foram estudadas microscopicamente 82 laringes coletadas de adultos autopsiados sendo realizada a coloração da Hematoxilina-eosina para visualizar as alterações morfológicas microscópicas das PV. RESULTADOS: Das 82 PV analisadas, observamos que 42 (51% apresentaram reação inflamatória, sendo esta a única lesão encontrada. Quinze (18,3% casos apresentaram hiperplasia dos folículos linfóides, onze (13,4% casos infiltrado inflamatório difuso intenso e 16 (19,5%, reação inflamatória aguda. As doenças de base mais freqüentemente encontradas foram as do grupo de doenças do aparelho circulatório 31 (37,8% e nestas 20 (67,8% apresentavam reação inflamatória das PV. As doenças infecciosas foram a causa de morte mais freqüente nos pacientes com reação inflamatória das pregas vestibulares. CONCLUSÃO: Além da função anatômica as PV parecem possuir uma função imunológica em relação à infeccção das vias aéreas inferiores. Nosso estudo demonstrou a presença de reação inflamatória nas cordas vocais em pacientes com doenças infecciosas como causa de morte, podendo este achado estar relacionado com o processo séptico generalizado que levou o indivíduo à morte ou ser uma das formas do organismo prevenir a

{sup 11}C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas

Energy Technology Data Exchange (ETDEWEB)

Park, Eunkyung; Gallezot, Jean-Dominique; Planeta, Beata; Lin, Shu-Fei; Lim, Keunpoong; Chen, Ming-Kai; Huang, Yiyun; Carson, Richard E. [Yale School of Medicine, PET Center, Department of Diagnostic Radiology, 801 Howard Avenue, PO Box 208048, New Haven, CT (United States); Delgadillo, Aracely; Liu, Shuang; O' Connor, Kevin C.; Lee, Jae-Yun; Chastre, Anne; Pelletier, Daniel [Yale School of Medicine, Department of Neurology, New Haven, CT (United States); Seneca, Nicholas; Leppert, David [Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel (Switzerland)

2015-04-02

Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). Microglial activation can be measured in vivo using a positron emission tomography (PET) ligand {sup 11}C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of {sup 11}C-PBR28 binding in MS subjects and healthy controls (HCs) with high-resolution PET. Four clinically and radiologically stable relapsing-remitting MS subjects (age 41 ± 7 years, two men/two women) and four HCs (age 42 ± 8 years, 2 two men/two women), matched for translocator protein genotype [two high- and two medium-affinity binders according to DNA polymorphism (rs6971) in each group], were studied for TRV. Another MS subject (age 41 years, male) with clinical and radiological activity was studied for lesion detectability. Dynamic data were acquired over 120 min after injection of 634 ± 101 MBq {sup 11}C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V{sub T}) derived from multilinear analysis (MA1) modeling (t* = 30 min, using arterial input data) was the main outcome measure. Mean test V{sub T} values (ml cm{sup -3}) were 3.9 ± 1.4 in the whole brain gray matter (GM), 3.6 ± 1.2 in the whole brain white matter (WM) or normal-appearing white matter (NAWM), and 3.3 ± 0.6 in MS WM lesions; mean retest V{sub T} values were 3.7 ± 1.0 in GM, 3.3 ± 0.9 in WM/NAWM, and 3.3 ± 0.7 in MS lesions. Test-retest results showed a mean absolute TRV ranging from 7 to 9 % across GM, WM/NAWM, and MS lesions. High-affinity binders demonstrated 30 % higher V{sub T} than medium-affinity binders in GM. Focal {sup 11}C-PBR28 uptake was detected in two enhancing lesions of the active MS patient. High-resolution {sup 11}C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. {sup 11}C-PBR28 PET is likely to be valuable for monitoring both

Therapeutic intervention scoring system-28 (TISS-28: diretrizes para aplicação Therapeutic intervention scoring system-28 (tiss-28: directrices para su aplicación Therapeutic intervention scoring system-28 (tiss-28: directions for application

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Katia Grillo Padilha

2005-06-01

Full Text Available O Therapeutic Intervention Scoring System-28 (TISS-28 é um instrumento que permite dimensionar carga de trabalho de enfermagem em Unidade de Terapia Intensiva e estimar gravidade da doença. Apresenta-se nesta publicação as definições operacionais para sua aplicação, proposta por um grupo de especialistas na área, com vistas a uniformizar o significado de cada um dos itens e evitar vieses de interpretação.El Therapeutic Intervention Scoring System-28 (TISS-28 es un instrumento que permite dimensionar carga de trabajo de enfermería en una Unidad de Terapia Intensiva y estimar la gravedad de la enfermedad. Se presenta en esta publicación las definiciones operacionales para su aplicación, propuesta por un grupo de especialistas en el área, con vistas a uniformizar el significado de cada uno de los items y evitar sesgos de interpretación.Therapeutic Intervention Scoring System-28 (TISS-28 is a tool that enables the measurement of the nursing work load in Intensive Care Units and the estimate of how grave the disease is. In this study are presented the operational definitions for its application, proposed by a group of specialists in the area, with the aim of rendering uniform the meaning of each of the items and preventing interpretation biases.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries

NARCIS (Netherlands)

Mahler, V.; Aalto-Korte, K.; Alfonso, J. H.; Bakker, J. G.; Bauer, A.; Bensefa-Colas, L.; Boman, A.; Bourke, J.; Bubaš, M.; Bulat, P.; Chaloupka, J.; Constandt, L.; Danielsen, T. E.; Darlenski, R.; Dugonik, A.; Ettler, K.; Gimenez-Arnau, A.; Gonçalo, M.; Johansen, J. D.; John, S. M.; Kiec-Swierczynska, M.; Koch, P.; Kohánka, V.; Krecisz, B.; Larese Filon, F.; Ljubojević, S.; Macan, J.; Marinović, B.; Matura, M.; Mihatsch, P. W.; Mijakoski, D.; Minov, J.; Pace, J.; Pesonen, M.; Ramada Rodilla, J. M.; Rast, H.; Reljic, V.; Salavastru, C.; Schuster, C.; Schuttelaar, M. L.; Simon, D.; Spiewak, R.; Jurakic Tončić, R.; Urbanček, S.; Valiukevičienė, S.; Weinert, P.; Wilkinson, M.; Uter, W.

2017-01-01

Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases,

Novel pandemic influenza A(H1N1 viruses are potently inhibited by DAS181, a sialidase fusion protein.

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Gallen B Triana-Baltzer

2009-11-01

Full Text Available The recent emergence of a novel pandemic influenza A(H1N1 strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV. Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1. Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1 viruses.The activity of DAS181 against several pandemic influenza A(H1N1 virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1 strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1 strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1 viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y, DAS181 may be active against the antigenically novel pandemic influenza A(H1N1 virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for

The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28.

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Kristin E Murphy

Full Text Available KRAB domain Zinc finger proteins are one of the most abundant families of transcriptional regulators in higher vertebrates. The prevailing view is that KRAB domain proteins function as potent transcriptional repressors by recruiting TRIM28 and promoting heterochromatin spreading. However, the extent to which all KRAB domain proteins are TRIM28-dependent transcriptional repressors is currently unclear. Our studies on mouse ZFP568 revealed that TRIM28 recruitment by KRAB domain proteins is not sufficient to warrant transcriptional repressive activity. By using luciferase reporter assays and yeast two-hybrid experiments, we tested the ability of ZFP568 and other mouse KRAB domain proteins to repress transcription and bind TRIM28. We found that some mouse KRAB domain proteins are poor transcriptional repressors despite their ability to recruit TRIM28, while others showed strong KRAB-dependent transcriptional repression, but no TRIM28 binding. Together, our results show that the transcriptional repressive activity of KRAB-ZNF proteins does not correlate with their ability to recruit TRIM28, and provide evidence that KRAB domains can regulate transcription in a TRIM28-independent fashion. Our findings challenge the current understanding of the molecular mechanisms used by KRAB domain proteins to control gene expression and highlight that a high percentage of KRAB domain proteins in the mouse genome differ from the consensus KRAB sequence at amino acid residues that are critical for TRIM28 binding and/or repressive activity.

The role of {sup 18}F-FDG PET in characterising disease activity in Takayasu arteritis

Energy Technology Data Exchange (ETDEWEB)

Webb, Myles; Chambers, Anthony; AL-Nahhas, Adil; Maudlin, Lucy; Rahman, Lucy; Frank, John [Department of Nuclear Medicine, Hammersmith Hospital, Du Cane Road, W12 0HS, London (United Kingdom); Mason, Justin C. [Department of Rheumatology, Hammersmith Hospital, London (United Kingdom)

2004-05-01

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 {sup 18}F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists' criteria for TA. {sup 18}F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that {sup 18}F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment. (orig.)

Mesozooplankton of the estuarine system of Barra das Jangadas, Pernambuco, Brazil

OpenAIRE

Cavalcanti, Eliane A. H.; Neumann-Leitão, Sigrid; Vieira, Dilma A. do N.

2008-01-01

Estudos sobre o mesozooplâncton foram realizados no sistema estuarino de Barra das Jangadas, Pernambuco, Brasil (8º14'36"S, 34º56'28"W) visando analisar a estrutura da comunidade. As amostras foram obtidas com rede de plâncton, com malha de 300 µm, durante os períodos, seco (janeiro/2001) e chuvoso (julho/2001), nas marés de sizígia e de quadratura, em intervalos de três horas. Foram identificados 37 taxa, destacando-se Copepoda com as espécies Pseudodiaptomus acutus (F. Dahl, 1894), Pseudodi...

Caracterização das frações que constituem as proteínas e os carboidratos, e respectivas taxas de digestão, do feno de capim-tifton 85 de diferentes idades de rebrota

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Ribeiro Karina Guimarães

2001-01-01

Full Text Available Avaliaram-se a composição bromatológica, as frações da proteína bruta (A, B1, B2, B3 e C e dos carboidratos totais (A, B1, B2 e C e as respectivas taxas de digestão das frações B1, B2 e B3 de proteínas e das frações A + B1 e B2 de carboidratos e do feno de capim-tifton 85, obtido de plantas colhidas com 28, 35, 42 e 56 dias de rebrota, adubadas com 75 kg/ha/corte de N. Os teores protéicos dos fenos com idades de rebrota de 28 a 56 dias variaram de 17,58 a 12,58%. Os valores das frações protéicas A, B1, B2, B3 e C apresentaram-se, respectivamente, entre 22,10 e 35,53%; 0,24 e 4,55%; 30,37 e 31,34%; 26,55 e 36,62%; e 5,75 e 6,76%, como proporções da proteína bruta total, nos fenos com idades de rebrota entre 28 e 56 dias. As taxas de digestão das frações protéicas B1, B2 e B3 encontraram-se entre 0,319 e 1,324; 0,0724 e 0,0936; e 0,0077 e 0,012 h -1, respectivamente, nos fenos com idades de rebrota entre 28 e 56 dias. Os teores de carboidratos totais variaram de 72,98 a 78,77%, em fenos com 28 a 56 dias de rebrota. Os valores das frações A, B1, B2 e C de carboidratos apresentaram-se entre 2,73 e 5,44%; 1,91 e 2,35%; 77,49 e 80,59%; e 13,59 e 17,87%, respectivamente, como proporções dos carboidratos totais, em fenos com idades entre 28 e 56 dias de rebrota. As taxas de digestão das frações de carboidratos A + B1 e B2 encontraram-se entre 0,181 e 0,20 e 0,04 e 0,0466 h -1, respectivamente, em fenos com idades entre 28 e 56 dias de rebrota.

Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).

Science.gov (United States)

Franklyn, Kate; Lau, Chak Sing; Navarra, Sandra V; Louthrenoo, Worawit; Lateef, Aisha; Hamijoyo, Laniyati; Wahono, C Singgih; Chen, Shun Le; Jin, Ou; Morton, Susan; Hoi, Alberta; Huq, Molla; Nikpour, Mandana; Morand, Eric F

2016-09-01

Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Correlation between Epstein-Barr Virus Infection and Disease Activity of Systemic Lupus Erythematosus: a Cross-Sectional Study

Science.gov (United States)

Piroozmand, Ahmad; Haddad Kashani, Hamed; Zamani, Batool

2017-02-01

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease for whose pathogenesis viral infections are important. The Epstein-Barr virus (EBV) is the main infectious etiological agent. This study aimed to quantitative evaluation of EBV in SLE patients. Materials and Methods: In this cross-sectional study, 40 patients with SLE diagnosed based on American College of Rheumatology criteria were selected using purposive sampling. All were included in the study after obtaining informed consent for participation. Whole blood samples were taken and buffy coat preparations were isolated to determine viral load using the real-time polymerase chain reaction method and assessment with the SLE disease activity index (SLE-DAI). Results: From a total of 40 patients, 37 cases (92.5%) were women. The EBV test was positive in 67.5% and mean viral load was 5396 ± 1891.9 copy/ml. Twenty of forty patients had active and 50% inactive disease, mean EBV viral loads being 6798 and 28.25 copy/ml, respectively (P-value = 0.003). In terms of the severity of disease activity, 17.5 % of female patients had mild to moderate activity, whilst 32.5% of them had severe activity, with respective viral loads of 5,803.3 and 29.73 copy/ml (P-value = 0.003). Conclusion: The Epstein-Barr viral load in SLE patients with active disease was found to be markedly higher than in inactive cases. Thus, EBV may have an important role in the pathogenesis and activity of SLE. Creative Commons Attribution License

Environment-dependent regulation of spliceosome activity by the LSM2-8 complex in Arabidopsis.

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Carrasco-López, Cristian; Hernández-Verdeja, Tamara; Perea-Resa, Carlos; Abia, David; Catalá, Rafael; Salinas, Julio

2017-07-07

Spliceosome activity is tightly regulated to ensure adequate splicing in response to internal and external cues. It has been suggested that core components of the spliceosome, such as the snRNPs, would participate in the control of its activity. The experimental indications supporting this proposition, however, remain scarce, and the operating mechanisms poorly understood. Here, we present genetic and molecular evidence demonstrating that the LSM2-8 complex, the protein moiety of the U6 snRNP, regulates the spliceosome activity in Arabidopsis, and that this regulation is controlled by the environmental conditions. Our results show that the complex ensures the efficiency and accuracy of constitutive and alternative splicing of selected pre-mRNAs, depending on the conditions. Moreover, miss-splicing of most targeted pre-mRNAs leads to the generation of nonsense mediated decay signatures, indicating that the LSM2-8 complex also guarantees adequate levels of the corresponding functional transcripts. Interestingly, the selective role of the complex has relevant physiological implications since it is required for adequate plant adaptation to abiotic stresses. These findings unveil an unanticipated function for the LSM2-8 complex that represents a new layer of posttranscriptional regulation in response to external stimuli in eukaryotes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

Science.gov (United States)

Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

2005-10-06

US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

Estudo epidemiológico das doenças dermatológicas imunologicamente mediadas na cavidade oral An epidemiological study of immune-mediated skin diseases affecting the oral cavity

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Cyntia Helena Pereira de Carvalho

2011-10-01

Full Text Available FUNDAMENTO: As doenças dermatológicas imunologicamente mediadas compõem diversas patologias que apresentam formas variadas de manifestação no organismo. OBJETIVO: Foi proposição desta pesquisa, estabelecer a prevalência das principais doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral. MÉTODOS: Foram avaliados laudos histopatológicos de 10.292 casos arquivados no Serviço de Anatomia Patológica da Disciplina de Patologia Oral da Universidade Federal do Rio Grande do Norte, no período de 1988 a 2009. Dos casos diagnosticados como algum tipo de doença em estudo, coletaram-se dados clínicos como sexo, idade, raça, sítio anatômico e sintomatologia das doenças. RESULTADOS: Do total de casos registrados, no serviço supracitado, 82 (0,8% corresponderam a doenças dermato lógicas imunologicamente mediadas com manifestação na cavidade oral. As doenças encontradas neste estudo foram: líquen plano oral, pênfigo vulgar e penfigoide benigno das membranas mucosas, sendo o líquen plano oral a lesão mais prevalente, representando 68,05% dos casos analisados, dos quais 64,3% apresentavam-se em mu lheres, sendo a mucosa jugal o sítio anatômico mais acometido (46,8%. CONCLUSÃO: A ocorrência de doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral ainda é um fato incomum, semelhante ao observado na maioria das regiões mundiais. No entanto, a busca pelo diagnóstico precoce é um requisito essencial para a condução do tratamento dessas doenças, tendo em vista o possível comprometimento sistêmico do organismo nos pacientes.BACKGROUND: Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. OBJECTIVE: The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. METHODS: A total of 10,292 histopathology reports stored in the archives of the

11C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease

OpenAIRE

Kreisl, William C.; Lyoo, Chul Hyoung; Liow, Jeih-San; Wei, Monica; Snow, Joseph; Page, Emily; Jenko, Kimberly J.; Morse, Cheryl L.; Zoghbi, Sami S.; Pike, Victor W.; Turner, R. Scott; Innis, Robert B.

2016-01-01

This longitudinal study sought to determine whether the 18 kDa translocator protein (TSPO), a marker of neuroinflammation, increases over time in Alzheimer’s disease. Positron emission tomography (PET) imaging with the TSPO radioligand 11C-PBR28 imaging was performed at baseline and after a median follow-up of 2.7 years in 14 amyloid-positive patients and eight amyloid-negative controls. Patients had a greater increase in TSPO binding than controls in inferior parietal lobul...

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

Science.gov (United States)

Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

2007-01-01

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

Analysis of association between polymorphisms of MTHFR, MTHFD1 and RFC1 genes and efficacy and toxicity of methotrexate in rheumatoid arthritis patients

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Vejnovic Dubravka

2016-01-01

Full Text Available A folate analogue methotrexate (MTX is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis. However, the clinical response of RA patients treated with MTX shows interindividual differences and 30% of patients discontinue therapy due to the side effects. In a group of 184 RA patients treated with MTX we have investigated whether polymorphisms in MTHFR (rs1801133, rs1801131, MTHFD1 (rs2236225 and RFC1 (rs144320551 genes may have impact on MTX efficacy and/or adverse drugs effects (ADEs. The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR based on EULAR criteria and relative DAS28 values (rDAS28 and all adverse drug events were recorded. Patients were genotyped for selected polymorphism by PCR-RFLP method. According to the EULAR response criteria after 6 months of MTX therapy 146 (79.3% patients were classified as responders, (17 patients (11.6% were good and 129 patients (88.4% were moderate responders and 38 patients (20.7% as non-responders. ADEs were observed in 53 (28.8% patients. The majority of ADEs were mild (36 (19.56% patients to moderate (12 (6.25% patients. Five patients (2.7% had serious ADEs. Association studies have been conducted between obtained genotypes and the efficacy and toxicity of MTX. We have observed no association between polymorphisms and efficacy or toxicity of MTX in RA patients. [Projekat Ministarstva nauke Republike Srbije, br. 175091

Occupational skin diseases : Actual state analysis of patient management pathways in 28 European countries

NARCIS (Netherlands)

Mahler, V.; Aalto-Korte, K.; Alfonso, J. H.; Bakker, J. G.; Bauer, A.; Bensefa-Colas, L.; Boman, A.; Bourke, J.; Bubas, M.; Bulat, P.; Chaloupka, J.; Constandt, L.; Danielsen, T. E.; Darlenski, R.; Dugonik, A.; Ettler, K.; Gimenez-Arnau, A.; Goncalo, M.; Johansen, J. D.; John, S. M.; Kiec-Swierczynska, M.; Koch, P.; Kohanka, V.; Krecisz, B.; Filon, F. Larese; Ljubojevic, S.; Macan, J.; Marinovic, B.; Matura, M.; Mihatsch, P. W.; Mijakoski, D.; Minov, J.; Pace, J.; Pesonen, M.; Rodilla, J. M. Ramada; Rast, H.; Reljic, V.; Salavastru, C.; Schuster, C.; Schuttelaar, M. L.; Simon, D.; Spiewak, R.; Toncic, R. Jurakic; Urbancek, S.; Valiukeviciene, S.; Weinert, P.; Wilkinson, M.; Uter, W.

Background: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal

Real-life effectiveness of Golimumab in biologic-naïve patients with rheumatoid arthritis - data from the Rheumatic Diseases Portuguese Register (Reuma.pt

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Ana Filipa Mourão

2017-04-01

Full Text Available Objectives. To assess the effectiveness of subcutaneous Golimumab 50 mg/monthly combined with methotrexate (SC GLM + MTX over 52 weeks of treatment, in biologic-naïve RA patients, in a multicentre nationwide cohort from the Rheumatic Diseases Portuguese Register (Reuma.pt. Methods. Data for this observational study was collected from March 2011 to August 2015. Disease activity (DAS28, functional capacity (HAQ and Patient Global Disease Assessment (PGDA were measured at baseline and weeks 12, 24 and 52 of treatment. The primary objective was clinical remission over 52 weeks (1 year and secondary objectives were: functional response and functional remission over 52 weeks, variation of individual components of DAS over time and treatment persistence at week 52. Comparison between baseline variables of subjects with and without clinical remission was performed. The SC GLM + MTX persistence rate was estimated by the Kaplan-Meier analysis. Cox proportional hazard model approach was used to evaluate predictive factors of persistence, response and remission. Results. A total of 109 patients were enrolled in the study: 94 (86.2% female, mean age 55.5±13.2 years, mean age at diagnosis 45.5±13.5 years, mean age at beginning of treatment with biologic agents 53.1±13.1 years; 78.1% positive for serum rheumatoid factor. All patients were biologic-naïve and had active disease, despite previous treatment with conventional DMARDs. At the time of this analysis, 93 patients had a follow-up time of at least 52 weeks (i.e. started treatment before August 2014. Of this group, 38.3% achieved clinical remission, 91.9% functional response and 35.2% functional remission, over 52 weeks. Treatment persistence was 75.3% at 1 year. Disease activity indices were all statistically significantly lower at 12, 24 and 52 weeks when compared to baseline. Older age at diagnosis was associated to a lower probability of clinical remission (HR= 0.96, p= 0.031 whereas higher C

Active Vaccines for Alzheimer Disease Treatment.

Science.gov (United States)

Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

2016-09-01

Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Work Productivity in Rheumatoid Arthritis: Relationship with Clinical and Radiological Features

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Rafael Chaparro del Moral

2012-01-01

Full Text Available Objective. To assess the relationship between work productivity with disease activity, functional capacity, life quality and radiological damage in patients with rheumatoid arthritis (RA. Methods. The study included consecutive employed patients with RA (ACR'87, aged over 18. Demographic, disease-related, and work-related variables were determined. The reduction of work productivity was assessed by WPAI-RA. Results. 90 patients were evaluated, 71% women. Age average is 50 years old, DAS28 4, and RAQoL 12. Median SENS is 18 and HAQ-A 0.87. Mean absenteeism was of 14%, presenting an average of 6.30 work hours wasted weekly. The reduction in performance at work or assistance was of 38.4% and the waste of productivity was of 45%. Assistance correlated with DAS28 (r = 0.446; P 18 showed lower work productivity than those with SENS < 18 (50 versus 34; P=0.04. In multiple regression analysis, variables associated with reduction of total work productivity were HAQ-A and RAQoL. Conclusion. RA patients with higher disease severity showed higher work productivity compromise.

Histórico das hepatites virais History of viral hepatitis

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José Carlos Ferraz da Fonseca

2010-06-01

Full Text Available INTRODUÇÃO: A história das hepatites virais remonta milhares de anos e é fascinante. Quando o ser humano sofreu pela primeira vez a invasão do seu organismo por tais agentes, iniciou-se um ciclo natural e repetitivo capaz de infectar bilhões de seres humanos, dizimar e sequelar milhares de vida. MÉTODOS: Este artigo rever informações científicas disponíveis sobre o histórico das hepatites virais. Todas as informações foram obtidas através de extensa revisão bibliográfica, compreendendo artigos originais e de revisão e consultas na rede internet. RESULTADOS: Existem relatos de surtos de icterícia epidêmica na China há mais de 5.000 anos e na Babilônia, há mais de 2.500 anos. A história catastrófica das grandes epidemias ou pandemias ictéricas são conhecidas e geralmente estão associadas às grandes guerras. Na guerra da Secessão Americana, 40 mil casos ocorreram entre militares da União. Em 1885, um surto de icterícia catarral acometeu 191 trabalhadores do estaleiro de Bremen (Alemanha após vacinação contra varíola. Em 1942, 28.585 soldados contraíram hepatite após inoculação da vacina contra a febre amarela. O número de casos de hepatite durante a Segunda Grande Guerra foi estimado em 16 milhões. Somente no século XX, foram identificados os principais agentes causadores das hepatites virais. O vírus da hepatite B foi o primeiro a ser descoberto. CONCLUSÕES: Neste artigo, a revisão da história das grandes epidemias ocasionadas pelos vírus das hepatites e a descoberta desses agentes revelam singulares peculiaridades, citando como exemplo, a descoberta acidental ou por acaso dos vírus da hepatite B e D.INTRODUCTION: The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives

Indicações para ceratoplastia penetrante no Hospital das Clínicas-UNICAMP Penetrating keratoplasty indications in "Hospital das Clínicas-UNICAMP"

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Vanessa Gonçalves Crespi Flores

2007-06-01

Full Text Available OBJETIVO: Determinar as principais causas de indicação de transplante penetrante no Hospital das Clínicas-UNICAMP no período de janeiro de 1999 a dezembro de 2003. MÉTODOS: Estudo de série de casos, retrospectivo, não comparativo. Os autores revisaram os prontuários de 857 pacientes submetidos à ceratoplastia penetrante no Hospital das Clínicas-UNICAMP entre 1999-2003 e os classificaram em categorias diagnósticas de indicação para cirurgia. RESULTADOS: Dentre os 857 prontuários revisados a idade variou de 0-88 anos (média 44 anos±1,2. Dentre as principais causas de indicação de transplante de córnea encontramos: ceratocone em 427 casos (49,82%; úlcera de córnea infecciosa perfurada ou não, 152 casos (17,74%; falência de transplante prévio, 87 casos (10,15%; ceratopatia bolhosa, 72 casos (8,40%; distrofia de Fuchs, 59 casos (6,88%; seqüela de tracoma, 28 casos (3,27%; outras causas, 32 casos (3,74%. Entre as crianças até 10 anos a principal causa de indicação de transplante foram as úlceras infecciosas (77,78% e entre 11-50 anos o ceratocone foi a principal causa (71,65%. CONCLUSÕES: Este estudo foi composto por uma população jovem e as principais causas de indicação de transplante foram o ceratocone e os transplantes tectônicos.PURPOSE: To determine the main causes of penetrating keratoplasty indications at "Hospital das Clínicas-UNICAMP" (January, 1999 to December, 2003. METHODS: A non-comparative, retrospective series of case studies. The authors reviewed the files of 857 patients who underwent penetrating keratoplasty at "Hospital das Clínicas-UNICAMP" between 1999-2003 and classified them into different categories according to diagnostic indication for surgery. RESULTS: The age range was between 0-88 years (average 44 years ±1.2. The main causes of penetrating keratoplasty were: keratoconus in 427 cases (49.82%; 152 cases (17.74% of corneal ulceration (perforated or not; corneal graft failure in 87

Das Bauhaus in Bewegung - wie das Bauhausgebäude in Dessau funktioniert

OpenAIRE

Seyler Thomas

2016-01-01

Analyse und Deutung des Bauhausentwurfs - wie das Bauhaus funktioniert Ein Architekt analysiert und deutet den Bauhausentwurf Das Bauhaus in Dessau gilt als Inbegriff einer räumlich freien Anordnung. Diese lässt sich jedoch auf den Prozess einer Entfaltung zurückführen. Der Autor erklärt Schritt für Schritt die Systematik des Entwurfs aus seiner beruflichen Erfahrung.

Pattern of systemic lupus erythematosus in Egyptian patients: the impact of disease activity on the quality of life

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Nagwa Ibrahim

2010-08-01

Full Text Available INTRODUCTION: Systemic lupus erythematosus (SLE afflicts young people disproportionately, often at a crucial time in their lives when they are trying to establish relationships, start families and launch careers. As a result, persons with SLE may experience a wide range of physical and psychosocial problems that are not always fully captured by descriptions of the disease’s physiological consequences alone. METHODS: In order to characterize the spectrum of the effects of SLE with regards to disease activity and its impact on the quality of life (QoL, a case control study involving 59 SLE Egyptian patients (mean age 28.6 years , 94.9% females and 20 healthy controls was undertaken. Disease activity was measured by SLE Disease Activity Index (SLEDAI, and quality of life was measured by Short Form 36 health questionnaire (SF-36. RESULTS: Mucocutaneous and hematological manifestations were present in most of the patients and arthralgia in half of them. All domains of SF-36 including general health, physical functions, physical limitations, energy/fatigue, emotional well-being, pain, social functions, and health changes were significantly lower in SLE patients compared to controls. Except for emotional limitations, all domains were correlated with disease activity and low in class IV-V lupus nephritis. CONCLUSION: Physicians should focus on QoL and how to improve it; health education regarding the negative impact of disease activity on the patients should be given attention. The results of QoL studies help physicians to understand and provide better support to SLE patients beside rapid meticulous control of disease activity

Parkinson's Disease Videos

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Full Text Available ... Patients with Parkinson's Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis CareMAP: Movimientos y Caídas, Parte 2 What Are Some Strategies for Problems with Urination? Caregiver ...

Successful pipeline installation for Parque das Conchas development; Subsea installation

Energy Technology Data Exchange (ETDEWEB)

Bartz, Cesar

2010-07-01

Subsea 7 has successfully delivered again in Brazilian deep-waters. The subsea engineering and construction company has recently completed pipeline installation activities for the Parque das Conchas (BC-10) development, offshore Brazil. (AG)

Does expert opinion match the operational definition of the Lupus Low Disease Activity State (LLDAS)? A case-based construct validity study.

Science.gov (United States)

Golder, Vera; Huq, Molla; Franklyn, Kate; Calderone, Alicia; Lateef, Aisha; Lau, Chak Sing; Lee, Alfred Lok Hang; Navarra, Sandra Teresa V; Godfrey, Timothy; Oon, Shereen; Hoi, Alberta Yik Bun; Morand, Eric Francis; Nikpour, Mandana

2017-06-01

To evaluate the construct validity of the Lupus Low Disease Activity State (LLDAS), a treatment target in systemic lupus erythematosus (SLE). Fifty SLE case summaries based on real patients were prepared and assessed independently for meeting the operational definition of LLDAS. Fifty international rheumatologists with expertise in SLE, but with no prior involvement in the LLDAS project, responded to a survey in which they were asked to categorize the disease activity state of each case as remission, low, moderate, or high. Agreement between expert opinion and LLDAS was assessed using Cohen's kappa. Overall agreement between expert opinion and the operational definition of LLDAS was 77.96% (95% CI: 76.34-79.58%), with a Cohen's kappa of 0.57 (95% CI: 0.55-0.61). Of the cases (22 of 50) that fulfilled the operational definition of LLDAS, only 5.34% (59 of 22 × 50) of responses classified the cases as moderate/high activity. Of the cases that did not fulfill the operational definition of LLDAS (28 of 50), 35.14% (492 of 28 × 50) of responses classified the cases as remission/low activity. Common reasons for discordance were assignment to remission/low activity of cases with higher corticosteroid doses than defined in LLDAS (prednisolone ≤ 7.5mg) or with SLEDAI-2K >4 due to serological activity (high anti-dsDNA antibody and/or low complement). LLDAS has good construct validity with high overall agreement between the operational definition of LLDAS and expert opinion. Discordance of results suggests that the operational definition of LLDAS is more stringent than expert opinion at defining a low disease activity state. Copyright © 2017 Elsevier Inc. All rights reserved.

I M L Das

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. I M L Das. Articles written in Bulletin of Materials Science. Volume 33 Issue 4 August 2010 pp 383-390 Electrical Properties. Temperature dependence of electromechanical properties of PLZT /57/43 ceramics · A K Shukla V K Agrawal I M L Das Janardan Singh S L Srivastava.

Obesidade: Estudo das Representações Sociais de Endocrinologistas em Hospital Público.

OpenAIRE

Dinorah Fernandes Gioia Martins

1998-01-01

O presente trabalho teve como objetivo estudar a psicodinâmica das Representações Sociais (RS) de endocrinologistas de hospital público sobre obesidade, identificando-as e buscando detectar seu inconsciente relativo, ou seja, a lógica emocional segundo a qual se estruturam. Foram realizadas 10 (dez) entrevistas com médicos endocrinologistas de rede pública, (05 do sexo feminino e 05 do sexo masculino) com idade variável de 28 a 44 anos de idade. O tempo de especialização variou de dois a dezo...

Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis

DEFF Research Database (Denmark)

de Thurah, Annette; Esbensen, Bente Appel; Roelsgaard, Ida Kristiane

2017-01-01

difference (SMD) -0.17 (95 % CI -1.0 to 0.67), whereas a statistical significant difference in favour of nurse-led follow-up was seen after 2 years (SMD: 0.6 (95% CI -0.00 to 1.20)). CONCLUSION: After 1 year no difference in disease activity, indicated by DAS-28, were found between embedded nurse-led follow...

Lupus nephritis: prolonged immunoadsorption (IAS) reduces proteinuria and stabilizes global disease activity.

Science.gov (United States)

Stummvoll, Georg H; Schmaldienst, Sabine; Smolen, Josef S; Derfler, Kurt; Biesenbach, Peter

2012-02-01

Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of

Associations of Physical Activity and Sedentary Behavior with Atopic Disease in United States Children.

Science.gov (United States)

Strom, Mark A; Silverberg, Jonathan I

2016-07-01

To determine if eczema, asthma, and hay fever are associated with vigorous physical activity, television/video game usage, and sports participation and if sleep disturbance modifies such associations. Data were analyzed from 2 cross-sectional studies including 133 107 children age 6-17 years enrolled in the 2003-2004 and 2007-2008 National Survey of Children's Health. Bivariate and multivariate survey logistic regression models were created to calculate the odds of atopic disease and atopic disease severity on vigorous physical activity, television/video game use, and sports participation. In multivariate logistic regression models controlling for sociodemographic factors, lifetime history of asthma was associated with decreased odds of ≥1 days of vigorous physical activity (aOR, 0.87; 95% CI, 0.77-0.99) and decreased odds of sports participation (0.91; 95% CI, 0.84-0.99). Atopic disease accompanied by sleep disturbance had significantly higher odds of screen time and lower odds of sports participation compared with children with either atopic disease or sleep disturbance alone. Severe eczema (aOR, 0.39; 95% CI, 0.19-0.78), asthma (aOR, 0.29; 95% CI, 0.14-0.61), and hay fever (aOR, 0.48; 95% CI, 0.24-0.97) were all associated with decreased odds of ≥1 days of vigorous physical activity. Moderate (aOR, 0.76; 95% CI, 0.57-0.99) and severe eczema (aOR, 0.45; 95% CI, 0.28-0.73), severe asthma (aOR, 0.47; 95% CI, 0.25-0.89), and hay fever (aOR, 0.53; 95% CI, 0.36-0.61) were associated with decreased odds of sports participation in the past year. Children with severe atopic disease, accompanied by sleep disturbance, have higher risk of sedentary behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship Between Work Productivity and Clinical Characteristics in Rheumatoid Arthritis.

Science.gov (United States)

Salazar-Mejía, Carlos Eduardo; Galarza-Delgado, Dionicio Ángel; Colunga-Pedraza, Iris Jazmín; Azpiri-López, José Ramón; Wah-Suárez, Martín; Wimer-Castillo, Blanca Otilia; Salazar-Sepúlveda, Laura Leticia

2018-03-01

This study assesses the relationship between the ability to perform productive activities and the clinical characteristics of RA, such as disease activity, quality of life, functional capacity, workload, pharmacotherapy, and comorbidities. A cross-sectional, observational and descriptive study was conducted. Patients aged 18-75years with a diagnosis of RA according to ACR/EULAR 2010 criteria who attended regularly to the Rheumatology service in the period between January and March 2017 were included. The questionnaires, WPAI-AR, HAQ-DI and RAQoL, were applied. RA disease activity was measured by DAS28-PCR. Correlations were made between the clinical data obtained and work productivity and activity impairment measured by WPAI-AR. Two hundred four patients with a diagnosis of RA were included, of whom 92.6% were women. Mean age was 54.46±9.3years. Regarding the percentage of impairment of daily life activities, we found a significant difference between employed and unemployed patients (P≤.002). A positive correlation was found between RA activity measured by DAS28-PCR, quality of life, and functional ability with the percentages of absenteeism, presenteeism, overall productivity loss, and impairment of daily life activities. A correlation between RA disease activity, functional capacity, quality of life, and working impairment was found. The strongest association was established with the degree of functional capacity. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

49 CFR 28.160 - Communications.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Communications. 28.160 Section 28.160 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.160 Communications...

Histologic scoring indices for evaluation of disease activity in Crohn's disease.

Science.gov (United States)

Novak, Gregor; Parker, Claire E; Pai, Rish K; MacDonald, John K; Feagan, Brian G; Sandborn, William J; D'Haens, Geert; Jairath, Vipul; Khanna, Reena

2017-07-21

Histologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear. A systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease. Electronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation). Any study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn's disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic or endoscopic criteria. Two authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.Two authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility. Sixteen reports of 14 studies describing 14 different numerical

Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine protease cathepsin L-Like rCPB2.8.

Directory of Open Access Journals (Sweden)

Wagner A S Judice

Full Text Available Cysteine protease B is considered crucial for the survival and infectivity of the Leishmania in its human host. Several microorganism pathogens bind to the heparin-like glycosaminoglycans chains of proteoglycans at host-cell surface to promote their attachment and internalization. Here, we have investigated the influence of heparin upon Leishmania mexicana cysteine protease rCPB2.8 activity.THE DATA ANALYSIS REVEALED THAT THE PRESENCE OF HEPARIN AFFECTS ALL STEPS OF THE ENZYME REACTION: (i it decreases 3.5-fold the k 1 and 4.0-fold the k -1, (ii it affects the acyl-enzyme accumulation with pronounced decrease in k 2 (2.7-fold, and also decrease in k 3 (3.5-fold. The large values of ΔG  =  12 kJ/mol for the association and dissociation steps indicate substantial structural strains linked to the formation/dissociation of the ES complex in the presence of heparin, which underscore a conformational change that prevents the diffusion of substrate in the rCPB2.8 active site. Binding to heparin also significantly decreases the α-helix content of the rCPB2.8 and perturbs the intrinsic fluorescence emission of the enzyme. The data strongly suggest that heparin is altering the ionization of catalytic (Cys(25-S(-/(His(163-Im(+ H ion pair of the rCPB2.8. Moreover, the interaction of heparin with the N-terminal pro-region of rCPB2.8 significantly decreased its inhibitory activity against the mature enzyme.Taken together, depending on their concentration, heparin-like glycosaminoglycans can either stimulate or antagonize the activity of cysteine protease B enzymes during parasite infection, suggesting that this glycoconjugate can anchor parasite cysteine protease at host cell surface.

Responsiveness of Endoscopic Indices of Disease Activity for Crohn's Disease

NARCIS (Netherlands)

Khanna, Reena; Zou, Guangyong; Stitt, Larry; Feagan, Brian G.; Sandborn, William J.; Rutgeerts, Paul; McDonald, John W. D.; Dubcenco, Elena; Fogel, Ronald; Panaccione, Remo; Jairath, Vipul; Nelson, Sigrid; Shackelton, Lisa M.; Huang, Bidan; Zhou, Qian; Robinson, Anne M.; Levesque, Barrett G.; D'Haens, Geert

2017-01-01

The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data

Cardiovascular Disease and Cancer: Student Awareness Activities.

Science.gov (United States)

Meyer, James H., Comp.

Awareness activities pertaining to cancer and cardiovascular disease are presented as a supplement for high school science classes. The exercises can be used to enrich units of study dealing with the circulatory system, the cell, or human diseases. Eight activities deal with the following topics: (1) cardiovascular disease risk factors; (2)…

49 CFR 28.102 - Application.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Application. 28.102 Section 28.102 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.102 Application. This part...

Genetic correlation between rheumatoid arthritis and periodontal disease: the role of sex and IL-10.

Science.gov (United States)

Azzi, L; Rania, S; Spadari, F; Vinci, R; Manfredini, M; Croveri, F; Boggio, A; Tettamanti, L; Tagliabue, A; Silvestre-Rangil, J; Bellintani, C

2017-01-01

The chronic stimulation of the immune system due to the presence of bacterial antigens within periodontal tissues has been associated with several autoimmune diseases, like diabetes mellitus, infective endocarditis or cardiovascular atherosclerosis. The current study aims at evaluating the correlation between Rheumatoid Arthritis (RA) and Periodontal Disease (PD) with special attention to genetic polymorphisms in cytokine expression. A total number of 34 patients affected by RA were recruited. Each of them underwent haematochemical analysis and data were collected for Rheumatoid Factor (RF), Anti-Citrullinated Protein’s Antibody (CCP) and HLA-BDR1. DAS-28 questionnaire for disease activity was fulfilled by the rheumatologist, while a periodontal examination was carried out by the dental clinician and crevicular fluid samples were collected to evaluate the IL-6, IL-10 and VDR polymorphysms. A connection between CCP and IL-10 polymorphisms was found, with IL-10 expressing protecting tendency against periodontal disease when CCP are found in the bloodstream (p=0.0017). Finally, males mainly expressed IL-10 predisposing genes (p=0.046), while females showed a greater tendency to express RF (p=0.014) and CCP (p=0.050). This paper corroborates the idea of a correlation between sex, IL-10 polymorphisms and RA, which should be studied in depth, since recent papers have shown that IL-10 injected into joints seems to decrease inflammation.

Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74

DEFF Research Database (Denmark)

McLean, Katherine A; Holst, Peter J; Martini, Lene

2004-01-01

The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74 from human herpesvirus 8 are both constitutively active. We show that both receptors constitutively activate the transcription factors nuclear factor of activated T cells (NFAT) and cAMP response element binding...

Complement Activation in Inflammatory Skin Diseases

Directory of Open Access Journals (Sweden)

Jenny Giang

2018-04-01

Full Text Available The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention.

Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).

Science.gov (United States)

Mueller, Ruediger B; Gengenbacher, Michael; Richter, Symi; Dudler, Jean; Möller, Burkhard; von Kempis, Johannes

2016-04-14

Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in

31 CFR 28.540 - Advertising.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Advertising. 28.540 Section 28.540... Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.540 Advertising. A recipient shall not in any advertising related to employment indicate preference, limitation, specification...

49 CFR 28.111 - Notice.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Notice. 28.111 Section 28.111 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.111 Notice. The Department shall...

49 CFR 28.140 - Employment.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Employment. 28.140 Section 28.140 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.140 Employment. (a) No qualified...

49 CFR 28.101 - Purpose.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Purpose. 28.101 Section 28.101 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.101 Purpose. The purpose of this...

Temporomandibular Joint Involvement in Association With Quality of Life, Disability, and High Disease Activity in Juvenile Idiopathic Arthritis.

Science.gov (United States)

Frid, Paula; Nordal, Ellen; Bovis, Francesca; Giancane, Gabriella; Larheim, Tore A; Rygg, Marite; Pires Marafon, Denise; De Angelis, Donato; Palmisani, Elena; Murray, Kevin J; Oliveira, Sheila; Simonini, Gabriele; Corona, Fabrizia; Davidson, Joyce; Foster, Helen; Steenks, Michel H; Flato, Berit; Zulian, Francesco; Baildam, Eileen; Saurenmann, Rotraud K; Lahdenne, Pekka; Ravelli, Angelo; Martini, Alberto; Pistorio, Angela; Ruperto, Nicolino

2017-05-01

To evaluate the demographic, disease activity, disability, and health-related quality of life (HRQOL) differences between children with juvenile idiopathic arthritis (JIA) and their healthy peers, and between children with JIA with and without clinical temporomandibular joint (TMJ) involvement and its determinants. This study is based on a cross-sectional cohort of 3,343 children with JIA and 3,409 healthy peers, enrolled in the Pediatric Rheumatology International Trials Organisation HRQOL study or in the methotrexate trial. Potential determinants of TMJ involvement included demographic, disease activity, disability, and HRQOL measures selected through univariate and multivariable logistic regression. Clinical TMJ involvement was observed in 387 of 3,343 children with JIA (11.6%). Children with TMJ involvement, compared to those without, more often had polyarticular disease course (95% versus 70%), higher Juvenile Arthritis Disease Activity Score (odds ratio [OR] 4.6), more disability, and lower HRQOL. Children with TMJ involvement experienced clearly more disability and lower HRQOL compared to their healthy peers. The multivariable analysis showed that cervical spine involvement (OR 4.6), disease duration >4.4 years (OR 2.8), and having more disability (Childhood Health Assessment Questionnaire Disability Index >0.625) (OR 1.6) were the most important determinants for TMJ involvement. Clinical TMJ involvement in JIA is associated with higher disease activity, higher disability, and impaired HRQOL. Our findings indicate the need for dedicated clinical and imaging evaluation of TMJ arthritis, especially in children with cervical spine involvement, polyarticular course, and longer disease duration. © 2016, American College of Rheumatology.

Monitoring patients with rheumatoid arthritis in routine care

DEFF Research Database (Denmark)

Hetland, Merete Lund; Jensen, Dorte Vendelbo; Krogh, Niels Steen

2014-01-01

disease activity, less disability and radiographic damage. By 2013, 19% of csDMARD (15% of bDMARD) patients were in ACR/Boolean remission. Coverage had increased to between 41% and 79% for patients with RA, for the bDMARD group it was 94%. CONCLUSIONS: Systematic monitoring of RA patients with real....../moderate/high disease activity (i.e. DAS28 (CRP-based, 4 variables) was calculated for each calendar year. RESULTS: From 2006-2013 the number of patients increased from 2,395 to 14,249. By 2013, 29.8% of patients were receiving bDMARD. Patients in the csDMARD group were older, had shorter disease duration, lower...

31 CFR 28.405 - Housing.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Housing. 28.405 Section 28.405 Money... in Education Programs or Activities Prohibited § 28.405 Housing. (a) Generally. A recipient shall not... offer different services or benefits related to housing, except as provided in this section (including...

Parkinson's Disease Videos

Medline Plus

Full Text Available ... library Topic Type Living Alone: Home Safety and Management in PD Expert Briefings: Marijuana and PD: What ... Patients with Parkinson's Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis CareMAP: Movimientos y Caídas, ...

Larvicidal activity of oil-resin fractions from the Brazilian medicinal plant Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae against Aedes aegypti (Diptera, Culicidae Atividade larvicida das frações do óleo-resina da planta medicinal brasileira Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae sobre o Aedes aegypti (Diptera, Culicidae

Directory of Open Access Journals (Sweden)

Heloísa Helena Garcia da Silva

2007-06-01

Full Text Available Oil-resin fractions from Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae were evaluated for larvicidal activity on third larval instars of Aedes aegypti, in searching for alternative control methods for this mosquito. The bioactive fractions were chemically monitored by thin-layer chromatography, ¹H and 13C nuclear magnetic resonance and mass spectrometry. Bioassays were performed using five repetitions, at a temperature of 28 ± 1°C, relative humidity of 80 ± 5% and light and dark cycles of 12h. Mortality was indicated by darkening of the cephalic capsule after 24h of exposure of the larvae to the solutions. The most active fractions were CRM1-4 (sesquiterpenes and CRM5-7 (labdane diterpenes, which showed LC50 values of 0.2 and 0.8ppm, respectively.A atividade larvicida das frações do óleo-resina de Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae foi avaliada em larvas de 3º estádio de Aedes aegypti, na busca de alternativas para o controle desse mosquito. As frações bioativas foram monitoradas quimicamente através de cromatografia de camada delgada, analisada por ressonância magnética nuclear de hidrogênio (¹H e 13C e espectrometria de massas. Os bioensaios foram realizados à temperatura de 28±1°C, 80±5% de umidade relativa e fotofase de 12h, com cinco repetições. A mortalidade foi determinada através do escurecimento da cápsula cefálica, após 24h de exposição das larvas às soluções. As frações mais ativas foram CRM1-4 (sesquiterpenos e CRM5-7 (diterpeno labdano, que mostraram os valores de CL50 de 0,2 e 0,8ppm, respectivamente.

EVALUATION OF A DECRESE IN WORK PRODUCTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

Olga Yuryevna Vakulenko

2013-01-01

Full Text Available Objective. To study the association between the clinical manifestations and work ability in patients with rheumatoid arthritis (RA and to elaborate mathematical methods for predicting work productivity indicators according to the evaluation of the functional status of patients and disease activity.Material and Methods. A total of 185 RA patients were examined; 105 of them were employed. The mean age was 48.2±11.3 years; RA duration was 77.9±70.7 months; DAS28 4.68±1.53; visual analogue scale (VAS score was 40.6±22.2; HAQ was 1.3±0.7. The employed patients in the test group had a longer duration but weaker activity of RA according to DAS28 as compared to those in the control group (p<0.05. The WPAI indicators in the test and control groups, respectively, were as follows: presenteeism – 39.0±26.3 vs. 57.9±16.8%; total productivity decrease (TPD – 54.6±34.1 vs. 65.2±23.3%; daily activity (DA – 52.3±26.3 vs. 55.3±14.8%. The multiple regression method was used to create prognostic equations. A significant divergence of the distribution of absenteeism rates from the normal distribution prevented selection of regression equations.Results. HAQ, VAS pain, and DAS28 turned out to be optimal for selecting equations. The Spearman correlation coefficients with WPAI indicators were higher than 0.4 in all the cases. The following prognostic equations were obtained:Presenteeism (% = 0.66 + 11.31 • HAQ + 0.44 • VAS pain + 2.17 • DAS28 (R2 = 0.46, TPD (% = 8.53 + 3.90 • HAQ + 0.47 • VAS pain + 4.73 • DAS28 (R2 = 0.28, DA (% = 11.27 + 11.87 • HAQ + 0.36 • VAS pain + 1.96 • DAS28 (R2 = 0.44.Verification of the predicted WPAI values using the data of an additional group has demonstrated the coincidence of the predicted and actual values for presenteeism and TPD. However, the correlation coefficient between the predicted and actual presenteeism indicators was considerably higher (0.68 vs. 0.51. The predicated DA differed

Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4.

Science.gov (United States)

Argyri, Letta; Dafnis, Ioannis; Theodossiou, Theodossis A; Gantz, Donald; Stratikos, Efstratios; Chroni, Angeliki

2014-05-02

The apolipoprotein (apo) E4 isoform has consistently emerged as a susceptibility factor for late-onset Alzheimer disease (AD), although the exact mechanism is not clear. A rare apoE4 mutant, apoE4[L28P] Pittsburgh, burdens carriers with an added risk for late-onset AD and may be a useful tool for gaining insights into the role of apoE4 in disease pathogenesis. Toward this end, we evaluated the effect of the L28P mutation on the structural and functional properties of apoE4. ApoE4[L28P] was found to have significantly perturbed thermodynamic properties, to have reduced helical content, and to expose a larger portion of the hydrophobic surface to the solvent. Furthermore, this mutant is thermodynamically destabilized and more prone to proteolysis. When interacting with lipids, apoE4[L28P] formed populations of lipoprotein particles with structural defects. The structural perturbations brought about by the mutation were accompanied by aberrant functions associated with the pathogenesis of AD. Specifically, apoE4[L28P] promoted the cellular uptake of extracellular amyloid β peptide 42 (Aβ42) by human neuroblastoma SK-N-SH cells as well as by primary mouse neuronal cells and led to increased formation of intracellular reactive oxygen species that persisted for at least 24 h. Furthermore, lipoprotein particles containing apoE4[L28P] induced intracellular reactive oxygen species formation and reduced SK-N-SH cell viability. Overall, our findings suggest that the L28P mutation leads to significant structural and conformational perturbations in apoE4 and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. We propose that these structural and functional changes underlie the observed added risk for AD development in carriers of apoE4[L28P].

31 CFR 28.510 - Recruitment.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recruitment. 28.510 Section 28.510... Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

Repercussão das medidas de correção das comorbidades no resultado da reabilitação vestibular de idosos The treatment of diseases related to balance disorders in the elderly and the effectiveness of vestibular rehabilitation

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Roseli Saraiva Moreira Bittar

2007-06-01

Full Text Available OBJETIVO: Considerando o aumento da população idosa e conseqüentemente as alterações de equilíbrio a ela relacionadas, realizamos um estudo para avaliar o impacto do tratamento adequado das doenças coexistentes ao desequilíbrio corporal no resultado da Reabilitação Vestibular (RV. MATERIAL E MÉTODOS: 52 idosos com queixa de tontura e/ou desequilíbrio com indicação RV participaram deste ensaio clínico aberto e prospectivo realizado no Ambulatório de Otoneurologia Geriátrica da Instituição, entre 2003 e 2005. Os pacientes do grupo de estudo foram previamente tratados das doenças clínicas diagnosticadas e posteriormente submetidos à RV. Foram então comparados com o grupo total de idosos tratados pela RV no mesmo período. RESULTADOS: Os pacientes do grupo de estudo apresentaram 65 comorbidades diagnosticadas, com média de 1,25 por paciente. A efetividade total foi de 84,5% neste grupo contra 81,8% no grupo controle, sem diferença significante. No entanto, a completa remissão dos sintomas ocorreu em 69,2% dos casos contra 43,18% dos controles, significante para pThe aim of this study was to assess the impact of adequate treatment of concomitant diseases in the elderly undergoing Vestibular Rehabilitation (VR. METHOD: 52 elderly patients with complaints of vertigo and/or imbalance requiring VR participated in this prospective study. The trial was designed as an open clinical assay at the Ear Nose and Throat Department Geriatric Otoneurology Clinic, and was done between 2003 and 2005. Patients were compared with the total group of elderly individuals treated with VR during the same period. RESULTS: 65 diseases were diagnosed in the study group, an average 1.25 diseases per patient. After the treatment of these diseases, patients underwent VR. The effectiveness of VR (remission and partial improvement rates was 84.5% in the study group against 81.8% in the control group, which was not significant. Remission of symptoms

Medicamentos de alto custo para doenças raras no Brasil: o exemplo das doenças lisossômicas High cost drugs for rare diseases in Brazil: the case of lysosomal storage disorders

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Mônica Vinhas de Souza

2010-11-01

Full Text Available Este artigo aborda, de forma crítica, aspectos das políticas públicas brasileiras para medicamentos, com ênfase nos de alto custo dirigidos às doenças raras. As doenças lisossômicas foram utilizadas como exemplo pela sua raridade e pela tendência mundial para o desenvolvimento de novos fármacos para seu tratamento. Três doenças foram abordadas: doença de Gaucher, doença de Fabry e mucopolissacaridose tipo I. Embora todas tenham medicamentos registrados no Brasil, a doença de Gaucher é a única com protocolo clínico e diretrizes de tratamento balizadas pelo Ministério da Saúde. Os autores almejam, com este artigo, fomentar a discussão sobre o papel da avaliação de tecnologias em saúde para o tratamento das doenças raras no Brasil, enfatizando a necessidade de políticas legitimadas dirigidas especialmente a elas. A despeito das dificuldades de se estabelecer uma política de saúde específica para cada doença rara, é possível o estabelecimento de modelos racionais para lidar com esse crescente desafio.This paper approaches in a critical way aspects of Brazilian public policies for drugs, emphasizing those classified as high cost and for rare diseases. The lysosomal storage diseases was taken as an example because of their rarity and the international trend for the development of new drugs for their treatment, all at high costs. Three lysosomal storage diseases were approached: Gaucher disease, Fabry disease and mucopolysaccharidosis type I. Gaucher disease has its treatment drug licensed in Brazil and guidelines for its use are established through a clinical protocol by the Ministry of Health. The others have their drug treatments registered in Brazil; however, no treatment guidelines for them have been developed by the government. The objective of the paper was to foster the discussion on the role of health technology assessment for high-cost drugs for rare diseases in Brazil, emphasizing the need for establishing

Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy.

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Hirano, Fumio; Yokoyama, Waka; Yamazaki, Hayato; Amano, Koichi; Kawakami, Atsushi; Hayashi, Taichi; Tamura, Naoto; Yasuda, Shinsuke; Dobashi, Hiroaki; Fujii, Takao; Ito, Satoshi; Kaneko, Yuko; Matsui, Toshihiro; Okuda, Yasuaki; Saito, Kazuyoshi; Suzuki, Fumihito; Yoshimi, Ryusuke; Sakai, Ryoko; Koike, Ryuji; Kohsaka, Hitoshi; Miyasaka, Nobuyuki; Harigai, Masayoshi

2017-09-01

To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T). In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS) 28), p = 0.004], baseline HAQ-DI [0.28 (0.18-0.45), p = 1.3 × 10 -7 ], and baseline vdH-mTSS [0.986 (0.976-0.996), p = 0.009]. A factor associated with ΔvdH-mTSS < SDC was SDAI remission at week 24 [3.53 (1.62-7.71), p = 0.002]. Predictive validity of SDAI remission for good outcomes was verified in a T2T-implementing cohort in the current clinical settings.

CD28 co-stimulation down regulates Th17 development.

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Salim Bouguermouh

Full Text Available Th17 cells are implicated in host defence and autoimmune diseases. CD28/B7 co-stimulation is involved in the induction and progression of autoimmune diseases, but its role in controlling murine Th17 cell fate remains to be clarified. We here report that soluble anti-CD28 mAb suppressed the differentiation of anti-CD3-stimulated naïve CD4(+ T cells into IL-17-producing cells. CD28 co-stimulation reduced the frequency of proliferating cells that produce IL-17. We provide evidence for an IL-2 and IFN-gamma-dependent mechanism of CD28-mediated IL-17 suppression. CD28 blockade of Th17 development was correlated with a decrease rather than an increase in the percentage of Foxp3(+ T cells. In APC/T cell co-cultures, mature dendritic cells (DC were less efficient than immature DC in their ability to support Th17 cell differentiation, while CTLA4-Ig, an agent blocking CD28/B7 and CTLA4/B7 interactions, facilitated both murine and human Th17 differentiation. This study identifies the importance of B7 co-stimulatory molecules in the negative regulation of Th17 development. These unexpected results caution targeting the CD28/B7 pathways in the treatment of human autoimmune diseases.

Estudo das características epidemiológicas e clínicas de pacientes portadores do vírus da imunodeficiência humana em Pronto Atendimento do Hospital das Clínicas da Universidade Federal de Minas Gerais Study on the clinical and epidemiological characteristics of patients with human immunodeficiency virus at the walk-in service of the teaching hospital of the Federal University of Minas Gerais

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Cecilia Gómez Ravetti

2009-04-01

.8% of the admissions. The T CD4+ lymphocyte count was less than 200 cells/mm³ in 45.7% of the patients. The most frequent complaints were increased body temperature, diarrhea, coughing and dyspnea. The respiratory tract was the region most affected. The most common opportunistic diseases were pneumocystosis, community-acquired pneumonia, diarrheal syndrome and oral candidiasis. The demand for admissions among HIV patients represented 2.8% of all admissions, with an average length of stay of 4.6 days. Most of the patients had low T CD4+ lymphocyte counts, and almost half of them were not taking highly active antiretroviral therapy. There was a tendency towards feminization. AIDS-related diseases continue to be the most frequent occurrences within our setting.

"Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

Science.gov (United States)

Lowsky, Martin

Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

Dynamic Measurement of Disease Activity in Acute Pancreatitis: The Pancreatitis Activity Scoring System.

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Wu, Bechien U; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J

2017-07-01

Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis.

Quantifying the inflammatory activity in Crohn's disease using CE dynamic MRI

International Nuclear Information System (INIS)

Pauls, S.; Schmidt, S.A.; Brambs, H.J.; Gabelmann, A.; Kratzer, W.; Mittrach, C.; Adler, G.; Rieber, A.

2003-01-01

Purpose: Evaluation of dynamic contrast enhanced MRI in patients with Crohn's disease to assess local inflammatory activity. Material and Methods: Prospective study of 13 patients with histologically proven Crohn's disease. Axial and coronal slices were acquired by a 1.5 T MR (Magnetom Vision, Siemens, Germany): T1 flash 2 D (TR 72.5 ms, TE 4.1 ms), T2 (TR 2730 ms, TE 138 ms), turbo-flash sequences T1 (TR 94.2 ms, TE 4.1 ms) post contrast media fat saturated (Magnevist circledR , 0.2 ml/kg, flow 4 ml/s). In area of maximal thickening of terminal ileal wall, axial dynamic T1 sequences (TR 11 ms, TE 4.2 ms) were acquired every 1.5 s post contrast media application for a total duration of 1 min. Contrast uptake was subjectively measured by semiquantitative score and computed assisted ROI evaluation. MR parameters were correlated with CDAI (Crohn's disease activity index) and SAI (severe activity index). Results: Contrast uptake in the intestinal wall occurred after 18.5 s (range: 3.0-28.0), contrast upslope until plateau phase lasted for 16.1 s (range: 8.0-50.0). Maximum contrast enhancement into the bowel wall was 266% (105-450%) of baseline. After maximum contrast uptake, we observed a plateau phase in all cases for the total duration of measurement. A significant correlation existed for maximum contrast uptake to CDAI (r = 0.591; p = 0.033), for beginning of contrast upslope to the time until plateau phase (r = 0.822; p = 0.001), and for the time until plateau phase to CDAI (r = 0.562; p = 0.046). CDAI was on average 108, median 106; SAI was on average 114, median 115. SAI correlated significantly to CDAI (r = 0.874). Maximum contrast uptake, beginning of contrast upslope, and time until plateau phase were independent to creeping fat, local lymphadenitis, laboratory parameters, temperature, body mass index, heart frequency and systolic blood pressure. Conclusion: Dynamic MRI enables to quantify local inflammatory activity of bowel wall in patients with Crohn

Adaptação transcultural da versão simplificada (s do Behçet's Disease Current Activity Form (BDCAF e comparação do desempenho das versões brasileiras dos dois instrumentos de avaliação da atividade da Doença de Behçet: BR-BDCAF e BR-BDCAF(s Cross-cultural adaptation of simplified version (s of Behçet's Disease Current Activity Form (BDCAF and comparison between two different instruments with Brazilian versions for evaluating Behçet's Disease Activity: BR-BDCAF and BR-BDCAF(s

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Fabrício de Souza Neves

2009-02-01

Full Text Available OBJETIVO: Um instrumento de avaliação da atividade da Doença de Behçet (DB denominado Behçet's Disease Current Activity Form (BDCAF foi originalmente elaborado em língua inglesa e adaptado para a língua portuguesa do Brasil na versão BR-BDCAF. Recentemente, um modelo simplificado desse protocolo (com 12 itens foi apresentado pela Sociedade Internacional para a Doença de Behçet (International Society for Behçet's Disease, ISBD para produzir um índice denominado BDAI (Behçet's Disease Activity Index. Por esse motivo, neste trabalho produzimos o modelo simplificado da versão brasileira, medimos sua confiabilidade e avaliamos a validade dos resultados de ambos os instrumentos, comparando seus desempenhos. MÉTODO: O modelo simplificado da versão brasileira BR-BDCAF, adaptada transculturalmente, foi denominado BR-BDCAF(s. Ambos os protocolos foram aplicados em 25 pacientes com DB. A confiabilidade do BR-BDCAF(s foi avaliada através das reprodutibilidades intra e interobservadores pela estatística kappa. A validade e as propriedades diagnósticas sensibilidade(S, especificidade(E e acurácia dos dois protocolos na definição de casos ativos da doença foram avaliadas pela comparação ao julgamento clínico de um reumatologista perito em DB, e os melhores pontos de corte foram estabelecidos para cada instrumento através da curva ROC (receive-operator characteristic. RESULTADOS E CONCLUSÕES: BR-BDCAF(s apresentou boa confiabilidade nas questões sobre manifestações mucocutâneas e articulares da DB. Os melhores pontos de corte para a definição de casos ativos foram índices maiores que quatro no BR-BDCAF (S = 80,0%, E = 86,7% e maiores que um no BR-BDCAF(s (S = 70,0%, E = 86,7%. Suas acurácias foram semelhantes, sugerindo que ambos podem ser utilizados como instrumentos de medida de atividade da DB.OBJECTIVE: Behçet's Disease Current Activity Form (BDCAF, an instrument for assessing activity of Behçet's Disease (BD, was

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

Science.gov (United States)

Hüppe, Angelika; Langbrandtner, Jana; Häuser, Winfried; Raspe, Heiner; Bokemeyer, Bernd

2018-05-09

 Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDI CD ) and UC (GIBDI UC ) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices.  Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements.  Rank correlations were 0.56 (pMS, GIBDI UC ) and 0.57 (HBI, GIBDI CD ), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories).  There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information. © Georg Thieme Verlag KG Stuttgart · New York.

QUAL O FUTURO DAS ESCOLAS NO CAMPO?

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Célia Regina Vendramini

2015-09-01

Full Text Available RESUMO:Tendo como ponto de partida a questão sobre o futuro das escolas rurais ou do campo, o artigo aborda o contexto social, político e econômico que suporta ou não a existência das escolas, bem como uma análise sobre a situação das escolas em diferentes contextos, particularmente no Brasil, em Portugal e nos Estados Unidos. Problematizamos as respostas dadas pelo poder público, acadêmicos e organizações e movimentos sociais sobre o fechamento, a redução do número de alunos e de comunidades rurais com escola, as condições de funcionamento, a distância percorrida pelos alunos, além das implicações das escolas para a vitalidade do campo. Concluímos que o futuro das escolas está diretamente relacionado com o futuro do campo.

RAPID3 scores and hand outcome measurements in RA patients: a preliminary study.

Science.gov (United States)

Qorolli, Merita; Hundozi-Hysenaj, Hajrije; Rexhepi, Sylejman; Rehxepi, Blerta; Grazio, Simeon

2017-06-01

The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported disease activity measure used to assess physical function, pain, and global health in patients with rheumatoid arthritis (RA) without formal joint counts. Since hand involvement and its decreased function are hallmarks of RA, the aim of our study was to investigate the performance of RAPID3 scores with regard to hand function and to confirm previous findings that the RAPID3 score as a disease activity measure is strongly correlated with the DAS28 score. Sixty-eight consecutive patients with RA (85% female), aged 18-75 years, were included in the study and were recruited during their outpatient visit. Apart from demographic and clinical data, the obtained parameters of interest included RAPID3 scores and assessments of the function of the hand, namely, the signal of functional impairment (SOFI)-hand, grip strength, and pulp-to-palm distance, as well the Health Assessment Questionnaire- Disability Index (HAQ-DI) and DAS28 scores. Pearson's correlation coefficient, Student's t test and linear regression were used in the statistical analysis of the results. The significance was set to p < 0.05. A positive correlation was found between RAPID3 scores and HAQ-DI scores, SOFI-hand scores, and pulp-to-palm distance, and negative correlation was observed between RAPID3 scores and grip strength. The order regarding the strength of correlations between RAPID3 scores and other variables (from the strongest to the weakest) was as follows: HAQ-DI, grip strength, SOFI-hand and pulp-to-palm distance. The hand assessment variables had stronger correlations with RAPID3 scores than with DAS28 scores. Our preliminary study showed that RAPID3 scores were strongly correlated with measurements of the functional ability of the hand, demonstrating that RAPID3 can be used as a measure of disease activity in clinical practice and to characterize hand function. Further studies are needed to confirm this result.

Impact of valvular heart disease on activities of daily living of nonagenarians: the Leiden 85-plus study a population based study.

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van Bemmel, Thomas; Delgado, Victoria; Bax, Jeroen J; Gussekloo, Jacobijn; Blauw, Gerard J; Westendorp, Rudi G; Holman, Eduard R

2010-04-01

Data on the prevalence of valvular heart disease in very old individuals are scarce and based mostly on in-hospital series. In addition, the potential detrimental effect of valvular heart disease on the activities of daily living is unknown. The present study evaluated the prevalence of significant valvular heart disease and the impact of valvular heart disease on the activities of daily living in community dwelling nonagenarians. Nested within the Leiden 85-plus study, a population based follow-up study of the oldest old, a sample of 81 nonagenarians was recruited. The left ventricular (LV) dimensions, function and the presence and severity of heart valvular disease were evaluated by echocardiography. Significant valvular heart disease included any mitral or aortic stenosis severity, moderate or severe mitral regurgitation, moderate or severe aortic regurgitation and moderate or severe tricuspid regurgitation. Activities of daily living were assessed using the Groningen Activity Restriction Scale (GARS). LV cavity diameters (end-diastolic diameter 47 +/- 8 mm, end-systolic diameter 30 +/- 8 mm) and systolic LV function (LV ejection fraction 66 +/- 13%) were within normal for the majority of the participants. Significant valvular disease was present in 57 (70%) individuals, with mitral regurgitation and aortic regurgitation as the most frequent valve diseases (49% and 28% respectively). The GARS score between individuals with and without significant valvular heart disease was similar (36.2 +/- 9.2 vs. 34.4 +/- 13.2, p = 0.5). Nonagenarian, outpatient individuals have a high prevalence of significant valvular heart disease. However, no relation was observed between the presence of significant valvular heart disease and the ability to perform activities of daily living.

Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

Energy Technology Data Exchange (ETDEWEB)

Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

2010-01-01

Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

State Mines Inspectorate of Saarland and Rheinland-Pfalz, Mines InspectorateSaarbruecken/ Mines Inspectorate Rheinland-Pfalz. Annual report 2000. Economic and technical aspects, industrial safety and enviromental protection, statistics, activities of the mining authorities; Oberbergamt fuer das Saarland und das Land Rheinland-Pfalz, Bergamt Saarbruecken/Bergamt Rheinland-Pfalz. Jahresbericht 2000. Bergwirtschaft, Bergtechnik, Arbeitsschutz, Umweltschutz, Statistiken, Taetigkeiten der Bergbehoerden

Energy Technology Data Exchange (ETDEWEB)

Boettcher, R.; Hugo, K.H.; Kuhn, M.; Strauch, T. (comps.)

2001-07-01

The annual report of the Saarland and Rheinland-Pfalz State Mines Inspectorate and the Mines Inspectorates of the two states provide an insight into the many activities of mines inspectorates and of the current trends in mining engineering. The importance of mining and regional raw materials management is stressed. [German] Der vorliegende Jahresbericht des Oberbergamtes fuer das Saarland und das Land Rheinland-Pfalz sowie der Bergaemter in beiden Bundeslaendern gibt einen Einblick in das vielfaeltige Arbeitsgebiet der Bergbehoerden. Gleichzeitig vermittelt er einen Ueberblick ueber die bergtechnische Entwicklung und unterstreicht die volkswirtschaftliche Bedeutung des Bergbaus und der standortgebundenen Rohstoffwirtschaft. (orig.)

State Mines Inspectorate of Saarland and Rheinland-Pfalz, Mines Inspectorate Saarbruecken / Mines Inspectorate Rheinland-Pfalz. Annual report 2001. Economic and technical aspects, industrial safety and environmental protection, statistics, activities of the mining authorities; Oberbergamt fuer das Saarland und das Land Rheinland-Pfalz, Bergamt Saarbruecken / Bergamt Rheinland-Pfalz. Jahresbericht 2001. Bergwirtschaft, Bergtechnik, Arbeitsschutz, Umweltschutz, Statistiken, Taetigkeiten der Bergbehoerden

Energy Technology Data Exchange (ETDEWEB)

Boettcher, R.; Hugo, K.H.; Kuhn, M.; Strauch, T. (comps.)

2002-07-01

The annual report of the Saarland and Rheinland-Pfalz State Mines Inspectorate and the Mines Inspectorates of the two states provide an insight into the many activities of mines inspectorates and of the current trends in mining engineering. The importance of mining and regional raw materials management is stressed. [German] Der vorliegende Jahresbericht des Oberbergamtes fuer das Saarland und das Land Rheinland-Pfalz sowie der Bergaemter in beiden Bundeslaendern gibt einen Einblick in das vielfaeltige Arbeitsgebiet der Bergbehoerden. Gleichzeitig vermittelt er einen Ueberblick ueber die bergtechnische Entwicklung und unterstreicht die volkswirtschaftliche Bedeutung des Bergbaus und der standortgebundenen Rohstoffwirtschaft.

Teoria das Restrições, Lean Manufacturing e Seis Sigma: limites e possibilidades de integração

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Diego Augusto de Jesus Pacheco

2014-12-01

Full Text Available O principal objetivo deste estudo foi analisar os pontos de convergência e as divergências entre a Teoria das Restrições, o Lean Manufacturing e o Seis Sigma quando usados de maneira integrada para a melhoria contínua operacional de sistemas produtivos. O eixo principal de discussão desse estudo foi buscar identificar na literatura características de exclusão e similaridades entre as três abordagens quando aplicadas de maneira integrada em sistemas produtivos. Para conduzir essa pesquisa, fez-se uma ampla pesquisa bibliográfica, entre 1995 e 2011, nas principais bases de dados nacionais e internacionais, em busca do estado da arte sobre o tema. Os resultados desse estudo sugerem que Teoria das Restrições, Lean Manufacturing e Seis Sigma possuem diversos elementos complementares que se sobrepõem aos pontos divergentes e que há um vasto campo de pesquisa a ser explorado sobre o tema. Como resultado, o presente estudo apresenta a análise crítica comparativa de 28 critérios relevantes à compreensão das três abordagens assim como uma agenda de pesquisa sobre o tema identificada a partir das lacunas encontradas.

Active life expectancy of Americans with diabetes: risks of heart disease, obesity, and inactivity.

Science.gov (United States)

Laditka, Sarah B; Laditka, James N

2015-01-01

Few researchers have studied whether diabetes itself is responsible for high rates of disability or mortality, or if factors associated with diabetes contribute importantly. We estimated associations of diabetes, heart disease, obesity, and physical inactivity with life expectancy (LE), the proportion of life with disability (DLE), and disability in the last year of life. Data were from the Panel Study of Income Dynamics (1999-2011 and 1986, African American and white women and men ages 55+, n=1,980, 17,352 person-years). Activities of daily living defined disability. Multinomial logistic Markov models estimated disability transition probabilities adjusted for age, sex, race/ethnicity, education, and the health factors. Microsimulation measured outcomes. White women and men exemplify results. LE was, for women: 3.5 years less with diabetes than without (95% confidence interval, 3.1-4.0), 11.1 less (10.3-12.0) adding heart disease, 21.9 less with all factors (15.3-28.5), all pheart disease, 52.9% (38.9-66.8) with all factors, all pheart disease, obesity, and inactivity, risks that can be modified by health behaviors and medical care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Subclinical Synovitis Measured by Ultrasound in Rheumatoid Arthritis Patients With Clinical Remission Induced by Synthetic and Biological Modifying Disease Drugs.

Science.gov (United States)

Cruces, Marcos; Al Snih, Soham; Serra-Bonett, Natalí; Rivas, Juan C

2017-10-09

Rheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. To determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. Hospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. Out of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. Persistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

DEFF Research Database (Denmark)

Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M

2015-01-01

OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheuma......OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...... was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were...

HUMANIZAÇÃO DO DISCURSO DAS MARCAS DIANTE DAS NOVAS EXPERIÊNCIAS DE CONSUMO

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Rogério Luiz Covaleski

2014-01-01

Full Text Available Tendo em vista que o processo de consumo não se resume à compra de mercadorias, e que vivenciamos um momento de negociação de discursos entre consumidores e anunciantes, potencializado pelas ferramentas dos meios de comunicação pós-massivos, este artigo pretende refletir sobre o fenômeno da humanização do discurso das marcas. Para isso, tomaremos como referência as considerações sobre a mudança do fluxo comunicacional da linguagem publicitária (BEKESAS, 2012, as características da cibercultura (LEMOS; LÉVY, 2010, a cultura da participação (SHIRKY, 2011 e a necessidade de uma conduta ética para a manutenção da credibilidade das empresas (BLACKSHAW, 2010. Neste trabalho, também citaremos casos ilustrativos da humanização dos discursos das marcas colhidas nas redes sociais na Internet, como forma de exemplificar os esforços das empresas em manter a integridade da imagem da marca no atual cenário do refluxo comunicacional. Palavras-chave: Discurso. Marcas. Consumo. Refluxo comunicacional. Mídias sociais.

Comparison of CT enterography and MR enterography imaging features of active Crohn disease in children and adolescents

Energy Technology Data Exchange (ETDEWEB)

Gale, Heather I. [The Warren Alpert Medical School of Brown University, Department of Diagnostic Imaging, Rhode Island Hospital/Hasbro Children' s Children' s Hospital/Women and Infants Hospital, Providence, RI (United States); Sharatz, Steven M.; Nimkin, Katherine; Gee, Michael S. [MassGeneral Hospital for Children, Division of Pediatric Imaging, Department of Radiology, Harvard Medical School, Boston, MA (United States); Taphey, Mayureewan [Bumrungrad International Hospital, Bangkok (Thailand); Bradley, William F. [Cambridge Mobile Telematics, Cambridge, MA (United States)

2017-09-15

Assessment for active Crohn disease by CT enterography and MR enterography relies on identifying mural and perienteric imaging features. To evaluate the performance of established imaging features of active Crohn disease in children and adolescents on CT and MR enterography compared with histological reference. We included patients ages 18 years and younger who underwent either CT or MR enterography from 2007 to 2014 and had endoscopic biopsy within 28 days of imaging. Two pediatric radiologists blinded to the histological results reviewed imaging studies and scored the bowel for the presence or absence of mural features (wall thickening >3 mm, mural hyperenhancement) and perienteric features (mesenteric hypervascularity, edema, fibrofatty proliferation and lymphadenopathy) of active disease. We performed univariate analysis and multivariate logistic regression to compare imaging features with histological reference. We evaluated 452 bowel segments (135 from CT enterography, 317 from MR enterography) from 84 patients. Mural imaging features had the highest association with active inflammation both for MR enterography (wall thickening had 80% accuracy, 69% sensitivity and 91% specificity; mural hyperenhancement had 78%, 53% and 96%, respectively) and CT enterography (wall thickening had 84% accuracy, 72% sensitivity and 91% specificity; mural hyperenhancement had 76%, 51% and 91%, respectively), with perienteric imaging features performing significantly worse on MR enterography relative to CT enterography (P < 0.001). Mural features are predictors of active inflammation for both CT and MR enterography, while perienteric features can be distinguished better on CT enterography compared with MR enterography. This likely reflects the increased conspicuity of the mesentery on CT enterography and suggests that mural features are the most reliable imaging features of active Crohn disease in children and adolescents. (orig.)

Detection of activities of daily living impairment in Alzheimer's disease and mild cognitive impairment using information and communication technology

Directory of Open Access Journals (Sweden)

Sacco G

2012-12-01

Full Text Available Guillaume Sacco,1–3 Véronique Joumier,1,4 Nelly Darmon,1 Arnaud Dechamps,1,5 Alexandre Derreumaux,1,3 Ji-Hyun Lee,2 Julie Piano,2 Nathalie Bordone,2 Alexandra Konig,1,6 Bernard Teboul,3 Renaud David,1,2 Olivier Guerin,1,3 François Bremond,1,4 Philippe Robert1,21EA CoBTeK, Université de Nice Sophia-Antipolis, 2Centre Mémoire de Ressource et de Recherche, CHU de Nice, 3Plateforme Patient du Centre d'Innovation et d'Usage en Santé, CHU de Nice, 4Equipe Stars, Institut National de Recherche en Informatique et en Automatique (INRIA, Sophia-Antipolis, France; 5University of Pancasila, Department of Psychology, Jakarta, Indonesia; 6University of Maastricht, Faculty of Psychology and Neuropsychology, Department of Psychiatry and Neuropsychology, Maastricht, The NetherlandsBackground: One of the key clinical features of Alzheimer's disease (AD is impairment in daily functioning. Patients with mild cognitive impairment (MCI also commonly have mild problems performing complex tasks. Information and communication technology (ICT, particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs in AD and in MCI.Methods: The aim of the study is to propose a daily activity scenario (DAS score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC. Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1 and 19 MCI matched with 19 NC for protocol 2 (P2. Each participant was asked to undertake a set of daily tasks in the setting of a “smart home” equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints. The DAS score was then computed

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

Science.gov (United States)

Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

2014-09-01

Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

SILENT MYOCARDIAL ISCHEMIA AND CARDIAC RHYTHM DISTURBANCES IN WOMEN WITH RHEUMATOID ARTHRITIS

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D. S. Novikova

2014-07-01

Full Text Available Objective: to assess the rate of silent myocardial ischemia (SMI and the pattern of cardiac rhythm disturbances in women with rheumatoidarthritis (RA, their association with traditional risk factors (TRF for cardiovascular diseases (CVD, with subclinical structural and functionalchanges in the heart and vessels, with the activity and severity of rheumatoid inflammation.Subjects and methods. Two hundred and ninety-one female patients aged less than 60 years with a valid diagnosis of RA and no clinicalsigns were examined. A control group consisted of 125 women without rheumatic diseases. In addition to the clinical manifestations, activity,and severity of RA, the authors assessed major TRFs for CVD, performed Holter ECG monitoring, common carotid artery duplex scanning, transthoracic echocardiographic study, and determined the levels of serum inflammatory markers.Results. The women with RA differ from the control group in the higher incidence of SMI, supraventricular arrhythmias (SVA and highgradepremature ventricular contractions (PVC. The patients with RA and SMI are characterized in terms of age-adjustment by higher disease activity (DAS28, systemic manifestations, cumulative larger-dose glucocorticoids (GC and a higher percentage of patients receiving disease-modifying anti-rheumatic drugs as compared with those with RA and no SMI with adjustment for age. High disease activity(DAS28, level of inflammatory markers, IgM rheumatoid arthritis seropositivity, and GC therapy are SVA-associated factors in women with RA; larger left ventricular end-diastolic dimension and serositis are factors associated with high-grade PVC.Conclusion. The RA women without clinical manifestations of CVD are recorded to have high rates of SMI, SVA, and high-grade PVC, which is primarily due to the activity and severity of rheumatoid inflammation.

49 CFR 28.110 - Self-evaluation.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Self-evaluation. 28.110 Section 28.110 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.110 Self-evaluation...

49 CFR 28.170 - Compliance procedures.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Compliance procedures. 28.170 Section 28.170 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION § 28.170 Compliance...

Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases

International Nuclear Information System (INIS)

Iacopino, A.M.; Christakos, S.

1990-01-01

The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases in calbindin·mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. These findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases

Teaching Foreign Cultural Literacy with Margarethe von Trotta's "Das Versprechen"

Science.gov (United States)

Kuttenberg, Eva

2003-01-01

This article describes model units for an in-depth cultural analysis of "Das Versprechen" in undergraduate college courses including intermediate German, German culture and civilization, advanced conversation and composition, and film. Practical suggestions for pre-viewing, viewing, and post-viewing activities as well as assessment in…

Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies.

Science.gov (United States)

Charles-Schoeman, Christina; van der Heijde, Désirée; Burmester, Gerd R; Nash, Peter; Zerbini, Cristiano A F; Connell, Carol A; Fan, Haiyun; Kwok, Kenneth; Bananis, Eustratios; Fleischmann, Roy

2018-02-01

Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies. Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)-erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score. Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone. Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a

EULAR Sjögren's syndrome disease activity index (ESSDAI)

DEFF Research Database (Denmark)

Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar

2015-01-01

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...

Erosividade e características hidrológicas das chuvas de Rio Grande (RS Erosivity and hydrological characteristics of rainfalls in Rio Grande (RS, Brazil

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Marcos Gabriel Peñalva Bazzano

2010-02-01

,0 % do intermediário e 24,2 % do atrasado. Da erosividade anual, 49,1 % correspondeu a chuvas do padrão avançado, 28,9 % a chuvas do padrão intermediário e 22,1 % a chuvas do padrão atrasado. O método da distribuição extrema tipo I foi adequado para obter as curvas de intensidade-duração-frequência. Os períodos de retorno da chuva podem ser calculados por meio das equações, utilizando os valores dos parâmetros encontrados, ou pelos gráficos das curvas de intensidade-duração-frequência.Specific rainfall characteristics vary among regions and their erosion potential must be known for the planning of agricultural and civil engineering activities. For Rio Grande (RS, Brazil, the erosivity and relationships with the precipitation and rainfall coefficient, rainfall hydrologic patterns and return period were determined based on rainfall data of 23 years. For each erosive rainfall the segments of the rainfall chart with the same intensity were separated together and the data registered in worksheets. The mean monthly and annual rainfall erosivity, the EI30 index in the International System of Units and the rainfall patterns were estimated using software Chuveros. The mean monthly values of precipitation and erosivity index were expressed as percentage of the mean annual values of these variables, resulting in the curve of accumulated distribution of precipitation and erosivity index in function of time. The rainfall coefficient (Rc was calculated. Pearson correlations and linear regressions between the erosivity index EI30 and the mean annual values of precipitation and rainfall coefficient were calculated. The rainfall return period was calculated for 2, 5, 10, 20, 50, and 100 years. The mean annual value of EI30 was 5135 MJ mm ha-1 h-1, which is to be used as "R" Factor in the Universal Soil Loss Equation (USLE for Rio Grande and surrounding regions with similar climatic conditions. The regression equations for EI30 and precipitation and rainfall

Influência das novas tecnologias na gestão das finanças pessoais: desenho de um robo-advisor

OpenAIRE

Pérez Ares, Iago Roi

2016-01-01

A crise económica global atual, junto com a profunda evolução das novas tecnologias, está a produzir a necessidade de aumentar a eficiência da gestão de numerosas atividades da nossa vida. Desta forma, uma das principais preocupações na vida das pessoas, como demonstram numerosos estudos, é a sua gestão das finanças familiares. Se a isto lhe for adicionado a crescente desconfiança no sector bancário, produzida em parte pela duvidosa gestão dos seus responsáveis, entende-se que a gestão patri...

Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

Energy Technology Data Exchange (ETDEWEB)

Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

2013-09-01

Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

International Nuclear Information System (INIS)

Kalayarasan, Srinivasan; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam

2013-01-01

Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells

A randomized controlled cross-over trial investigating the effect of anti-inflammatory diet on disease activity and quality of life in rheumatoid arthritis: the Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study protocol.

Science.gov (United States)

Winkvist, Anna; Bärebring, Linnea; Gjertsson, Inger; Ellegård, Lars; Lindqvist, Helen M

2018-04-20

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2 × 10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. The nutritional status of patients with RA often is

Activation of the Arabidopsis membrane-bound transcription factor bZIP28 is mediated by site-2 protease, but not site-1 protease.

Science.gov (United States)

Iwata, Yuji; Ashida, Makoto; Hasegawa, Chisa; Tabara, Kazuki; Mishiba, Kei-Ichiro; Koizumi, Nozomu

2017-08-01

The unfolded protein response (UPR) is a homeostatic cellular response conserved in eukaryotic cells to alleviate the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription factor activated by proteolytic cleavage in response to ER stress, thereby releasing its cytosolic portion containing the bZIP domain from the membrane to translocate into the nucleus where it induces the transcription of genes encoding ER-resident molecular chaperones and folding enzymes. It has been widely recognized that the proteolytic activation of bZIP28 is mediated by the sequential cleavage of site-1 protease (S1P) and site-2 protease (S2P). In the present study we provide evidence that bZIP28 protein is cleaved by S2P, but not by S1P. We demonstrated that wild-type and s1p mutant plants produce the active, nuclear form of bZIP28 in response to the ER stress inducer tunicamycin. In contrast, tunicamycin-treated s2p mutants do not accumulate the active, nuclear form of bZIP28. Consistent with these observations, s2p mutants, but not s1p mutants, exhibited a defective transcriptional response of ER stress-responsive genes and significantly higher sensitivity to tunicamycin. Interestingly, s2p mutants accumulate two membrane-bound bZIP28 fragments with a shorter ER lumen-facing C-terminal domain. Importantly, the predicted cleavage sites are located far from the canonical S1P recognition motif previously described. We propose that ER stress-induced proteolytic activation of bZIP28 is mediated by the sequential actions of as-yet-unidentified protease(s) and S2P, and does not require S1P. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study

DEFF Research Database (Denmark)

Nørgård, Bente; Hundborg, Heidi H; Jacobsen, Bent Ascanius

2007-01-01

OBJECTIVES: CD is associated with increased risk of adverse birth outcomes, but existing studies have not assessed the impact of disease activity during pregnancy. We examined the impact of disease activity on birth outcomes: LBW, preterm birth, LBW at term, and CAs. METHODS: All births by CD wom...... disease activity). Further research is needed to assess the critical impact of disease activity in larger cohorts of CD women....

Clinical response to anti-TNFα therapy in patients with rheumatoid arthritis faulted or intolerance in non-biological DMARD in the Hospital San Juan de Dios in the period January 2006 to December 2011

International Nuclear Information System (INIS)

Salas Mena, Claudio

2014-01-01

Various clinical studies are performed globally using anti-TNFα therapy and has proven its clinical effectiveness in the management of rheumatoid arthritis patients, that have failed or have presented intolerance to the use of non-biological DMARDs. The clinical response to treatment of anti-TNFα was determined in patients with rheumatoid arthritis who have presented without respond, have showed intolerance or secondary effects to DMARDs no biological, in the Servicio de Reumatologia del Hospital San Juan de Dios, in the period January 2006 to December 2011. Study has been descriptive, retrospective, observational, by reviewing dossiers of patients with rheumatoid arthritis to initiate anti-TNFα therapy where has valued the DAS28 and initial VES, then at 6 months and 12 months after starting treatment. In the period analyzed, 47 patients evaluated with traditional DMARD failure who have received anti-TNFα therapy, according to DAS28, 32 patients were cataloged as severe activity and 15 of them with moderate activity. A total of 41 patients have used etanercept, with adalimumab 6 patients. The DAS28 initial average was 5,63 in all patients, 6,16 in the subgroup of patients with severe activity, and 4,49 in the subgroup of moderate activity. After 6 months of treatment, the DAS28 has descended to 3,25 in all patients, with 3,67 in the subgroup of severe clinical activity, and 2,35 in the subgroup of moderate clinical activity. One year after treatment values DAS28 have been 3,13 for all patients, 3,53 in severe activity and 2,28 in the subgroup of activity clinical moderate. In all groups and subgroups of patients, difference was demonstrated statistically significant at p less than 0,05. Between the subgroups of patients according to clinical activity is keeped without significant difference, or the type of anti-TNFα therapy employed. The anti-TNFα therapy has proven to be effective for improvement of clinical activity of rheumatoid arthritis, regardless of

CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer

Science.gov (United States)

Cepeda, Diana; Ng, Hwee-Fang; Sharifi, Hamid Reza; Mahmoudi, Salah; Cerrato, Vanessa Soto; Fredlund, Erik; Magnusson, Kristina; Nilsson, Helén; Malyukova, Alena; Rantala, Juha; Klevebring, Daniel; Viñals, Francesc; Bhaskaran, Nimesh; Zakaria, Siti Mariam; Rahmanto, Aldwin Suryo; Grotegut, Stefan; Nielsen, Michael Lund; Szigyarto, Cristina Al-Khalili; Sun, Dahui; Lerner, Mikael; Navani, Sanjay; Widschwendter, Martin; Uhlén, Mathias; Jirström, Karin; Pontén, Fredrik; Wohlschlegel, James; Grandér, Dan; Spruck, Charles; Larsson, Lars-Gunnar; Sangfelt, Olle

2013-01-01

SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. PMID:23776131

VALIDATION OF THE RUSSIAN-LANGUAGE VERSION OF THE RAPID-3 QUESTIONNAIRE

Directory of Open Access Journals (Sweden)

A S Starkova

2011-01-01

There were high correlations of RAPID-3 values with clinical parameters: the number of swollen joints (R=0.61 and tender joints (R = 0.46, combined DAS 28 indices (R=0.72, simple (R=0.60 and clinical (R=063 disease activity indices (SDAI and CDAI, inflammation activity index (IAI (R=0.62, health assessment questionnaire (HAQ (R=0.64, and quality of life questionnaire (EQ-5D scores (R=0.52. Conclusion. The RAPID-3 index is a reliable, sensitive, and valid tool to evaluate inflammation activity and functional status in patients with RA