Influence of the timing of biological treatment initiation on Juvenile Idiopathic Arthritis long-term outcomes.

BACKGROUND: Juvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying antirheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL). METHODS: Adult JIA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) and ever treated with bDMARD were included. Data regarding socio-demographic, JIA-related characteristics, disease activity, physical disability (HAQ-DI), HRQoL (SF-36), and treatments were collected at the last visit. Patients were divided into 3 groups (≤ 2 years, 2-5 years, or > 5 years), according to the time from disease onset to bDMARD initiation. Regression models were obtained considering remission on/off medication, HAQ-DI, SF-36, and joint surgeries as outcomes and time from disease onset to bDMARD start as an independent variable. RESULTS: Three hundred sixty-one adult JIA patients were evaluated, with a median disease duration of 20.3 years (IQR 12.1; 30.2). 40.4% had active disease, 35.1% were in remission on medication, and 24.4% were in drug-free remission; 71% reported some degree of physical disability. Starting a bDMARD > 5 years after disease onset decreased the chance of achieving remission off medication (OR 0.24; 95% CI 0.06, 0.92; p = 0.038). Patients who started a bDMARD after 5 years of disease onset had a higher HAQ and worse scores in the physical component, vitality, and social function domains of SF-36, and more joint surgeries when compared to an earlier start. CONCLUSION: Later initiation of bDMARDs in JIA is associated with a greater physical disability, worse HRQoL, and lower chance of drug-free remission in adulthood.

Pertinencia de los laboratorios de simulación como herramienta de educación avanzada en salud / Relevance of simulation laboratories as a tool for advanced health education

RESUMEN El constante perfeccionamiento del proceso educativo del hombre demanda el enriquecimiento de las prácticas de la educación avanzada. Es preciso efectuar transformaciones en el trabajo educativo, por lo que resulta indispensable que se oriente de forma tal que permita potenciar en cada estudiante aquellos aspectos que le faciliten conocer, de una manera más significativa, el momento histórico en que viven. Los simuladores virtuales, como método de aprendizaje en ciencias médicas, son potenciadores del aprendizaje y ayudan a evadir el obstáculo de horas limitadas en la práctica clínica, grupos numerosos, inconsistencias en la observación de enfermedades de alto riesgo o inusuales. En Cuba, la utilización de estos no ha sido explotada al máximo. Los estudios que han evaluado la efectividad de estos simuladores en la mejoría del desempeño de los profesionales de la salud, han arrojado resultados muy positivos, pero el elevado precio de los simuladores ha constituido la mayor barrera para su completa introducción en Cuba. Este trabajo expresa la posición de los autores sobre la pertinencia de los laboratorios de simulación como herramienta de educación avanzada en salud. El uso de los laboratorios de simulación en la educación médica, es una práctica positiva en el perfeccionamiento de las competencias profesionales y ofrece la seguridad de la atención sanitaria; no es un sustituto de la práctica supervisada en entorno real, sino un complemento deseable para una pericia segura y efectiva que permite desarrollar habilidades, conocimientos y actitudes, es decir, capacidades para su óptimo desempeño.

ABSTRACT The constant improvement of the educational process of man demands the enrichment of the practices of advanced education. It is necessary to carry out transformations in the educational work, so it is essential that it be oriented in such a way that it allows each student to enhance those aspects that make it easier for them to know, in a more significant way, the historical moment in which they live. Virtual simulators, as a learning method in medical sciences, are learning enhancers and help to avoid the obstacle of limited hours in clinical practice, large groups, inconsistencies in the observation of high-risk or unusual diseases. In Cuba, the use of these has not been exploited to the maximum. The studies that have evaluated the effectiveness of these simulators in improving the performance of health professionals have yielded very positive results, but the high price of the simulators has constituted the greatest barrier to their full introduction in Cuba. This work expresses the position of the authors on the relevance of simulation laboratories as a tool for advanced health education. The use of simulation laboratories in medical education is a positive practice in the improvement of professional skills and offers the security of health care, it is not a substitute for supervised practice in a real environment, but a desirable complement to an expertise safe and effective, which allows developing skills, knowledge and attitudes, that is, capacities for optimal performance.

Health-related quality of life and disability in adults with juvenile idiopathic arthritis: comparison with adult-onset rheumatic diseases.

OBJECTIVE: To compare physical disability, mental health, fatigue and health-related quality of life (HRQoL) across juvenile idiopathic arthritis (JIA) categories in adulthood and between JIA and adult-onset rheumatic diseases. METHODS: Cross-sectional analysis nested in a cohort of adult patients with JIA registered in the Rheumatic Diseases Portuguese Register (Reuma.pt). Physical disability (Health Assessment Questionnaire-Disability Index), mental health symptoms (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F)) and HRQoL (EuroQol-5D (EQ5D) and Short Form (SF-36)) were compared across JIA categories. Patients with polyarticular JIA and enthesis-related arthritis (ERA) JIA were compared respectively to patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), matched for gender and age, adjusted for disease duration and activity. RESULTS: 585 adult patients with JIA were included. Comparison across JIA categories showed that persistent oligoarthritis and patients with ERA reported a higher score in EQ5D and SF-36 physical component when compared with other JIA categories.Polyarticular JIA reported less disability and fatigue than patients with RA (median Health Assessment Questionnaire of 0.25 vs 0.63; p<0.001 and median FACIT-F score 42 vs 40 ; p=0.041). Polyarticular JIA had also better scores on EQ5D and all domains of SF-36, than patients with RA. Patients with ERA reported less depression and anxiety symptoms (0% vs 14.8%; p=0.003% and 9% vs 21.3%; p=0.002) and less fatigue symptoms (45 vs 41; p=0.01) than patients with SpA. CONCLUSION: Persistent oligoarticular JIA and ERA are the JIA categories in adulthood with better HRQoL. Overall, adult polyarticular and patients with ERA JIA have lower functional impairment and better quality-of-life than patients with RA and SpA.

Association of body mass index with Juvenile Idiopathic Arthritis disease activity: a Portuguese and Brazilian collaborative analysis.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). METHODS: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Age- and sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P <3), normal weight (3≤P≤85), overweight (85

97). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariate analyses were performed. RESULTS: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p <0.001), patient's/parent's global assessment of disease activity (PGA) (p=0.020), physician's global assessment of disease activity (PhGA) (p <0.001), erythrocyte sedimentation rate (ESR) (p=0.032) and overall higher JADAS-27 (p <0.001), compared to patients with normal weight, overweight and obesity. In the multivariate regression, underweight persisted significantly associated with higher disease activity, compared to normal weight (B=-9.430, p <0.001), overweight (B=-9.295, p=0.001) and obesity (B=-9.120, p=0.001), when adjusted for age, gender, country, ethnicity, JIA category and therapies used. The diagnosis of RF- (B=3.653, p=0.006) or RF+ polyarticular JIA (B=5.287, p=0.024), the absence of DMARD therapy (B=5.542, p <0.001) and the use of oral GC (B=4.984, p=0.002) were also associated with higher JADAS-27. CONCLUSION: We found an independent association between underweight and higher disease activity in patients with JIA. Further studies are needed to understand the underlying mechanisms of this association.

Infliximab-Induced Lupus: A Case Report.

We report the case of a 48-year-old, leukodermic female diagnosed with ulcerative proctitis for 4 years and latent tuberculosis. She was allergic to salicylates and had a minor allergic reaction to infliximab (rash, vertigo, and headache). Thereafter, she started azathioprine (2.5 mg/kg/day). She maintained intravenous infliximab, together with prophylaxis with clemastine and hydrocortisone, due to the steroid-dependent proctitis. The therapy was continued every 8 weeks with anti-tumor necrosis factor for about 3 years. The analytical evaluation when she was diagnosed with ulcerative proctitis (February 2011) showed negative antinuclear antibodies (ANA), double-stranded-DNA antibodies (anti-dsDNA), antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, and a positive outer membrane protein antibody. About 2 years and 6 months after starting infliximab (November 2013), the patient complained of inflammatory symmetrical polyarthralgia (knee, shoulder, elbow, and wrist) without synovitis, which started every week before the administration of infliximab. Resolution of symptoms was observed after each infliximab infusion. In July 2014, the autoantibody re-evaluation showed positive ANA with a homogeneous pattern with a titer of 1:640, weak positive anti-dsDNA (30.2), and positive anti-histone with C3 decreased (80.3). She was then diagnosed with lupus induced by infliximab and initiated hydroxychloroquine 400 mg. Infliximab was suspended. On re-evaluation, the erythrocyte sedimentation rate was 25 mm/h (1st hour), C-reactive protein 0.5 mg/dL (previously erythrocyte sedimentation rate 15 mm/h and C-reactive protein 1.2 mg/dL), and endoscopically, the mucosa was scarred, with some atrophy and scarce mucus in the lower rectum. About 10 months after discontinuation of infliximab, repeated autoantibodies proved all negative, keeping only low C3 (87). The patient also reported complete resolution of the arthralgia.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - 2016 update.

OBJECTIVE: To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment), assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%), and strategy in the presence of an inadequate response (where switching is recommended) or in the presence of long-term remission (where a process of biological therapy optimization can be considered, either a gradual increase in the interval between doses or a decrease of each dose of the biological therapy). CONCLUSION: These recommendations may be used for guidance in deciding which patients with axSpA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese Recommendations for the use of biological therapies in patients with rheumatoid arthritis- 2016 update.

OBJECTIVE: To update the recommendations for the treatment of Rheumatoid Arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Portuguese recommendations for the use of methotrexate in rheumatic diseases - 2016 update.

BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. RESULTS: Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. CONCLUSION: The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice.

Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage.

OBJECTIVES: To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. METHODS: Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index-articular (JADI-A) and Juvenile Arthritis Damage Index-extra-articular (JADI-E) damage index and disease activity were analysed. RESULTS: 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still's disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. CONCLUSIONS: Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive of higher disability and decreased the chance of inactive disease.

Genetic Predictors of Poor Prognosis in Portuguese Patients with Juvenile Idiopathic Arthritis: Data from Reuma.pt.

INTRODUCTION: This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). METHODS: Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. RESULTS: Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define "poor prognosis." In univariate analysis, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847, and allele G of PTPN2 rs7234029. In multivariate models, the associations with TRAF1/C5 (1.96 [1.17-3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. CONCLUSION: Our study does not confirm the association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA.

Using the Juvenile Arthritis Disease Activity Score based on erythrocyte sedimentation rate or C-reactive protein level: results from the Portuguese register.

OBJECTIVE: Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27-joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C-reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27-ESR and clinical JADAS27 (JADAS27 without ESR). METHODS: A nationwide cohort of patients with JIA registered in the Portuguese Register, Reuma.pt, was studied. JADAS27-CRP was adapted by replacing ESR with CRP level as the inflammatory marker. JADAS27-CRP was calculated similarly to JADAS27-ESR as the simple linear sum of its 4 components. Pearson's correlations and K statistics were used in the analyses. RESULTS: A total of 358 children had full data to calculate JADAS27; 65.4% were female and the mean ± SD disease duration was 11.8 ± 9.1 years. The correlation coefficient between JADAS27-ESR and JADAS27-CRP was 0.967 (P < 0.0001), although the correlation coefficient between ESR and CRP level was 0.335 (P < 0.0001). The strong correlation between JADAS27-ESR and JADAS27-CRP was maintained when compared within each JIA category. The agreement between JADAS27-ESR and JADAS27-CRP across the 4 activity states was very good, showing 91.1% of the observations in agreement; K = 0.867 (95% confidence interval 0.824-0.91). The correlation between JADAS27 with ESR and JADAS27 without ESR was high (r = 0.97, P < 0.0001). CONCLUSION: JADAS27 based on CRP level correlated closely with JADAS27-ESR across all disease activity states and JIA categories, indicating that both measures can be used in clinical practice. Moreover, the correlation of JADAS27 with and without ESR was also high, suggesting that this tool might be useful even in the absence of laboratorial measures.

Effect of the combination of uridine nucleotides, folic acid and vitamin B12 on the clinical expression of peripheral neuropathies.

AIMS: Peripheral neuropathy (PN) is a common condition whose incidence is approximately 8% in elderly persons. Neuropathic pain (NeP) has a significant incidence in the general population and affects more than half of all patients with PN. The pathophysiology of PN is characterized by lesions of myelin-producing Schwann cells in peripheral nerves. Regeneration/protection of the myelin sheath after a nerve lesion is a fundamental element of repair in PN. Nucleotides such as uridine monophosphate (UMP) have proven to be efficacious in treating the cause of the myelin sheath lesion in several experimental and clinical models. Our objective was to evaluate clinical improvement in patients with PN and NeP treated with a combination of UMP+folic acid+vitamin B12 (Keltican). PATIENTS AND METHODS: We performed an exploratory, open-label, multicenter, study of 212 patients followed for 2 months. Pain was assessed using the painDETECT questionnaire (PDQ). RESULTS: The intensity of the NeP assessed at the time of the consultation progressed favorably and decreased significantly (p<0.001) in all the types of PN included. The global score for pain assessed using PDQ decreased from 17.5 points to 8.8 points at the final evaluation (p<0.001). Nonsteroidal anti-inflammatory drugs were decreased/withdrawn in 77.4% of patients. CONCLUSIONS: The combination of UMP+folic acid+vitamin B12 is effective against NeP associated with PN. It leads to statistically significant reductions not only in the total PDQ score but also in the intensity of pain, number of areas affected, and pain radiation. Furthermore, it makes it possible to reduce the dosage of concomitant medication.

Neonatal stroke associated with de novo antiphospholipid antibody and homozygous 1298C/C methylenetetrahydrofolate reductase mutation.

Antiphospholipid antibodies are a recognised prothrombotic risk factor associated with acute ischaemic infarction. Most autoimmune diseases are rare in infants, and in the neonatal period, autoimmunity is related to transplacental passage of maternal immunoglobulin G autoantibodies. Distinguishing between de novo and acquired autoimmunity has important therapeutic implications and is crucial for determining the prognosis. We present a case of a neonatal thrombotic stroke associated with de novo synthesis of antiphospholipid antibodies, a homozygous 1298C/C methylene-tetrahydrofolate reductase mutation and a double-homozygous plasminogen activator inhibitor 1 polymorphism (PAI-1 844A/A and 675 4G/4G), which may have increased the final thrombotic risk. Her mother was not positive for antiphospholipid antibodies. The authors highlight an unequivocal evidence of a de novo case of paediatric antiphospholipid antibody syndrome and emphasise the need for a thorough investigation in cases of neonatal stroke including molecular thrombophilia study.

Ele não chega nunca... experiências de mulheres no contexto do trabalho escravo / He never comes back... experiences of women in the slave labor context

O artigo discute situações de medo, resistência e estranhamento vividos em consequência de migrações, a partir do discurso de três camponesas do Piauí. Elas têm em comum a região de moradia, o trabalho rural, a baixa escolaridade, a situação de pobreza, a “invisibilidade” de gênero, e, sobretudo, a existência de familiares masculinos aliciados e levados ao sul do Estado do Pará: muitos desses homens, frequentemente submetidos ao que tem sido reconhecido como trabalho escravo por dívida em empresas agropecuárias, passam por situações de violência e as suas famílias não têm notícias sobre eles. Nas comunidades de origem, esposas, mães, filhas, mantêm a vida cotidiana, compartilhando redes de relações materiais e simbólicas.(AU)

This article discusses situations of fear, resistance and estrangement due to migration, based on the discourse of three peasant women in Piauí, Northeast Brazil. These women have much in common: housing conditions, rural work, poor education, poverty, “invisibility” of gender, and male relatives who were deceived and taken to south Pará, North Brazil. Many of these men, often subjected to what has been recognized as debt bondage in agricultural companies, are submitted to violence situations and their families have no news of them. In their origin communities, wives, mothers and daughters lead their daily life by sharing networks of material and symbolic relations.(AU)

[Fibrous dysplasia of bone--a case of polyostotic fibrous dysplasia]. / Displasia fibrosa ósse--um caso clinico de displasia fibrosa poliostótica.

Fibrous Dysplasia FD of bone is a rare non-inheritable congenital disease characterized by a focal proliferation of fibrous tissue in the bone marrow leading to osteolytic lesions deformities and fractures. FD can be presented in a monostotic or polyostotic form this last one is usually more severe. FD primarily affects adolescents and young adults and in some cases in an asymptomatic way. We describe the case of a male patient with long evolution form of polyostotic fibrous dysplasia of bone with delayed clinical presentation. It is also highlighted the importance of an activity and involvement form evaluation as well as possible endocrine abnormalities associated in order to establish the correct treatment and prognosis.