Susceptibility and prognostic factors in portuguese patients with juvenile idiopathic arthritis

ABSTRACT: Objectives: This study aimed to confirm whether 15 single nucleotide polymorphisms (SNPs) of selected genes are also associated with susceptibility for Juvenile idiopathic Arthritis (JIA) in thePortuguese population. Methods: Our study was conducted on Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA receiving biological therapies and synthetic Disease Modifying Anti Rheumatic Drugs (DMARDs) since June 2001. Fifteen SNPs were investigated using Taqman® SNP genotyping assays in 291 Portuguese patients with JIA and 300 ethnically matched healthy controls. Results: Prior to Bonferroni correction for multiple testing, significant genotype association between one SNP and overall group of JIA was observed (PTPN22 rs2476601). In subgroup analysis, associations between six SNPs and the subgroup of patients with rheumatoid factor (RF)-positive Polyarticular (PTPN2 rs7234029), Extended oligoarticular (PTPN22 rs2476601), Systemic (PTPRC rs10919563, ANGPT1 rs7151781 and TNF rs361525) and Psoriatic JIA (IL2RA/CD25 rs2104286) were found. After Bonferroni correction for multiple testing, 3 genotype associations remained significant in the subgroup of patients with RF-positive polyarticular JIA (PTPN2 rs7234029 [corrected P 0.026]), extended oligoarticular (PTPN22 rs2476601 [corrected P 0.026]) and systemic JIA (ANGPT1 rs7151781 [corrected P 0.039]). Conclusion: Our results provide additional evidence for an association between polymorphisms in genes PTPN2, PTPN22 and ANGPT1 and the risk of RF-positive polyarticular, extended oligoarticular and systemic JIA, respectively, in a Portuguese population

Avaliação in vitro de estratégias antimicrobianas inovadoras para controlo de otites externas por Pseudomonas aeruginosa no cão

Dissertação de Mestrado Integrado em Medicina VeterináriaO desenvolvimento e disseminação de microrganismos resistentes a antimicrobianos causados pelo uso inadequado desses compostos é uma grande preocupação de saúde pública, pressionando para o desenvolvimento de novas estratégias terapêuticas. A otite externa (OE) é uma das doenças dermatológicas mais comumente diagnosticadas em cães, tendo uma etiologia multifatorial. Entre os agentes bacterianos mais frequentemente associados à OE canina, Pseudomonas aeruginosa é de especial preocupação, devido ao seu frequente perfil de multirresistências e notável capacidade de formar biofilmes, estruturas que tornam os tratamentos desafiadores e propiciam para a cronicidade e recorrência das infeções. O aumento da prevalência de resistência antimicrobiana entre bactérias em cães com OE leva à necessidade de se encontrar novos agentes terapêuticos, incluindo o uso de óleos essenciais ou géis contendo péptidos antimicrobianos, como o Peptivet®. O objetivo principal deste estudo foi comparar a eficácia de diferentes antimicrobianos no controlo da OE canina de P. aeruginosa, incluindo Gentamicina, um antibiótico convencional, e Peptivet® e Óleo Essencial de Lavanda (OEL), duas estratégias antimicrobianas inovadoras. O outro objetivo foi avaliar o impacto do cerúmen canino na atividade inibitória do Peptivet® com o objetivo de avaliar se esta é mantida em condições que melhor mimetizem as OE in vivo, dado que o cerúmen e o conteúdo lipídico, que estão alterados na OE, podem influenciar a penetração e ação de compostos antimicrobianos. Dos antimicrobianos avaliados, o OEL apresentou a maior eficácia após 30 minutos de incubação, demonstrando capacidade de inibir e erradicar os biofilmes formados por 61,5% dos isolados em estudo, e a Gentamicina apresentou a maior eficácia após 24 horas de incubação, demonstrando capacidade para inibir e erradicar biofilmes formados por 100% dos isolados em estudo. O Peptivet® apresentou a menor eficácia, tendo sido aproximadamente metade da eficácia do OEL após 30 minutos de incubação. Os resultados deste estudo indicam que o Óleo Essencial de Lavanda avaliado pode ser considerado uma alternativa inovadora com grande potencial para o tratamento e prevenção da OE causada por P. aeruginosa em cães, sugerindo a necessidade de continuar esta linha de investigação com o objetivo da sua utilização futura em contexto clínico.ABSTRACT - In vitro evaluation of innovative antimicrobial approaches aiming at controlling otitis by Pseudomonas aeruginosa in dogs - The development and spread of antimicrobial resistant microorganisms caused by the inappropriate use of these compounds is a major public health concern, pressing for the development of new therapeutic strategies. Otitis externa (OE) is one of the most commonly diagnosed dermatological diseases in dogs, having a multifactorial etiology. Among the most frequent bacterial agents associated with canine OE, Pseudomonas aeruginosa is of special concern, due to its frequent multidrug resistance profile and its remarkable ability to form biofilms, structures that make treatments challenging and predispose to the chronicity and recurrence of infections. The increasing prevalence of antimicrobial resistance among bacteria in dogs with OE leads to the need to find new therapeutic agents including the use of Essential Oils or gels containing antimicrobial peptides, such as Peptivet®. The main objective of this study was to compare the antimicrobial potential of different antimicrobials to control P. aeruginosa canine OE, including Gentamicin, a conventional antibiotic, and Peptivet® and Lavanda Essential Oil (OEL), two innovative antimicrobial strategies. The other objective was to assess the impact of canine cerumen on the inhibitory activity of Peptivet®, aiming at evaluating if its inhibitory potential is maintained in conditions which better mimic the ears in vivo environment, since the skin cerumen and lipid content, which are altered in ears with otitis, may influence the penetration and action of antimicrobial compounds. Of the antimicrobials evaluated, the ones that showed the best effectiveness were Lavender Essential Oil after 30 minutes incubation, which demonstrated the ability to inhibit and eradicate the biofilms formed by 61.5% of the isolates under study, and Gentamicin after 24 hours incubation, which demonstrated the ability to inhibit and eradicate biofilms formed by 100% of the isolates under study. Peptivet® had the lowest effectiveness, having approximately half the effectiveness of the oil after 30 minutes of incubation. The results of this study indicate that the evaluated Lavender Essential Oil can be considered an innovative alternative with great potential for the treatment and prevention of external otitis caused by P. aeruginosa in dogs, suggesting the need to continue this line of research in terms of its future use in a clinical context.N/

O poder da imagem mediática de Marcelo Rebelo de Sousa: o perfil de um candidato atípico

A política e os media relacionam-se intimamente e cada vez mais na sociedade atual. Os meios de comunicação são o palco da política, é neles que ela ocorre e decorre. É através deles que os cidadãos têm acesso a representações da realidade, que têm contacto com a política quase de forma exclusiva. Estar presente nos "media" é existir para os cidadãos e é através dos "media" que se conquista o eleitorado. Como tal, torna-se interessante analisar o caso de Marcelo Rebelo de Sousa enquanto candidato às presidenciais de 2016; um candidato que desde o início da campanha já era dado como favorito e vencedor, muito devido ao facto de ter tido uma presença assídua no quotidiano dos portugueses enquanto comentador político televisivo, o que lhe conferiu um perfil de um candidato atípico na forma como foi representado pelos "media" durante o período de campanha eleitoral.Politics and media are intimate and even more in nowadays society. Mass media are the politics stage, where it occurs and proceeds. It is through them that citizens have access to reality representations, that they get in touch with politics in an almost exclusive way. Being present in the media means existing to citiziens and it is through them that you win voters. Then, it is interesting to analize Marcelo Rebelo de Sousa’s case as a presidential candidate in 2016’s elections; a candidate that since the beggining of the campaign was told to be the favorite and the winner, all because of the fact of being present in the everyday life of the portuguese people as a political pundit, which has given him an atypical profile in the way he was represented by the media during the electoral campaign

Um guia para início de percurso nas ciências da comunicação: breve nota sobre uma obra sempre em construção

[Excerto] “Rotas Para a Investigação em Comunicação” é o mote para pensar o percurso individual de quem investiga e para construir um caminho coletivo nas ciências da comunicação. Este caminho é também delineado por quem inicia o seu percurso académico. É a esse público que se destina esta publicação, construída tendo, sobretudo, como base intervenções daqueles que já têm um reconhecido percurso académico neste domínio. Esta compilação de breves textos pretende ser um guia orientador para o início do percurso académico em ciências da comunicação. Não é um livro de dicas, apesar de conter algumas. É, sobretudo, uma obra que pretende dar a conhecer o ecossistema científico, o seu funcionamento, os seus desafios e as suas oportunidades, bem como o espaço existente para que cada pessoa individual e coletivamente possa criar a sua própria rota

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.publishersversionpublishe

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 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.publishersversionpublishe

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.publishersversionpublishe

a detailed view of the methodology

Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal.publishersversionpublishe

Comparative effectiveness and predictors of response to tumour necrosis factor inhibitor therapies in rheumatoid arthritis

Funding Information: positions on two Pfizer sponsored trials and has directed an educational course supported by Bristol Myers Squibb. He serves as an epidemiology consultant to CORRONA. J.A.P.S. has received honoraria as a speaker or consultant and benefited from research support from several pharmaceutical companies involved in the production of biologic agents (Abbott, Amgen, MSD, Pfizer and Roche), always at sums less than E10 000. All other authors have declared no conflicts of interest. Funding Information: Funding: This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/ 2010.Objectives: Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort.Methods: Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.Results: The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.Conclusion: Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.publishersversionpublishe