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

Conservation Biogeography of the Sahara‐Sahel: additional protected areas are needed to secure unique biodiversity

Aim Identification of priority conservation areas and evaluation of coverage of the current protected areas are urgently needed to halt the biodiversity loss. Identifying regions combining similar environmental traits (climate regions) and species assemblages (biogroups) is needed for conserving the biodiversity patterns and processes. We identify climate regions and biogroups and map species diversity across the Sahara-Sahel, a large geographical area that exhibits wide environmental heterogeneity and multiple species groups with distinct biogeographical affinities, and evaluate the coverage level of current network of protected areas for biodiversity conservation. Location Sahara-Sahel, Africa. Methods We use spatially explicit climate data with the principal component analysis and model-based clustering techniques to identify climate regions. We use distributions of 1147 terrestrial vertebrates (and of 125 Sahara-Sahel endemics) and apply distance clustering methods to identify biogroups for both species groups. We apply reserve selection algorithms targeting 17% of species distribution, climate regions and biogroups to identify priority areas and gap analysis to assess their representation within the current protected areas. Results Seven climate regions were identified, mostly arranged as latitudinal belts. Concentrations of high species richness were found in the Sahel, but the central Sahara gathers most endemic and threatened species. Ten biogroups (five for endemics) were identified. A wide range of biogroups tend to overlap in specific climate regions. Identified priority areas are inadequately represented in protected areas, and six new top conservation areas are needed to achieve conservation targets. Main conclusions Biodiversity distribution in Sahara-Sahel is spatially structured and apparently related to environmental variation. Although the majority of priority conservation areas are located outside the areas of intense human activities, many cross multiple political borders and require internationally coordinated efforts for implementation and management. Optimized biodiversity conservation solutions at regional scale are needed. Our work contradicts the general idea that deserts are uniform areas and provide options for the conservation of endangered species.info:eu-repo/semantics/publishedVersio

TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/2010. Daniel H. Solomon received support for this work from the NIH (K24-AR-055989). Elizabeth W. Karlson received support for this work from NIH (K24-AR-AR0524). Reuma.pt received unrestricted grants from Abbott, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, and UCB Pharma

Labeling of Multiple HIV-1 Proteins with the Biarsenical-Tetracysteine System

Due to its small size and versatility, the biarsenical-tetracysteine system is an attractive way to label viral proteins for live cell imaging. This study describes the genetic labeling of the human immunodeficiency virus type 1 (HIV-1) structural proteins (matrix, capsid and nucleocapsid), enzymes (protease, reverse transcriptase, RNAse H and integrase) and envelope glycoprotein 120 with a tetracysteine tag in the context of a full-length virus. We measure the impact of these modifications on the natural virus infection and, most importantly, present the first infectious HIV-1 construct containing a fluorescently-labeled nucleocapsid protein. Furthermore, due to the high background levels normally associated with the labeling of tetracysteine-tagged proteins we have also optimized a metabolic labeling system that produces infectious virus containing the natural envelope glycoproteins and specifically labeled tetracysteine-tagged proteins that can easily be detected after virus infection of T-lymphocytes. This approach can be adapted to other viral systems for the visualization of the interplay between virus and host cell during infection

Resiliência em Crianças Institucionalizadas

Risco, proteção e, sobretudo, resiliência que segundo Anaut (2005) consiste fundamentalmente no desenvolvimento normal de uma criança perante circunstâncias dificeis e adversas, são temas presentes na pesquisa do trabalho que nos propusemos dedicar ao crescimento das crianças confindas numa instituição. O conceito de fator de risco já está delimitado, mas o fator de proteção ainda se misturam. Os fatores de risco referem-se aos fatores ambientais que aumentam a probabilidade de ocorrer algum efeito indesejável no desenvolvimento da criança ou jovem. Por outro lado os fatores de proteção estão associados às características da criança, diminuindo o efeito de risco. A resiliência está relacionada com fatores protetores individuais que trazem consequências positivas na criança exposta a fatores que tornam a criança menos vulnerável. Verifica-se que há crianças que perante uma adversidade, conseguem superar ou atenuar os fatores de risco. Com o objetivo de analisar as estratégias de resiliência em crianças institucionalizadas, realizamos um estudo quantitativo-descritivo, percebendo como a criança perante fatores de risco, isto é, os maus-tratos que sofreram antes da sua institucionalização, ultrapassam esses momentos marcantes. O estudo foi feito num grupo de 92 crianças institucionalizadas, pertencente ao distrito da Guarda com idades compreendidas entre os 10 e 18 anos, resultando que 71 crianças desse grupo estudado revelaram um nível elevado de resiliência, enquanto 21 desse mesmo grupo apresentavam um nível médio. Foram utilizadas como hipóteses de investigação a relação entre as variáveis sociodemográficas o género, idade, e escolaridade e as variáveis quanto aos sentimentos iniciais e atuais face à institucionalização. Concluiu-se que só o género influencia as estratégias de resiliência na criança institucionalizada

O manual escolar como facilitador da construção do conhecimento científico: o caso do tema "Reacções de oxidação-redução" do 9º ano de escolaridade

Instituto de Inovação Educacional (IIE)