Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Common garden experiments in the genomic era : new perspectives and opportunities

PdV was supported by a doctoral studentship from the French Ministère de la Recherche et de l’Enseignement Supérieur. OEG was supported by the Marine Alliance for Science and Technology for Scotland (MASTS)The study of local adaptation is rendered difficult by many evolutionary confounding phenomena (e.g. genetic drift and demographic history). When complex traits are involved in local adaptation, phenomena such as phenotypic plasticity further hamper evolutionary biologists to study the complex relationships between phenotype, genotype and environment. In this perspective paper, we suggest that the common garden experiment, specifically designed to deal with phenotypic plasticity has a clear role to play in the study of local adaptation, even (if not specifically) in the genomic era. After a quick review of some high-throughput genotyping protocols relevant in the context of a common garden, we explore how to improve common garden analyses with dense marker panel data and recent statistical methods. We then show how combining approaches from population genomics and genome-wide association studies with the settings of a common garden can yield to a very efficient, thorough and integrative study of local adaptation. Especially, evidence from genomic (e.g. genome scan) and phenotypic origins constitute independent insights into the possibility of local adaptation scenarios, and genome-wide association studies in the context of a common garden experiment allow to decipher the genetic bases of adaptive traits.PostprintPeer reviewe

Correlaciones bioestratigráficas en el Toarciense de la Península Ibérica.

[ES] La comparación entre las escalas bioestratigráficas del Toarciense de las Cordilleras Ibérica y Béticas y de Portugal ha permitido el establecimiento de varias correlaciones, a pesar de un cierto número de problemas (asociaciones fánicas de afinidades distintas, diferencia de criterios en la definición de las unidades cronológicas, ausencia local de ciertos indicadores paleontológicos, diversidad de las concepciones taxonómicas de los autores)[FR] La comparaison entre les échelles biostratigraphiques du Toarcien des Cordilléres lbérique et Bétiques et du Portugal a permit to l’établissement de plusieurs correlations. Malgré un certain nombre de problémes (associations fauniques d´affinitié. defferences de critères dans la définítion des unités cronologiques, absence locale de certaíns repères palèontologiques deversité des conceptions taxomiomiques des auteurs.[EN] Comparisons among biostratigraphic of the lberian Range. Betic Range and Portugal pcrmit to stablis correlations. Nevertheless some dificulties were present: faunics associations of different affinities. different criteria in the definition of the cronologic units local absence of some paleontological indicators and the contrasted opinions of the a uthíors about the taxomiomic concepts.Peer reviewe

Predictors of radiographic progression in the ESPOIR cohort: the season of first symptoms may influence the short-term outcome in early arthritis.

International audienceOBJECTIVES: To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis. METHODS: Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves. RESULTS: From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers. CONCLUSION: The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis