Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO\u2082, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV\u2081) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 \u3bcg\ub7m(-3) increase in NO\u2082 exposure was associated with lower levels of FEV\u2081 (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 \u3bcg\ub7m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV\u2081 (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Competencies in radiation oncology: a new approach for education and training of professionals for Radiotherapy and Oncology in Europe

Progress in radiation oncology has been significant during the last decade and will continue to undergo even more dynamic development in the decade to come [1], [2], [3] and [4]. Cancer is recognized as one of the major diseases with increasing frequency and relevance not only in the western world but also from the global perspective [5]. One major reason is the aging population, which provides great challenges with respect to management and maintaining the quality of life. In this respect radiation oncology, as a minimally invasive procedure, will provide a real opportunity to achieve this

EULAR recommendations for the management of Beh\ue7et disease

To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Beh\ue7et disease (BD) supplemented where necessary by expert opinion

Management of Beh\ue7et disease: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for the management of Beh\ue7et disease

To present and analyse the literature sources regarding the management of Beh\ue7et disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD

Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G 7 E), however, so far, thorough replication of findings is rare and G 7 E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G 7 E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G 7 E in schizophrenia. While such investigations are now well underway, new challenges emerge for G 7 E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. \ua9 2014 The Author

Recommendations on the use of magnetic resonance imaging for collaborative multicenter studies in PSC

Recently, the MRI working group of the International PSC Study Group (IPSCSG) has published a position statement on the use of MRI regarding diagnosis and follow-up of PSC patients. These guidelines are intended for use by physicians in daily clinical routine. In addition, the group has outlined several areas of research, which need to be addressed in the near future. As PSC is a rare disease with the clinical outcome being determined by the development of end-stage liver disease and hepatobiliary malignancy. This article is protected by copyright. All rights reserved

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes

none44noneKnobler, R.*; Moinzadeh, P.; Hunzelmann, N.; Kreuter, A.; Cozzio, A.; Mouthon, L.; Cutolo, M.; Rongioletti, F.; Denton, C.P.; Rudnicka, L.; Frasin, L.A.; Smith, V.; Gabrielli, A.; Aberer, E.; Bagot, M.; Bali, G.; Bouaziz, J.; Braae Olesen, A.; Foeldvari, I.; Frances, C.; Jalili, A.; Just, U.; Kähäri, V.; Kárpáti, S.; Kofoed, K.; Krasowska, D.; Olszewska, M.; Orteu, C.; Panelius, J.; Parodi, A.; Petit, A.; Quaglino, P.; Ranki, A.; Sanchez Schmidt, J.M.; Seneschal, J.; Skrok, A.; Sticherling, M.; Sunderkötter, C.; Taieb, A.; Tanew, A.; Wolf, P.; Worm, M.; Wutte, N.J.; Krieg, T.Knobler, R.; Moinzadeh, P.; Hunzelmann, N.; Kreuter, A.; Cozzio, A.; Mouthon, L.; Cutolo, M.; Rongioletti, F.; Denton, C. P.; Rudnicka, L.; Frasin, L. A.; Smith, V.; Gabrielli, A.; Aberer, E.; Bagot, M.; Bali, G.; Bouaziz, J.; Braae Olesen, A.; Foeldvari, I.; Frances, C.; Jalili, A.; Just, U.; Kähäri, V.; Kárpáti, S.; Kofoed, K.; Krasowska, D.; Olszewska, M.; Orteu, C.; Panelius, J.; Parodi, A.; Petit, A.; Quaglino, P.; Ranki, A.; Sanchez Schmidt, J. M.; Seneschal, J.; Skrok, A.; Sticherling, M.; Sunderkötter, C.; Taieb, A.; Tanew, A.; Wolf, P.; Worm, M.; Wutte, N. J.; Krieg, T

Characteristics of joint involvement and relationship with systemic inflammation in systemic sclerosis: result from the EULAR scleroderma trial and research (EUSTAR) database.

To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation