Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George’s Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations

Ostracods from a Marmara Sea lagoon (Turkey) as tsunami indicators

This is the post print version of the article. The official published version can be obtained from the link below - Copyright @ Elsevier Ltd.A 352 cm long sediment core from Hersek Lagoon (Gulf of İzmit) was investigated for its ostracod species composition in order to evaluate the potential of ostracods to detect tsunami deposits in coastal environments. The Gulf of İzmit is the eastern bay of the Marmara Sea which is tectonically controlled by the North Anatolian Fault. Ostracod shells are rare in the lower third of the core, which probably represents a coastal wetland environment. According to radiocarbon dating of terrestrial plant remains, this unit was deposited between AD 500 and AD 800. Above, ostracod shells are abundant and dominantly monospecific, composed almost exclusively of the widespread brackish water ostracod Cyprideis torosa. This almost monospecific occurrence indicates the establishment and maintenance of the Hersek Lagoon after AD 800. Three distinct layers of mollusc shells and fragments contain ostracod shells of marine and to a lesser extent non-marine origin in addition to those of C. torosa. The shell layers are further characterized by significant maxima in total ostracod shell numbers. The high concentration of ostracod shells, the higher species numbers and the mixture of marine, lagoonal and non-marine ostracod shells shows that shell layers were formed as high-energy deposits resulting from tsunamis or large storms in the Marmara Sea. The partial occurrence of non-marine ostracod shells in the shell layers possibly indicates that tsunamis with extensive run-ups and significant backwash flows caused the high-energy deposits rather than large storms. The investigated sediments show that lagoonal ostracods can serve as good proxies for tsunamis or large storms through significant variations in total shell numbers, species numbers and the mixing of shells of different origin.Funding was provided by the European Union in the framework of the REL.I.E.F. (RELiable Information on Earthquake Faulting) project (EVG1-CT-2002-00069)

Methionine and Related Compounds and Selenium Poisoning

The problem of selenium poisoning has been known for many years, but the mechanism by which this element exerts its toxicity has not been clarified. As a result, what control measures are now available are of an empirical nature, and they fail to the give the most desirable protection. In search of a better control mechanism, the role of compounds containing biologically active methyl groups has been studied. Some experimental work indicated that these types of compounds might indeed be involved in the metabolism of selenium. However, not all workers’ data were in agreement, and it was felt that further studies were needed

Croí: Un proceso para una enseñanza fundamental y responsable del diseño de la comunicación gráfica

Research has shown that addressing personal values and conviction is crucial for long-lasting Education for Sustainable Development. However, there is a shortage of theory and evidence-based value-focused processes in Graphic Communication Design Education literature. This article presents a novel personal value thinking and doing process called Croí (pronounced Cree) that can be used as a precursor to Education for Sustainable Development in Graphic Communication Design Education. Croí aims to stimulate sustainable transitions by disrupting behaviour development. Over five years, five rounds of Action Research were conducted with third-level educators and students to explore how Croí could facilitate value (or core) design, with the broad aim to encourage sustainable Graphic Communication Design. The initial Croí prototype developed over Cycles One and Two is briefly summarised, with focus on Cycles Three, Four, and Five, where Croí was further developed and evaluated. Data collection included researcher field notes, semi-structured interviews, and written reflections, analysed through Thematic Analysis. Key discussion points include fundamental process elements, Croí\u27s impact on core thinking and doing and responsible thinking and doing, and its potential to facilitate behaviour development. The research concludes that Croí promotes core and responsible thinking and core doing, increasing the likelihood of responsible doing. It offers educators an innovative way to facilitate plural, practical, and core development for graphic communication design students, potentially influencing change in the profession. Croí is not a panacea for the complex issue of Sustainable Development, but it provides a novel and meaningful foundation for disrupting behaviour. La investigación ha demostrado que abordar los valores y las convicciones personales es crucial hacia una educación duradera para el Desarrollo Sostenible. Sin embargo, en la literatura acerca de la educación para el diseño de la comunicación gráfica hay escasez de teoría y procesos centrados en los valores. Este artículo presenta un novedoso proceso de pensamiento y acción sobre valores personales denominado Croí (pronunciado Cree) que puede utilizarse como precursor de la educación para el desarrollo sostenible en la enseñanza del diseño de la comunicación gráfica. Croí pretende estimular las transiciones sostenibles alterando el desarrollo del comportamiento. A lo largo de cinco años, se llevaron a cabo cinco rondas de investigación-acción con educadores y estudiantes de tercer ciclo para explorar cómo Croí podía facilitar el diseño de valor (o fundamental). El objetivo general fue fomentar el diseño sostenible de la comunicación gráfica. Se resume brevemente el prototipo inicial de Croí desarrollado en los ciclos uno y dos, haciendo hincapié en los ciclos tres, cuatro y cinco, en los que se siguió desarrollando y evaluando Croí. La recolección de datos incluyó notas de campo del investigador, entrevistas semiestructuradas y reflexiones escritas, analizadas mediante análisis temático. Los puntos clave del debate incluyen los elementos fundamentales del proceso, el impacto de Croí en el pensamiento y la acción fundamentales y en el pensamiento y la acción responsables, y su potencial para facilitar el desarrollo del comportamiento. La investigación concluye que Croí fomenta el pensamiento y la práctica fundamentales y responsables, aumentando la probabilidad de una práctica responsable. Ofrece a los educadores una forma innovadora de facilitar el desarrollo plural, práctico y fundamental de los estudiantes de diseño de comunicación gráfica, lo que puede influir en el cambio de la profesión. Croí no es una panacea para el complejo problema del desarrollo sostenible, pero proporciona una base novedosa y significativa para alterar comportamientos.

Naturaleza y objeto jurídico del habeas corpus en el Ecuador

El presente estudio tuvo como fin analizar la naturaleza y objeto del Habeas Corpus en la legislación ecuatoriana como instrumento de protección a la libertad personal, justificando su investigación en la privación ilegal de la libertad personal dentro de un Estado constitucional de derechos y de justicia. La metodología aplicada tuvo un enfoque cualitativo, empleando los métodos: inductivo, deductivo, y analítico, los cuales determinaron el verdadero alcance jurisdiccional del Habeas Corpus en el Ecuador. Los resultados obtenidos identificaron que esta acción jurídica es poco utilizada por los abogados que emanan de éste. Finalmente se concluye que existe la necesidad que el ordenamiento jurídico ecuatoriano reconozca los diferentes tipos de Habeas Corpus, desarrollados a la altura de la doctrina y jurisprudencia internacional, con el objeto de que el alcance de protección de esta garantía no solo comprenda el derecho a la libertad personal sino también a los demás derechos conexos

Blood eosinophils: a biomarker of COPD exacerbation reduction with inhaled corticosteroids

Background Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS). We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD. Methods The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone. Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George’s Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0–1,000 eosinophils/μL in FORWARD, 0–993 eosinophils/μL in Dransfield). Results In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts. In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/μL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm. In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/μL, and from 0.56 to 1.75 per year in the LABA-only arm. Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies. ICS/LABA led to greater improvements in St George’s Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with $67 eosinophils/μL. Conclusion Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction. Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations

The Effect of ICS Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study: A Randomized, Double-blind Multicenter Trial

RATIONALE: In the IMPACT trial fluticasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations. OBJECTIVES: Understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results given direct transition from prior maintenance medication to study medication at randomization. METHODS: Exacerbations and change from baseline in trough forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) were analyzed by prior ICS use. Exacerbations were also analyzed excluding data from the first 30 days. MEASUREMENTS AND MAIN RESULTS: FF/UMEC/VI significantly reduced annual moderate/severe exacerbation rate versus UMEC/VI in prior ICS users (29% reduction; p<0.001), but only a numerical reduction was seen among prior ICS non-users (12% reduction; p=0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce annual on-treatment moderate/severe exacerbation rate (19%; p<0.001) versus UMEC/VI. Benefit of FF/UMEC/VI versus UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users: 35% reduction, p<0.001; non-ICS users: 35% reduction, p=0.018) and overall when excluding the first 30 days (29%, p<0.001). Improvements from baseline with FF/UMEC/VI versus UMEC/VI were also maintained throughout the study for both trough FEV1 and SGRQ regardless of prior ICS use. CONCLUSIONS: These data support important treatment effects from FF/UMEC/VI combination therapy on exacerbation reduction, lung function and quality of life that do not appear to be related to abrupt ICS withdrawal. FUNDING: GSK (CTT116855/NCT02164513). Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02164513. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations

Background: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. Methods: 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). Results: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. Conclusions: Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. Trial registration: NCT0216451

Prognostic value of clinically important deterioration in COPD: IMPACT trial analysis

Introduction: Clinically important deterioration (CID) is a multicomponent measure for assessing disease worsening in chronic obstructive pulmonary disease (COPD). This analysis investigated the prognostic value of a CID event on future clinical outcomes and the effect of single-inhaler triple versus dual therapy on reducing CID risk in patients in the IMPACT trial. Methods: IMPACT was a phase III, double-blind, 52-week, multicentre trial. Patients with symptomatic COPD and at least one moderate/severe exacerbation in the prior year were randomised 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg, FF/VI 100/25 µg or UMEC/VI 62.5/25 µg. CID at the time-point of interest was defined as a moderate/severe exacerbation, ≥100 mL decrease in trough forced expiratory volume in 1 s or deterioration in health status (increase of ≥4.0 units in St George's Respiratory Questionnaire total score or increase of ≥2.0 units in COPD Assessment Test score) from baseline. A treatment-independent post hoc prognostic analysis compared clinical outcomes up to week 52 in patients with/without a CID by week 28. A prospective analysis evaluated time to first CID with each treatment. Results: Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52 (all p<0.001), and increased risk of all-cause mortality after week 28 versus patients who were CID-free. FF/UMEC/VI significantly reduced CID risk versus dual therapies (all p<0.001). Conclusions: Prevention of short-term disease worsening was associated with better long-term clinical outcomes. FF/UMEC/VI reduced CID risk versus dual therapies; this effect may improve long-term prognosis in this population