Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS

Phylogenomic evidence for a common ancestor of mitochondria and the SAR11 clade

Mitochondria share a common ancestor with the Alphaproteobacteria, but determining their precise origins is challenging due to inherent difficulties in phylogenetically reconstructing ancient evolutionary events. Nonetheless, phylogenetic accuracy improves with more refined tools and expanded taxon sampling. We investigated mitochondrial origins with the benefit of new, deeply branching genome sequences from the ancient and prolific SAR11 clade of Alphaproteobacteria and publicly available alphaproteobacterial and mitochondrial genome sequences. Using the automated phylogenomic pipeline Hal, we systematically studied the effect of taxon sampling and missing data to accommodate small mitochondrial genomes. The evidence supports a common origin of mitochondria and SAR11 as a sister group to the Rickettsiales. The simplest explanation of these data is that mitochondria evolved from a planktonic marine alphaproteobacterial lineage that participated in multiple inter-specific cell colonization events, in some cases yielding parasitic relationships, but in at least one case producing a symbiosis that characterizes modern eukaryotic life

ERS Statement: A core outcome set for clinical trials evaluating the management of chronic obstructive pulmonary disease (COPD) exacerbations

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritized for inclusion in the core outcome set through a two-round Delphi survey that was completed by 1,063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in 5 continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to (i) finalize the core outcome set and (ii) prioritize a single measurement instrument to be used for evaluating each of the prioritized outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for in all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, need for higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimize some of the selected measurement instruments. The panel did not consider the prioritized set of outcomes and associated measurement instruments burdensome for patients and health professionals to use