Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. 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/)

From Spatial Concepts to Time in the History of English: Continuity and Remoteness in Time Metonymy and Metaphor

The study highlights the transition of the temporal adverbs always/algates, expressing continuity in time, and ago, expressing remoteness in time, from their historical prototypical concept of space to that of time and beyond. In these processes both metonymy and metaphor play an important role. The data regarding always and algates suggest a gradual cline from SPACE to TIME and an array of other meanings, subsumed under the cover-term UNCONSTRAINEDNESS. The SPACE-TIME-X chain (with X standing for other more abstract meanings) seems to occur in most languages. The semantic development of these adverbs also features all the properties associated with a change like this: metonymy followed by ever increasing or proliferating metaphorization, fuzzy or non-discrete categories (mostly in the stages of transition). Ago owes its origin to the grammaticalization of the past participle of a verb of movement. This spatial concept is metaphorically mapped on to a new temporal prototype. As compared with always/algates, the temporal frame of ago is monosemous and marked throughout by metaphorization from ‘remoteness in space’ to ‘remoteness in time’