Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Elaboration of the side-chain of amino acid derivatives by palladium catalysed couplings

The palladium-catalysed couplings of aryl halides and triflates with propargyl amino amides and the couplings of aryl and vinyl halides and triflates with an ethynyl oxazolidine are reported.Geoffrey T. Crisp, Yu-Lin Jiang, Peter J. Pullman, Chris De Sav

Syntheses of the D-aldopentoses from non-carbohydrate sources

The cis-1,2-dihydrocatechols 5-7, which are obtained in high yield and ca. 99.8% ee by microbial oxidation of the corresponding aromatic compound, have been converted, via reaction sequences involving three distinct types of one-carbon deletion processes, into the four D-aldopentoses

Programmable multi-granular optical networks: requirements and architecture

This paper presents a programmable multi-granular optical cross connect (MG-OXC) and network architecture deployable in multi-service and multi-provider networks. The concept of programmable MG-OXC is introduced to provide a way of utilizing multiple switching/transport granularities to efficiently support the emerging traffic demands in both core and metro networks. For this reason, the supported bandwidth granularities include full lambdas, sub- and super-lambdas and multiple transport formats such as bursts, flows and packets. The programmability is envisaged by a software/hardware platform that simplifies network control, re-planning at the logical level and end-to-end service transparency, by translating the technology-specific information to technology independent services in an abstracted and logical manner

Efficacious Inhaled PDE4 Inhibitors with Low Emetic Potential and Long Duration of Action for the Treatment of COPD

Oral phosphodiesterase 4 (PDE4) inhibitors, such as cilomilast and roflumilast, have been shown to be efficacious against chronic obstructive pulmonary disease (COPD). However, these drugs have been hampered by mechanism-related side effects such as nausea and emesis at high doses. Compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index required to overcome side effects. This paper describes systematic and rational lead optimization to deliver highly potent, long-acting, and efficacious preclinical inhaled PDE4 inhibitors with low emetic potential

Optimization of a Novel Binding Motif to (<i>E</i>)‑3-(3,5-Difluoro-4-((1<i>R</i>,3<i>R</i>)‑2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro‑1<i>H</i>‑pyrido[3,4‑<i>b</i>]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist

The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahydro-1<i>H</i>-pyrido­[3,4-<i>b</i>]­indole motif as a novel, druglike ER ligand. Aided by crystal structures of novel ligands bound to an ER construct, medicinal chemistry iterations led to (<i>E</i>)-3-(3,5-difluoro-4-((1<i>R</i>,3<i>R</i>)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1<i>H</i>-pyrido­[3,4-<i>b</i>]­indol-1-yl)­phenyl)­acrylic acid (<b>30b</b>, AZD9496), a clinical candidate with high oral bioavailability across preclinical species that is currently being evaluated in phase I clinical trials for the treatment of advanced estrogen receptor (ER) positive breast cancer