The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6

The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.Peer reviewe

Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study

AbstractBackground: Procalcitonin (PCT), an inflammatory blood biomarker, is well studied in infectious diseases. Its prognostic value in unselected emergency department (ED) patients remains yet undefined. Herein, we investigated association of admission PCT levels and mortality in a large, international-multicenter ED patient cohort. Methods: We prospectively enrolled 6970 unselected, consecutive, adult, medical patients seeking ED care in three tertiary-care hospitals in Switzerland, France and the USA. We used multivariable logistic regression models to examine association of admission PCT levels (as a continuous predictor and across cut-offs) and 30-day mortality. We also investigated subgroup effects by main diagnosis, comorbidities and clinical features at presentation. Results: During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%, 13% to 15%, respectively. This association was also confirmed in a fully-adjusted model including age, gender, main symptom, main diagnosis and vital parameters on admission. Receiver operating characteristic (ROC) curve analysis showed that PCT differentiated well between survivors and non-survivors in the overall cohort (area under ROC curve [AUC] 0.75) with best results for patient with metabolic (AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved the prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other secondary endpoints including intensive care unit (ICU) admission and hospital readmission. Conclusions: In this large and heterogenous medical ED patient cohort, admission PCT was a strong and independent outcome predictor for 30-day mortality across different medical diagnoses independent of underlying infection. PCT may help to improve risk stratification in unselected medical ED patients

HighResMIP versions of EC-Earth : EC-Earth3P and EC-Earth3P-HR - description, model computational performance and basic validation

A new global high-resolution coupled climate model, EC-Earth3P-HR has been developed by the EC-Earth consortium, with a resolution of approximately 40 km for the atmosphere and 0.25∘ for the ocean, alongside with a standard-resolution version of the model, EC-Earth3P (80 km atmosphere, 1.0∘ ocean). The model forcing and simulations follow the High Resolution Model Intercomparison Project (HighResMIP) protocol. According to this protocol, all simulations are made with both high and standard resolutions. The model has been optimized with respect to scalability, performance, data storage and post-processing. In accordance with the HighResMIP protocol, no specific tuning for the high-resolution version has been applied. Increasing horizontal resolution does not result in a general reduction of biases and overall improvement of the variability, and deteriorating impacts can be detected for specific regions and phenomena such as some Euro-Atlantic weather regimes, whereas others such as the El Niño–Southern Oscillation show a clear improvement in their spatial structure. The omission of specific tuning might be responsible for this. The shortness of the spin-up, as prescribed by the HighResMIP protocol, prevented the model from reaching equilibrium. The trend in the control and historical simulations, however, appeared to be similar, resulting in a warming trend, obtained by subtracting the control from the historical simulation, close to the observational one.The EC-Earth simulations from SMHI were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC). The EC-EARTH simulations from BSC were performed on resources provided by ECMWF and the Partnership for Advanced Computing in Europe (PRACE; MareNostrum, Spain). Froila M. Palmeiro and Javier García-Serrano were partially supported by the Spanish GRAVITOCAST project (ERC2018-092835) and the “Ramón y Cajal” program (RYC-2016-21181), respectively, and MR was supported by “Beca de collaboració amb la Universitat de Barcelona” (2019.4.FFIS.1). The EC-Earth simulations from CNR were performed on resources provided by CINECA and ECMWF (special projects SPITDAVI and SPITMAVI). The EC-Earth simulations from KNMI were partly performed on resources provided by ECMWF (special project SPNLHAAR).Peer ReviewedPostprint (published version

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections

BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES: The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. MAIN RESULTS: From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. AUTHORS' CONCLUSIONS: This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.

BACKGROUND: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. METHODS: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. FINDINGS: We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0\ub783 [95% CI 0\ub770 to 0\ub799], p=0\ub7037). This mortality benefit was similar across subgroups by setting and type of infection (pinteractions&gt;0\ub705), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2\ub74-day reduction in antibiotic exposure (5\ub77 vs 8\ub71 days [95% CI -2\ub771 to -2\ub715], p&lt;0\ub70001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0\ub768 [95% CI 0\ub757 to 0\ub782], p&lt;0\ub70001). INTERPRETATION: Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance