| 1. |
- Maddali, Manoj V., et al.
(författare)
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Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data : an observational, multicohort, retrospective analysis
- 2022
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600. ; 10:4, s. 367-377
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Tidskriftsartikel (refereegranskat)abstract
- Background: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine.
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| 2. |
- Papp, Zoltan, et al.
(författare)
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Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use
- 2020
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Ingår i: Journal of Cardiovascular Pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446 .- 1533-4023. ; 76:1, s. 4-22
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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| 3. |
- Tumanov, Nikolay A., et al.
(författare)
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High-Pressure Study of Mn(BH4)(2) Reveals a Stable Polymorph with High Hydrogen Density
- 2016
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 28:1, s. 274-283
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Tidskriftsartikel (refereegranskat)abstract
- High-pressure behavior of alpha-Mn(BH4)(2) was studied up to 29.4 GPa in diamond anvil cells using powder Xray diffraction combined with DFT calculations and Raman spectroscopy, and two new polymorphs were discovered. The first polymorph, delta-Mn(BH4)(2), forms near 1 GPa and is isostructural to the magnesium analogue delta-Mg(BH4)(2). This polymorph is stable upon decompression to ambient conditions and can also be obtained by compression of alpha-Mn(BH4)(2) in a large-volume steel press as well as by high-energy ball milling. It shows a high volumetric density of hydrogen of 125 g H-2/L at ambient conditions. delta-Mn(BH4)(2) was refined in the space group I4(1)/acd with the cell parameters a = 7.85245(6), c = 12.1456(2) angstrom, and V = 748.91(1) angstrom(3) at ambient conditions; it can also be described in a stable P-4n2 superstructure. Its thermal stability was studied by in situ X-ray powder diffraction and thermal analysis coupled with mass-spectroscopy. delta-Mn(BH4)(2) transforms back to alpha-Mn(BH4)(2) upon heating in the temperature range of 67-109 degrees C in Ar (1 bar) or H-2 (100 bar) atmosphere, and a decomposition is initiated at 130 degrees C with the release of hydrogen and some diborane. Mn(BH4)(2) undergoes a second phase transition to delta'-Mn(BH4)(2) in the pressure range of 8.6-11.8 GPa. delta'-phase is not isostructural to the second high-pressure phase of Mg(BH4)(2), and its structure was determined in the root 2a X c supercell compared to the delta-phase and refined in the space group Fddd with a = 9.205(17), b = 9.321(10), c = 12.638(15) angstrom, and V = 1084(3) angstrom(3) at 11.8 GPa. Equations of state were determined for alpha- and delta-Mn(BH4)(2).
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| 4. |
- Whitaker, David, et al.
(författare)
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The European Board of Anaesthesiology recommendations for safe medication practice : First update
- 2017
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Ingår i: European Journal of Anaesthesiology. - 0265-0215. ; 34:1, s. 4-7
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Tidskriftsartikel (refereegranskat)abstract
- These European Board of Anaesthesiology (EBA) recommendations for safe medication practice replace the first edition of the EBA recommendations published in 2011. They were updated because evidence from critical incident reporting systems continues to show that medication errors remain a major safety issue in anaesthesia, intensive care, emergency medicine and pain medicine, and there is an ongoing need for relevant up-to-date clinical guidance for practising anaesthesiologists. The recommendations are based on evidence wherever possible, with a focus on patient safety, and are primarily aimed at anaesthesiologists practising in Europe, although many will be applicable elsewhere. They emphasise the importance of correct labelling practice and the value of incident reporting so that lessons can be learned, risks reduced and a safety culture developed.
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