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      Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation

      research-article
      1 , 2 , 2 , 3 , 4 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 3 , 2 , 17 , , 1
      BMC Medical Informatics and Decision Making
      BioMed Central
      Critical care medicine, Machine learning, ICU, Risk stratification, Mechanical ventilation

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          Abstract

          Background

          Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid–base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters.

          Methods

          We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders.

          Results

          Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders.

          Conclusion

          The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes.

          Trial registration: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898), prospectively registered on April 8, 2016.

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          Most cited references30

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          Long Short-Term Memory

          Learning to store information over extended time intervals by recurrent backpropagation takes a very long time, mostly because of insufficient, decaying error backflow. We briefly review Hochreiter's (1991) analysis of this problem, then address it by introducing a novel, efficient, gradient-based method called long short-term memory (LSTM). Truncating the gradient where this does not do harm, LSTM can learn to bridge minimal time lags in excess of 1000 discrete-time steps by enforcing constant error flow through constant error carousels within special units. Multiplicative gate units learn to open and close access to the constant error flow. LSTM is local in space and time; its computational complexity per time step and weight is O(1). Our experiments with artificial data involve local, distributed, real-valued, and noisy pattern representations. In comparisons with real-time recurrent learning, back propagation through time, recurrent cascade correlation, Elman nets, and neural sequence chunking, LSTM leads to many more successful runs, and learns much faster. LSTM also solves complex, artificial long-time-lag tasks that have never been solved by previous recurrent network algorithms.
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            The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

            Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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              The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation

              Background To evaluate binary classifications and their confusion matrices, scientific researchers can employ several statistical rates, accordingly to the goal of the experiment they are investigating. Despite being a crucial issue in machine learning, no widespread consensus has been reached on a unified elective chosen measure yet. Accuracy and F1 score computed on confusion matrices have been (and still are) among the most popular adopted metrics in binary classification tasks. However, these statistical measures can dangerously show overoptimistic inflated results, especially on imbalanced datasets. Results The Matthews correlation coefficient (MCC), instead, is a more reliable statistical rate which produces a high score only if the prediction obtained good results in all of the four confusion matrix categories (true positives, false negatives, true negatives, and false positives), proportionally both to the size of positive elements and the size of negative elements in the dataset. Conclusions In this article, we show how MCC produces a more informative and truthful score in evaluating binary classifications than accuracy and F1 score, by first explaining the mathematical properties, and then the asset of MCC in six synthetic use cases and in a real genomics scenario. We believe that the Matthews correlation coefficient should be preferred to accuracy and F1 score in evaluating binary classification tasks by all scientific communities.
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                Author and article information

                Contributors
                bmandipoor@fbk.eu
                ffrutos@ucigetafe.com
                openuelas@gmail.com
                r.rezar@salk.at
                Raymondos.Konstantinos@mh-hannover.de
                alfonso.muriel@hrc.es
                dubin98@gmail.com
                aw.thille@gmail.com
                fernandrios@gmail.com
                marcogonzalez3110@gmail.com
                Lorenzo.delSorbo@uhn.ca
                marincita75@hotmail.com
                bvallepinheiro@gmail.com
                marcosoaresreis@gmail.com
                niconin@hotmail.com
                salvatore.maggiore@unich.it
                andrew.bersten@flinders.edu.au
                malte.kelm@med.uni-duesseldorf.de
                pamin@vsnl.com
                cakarn@yahoo.com
                smccritcare@gmail.com
                f.abroug@rns.tn
                mjibaja79@gmail.com
                dmatamis@gmail.com
                aazeggwagh@invivo.edu
                sutherasan_yuda@yahoo.com
                anzueto@uthscsa.edu
                bernhard@wernly.at
                aesteban@ucigetafe.com
                christian.jung@med.uni-duesseldorf.de
                vosmani@fbk.eu
                Journal
                BMC Med Inform Decis Mak
                BMC Med Inform Decis Mak
                BMC Medical Informatics and Decision Making
                BioMed Central (London )
                1472-6947
                7 May 2021
                7 May 2021
                2021
                : 21
                : 152
                Affiliations
                [1 ]GRID grid.11469.3b, ISNI 0000 0000 9780 0901, Fondazione Bruno Kessler Research Institute, ; Trento, Italy
                [2 ]GRID grid.411244.6, ISNI 0000 0000 9691 6072, Hospital Universitario de Getafe & Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), ; Madrid, Spain
                [3 ]GRID grid.21604.31, ISNI 0000 0004 0523 5263, Clinic of Internal Medicine II, Department of Cardiology, , Paracelsus Medical University of Salzburg, ; 5020 Salzburg, Austria
                [4 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Medizinische Hochschule Hannover, ; Hannover, Germany
                [5 ]GRID grid.420232.5, ISNI 0000 0004 7643 3507, Unidad de Bioestadística Clinica Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS) & Centro de Investigación en Red de Epidemiología y Salud Pública (CIBERESP), ; Madrid, Spain
                [6 ]GRID grid.413106.1, ISNI 0000 0000 9889 6335, Peking Union Medical College Hospital, ; Beijing, People’s Republic of China
                [7 ]GRID grid.411162.1, ISNI 0000 0000 9336 4276, University Hospital of Poitiers, ; Poitiers, France
                [8 ]Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina
                [9 ]GRID grid.412249.8, ISNI 0000 0004 0487 2295, Clínica Medellín & Universidad Pontificia Bolivariana, ; Medellín, Colombia
                [10 ]Interdepartmental Division of Critical Care Medicine, Toronto, ON Canada
                [11 ]GRID grid.420239.e, ISNI 0000 0001 2113 9210, Hospital Regional 1° de Octubre, Instituto de Seguridad Y Servicios Sociales de Los Trabajadores del Estado (ISSSTE), ; México, DF México
                [12 ]GRID grid.411198.4, ISNI 0000 0001 2170 9332, Pulmonary Research Laboratory, , Federal University of Juiz de Fora, ; Juiz de Fora, Brazil
                [13 ]Hospital Universitario Sao Jose, Belo Horizonte, Brazil
                [14 ]Hospital Español, Montevideo, Uruguay
                [15 ]GRID grid.412451.7, ISNI 0000 0001 2181 4941, Università Degli Studi G. d’Annunzio Chieti e Pescara, ; Chieti, Italy
                [16 ]GRID grid.1014.4, ISNI 0000 0004 0367 2697, Department of Critical Care Medicine, , Flinders University, ; Adelaide, South Australia Australia
                [17 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, , University of Düsseldorf, ; Moorenstraße 5, 40225 Düsseldorf, Germany
                [18 ]GRID grid.414537.0, ISNI 0000 0004 1766 7856, Bombay Hospital Institute of Medical Sciences, ; Mumbai, India
                [19 ]GRID grid.9601.e, ISNI 0000 0001 2166 6619, Istanbul Faculty of Medicine, ; Istanbul, Turkey
                [20 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Department of Critical Care Medicine, Samsung Medical Center, , Sungkyunkwan University School of Medicine, ; Seoul, South Korea
                [21 ]Hospital Fattouma Bourguina, Monastir, Tunisia
                [22 ]Hospital de Especialidades Eugenio Espejo, Quito, Ecuador
                [23 ]GRID grid.417144.3, Papageorgiou Hospital, ; Thessaloniki, Greece
                [24 ]GRID grid.31143.34, ISNI 0000 0001 2168 4024, Centre Hospitalier Universitarie Ibn Sina - Mohammed V University, ; Rabat, Morocco
                [25 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Faculty of Medicine Ramathibodi Hospital, , Mahidol University, ; Bangkok, Thailand
                [26 ]GRID grid.280682.6, ISNI 0000 0004 0420 5695, South Texas Veterans Health Care System and University of Texas Health Science Center, ; San Antonio, TX USA
                Author information
                http://orcid.org/0000-0001-8325-250X
                Article
                1506
                10.1186/s12911-021-01506-w
                8102841
                33962603
                06e9c163-34fb-40df-bf1f-ff245bda148f
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 December 2020
                : 26 April 2021
                Funding
                Funded by: Universitätsklinikum Düsseldorf. Anstalt öffentlichen Rechts (8911)
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Bioinformatics & Computational biology
                critical care medicine,machine learning,icu,risk stratification,mechanical ventilation

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