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      Machine learning for the prediction of sepsis: a systematic review and meta-analysis of diagnostic test accuracy

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          Abstract

          Purpose

          Early clinical recognition of sepsis can be challenging. With the advancement of machine learning, promising real-time models to predict sepsis have emerged. We assessed their performance by carrying out a systematic review and meta-analysis.

          Methods

          A systematic search was performed in PubMed, Embase.com and Scopus. Studies targeting sepsis, severe sepsis or septic shock in any hospital setting were eligible for inclusion. The index test was any supervised machine learning model for real-time prediction of these conditions. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, with a tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist to evaluate risk of bias. Models with a reported area under the curve of the receiver operating characteristic (AUROC) metric were meta-analyzed to identify strongest contributors to model performance.

          Results

          After screening, a total of 28 papers were eligible for synthesis, from which 130 models were extracted. The majority of papers were developed in the intensive care unit (ICU, n = 15; 54%), followed by hospital wards ( n = 7; 25%), the emergency department (ED, n = 4; 14%) and all of these settings ( n = 2; 7%). For the prediction of sepsis, diagnostic test accuracy assessed by the AUROC ranged from 0.68–0.99 in the ICU, to 0.96–0.98 in-hospital and 0.87 to 0.97 in the ED. Varying sepsis definitions limit pooling of the performance across studies. Only three papers clinically implemented models with mixed results. In the multivariate analysis, temperature, lab values, and model type contributed most to model performance.

          Conclusion

          This systematic review and meta-analysis show that on retrospective data, individual machine learning models can accurately predict sepsis onset ahead of time. Although they present alternatives to traditional scoring systems, between-study heterogeneity limits the assessment of pooled results. Systematic reporting and clinical implementation studies are needed to bridge the gap between bytes and bedside.

          Electronic supplementary material

          The online version of this article (10.1007/s00134-019-05872-y) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

          Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
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            A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: a systematic review and meta-analysis

            Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging.
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              A targeted real-time early warning score (TREWScore) for septic shock

              Sepsis is a leading cause of death in the United States, with mortality highest among patients who develop septic shock. Early aggressive treatment decreases morbidity and mortality. Although automated screening tools can detect patients currently experiencing severe sepsis and septic shock, none predict those at greatest risk of developing shock. We analyzed routinely available physiological and laboratory data from intensive care unit patients and developed "TREWScore," a targeted real-time early warning score that predicts which patients will develop septic shock. TREWScore identified patients before the onset of septic shock with an area under the ROC (receiver operating characteristic) curve (AUC) of 0.83 [95% confidence interval (CI), 0.81 to 0.85]. At a specificity of 0.67, TREWScore achieved a sensitivity of 0.85 and identified patients a median of 28.2 [interquartile range (IQR), 10.6 to 94.2] hours before onset. Of those identified, two-thirds were identified before any sepsis-related organ dysfunction. In comparison, the Modified Early Warning Score, which has been used clinically for septic shock prediction, achieved a lower AUC of 0.73 (95% CI, 0.71 to 0.76). A routine screening protocol based on the presence of two of the systemic inflammatory response syndrome criteria, suspicion of infection, and either hypotension or hyperlactatemia achieved a lower sensitivity of 0.74 at a comparable specificity of 0.64. Continuous sampling of data from the electronic health records and calculation of TREWScore may allow clinicians to identify patients at risk for septic shock and provide earlier interventions that would prevent or mitigate the associated morbidity and mortality.
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                Author and article information

                Contributors
                l.fleuren@amsterdamumc.nl
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                21 January 2020
                21 January 2020
                2020
                : 46
                : 3
                : 383-400
                Affiliations
                [1 ]Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Sciences (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, location VUmc, VU Amsterdam, Amsterdam, The Netherlands
                [2 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Computational Intelligence Group, Department of Computer Science, , VU Amsterdam, ; Amsterdam, The Netherlands
                [3 ]Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUmc, VU Amsterdam, Amsterdam, The Netherlands
                [4 ]Medical Library, Amsterdam UMC, location VUmc, VU Amsterdam, Amsterdam, The Netherlands
                [5 ]Department of Pharmacy, Amsterdam UMC, location VUmc, VU Amsterdam, Amsterdam, The Netherlands
                [6 ]GRID grid.5335.0, ISNI 0000000121885934, Division of Anaesthesia, , University of Cambridge, ; Cambridge, UK
                [7 ]GRID grid.489664.1, ISNI 0000 0001 1034 0437, Data Science Section, , European Society of Intensive Care Medicine, ; Brussels, Belgium
                Author information
                http://orcid.org/0000-0002-4056-1692
                Article
                5872
                10.1007/s00134-019-05872-y
                7067741
                31965266
                c4fc7b81-6a3d-4b9a-a442-b58f5e65b685
                © The Author(s) 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 14 August 2019
                : 16 November 2019
                Categories
                Systematic Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Emergency medicine & Trauma
                machine learning,sepsis,septic shock,prediction,systematic review,meta-analysis

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