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      Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research

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          Abstract

          Background

          Ventilator-associated pneumonia (VAP) is a significant cause of mortality in the intensive care unit. Early diagnosis of VAP is important to provide appropriate treatment and reduce mortality. Developing a noninvasive and highly accurate diagnostic method is important. The invention of electronic sensors has been applied to analyze the volatile organic compounds in breath to detect VAP using a machine learning technique. However, the process of building an algorithm is usually unclear and prevents physicians from applying the artificial intelligence technique in clinical practice. Clear processes of model building and assessing accuracy are warranted. The objective of this study was to develop a breath test for VAP with a standardized protocol for a machine learning technique.

          Methods

          We conducted a case-control study. This study enrolled subjects in an intensive care unit of a hospital in southern Taiwan from February 2017 to June 2019. We recruited patients with VAP as the case group and ventilated patients without pneumonia as the control group. We collected exhaled breath and analyzed the electric resistance changes of 32 sensor arrays of an electronic nose. We split the data into a set for training algorithms and a set for testing. We applied eight machine learning algorithms to build prediction models, improving model performance and providing an estimated diagnostic accuracy.

          Results

          A total of 33 cases and 26 controls were used in the final analysis. Using eight machine learning algorithms, the mean accuracy in the testing set was 0.81 ± 0.04, the sensitivity was 0.79 ± 0.08, the specificity was 0.83 ± 0.00, the positive predictive value was 0.85 ± 0.02, the negative predictive value was 0.77 ± 0.06, and the area under the receiver operator characteristic curves was 0.85 ± 0.04. The mean kappa value in the testing set was 0.62 ± 0.08, which suggested good agreement.

          Conclusions

          There was good accuracy in detecting VAP by sensor array and machine learning techniques. Artificial intelligence has the potential to assist the physician in making a clinical diagnosis. Clear protocols for data processing and the modeling procedure needed to increase generalizability.

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          Most cited references37

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          Nosocomial infections in combined medical-surgical intensive care units in the United States.

          To describe the epidemiology of nosocomial infections in combined medical-surgical (MS) intensive care units (ICUs) participating in the National Nosocomial Infection Surveillance (NNIS) System. Analysis of surveillance data on 498,998 patients with 1,554,070 patient-days, collected between 1992 and 1998 from 205 MS ICUs following the NNIS Intensive Care Unit protocol, representing 152 participating NNIS hospitals in the United States. Infections at three major sites represented 68% of all reported infections (nosocomial pneumonia, 31%; urinary tract infections (UTIs), 23%; and primary bloodstream infections (BSIs), 14%: 83% of episodes of nosocomial pneumonia were associated with mechanical ventilation, 97% of UTIs occurred in catheterized patients, and 87% of primary BSIs in patients with a central line. In patients with primary BSIs, coagulase-negative staphylococci (39%) were the most common pathogens reported; Staphylococcus aureus (12%) was as frequently reported as enterococci (11%). Coagulase-negative staphylococcal BSIs were increasingly reported over the 6 years, but no increase was seen in candidemia or enterococcal bacteremia. In patients with pneumonia, S. aureus (17%) was the most frequently reported isolate. Of reported isolates, 59% were gram-negative bacilli. In patients with UTIs, Escherichia coli (19%) was the most frequently reported isolate. Of reported isolates, 31% were fungi. In patients with surgical-site infections, Enterococcus (17%) was the single most frequently reported pathogen. Device-associated nosocomial infection rates for BSIs, pneumonia, and UTIs did not correlate with length of ICU stay, hospital bed size, number of beds in the ICU, or season. Combined MS ICUs in major teaching hospitals had higher device-associated infection rates compared to all other hospitals with combined medical-surgical units. Nosocomial infections in MS ICUs at the most frequent infection sites (bloodstream, urinary, and respiratory tract) almost always were associated with use of an invasive device. Device-associated infection rates were the best available comparative rates between combined MS ICUs, but the distribution of device-associated rates should be stratified by a hospital's major teaching affiliation status.
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            Human exhaled air analytics: biomarkers of diseases.

            Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed. Copyright 2007 John Wiley & Sons, Ltd.
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              The Role of Balanced Training and Testing Data Sets for Binary Classifiers in Bioinformatics

              Training and testing of conventional machine learning models on binary classification problems depend on the proportions of the two outcomes in the relevant data sets. This may be especially important in practical terms when real-world applications of the classifier are either highly imbalanced or occur in unknown proportions. Intuitively, it may seem sensible to train machine learning models on data similar to the target data in terms of proportions of the two binary outcomes. However, we show that this is not the case using the example of prediction of deleterious and neutral phenotypes of human missense mutations in human genome data, for which the proportion of the binary outcome is unknown. Our results indicate that using balanced training data (50% neutral and 50% deleterious) results in the highest balanced accuracy (the average of True Positive Rate and True Negative Rate), Matthews correlation coefficient, and area under ROC curves, no matter what the proportions of the two phenotypes are in the testing data. Besides balancing the data by undersampling the majority class, other techniques in machine learning include oversampling the minority class, interpolating minority-class data points and various penalties for misclassifying the minority class. However, these techniques are not commonly used in either the missense phenotype prediction problem or in the prediction of disordered residues in proteins, where the imbalance problem is substantial. The appropriate approach depends on the amount of available data and the specific problem at hand.
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                Author and article information

                Contributors
                hyang@ntu.edu.tw
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                7 February 2020
                7 February 2020
                2020
                : 21
                : 45
                Affiliations
                [1 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, , National Taiwan University Hospital Yunlin Branch, ; Douliu, Taiwan
                [2 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Institute of Occupational Medicine and Industrial Hygiene, , National Taiwan University College of Public Health, ; Taipei, Taiwan
                [3 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Institute of Environmental and Occupational Health Sciences, , National Taiwan University College of Public Health, ; Taipei, Taiwan
                [4 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Department of Public Health, , National Taiwan University College of Public Health, ; Taipei, Taiwan
                [5 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Department of Environmental and Occupational Medicine, , National Taiwan University Hospital, ; Taipei, Taiwan
                [6 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, , National Taiwan University, ; Taipei, Taiwan
                Author information
                http://orcid.org/0000-0001-5298-2462
                Article
                1285
                10.1186/s12931-020-1285-6
                7006122
                32033607
                38c8204e-d411-4e8c-abad-77c6c47e319f
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted 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. 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.

                History
                : 1 September 2019
                : 7 January 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: 106-2314-B-002-107, 107-2314-B-002-198, 108-2918-I-002-031, 107‐3017‐F‐002‐003
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100010002, Ministry of Education;
                Award ID: NTU-107L9003
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                electronic nose,breath test,machine learning,ventilator-associated pneumonia,volatile organic compounds

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