We define breathomics as the metabolomics study of exhaled air. It is a strongly emerging metabolomics research field that mainly focuses on health-related volatile organic compounds (VOCs). Since the amount of these compounds varies with health status, breathomics holds great promise to deliver non-invasive diagnostic tools. Thus, the main aim of breathomics is to find patterns of VOCs related to abnormal (for instance inflammatory) metabolic processes occurring in the human body. Recently, analytical methods for measuring VOCs in exhaled air with high resolution and high throughput have been extensively developed. Yet, the application of machine learning methods for fingerprinting VOC profiles in the breathomics is still in its infancy. Therefore, in this paper, we describe the current state of the art in data pre-processing and multivariate analysis of breathomics data. We start with the detailed pre-processing pipelines for breathomics data obtained from gas-chromatography mass spectrometry and an ion-mobility spectrometer coupled to multi-capillary columns. The outcome of data pre-processing is a matrix containing the relative abundances of a set of VOCs for a group of patients under different conditions (e.g. disease stage, treatment). Independently of the utilized analytical method, the most important question, 'which VOCs are discriminatory?', remains the same. Answers can be given by several modern machine learning techniques (multivariate statistics) and, therefore, are the focus of this paper. We demonstrate the advantages as well the drawbacks of such techniques. We aim to help the community to understand how to profit from a particular method. In parallel, we hope to make the community aware of the existing data fusion methods, as yet unresearched in breathomics.
Ventilator-associated pneumonia (VAP) is a nosocomial infection occurring in the intensive care unit (ICU). The diagnostic standard is based on clinical criteria and bronchoalveolar lavage (BAL). Exhaled breath analysis is a promising non-invasive method for rapid diagnosis of diseases and contains volatile organic compounds (VOCs) that can differentiate diseased from healthy individuals. The aim of this study was to determine whether analysis of VOCs in exhaled breath can be used as a non-invasive monitoring tool for VAP. One hundred critically ill patients with clinical suspicion of VAP underwent BAL. Before BAL, exhaled air samples were collected and analysed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). The clinical suspicion of VAP was confirmed by BAL diagnostic criteria in 32 patients [VAP(+)] and rejected in 68 patients [VAP(−)]. Multivariate statistical comparison of VOC profiles between VAP(+) and VAP(−) revealed a subset of 12 VOCs that correctly discriminated between those two patient groups with a sensitivity and specificity of 75.8% ± 13.5% and 73.0% ± 11.8%, respectively. These results suggest that detection of VAP in ICU patients is possible by examining exhaled breath, enabling a simple, safe and non-invasive approach that could diminish diagnostic burden of VAP.
The identification of specific volatile organic compounds (VOCs) produced by microorganisms may assist in developing a fast and accurate methodology for the determination of pulmonary bacterial infections in exhaled air. As a first step, pulmonary bacteria were cultured and their headspace analyzed for the total amount of excreted VOCs to select those compounds which are exclusively associated with specific microorganisms. Development of a rapid, noninvasive methodology for identification of bacterial species may improve diagnostics and antibiotic therapy, ultimately leading to controlling the antibiotic resistance problem. Two hundred bacterial headspace samples from four different microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae) were analyzed by gas chromatography-mass spectrometry to detect a wide array of VOCs. Statistical analysis of these volatiles enabled the characterization of specific VOC profiles indicative for each microorganism. Differences in VOC abundance between the bacterial types were determined using ANalysis of VAriance-principal component analysis (ANOVA-PCA). These differences were visualized with PCA. Cross validation was applied to validate the results. We identified a large number of different compounds in the various headspaces, thus demonstrating a highly significant difference in VOC occurrence of bacterial cultures compared to the medium and between the cultures themselves. Additionally, a separation between a methicillin-resistant and a methicillin-sensitive isolate of S. aureus could be made due to significant differences between compounds. ANOVA-PCA analysis showed that 25 VOCs were differently profiled across the various microorganisms, whereas a PCA score plot enabled the visualization of these clear differences between the bacterial types. We demonstrated that identification of the studied microorganisms, including an antibiotic susceptible and resistant S. aureus substrain, is possible based on a selected number of compounds measured in the headspace of these cultures. These in vitro results may translate into a breath analysis approach that has the potential to be used as a diagnostic tool in medical microbiology.
Highlights Typically encountered CT exposure variations result in radiomics values distortion. Proposed correction method suppresses the non-tumor related variation in radiomics. The clinical relevance was shown using a 221 lung cancer patient cohort.
Prediction modelling with radiomics is a rapidly developing research topic that requires access to vast amounts of imaging data. Methods that work on decentralized data are urgently needed, because of concerns about patient privacy. Previously published computed tomography medical image sets with gross tumour volume (GTV) outlines for non-small cell lung cancer have been updated with extended follow-up. In a previous study, these were referred to as Lung1 (n = 421) and Lung2 (n = 221). The Lung1 dataset is made publicly accessible via The Cancer Imaging Archive (TCIA; https://www.cancerimagingarchive.net). We performed a decentralized multi-centre study to develop a radiomic signature (hereafter “ZS2019”) in one institution and validated the performance in an independent institution, without the need for data exchange and compared this to an analysis where all data was centralized. The performance of ZS2019 for 2-year overall survival validated in distributed radiomics was not statistically different from the centralized validation (AUC 0.61 vs 0.61; p = 0.52). Although slightly different in terms of data and methods, no statistically significant difference in performance was observed between the new signature and previous work (c-index 0.58 vs 0.65; p = 0.37). Our objective was not the development of a new signature with the best performance, but to suggest an approach for distributed radiomics. Therefore, we used a similar method as an earlier study. We foresee that the Lung1 dataset can be further re-used for testing radiomic models and investigating feature reproducibility.
Shared decision making (SDM) and patient-centered care require patients to actively participate in the decision-making process. Yet with the increasing number and complexity of cancer treatment options, it can be a challenge for patients to evaluate clinical information and make risk–benefit trade-offs to choose the most appropriate treatment. Clinicians face time constraints and communication challenges, which can further hamper the SDM process. In this article, we review patient decision aids (PDAs) as a means of supporting SDM by presenting clinical information and risk data to patients in a format that is accessible and easy to understand. We outline the benefits and limitations of PDAs as well as the challenges in their development, such as a lengthy and complex development process and implementation obstacles. Lastly, we discuss future trends and how change on multiple levels—PDA developers, clinicians, hospital administrators, and health care insurers—can support the use of PDAs and consequently SDM. Through this multipronged approach, patients can be empowered to take an active role in their health and choose treatments that are in line with their values.
Despite the increasing availability of Open Science (OS) infrastructure and the rise in policies to change behaviour, OS practices are not yet the norm. While pioneering researchers are developing OS practices, the majority sticks to status quo. To transition to common practice, we must engage a critical proportion of the academic community. In this transition, OS Communities (OSCs) play a key role. OSCs are bottom-up learning groups of scholars that discuss OS within and across disciplines. They make OS knowledge more accessible and facilitate communication among scholars and policymakers. Over the past two years, eleven OSCs were founded at several Dutch university cities. In other countries, similar OSCs are starting up. In this article, we discuss the pivotal role OSCs play in the large-scale transition to OS. We emphasize that, despite the grassroot character of OSCs, support from universities is critical for OSCs to be viable, effective, and sustainable.
Background Patient decision aids (PDAs) can support the treatment decision making process and empower patients to take a proactive role in their treatment pathway while using a shared decision-making (SDM) approach making participatory medicine possible. The aim of this study was to develop a PDA for prostate cancer that is accurate and user-friendly. Methods We followed a user-centered design process consisting of five rounds of semi-structured interviews and usability surveys with topics such as informational/decisional needs of users and requirements for PDAs. Our user-base consisted of 8 urologists, 4 radiation oncologists, 2 oncology nurses, 8 general practitioners, 19 former prostate cancer patients, 4 usability experts and 11 healthy volunteers. Results Informational needs for patients centered on three key factors: treatment experience, post-treatment quality of life, and the impact of side effects. Patients and clinicians valued a PDA that presents balanced information on these factors through simple understandable language and visual aids. Usability questionnaires revealed that patients were more satisfied overall with the PDA than clinicians; however, both groups had concerns that the PDA might lengthen consultation times (42 and 41%, respectively). The PDA is accessible on http://beslissamen.nl/ . Conclusions User-centered design provided valuable insights into PDA requirements but challenges in integrating diverse perspectives as clinicians focus on clinical outcomes while patients also consider quality of life. Nevertheless, it is crucial to involve a broad base of clinical users in order to better understand the decision-making process and to develop a PDA that is accurate, usable, and acceptable. Electronic supplementary material The online version of this article (10.1186/s12911-019-0862-4) contains supplementary material, which is available to authorized users.
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