A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. METHODS: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. RESULTS: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. CONCLUSION: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Deep Neural Network Driven Speech Classification for Relevance Detection in Automatic Medical Documentation.

The automation of medical documentation is a highly desirable process, especially as it could avert significant temporal and monetary expenses in healthcare. With the help of complex modelling and high computational capability, Automatic Speech Recognition (ASR) and deep learning have made several promising attempts to this end. However, a factor that significantly determines the efficiency of these systems is the volume of speech that is processed in each medical examination. In the course of this study, we found that over half of the speech, recorded during follow-up examinations of patients treated with Intra-Vitreal Injections, was not relevant for medical documentation. In this paper, we evaluate the application of Convolutional and Long Short-Term Memory (LSTM) neural networks for the development of a speech classification module aimed at identifying speech relevant for medical report generation. In this regard, various topology parameters are tested and the effect of the model performance on different speaker attributes is analyzed. The results indicate that Convolutional Neural Networks (CNNs) are more successful than LSTM networks, and achieve a validation accuracy of 92.41%. Furthermore, on evaluation of the robustness of the model to gender, accent and unknown speakers, the neural network generalized satisfactorily.

XplOit: An Ontology-Based Data Integration Platform Supporting the Development of Predictive Models for Personalized Medicine.

Predictive models can support physicians to tailor interventions and treatments to their individual patients based on their predicted response and risk of disease and help in this way to put personalized medicine into practice. In allogeneic stem cell transplantation risk assessment is to be enhanced in order to respond to emerging viral infections and transplantation reactions. However, to develop predictive models it is necessary to harmonize and integrate high amounts of heterogeneous medical data that is stored in different health information systems. Driven by the demand for predictive instruments in allogeneic stem cell transplantation we present in this paper an ontology-based platform that supports data owners and model developers to share and harmonize their data for model development respecting data privacy.

The p-medicine portal-a collaboration platform for research in personalised medicine.

The European project p-medicine creates an information technology infrastructure that facilitates the development from current medical practice to personalised medicine. The main access point to this infrastructure is the p-medicine portal that provides clinicians, patients, and researchers a platform to collaborate, share data and expertise, and use tools and services to improve personalised treatments of patients. In this document, we describe the community-based structure of the p-medicine portal and provide information about the p-medicine security framework implemented in the portal. Finally, we show the user interface and describe the p-medicine tools and services integrated in the portal.

p-BioSPRE-an information and communication technology framework for transnational biomaterial sharing and access.

Biobanks represent key resources for clinico-genomic research and are needed to pave the way to personalised medicine. To achieve this goal, it is crucial that scientists can securely access and share high-quality biomaterial and related data. Therefore, there is a growing interest in integrating biobanks into larger biomedical information and communication technology (ICT) infrastructures. The European project p-medicine is currently building an innovative ICT infrastructure to meet this need. This platform provides tools and services for conducting research and clinical trials in personalised medicine. In this paper, we describe one of its main components, the biobank access framework p-BioSPRE (p-medicine Biospecimen Search and Project Request Engine). This generic framework enables and simplifies access to existing biobanks, but also to offer own biomaterial collections to research communities, and to manage biobank specimens and related clinical data over the ObTiMA Trial Biomaterial Manager. p-BioSPRE takes into consideration all relevant ethical and legal standards, e.g., safeguarding donors' personal rights and enabling biobanks to keep control over the donated material and related data. The framework thus enables secure sharing of biomaterial within open and closed research communities, while flexibly integrating related clinical and omics data. Although the development of the framework is mainly driven by user scenarios from the cancer domain, in this case, acute lymphoblastic leukaemia and Wilms tumour, it can be extended to further disease entities.

The ACGT Master Ontology and its applications--towards an ontology-driven cancer research and management system.

OBJECTIVE: This paper introduces the objectives, methods and results of ontology development in the EU co-funded project Advancing Clinico-genomic Trials on Cancer-Open Grid Services for Improving Medical Knowledge Discovery (ACGT). While the available data in the life sciences has recently grown both in amount and quality, the full exploitation of it is being hindered by the use of different underlying technologies, coding systems, category schemes and reporting methods on the part of different research groups. The goal of the ACGT project is to contribute to the resolution of these problems by developing an ontology-driven, semantic grid services infrastructure that will enable efficient execution of discovery-driven scientific workflows in the context of multi-centric, post-genomic clinical trials. The focus of the present paper is the ACGT Master Ontology (MO). METHODS: ACGT project researchers undertook a systematic review of existing domain and upper-level ontologies, as well as of existing ontology design software, implementation methods, and end-user interfaces. This included the careful study of best practices, design principles and evaluation methods for ontology design, maintenance, implementation, and versioning, as well as for use on the part of domain experts and clinicians. RESULTS: To date, the results of the ACGT project include (i) the development of a master ontology (the ACGT-MO) based on clearly defined principles of ontology development and evaluation; (ii) the development of a technical infrastructure (the ACGT Platform) that implements the ACGT-MO utilizing independent tools, components and resources that have been developed based on open architectural standards, and which includes an application updating and evolving the ontology efficiently in response to end-user needs; and (iii) the development of an Ontology-based Trial Management Application (ObTiMA) that integrates the ACGT-MO into the design process of clinical trials in order to guarantee automatic semantic integration without the need to perform a separate mapping process.

The ObTiMA system - ontology-based managing of clinical trials.

Clinical Trial Management Systems promise to help researchers in managing the large amounts of data occurring in clinical trials. In such systems Case Report Forms for capturing all patient data can usually be defined freely for a given trial. But if database definitions are automatically derived from such trial-specific definitions then the collected data cannot be easily compared to or integrated into other trials. We address this interoperability issue with an approach based on ontology and semantic data mediation. This resulted in the development of the ObTiMA system which is composed of a component for setting-up clinical trials and another for handling patient data during trials. Both components offer data reusability by relying on shared concepts defined in an ontology covering the whole cancer care and research spectrum.

Ontology based data management systems for post-genomic clinical trials within a European Grid Infrastructure for Cancer Research.

Data management in post-genomic clinical trials is the process of collecting and validating clinical and genomic data with the goal to answer research questions and to preserve it for future scientific investigation. Comprehensive metadata describing the semantics of the data are needed to leverage it for further research like cross-trial analysis. Current clinical trial management systems mostly lack sufficient metadata and are not semantically interoperable. This paper outlines our approach to develop an application that allows trial chairmen to design their trial and especially the required data management system with comprehensive metadata according to their needs, integrating a clinical trial ontology into the design process. To demonstrate the built-in interoperability of data management systems developed in this way, we integrate these applications into a European biomedical Grid for cancer research in a way that the research data collected in the data management systems can be seamlessly analyzed and mined by researchers.