Archetype modeling methodology.

Clinical Information Models (CIMs) expressed as archetypes play an essential role in the design and development of current Electronic Health Record (EHR) information structures. Although there exist many experiences about using archetypes in the literature, a comprehensive and formal methodology for archetype modeling does not exist. Having a modeling methodology is essential to develop quality archetypes, in order to guide the development of EHR systems and to allow the semantic interoperability of health data. In this work, an archetype modeling methodology is proposed. This paper describes its phases, the inputs and outputs of each phase, and the involved participants and tools. It also includes the description of the possible strategies to organize the modeling process. The proposed methodology is inspired by existing best practices of CIMs, software and ontology development. The methodology has been applied and evaluated in regional and national EHR projects. The application of the methodology provided useful feedback and improvements, and confirmed its advantages. The conclusion of this work is that having a formal methodology for archetype development facilitates the definition and adoption of interoperable archetypes, improves their quality, and facilitates their reuse among different information systems and EHR projects. Moreover, the proposed methodology can be also a reference for CIMs development using any other formalism.

A Standardized and Data Quality Assessed Maternal-Child Care Integrated Data Repository for Research and Monitoring of Best Practices: A Pilot Project in Spain.

We present the results of a pilot project of the Spanish Ministry of Health, Social Services and Equality, envisaged to the development of a national integrated data repository of maternal-child care information. Based on health information standards and data quality assessment procedures, the developed repository is aimed to a reliable data reuse for (1) population research and (2) the monitoring of healthcare best practices. Data standardization was provided by means of two main ISO 13606 archetypes (composed of 43 sub-archetypes), the first dedicated to the delivery and birth information and the second about the infant feeding information from delivery up to two years. Data quality was assessed by means of a dedicated procedure on seven dimensions including completeness, consistency, uniqueness, multi-source variability, temporal variability, correctness and predictive value. A set of 127 best practice indicators was defined according to international recommendations and mapped to the archetypes, allowing their calculus using XQuery programs. As a result, a standardized and data quality assessed integrated data respository was generated, including 7857 records from two Spanish hospitals: Hospital Virgen del Castillo, Yecla, and Hospital 12 de Octubre, Madrid. This pilot project establishes the basis for a reliable maternal-child care data reuse and standardized monitoring of best practices based on the developed information and data quality standards.

Stability metrics for multi-source biomedical data based on simplicial projections from probability distribution distances.

Biomedical data may be composed of individuals generated from distinct, meaningful sources. Due to possible contextual biases in the processes that generate data, there may exist an undesirable and unexpected variability among the probability distribution functions (PDFs) of the source subsamples, which, when uncontrolled, may lead to inaccurate or unreproducible research results. Classical statistical methods may have difficulties to undercover such variabilities when dealing with multi-modal, multi-type, multi-variate data. This work proposes two metrics for the analysis of stability among multiple data sources, robust to the aforementioned conditions, and defined in the context of data quality assessment. Specifically, a global probabilistic deviation and a source probabilistic outlyingness metrics are proposed. The first provides a bounded degree of the global multi-source variability, designed as an estimator equivalent to the notion of normalized standard deviation of PDFs. The second provides a bounded degree of the dissimilarity of each source to a latent central distribution. The metrics are based on the projection of a simplex geometrical structure constructed from the Jensen-Shannon distances among the sources PDFs. The metrics have been evaluated and demonstrated their correct behaviour on a simulated benchmark and with real multi-source biomedical data using the UCI Heart Disease data set. The biomedical data quality assessment based on the proposed stability metrics may improve the efficiency and effectiveness of biomedical data exploitation and research.

Applying probabilistic temporal and multisite data quality control methods to a public health mortality registry in Spain: a systematic approach to quality control of repositories.

OBJECTIVE: To assess the variability in data distributions among data sources and over time through a case study of a large multisite repository as a systematic approach to data quality (DQ). MATERIALS AND METHODS: Novel probabilistic DQ control methods based on information theory and geometry are applied to the Public Health Mortality Registry of the Region of Valencia, Spain, with 512 143 entries from 2000 to 2012, disaggregated into 24 health departments. The methods provide DQ metrics and exploratory visualizations for (1) assessing the variability among multiple sources and (2) monitoring and exploring changes with time. The methods are suited to big data and multitype, multivariate, and multimodal data. RESULTS: The repository was partitioned into 2 probabilistically separated temporal subgroups following a change in the Spanish National Death Certificate in 2009. Punctual temporal anomalies were noticed due to a punctual increment in the missing data, along with outlying and clustered health departments due to differences in populations or in practices. DISCUSSION: Changes in protocols, differences in populations, biased practices, or other systematic DQ problems affected data variability. Even if semantic and integration aspects are addressed in data sharing infrastructures, probabilistic variability may still be present. Solutions include fixing or excluding data and analyzing different sites or time periods separately. A systematic approach to assessing temporal and multisite variability is proposed. CONCLUSION: Multisite and temporal variability in data distributions affects DQ, hindering data reuse, and an assessment of such variability should be a part of systematic DQ procedures.

A platform for exploration into chaining of web services for clinical data transformation and reasoning.

The heterogeneity of clinical data is a key problem in the sharing and reuse of Electronic Health Record (EHR) data. We approach this problem through the combined use of EHR standards and semantic web technologies, concretely by means of clinical data transformation applications that convert EHR data in proprietary format, first into clinical information models based on archetypes, and then into RDF/OWL extracts which can be used for automated reasoning. In this paper we describe a proof-of-concept platform to facilitate the (re)configuration of such clinical data transformation applications. The platform is built upon a number of web services dealing with transformations at different levels (such as normalization or abstraction), and relies on a collection of reusable mappings designed to solve specific transformation steps in a particular clinical domain. The platform has been used in the development of two different data transformation applications in the area of colorectal cancer.

Combining Archetypes with Fast Health Interoperability Resources in Future-proof Health Information Systems.

Messaging standards, and specifically HL7 v2, are heavily used for the communication and interoperability of Health Information Systems. HL7 FHIR was created as an evolution of the messaging standards to achieve semantic interoperability. FHIR is somehow similar to other approaches like the dual model methodology as both are based on the precise modeling of clinical information. In this paper, we demonstrate how we can apply the dual model methodology to standards like FHIR. We show the usefulness of this approach for data transformation between FHIR and other specifications such as HL7 CDA, EN ISO 13606, and openEHR. We also discuss the advantages and disadvantages of defining archetypes over FHIR, and the consequences and outcomes of this approach. Finally, we exemplify this approach by creating a testing data server that supports both FHIR resources and archetypes.

Automated glioblastoma segmentation based on a multiparametric structured unsupervised classification.

Automatic brain tumour segmentation has become a key component for the future of brain tumour treatment. Currently, most of brain tumour segmentation approaches arise from the supervised learning standpoint, which requires a labelled training dataset from which to infer the models of the classes. The performance of these models is directly determined by the size and quality of the training corpus, whose retrieval becomes a tedious and time-consuming task. On the other hand, unsupervised approaches avoid these limitations but often do not reach comparable results than the supervised methods. In this sense, we propose an automated unsupervised method for brain tumour segmentation based on anatomical Magnetic Resonance (MR) images. Four unsupervised classification algorithms, grouped by their structured or non-structured condition, were evaluated within our pipeline. Considering the non-structured algorithms, we evaluated K-means, Fuzzy K-means and Gaussian Mixture Model (GMM), whereas as structured classification algorithms we evaluated Gaussian Hidden Markov Random Field (GHMRF). An automated postprocess based on a statistical approach supported by tissue probability maps is proposed to automatically identify the tumour classes after the segmentations. We evaluated our brain tumour segmentation method with the public BRAin Tumor Segmentation (BRATS) 2013 Test and Leaderboard datasets. Our approach based on the GMM model improves the results obtained by most of the supervised methods evaluated with the Leaderboard set and reaches the second position in the ranking. Our variant based on the GHMRF achieves the first position in the Test ranking of the unsupervised approaches and the seventh position in the general Test ranking, which confirms the method as a viable alternative for brain tumour segmentation.

Automatic generation of computable implementation guides from clinical information models.

Clinical information models are increasingly used to describe the contents of Electronic Health Records. Implementation guides are a common specification mechanism used to define such models. They contain, among other reference materials, all the constraints and rules that clinical information must obey. However, these implementation guides typically are oriented to human-readability, and thus cannot be processed by computers. As a consequence, they must be reinterpreted and transformed manually into an executable language such as Schematron or Object Constraint Language (OCL). This task can be difficult and error prone due to the big gap between both representations. The challenge is to develop a methodology for the specification of implementation guides in such a way that humans can read and understand easily and at the same time can be processed by computers. In this paper, we propose and describe a novel methodology that uses archetypes as basis for generation of implementation guides. We use archetypes to generate formal rules expressed in Natural Rule Language (NRL) and other reference materials usually included in implementation guides such as sample XML instances. We also generate Schematron rules from NRL rules to be used for the validation of data instances. We have implemented these methods in LinkEHR, an archetype editing platform, and exemplify our approach by generating NRL rules and implementation guides from EN ISO 13606, openEHR, and HL7 CDA archetypes.

Clinical information modeling processes for semantic interoperability of electronic health records: systematic review and inductive analysis.

OBJECTIVE: This systematic review aims to identify and compare the existing processes and methodologies that have been published in the literature for defining clinical information models (CIMs) that support the semantic interoperability of electronic health record (EHR) systems. MATERIAL AND METHODS: Following the preferred reporting items for systematic reviews and meta-analyses systematic review methodology, the authors reviewed published papers between 2000 and 2013 that covered that semantic interoperability of EHRs, found by searching the PubMed, IEEE Xplore, and ScienceDirect databases. Additionally, after selection of a final group of articles, an inductive content analysis was done to summarize the steps and methodologies followed in order to build CIMs described in those articles. RESULTS: Three hundred and seventy-eight articles were screened and thirty six were selected for full review. The articles selected for full review were analyzed to extract relevant information for the analysis and characterized according to the steps the authors had followed for clinical information modeling. DISCUSSION: Most of the reviewed papers lack a detailed description of the modeling methodologies used to create CIMs. A representative example is the lack of description related to the definition of terminology bindings and the publication of the generated models. However, this systematic review confirms that most clinical information modeling activities follow very similar steps for the definition of CIMs. Having a robust and shared methodology could improve their correctness, reliability, and quality. CONCLUSION: Independently of implementation technologies and standards, it is possible to find common patterns in methods for developing CIMs, suggesting the viability of defining a unified good practice methodology to be used by any clinical information modeler.

NABS: non-local automatic brain hemisphere segmentation.

In this paper, we propose an automatic method to segment the five main brain sub-regions (i.e. left/right hemispheres, left/right cerebellum and brainstem) from magnetic resonance images. The proposed method uses a library of pre-labeled brain images in a stereotactic space in combination with a non-local label fusion scheme for segmentation. The main novelty of the proposed method is the use of a multi-label block-wise label fusion strategy specifically designed to deal with the classification of main brain sub-volumes that process only specific parts of the brain images significantly reducing the computational burden. The proposed method has been quantitatively evaluated against manual segmentations. The evaluation showed that the proposed method was faster while producing more accurate segmentations than a current state-of-the-art method. We also present evidences suggesting that the proposed method was more robust against brain pathologies than the compared method. Finally, we demonstrate the clinical value of our method compared to the state-of-the-art approach in terms of the asymmetry quantification in Alzheimer's disease.

Incremental logistic regression for customizing automatic diagnostic models.

In the last decades, and following the new trends in medicine, statistical learning techniques have been used for developing automatic diagnostic models for aiding the clinical experts throughout the use of Clinical Decision Support Systems. The development of these models requires a large, representative amount of data, which is commonly obtained from one hospital or a group of hospitals after an expensive and time-consuming gathering, preprocess, and validation of cases. After the model development, it has to overcome an external validation that is often carried out in a different hospital or health center. The experience is that the models show underperformed expectations. Furthermore, patient data needs ethical approval and patient consent to send and store data. For these reasons, we introduce an incremental learning algorithm base on the Bayesian inference approach that may allow us to build an initial model with a smaller number of cases and update it incrementally when new data are collected or even perform a new calibration of a model from a different center by using a reduced number of cases. The performance of our algorithm is demonstrated by employing different benchmark datasets and a real brain tumor dataset; and we compare its performance to a previous incremental algorithm and a non-incremental Bayesian model, showing that the algorithm is independent of the data model, iterative, and has a good convergence.

Knowledge-Based Personal Health System to empower outpatients of diabetes mellitus by means of P4 Medicine.

Diabetes Mellitus (DM) affects hundreds of millions of people worldwide and it imposes a large economic burden on healthcare systems. We present a web patient empowering system (PHSP4) that ensures continuous monitoring and assessment of the health state of patients with DM (type I and II). PHSP4 is a Knowledge-Based Personal Health System (PHS) which follows the trend of P4 Medicine (Personalized, Predictive, Preventive, and Participative). It provides messages to outpatients and clinicians about the achievement of objectives, follow-up, and treatments adjusted to the patient condition. Additionally, it calculates a four-component risk vector of the associated pathologies with DM: Nephropathy, Diabetic retinopathy, Diabetic foot, and Cardiovascular event. The core of the system is a Rule-Based System which Knowledge Base is composed by a set of rules implementing the recommendations of the American Diabetes Association (ADA) (American Diabetes Association: http://www.diabetes.org/ ) clinical guideline. The PHSP4 is designed to be standardized and to facilitate its interoperability by means of terminologies (SNOMED-CT [The International Health Terminology Standards Development Organization: http://www.ihtsdo.org/snomed-ct/ ] and UCUM [The Unified Code for Units of Measure: http://unitsofmeasure.org/ ]), standardized clinical documents (HL7 CDA R2 [Health Level Seven International: http://www.hl7.org/index.cfm ]) for managing Electronic Health Record (EHR). We have evaluated the functionality of the system and its users' acceptance of the system using simulated and real data, and a questionnaire based in the Technology Acceptance Model methodology (TAM). Finally results show the reliability of the system and the high acceptance of clinicians.

Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations.

Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.

Nonlocal intracranial cavity extraction.

Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden.

Analysis of mobile health applications for a broad spectrum of consumers: a user experience approach.

Mobile health (m-health) apps can bring health prevention and promotion to the general population. The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences. This goal was defined following the strategic documents generated by the main prospective observatories of Information and Communications Technology for health. After a general exploration of the app markets, we analyze the entries of three specific themes focused in this article: type 2 diabetes, obesity, and breast-feeding. The user experiences reported in this study mostly cover the segments of (1) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes (Diab_Alert app), (2) information seekers through a mobile app for maternity (Lactation app) and partially (3) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment (SapoFit app). These apps were developed by the authors of this work.

Randomized pilot study and qualitative evaluation of a clinical decision support system for brain tumour diagnosis based on SV ¹H MRS: evaluation as an additional information procedure for novice radiologists.

The results of a randomized pilot study and qualitative evaluation of the clinical decision support system Curiam BT are reported. We evaluated the system's feasibility and potential value as a radiological information procedure complementary to magnetic resonance (MR) imaging to assist novice radiologists in diagnosing brain tumours using MR spectroscopy (1.5 and 3.0T). Fifty-five cases were analysed at three hospitals according to four non-exclusive diagnostic questions. Our results show that Curiam BT improved the diagnostic accuracy in all the four questions. Additionally, we discuss the findings of the users' feedback about the system, and the further work to optimize it for real environments and to conduct a large clinical trial.

Mobile clinical decision support systems and applications: a literature and commercial review.

The latest advances in eHealth and mHealth have propitiated the rapidly creation and expansion of mobile applications for health care. One of these types of applications are the clinical decision support systems, which nowadays are being implemented in mobile apps to facilitate the access to health care professionals in their daily clinical decisions. The aim of this paper is twofold. Firstly, to make a review of the current systems available in the literature and in commercial stores. Secondly, to analyze a sample of applications in order to obtain some conclusions and recommendations. Two reviews have been done: a literature review on Scopus, IEEE Xplore, Web of Knowledge and PubMed and a commercial review on Google play and the App Store. Five applications from each review have been selected to develop an in-depth analysis and to obtain more information about the mobile clinical decision support systems. Ninety-two relevant papers and 192 commercial apps were found. Forty-four papers were focused only on mobile clinical decision support systems. One hundred seventy-one apps were available on Google play and 21 on the App Store. The apps are designed for general medicine and 37 different specialties, with some features common in all of them despite of the different medical fields objective. The number of mobile clinical decision support applications and their inclusion in clinical practices has risen in the last years. However, developers must be careful with their interface or the easiness of use, which can impoverish the experience of the users.

Comparative study of probability distribution distances to define a metric for the stability of multi-source biomedical research data.

Research biobanks are often composed by data from multiple sources. In some cases, these different subsets of data may present dissimilarities among their probability density functions (PDF) due to spatial shifts. This, may lead to wrong hypothesis when treating the data as a whole. Also, the overall quality of the data is diminished. With the purpose of developing a generic and comparable metric to assess the stability of multi-source datasets, we have studied the applicability and behaviour of several PDF distances over shifts on different conditions (such as uni- and multivariate, different types of variable, and multi-modality) which may appear in real biomedical data. From the studied distances, we found information-theoretic based and Earth Mover's Distance to be the most practical distances for most conditions. We discuss the properties and usefulness of each distance according to the possible requirements of a general stability metric.

Diffusion weighted image denoising using overcomplete local PCA.

Diffusion Weighted Images (DWI) normally shows a low Signal to Noise Ratio (SNR) due to the presence of noise from the measurement process that complicates and biases the estimation of quantitative diffusion parameters. In this paper, a new denoising methodology is proposed that takes into consideration the multicomponent nature of multi-directional DWI datasets such as those employed in diffusion imaging. This new filter reduces random noise in multicomponent DWI by locally shrinking less significant Principal Components using an overcomplete approach. The proposed method is compared with state-of-the-art methods using synthetic and real clinical MR images, showing improved performance in terms of denoising quality and estimation of diffusion parameters.

Leveraging electronic healthcare record standards and semantic web technologies for the identification of patient cohorts.

BACKGROUND: The secondary use of electronic healthcare records (EHRs) often requires the identification of patient cohorts. In this context, an important problem is the heterogeneity of clinical data sources, which can be overcome with the combined use of standardized information models, virtual health records, and semantic technologies, since each of them contributes to solving aspects related to the semantic interoperability of EHR data. OBJECTIVE: To develop methods allowing for a direct use of EHR data for the identification of patient cohorts leveraging current EHR standards and semantic web technologies. MATERIALS AND METHODS: We propose to take advantage of the best features of working with EHR standards and ontologies. Our proposal is based on our previous results and experience working with both technological infrastructures. Our main principle is to perform each activity at the abstraction level with the most appropriate technology available. This means that part of the processing will be performed using archetypes (ie, data level) and the rest using ontologies (ie, knowledge level). Our approach will start working with EHR data in proprietary format, which will be first normalized and elaborated using EHR standards and then transformed into a semantic representation, which will be exploited by automated reasoning. RESULTS: We have applied our approach to protocols for colorectal cancer screening. The results comprise the archetypes, ontologies, and datasets developed for the standardization and semantic analysis of EHR data. Anonymized real data have been used and the patients have been successfully classified by the risk of developing colorectal cancer. CONCLUSIONS: This work provides new insights in how archetypes and ontologies can be effectively combined for EHR-driven phenotyping. The methodological approach can be applied to other problems provided that suitable archetypes, ontologies, and classification rules can be designed.