Archetype Modeling Methodology

[EN] 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.This work was partially funded by grant DI-14-06564 (Doctorados Industriales) of the Ministerio de Economia y Competitividad of Spain. The authors would also thank the participants of all R&D projects that have served to evaluate and improve the presented methodology.Moner Cano, D.; Maldonado Segura, JA.; Robles Viejo, M. (2018). Archetype Modeling Methodology. Journal of Biomedical Informatics. 79:71-81. https://doi.org/10.1016/j.jbi.2018.02.003S71817

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.Sáez Silvestre, C.; Robles Viejo, M.; García Gómez, JM. (2013). Comparative study of probability distribution distances to define a metric for the stability of multi-source biomedical research data. Engineering in Medicine and Biology Society (EMBC), 2013 35th Annual International Conference of the IEEE. 3226-3229. doi:10.1109/EMBC.2013.6610228S3226322

Corpus based learning of stochastic, context-free grammars combined with Hidden Markov Models for tRNA modelling

[EN] In this paper, a new method for modelling tRNA secondary structures is presented. This method is based on the combination of stochastic context-free grammars (SCFG) and Hidden Markov Models (HMM). HMM are used to capture the local relations in the loops of the molecule (nonstructured regions) and SCFG are used to capture the long term relations between nucleotides of the arms (structured regions). Given annotated public databases, the HMM and SCFG models are learned by means of automatic inductive learning methods. Two SCFG learning methods have been explored. Both of them take advantage of the structural information associated with the training sequences: one of them is based on a stochastic version of the Sakakibara algorithm and the other one is based on a Corpus based algorithm. A final model is then obtained by merging of the HMM of the nonstructured regions and the SCFG of the structured regions. Finally, the performed experiments on the tRNA sequence corpus and the non-tRNA sequence corpus give significant results. Comparative experiments with another published method are also presented.We would like to thank Diego Linares and Joan Andreu Sanchez for answering all our questions about SCFG, as well as Satoshi Sekine for his evaluation software. We would also like to thank the Ministerio de Sanidad y Consumo of Spain for the grants to the INBIOMED consortium.García Gómez, JM.; Benedí Ruiz, JM.; Vicente Robledo, J.; Robles Viejo, M. (2005). Corpus based learning of stochastic, context-free grammars combined with Hidden Markov Models for tRNA modelling. International Journal of Bioinformatics Research and Applications. 1(3):305-318. doi:10.1504/IJBRA.2005.007908S3053181

Applying probabilistic temporal and multi-site 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.This work was supported by the Spanish Ministry of Economy and Competitiveness grant numbers RTC-2014-1530-1 and TIN-2013-43457-R, and by the Universitat Politecnica de Valencia grant number SP20141432.Sáez Silvestre, C.; Zurriaga, O.; Pérez-Panadés, J.; Melchor, I.; Robles Viejo, M.; García Gómez, JM. (2016). Applying probabilistic temporal and multi-site data quality control methods to a public health mortality registry in Spain: A systematic approach to quality control of repositories. Journal of the American Medical Informatics Association. 23(6):1085-1095. https://doi.org/10.1093/jamia/ocw010S1085109523

Detailed Clinical Models Governance System in a Regional EHR Project

The final publication is available at Springer via http://dx.doi.org/ 10.1007/978-3-319-00846-2_313In this work we present the Concept Oriented Repository (ROC), a system developed for the management of clinical information models, also known as detailed clinical models (DCM). It has been developed to be used in the Electronic Health Record project of the Valencia regional health agency (AVS). The system uses DCMs as a way to define clinical models independently of the healthcare standard chosen by the organization. These definitions create a framework where different actors can come to agreements on which information has to be represented and managed in the project. These concepts can be used later for the definition of technical artifacts (archetypes, templates, forms or message definitions) to be used by AVS information systemsThis work has been funded by Electronic Health History project from Valencia Health Agency (HSEAVS).Boscá Tomás, D.; Marco Ruiz, L.; Moner Cano, D.; Maldonado Segura, JA.; Insa, L.; Robles Viejo, M. (2013). Detailed Clinical Models Governance System in a Regional EHR Project. En XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013. Springer. 1266-1269. doi:10.1007/978-3-319-00846-2_313S1266126

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

The final publication is available at Springer via http://dx.doi.org/10.1007/s10916-013-0004-y[EN] Background: 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. Objective: 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. Methods: 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. Results: 92 relevant papers and 192 commercial apps were found. 44 papers were focused only on mobile clinical decision support systems. 171 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. Conclusions: 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.This research has been partially supported by Ministerio de Economía y Competitividad, Spain. This research has been partially supported by the ICT-248765 EU-FP7 Project. This research has been partially supported by the IPT-2011-1126-900000 project under the INNPACTO 2011 program, Ministerio de Ciencia e Innovación.Martínez Pérez, B.; De La Torre Diez, I.; López Coronado, M.; Sainz De Abajo, B.; Robles Viejo, M.; García Gómez, JM. (2014). Mobile clinical decision support systems and applications: a literature and commercial review. Journal of Medical Systems. 38(1):1-10. https://doi.org/10.1007/s10916-013-0004-yS110381Van De Belt, T. H., Engelen, L. J., Berben, S. A., and Schoonhoven, L., Definition of Health 2.0 and Medicine 2.0: A systematic review. J Med Internet Res 2010:12(2), 2012.Oh, H., Rizo, C., Enkin, M., and Jadad, A., What is eHealth (3): A systematic review of published definitions. J Med Internet Res 7(1):1, 2005. PMID: 15829471.World Health Organization (2011) mHealth: New horizons for health through mobile technologies: Based on the findings of the second global survey on eHealth (Global Observatory for eHealth Series, Volume 3). World Health Organization. 2011. ISBN: 9789241564250Lin, C., Mobile telemedicine: A survey study. J Med Syst April 36(2):511–520, 2012.El Khaddar, M.A., Harroud, H., Boulmalf, M., Elkoutbi, M., Habbani, A., Emerging wireless technologies in e-health Trends, challenges, and framework design issues. 2012 International Conference on Multimedia Computing and Systems (ICMCS). 440–445, 2012.Luanrattana, R., Win, K. T., Fulcher, J., and Iverson, D., Mobile technology use in medical education. J Med Syst 36(1):113–122, 2012.Yang, S. C., Mobile applications and 4 G wireless networks: A framework for analysis. Campus-Wide Information Systems 29(5):344–357, 2012.Kumar, B., Singh, S.P., Mohan, A., Emerging mobile communication technologies for health. 2010 International Conference on Computer and Communication Technology, ICCCT-2010; Allahabad; pp. 828–832, 2010.Yan, H., Huo, H., Xu, Y., and Gidlund, M., Wireless sensor network based E-health system—implementation and experimental results. IEEE Transactions on Consumer Electronics 56(4):2288–2295, 2010.IDC (2013) Press release: Strong demand for smartphones and heated vendor competition characterize the worldwide mobile phone market at the end of 2012. http://www.idc.com/getdoc.jsp?containerId=prUS23916413#.UVBKiRdhWCn . Accessed 11 September 2013.IDC (2012) IDC Raises its worldwide tablet forecast on continued strong demand and forthcoming new product launches. http://www.idc.com/getdoc.jsp?containerId=prUS23696912#.US9x86JhWCl . Accessed 11 September 2013.International Data Corporation (2013) Android and iOS combine for 91.1 % of the worldwide smartphone OS market in 4Q12 and 87.6 % for the year. http://www.idc.com/getdoc.jsp?containerId=prUS23946013 . Accessed 11 September 2013.Jones, C., (2013) Apple and Google continue to gain US Smartphone market share. Forbes. http://www.forbes.com/sites/chuckjones/2013/01/04/apple-and-google-continue-to-gain-us-smartphone-market-share/ . Accessed 11 September 2013.Apple (2013) iTunes. http://www.apple.com/itunes/ . Accessed 11 September 2013.Google (2013) Google play. https://play.google.com/store . Accessed 11 September 2013.Rowinski, D., (2013) The data doesn’t lie: iOS apps are better than android. Readwrite mobile. http://readwrite.com/2013/01/30/the-data-doesnt-lie-ios-apps-are-better-quality-than-android . Accessed 11 September 2013.Rajan, S. P., and Rajamony, S., Viable investigations and real-time recitation of enhanced ECG-based cardiac telemonitoring system for homecare applications: A systematic evaluation. Telemed J E Health 19(4):278–286, 2013.Logan, A. G., Transforming hypertension management using mobile health technology for telemonitoring and self-care support. Can J Cardiol 29(5):579–585, 2013.Tamrat, T., and Kachnowski, S., Special delivery: An analysis of mHealth in maternal and newborn health programs and their outcomes around the world. Matern Child Health J 16(5):1092–1101, 2012.Martínez-Pérez, B., de la Torre-Díez, I., López-Coronado, M., and Herreros-González, J., Mobile Apps in Cardiology: Review. JMIR Mhealth Uhealth 1(2):e15, 2013.de Wit HA, Mestres Gonzalvo C, Hurkens KP, Mulder WJ, Janknegt R, et al., Development of a computer system to support medication reviews in nursing homes. Int J Clin Pharm. 26, 2013.Dahlström, O., Thyberg, I., Hass, U., Skogh, T., and Timpka, T., Designing a decision support system for existing clinical organizational structures: Considerations from a rheumatology clinic. J Med Syst 30(5):325–31, 2006.Lambin P, Roelofs E, Reymen B, Velazquez ER, Buijsen J, et al., ‘Rapid learning health care in oncology’ - An approach towards decision support systems enabling customised radiotherapy’. Radiother Oncol. 27, 2013.Graham, T. A., Bullard, M. J., Kushniruk, A. W., Holroyd, B. R., and Rowe, B. H., Assessing the sensibility of two clinical decision support systems. J Med Syst 32(5):361–8, 2008.Martínez-Pérez, B., de la Torre-Díez, I., and López-Coronado, M., Mobile health applications for the most prevalent conditions by the World Health Organization: Review and analysis. J Med Internet Res 15(6):e120, 2013.Savel, T. G., Lee, B. A., Ledbetter, G., Brown, S., LaValley, D., et al., PTT advisor: A CDC-supported initiative to develop a mobile clinical laboratory decision support application for the iOS platform. Online J Public Health Inform 5(2):215, 2013.Doctor Doctor Inc. (2009) iDoc. iTunes. https://itunes.apple.com/es/app/idoc/id328354734?mt=8 . Accessed 13 September 2013.Hardyman, W., Bullock, A., Brown, A., Carter-Ingram, S., and Stacey, M., Mobile technology supporting trainee doctors’ workplace learning and patient care: An evaluation. BMC Med Educ 13:6, 2013.Lee, N. J., Chen, E. S., Currie, L. M., Donovan, M., Hall, E. K., et al., The effect of a mobile clinical decision support system on the diagnosis of obesity and overweight in acute and primary care encounters. ANS Adv Nurs Sci 32(3):211–21, 2009.Divall, P., Camosso-Stefinovic, J., and Baker, R., The use of personal digital assistants in clinical decision making by health care professionals: A systematic review. Health Informatics J 19(1):16–28, 2013.Chignell, M, and Yesha, Y, Lo, J., New methods for clinical decision support in hospitals. In Proceedings of the 2010 Conference of the Center for Advanced Studies on Collaborative Research (CASCON’10). Toronto, ON; Canada, 2010Charani, E., Kyratsis, Y., Lawson, W., Wickens, H., Brannigan, E. T., et al., An analysis of the development and implementation of a smartphone application for the delivery of antimicrobial prescribing policy: Lessons learnt. J Antimicrob Chemother 68(4):960–7, 2013.Klucken, J., Barth, J., Kugler, P., Schlachetzki, J., Henze, T., et al., Unbiased and mobile gait analysis detects motor impairment in Parkinson’s disease. PLoS One 8(2):e56956, 2013.Hervás, R., Fontecha, J., Ausín, D., Castanedo, F., Bravo, J., et al., Mobile monitoring and reasoning methods to prevent cardiovascular diseases. Sensors (Basel) 13(5):6524–41, 2013.Di Noia, T., Ostuni, V. C., Pesce, F., Binetti, G., Naso, N., et al., An end stage kidney disease predictor based on an artificial neural networks ensemble. Expert Syst Appl 40(11):4438–4445, 2013.Velikova, M., van Scheltinga, J. T., Lucas, P. J. F., and Spaanderman, M., Exploiting causal functional relationships in Bayesian network modelling for personalised healthcare. Int J Approx Reason, 2013. doi: 10.1016/j.ijar.2013.03.016 .Medical Data Solutions (2012) Pediatric clinical pathways. Google play. https://play.google.com/store/apps/details?id=com.ipathways . 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Utilidad de los arquetipos ISO 13606 para representar modelos clínicos detallados

Objetivo: Evaluar la utilidad de los Arquetipos ISO/CEN 13606 y openEHR en la representación de modelos clínicos detallados. Metodología: como editores de arquetipos se utilizaron LinkERH para ISO/CEN 13606 y los editores de Ocean Informatics y LiU para openEHR. Como caso de uso se representaron los conjuntos de datos identificados en los modelos locales de tres sistemas (hospital, UCI y atención primaria) en el dominio de la úlcera por decúbito, abarcando la observación, evaluación, instrucción y acción. Los conceptos fueron enlazados con terminologías SNOMED CT y MedDRA. Se buscaron arquetipos relacionados con el dominio en los repositorios internacionales para ser reutilizados. Resultados: Se realizó un conjunto de arquetipos equivalentes ISO/CEN 13606 y openEHR, en español e inglés. Los arquetipos proporcionan un formalismo útil para especificar datos de un modelo detallado. Los modelos producidos por las herramientas de edición de arquetipos son comprensibles para los clínicos. Los arquetipos proporcionan un marco para la implementación de las terminologías en la HCE. Se requiere el desarrollo de técnicas para el diseño de arquetipos que garanticen su calidad.Serrano, P.; Moner Cano, D.; Sebastian, T.; Maldonado Segura, JA.; Navalón, R.; Robles Viejo, M.; Gómez, Á. (2009). Utilidad de los arquetipos ISO 13606 para representar modelos clínicos detallados. RevistaeSalud.com. 5(18):100-110. http://hdl.handle.net/10251/61364S10011051

Non-local intracranial cavity extraction

[EN] 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.The authors want to thank the IXI (EPSRC GR/S21533/02) and OASIS (P50 AG05681, P01 AG03991, R01 AG021910, P50 MH071616, U24 RR021382, and R01 MH56584) dataset promoters for making available this valuable resource to the scientific community which surely will boost the research in brain imaging. This work has been supported by the Spanish Grant TIN2011-26727 from Ministerio de Ciencia e Innovacion. This work was funded in part by operating grants ´ from the Canadian Institutes of Health Research, les Fonds de la recherche sante du Quebec, MINDLab UNIK initiative at ´ Aarhus University, funded by the Danish Ministry of Science, Technology and Innovation, Grant agreement no. 09-065250.Manjón Herrera, JV.; Eskildsen, SF.; Coupé, P.; Romero Gómez, JE.; Collins, L.; Robles Viejo, M. (2014). Non-local intracranial cavity extraction. International Journal of Biomedical Imaging. 2014:1-11. https://doi.org/10.1155/2014/820205S111201

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

Introduction 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. Our main objective is 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 (i.e., data level) and the rest using ontologies (i.e., 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 has been used and the patients have been successfully classified by the risk of developing colorectal cancer. Conclusion 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.This work was supported by the Ministerio de Economia y Competitividad and the FEDER program through grants TIN2010-21388-C01 and TIN2010-21388-C02. MCLG was supported by the Fundacion Seneca through grant 15555/FPI/2010.Fernández-Breis, JT.; Maldonado Segura, JA.; Marcos, M.; Legaz-García, MDC.; Moner Cano, D.; Torres-Sospedra, J.; Esteban-Gil, A.... (2013). Leveraging electronic healthcare record standards and semantic web technologies for the identification of patient cohorts. Journal of the American Medical Informatics Association. 20(E2):288-296. https://doi.org/10.1136/amiajnl-2013-001923S28829620E2Cuggia, M., Besana, P., & Glasspool, D. (2011). Comparing semi-automatic systems for recruitment of patients to clinical trials. International Journal of Medical Informatics, 80(6), 371-388. doi:10.1016/j.ijmedinf.2011.02.003Sujansky, W. 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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 diffi- cult 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. 2015 Elsevier Inc. All rights reserved.Boscá Tomás, D.; Maldonado Segura, JA.; Moner Cano, D.; Robles Viejo, M. (2015). Automatic generation of computable implementation guides from clinical information models. Journal of Biomedical Informatics. 55:143-152. doi:10.1016/j.jbi.2015.04.002S1431525