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

Augmented EHR: Enrichment of EHR with Contents from Semantic Web Sources

This work presents methods to combine data from the Semantic Web into existing EHRs, leading to an augmented EHR. An existing EHR extract is augmented by combining it with additional information from external sources, typically linked data sources. The starting point is a standardized EHR extract described by an archetype. The method consists of combining specific data from the original EHR with contents from the external information source by building a semantic representation, which is used to query the external source. The results are converted into a standardized EHR extract according to an archetype. This work sets the foundations to transform Semantic Web contents into normalized EHR extracts. Finally, to exemplify the approach, the work includes a practical use case in which the summarized EHR is augmented with drug–drug interactions and disease-related treatment information

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

Interoperability of clinical decision-support systems and electronic health records using archetypes: a case study in clinical trial eligibility

Clinical decision-support systems (CDSSs) comprise systems as diverse as sophisticated platforms to store and manage clinical data, tools to alert clinicians of problematic situations, or decision-making tools to assist clinicians. Irrespective of the kind of decision-support task CDSSs should be smoothly integrated within the clinical information system, interacting with other components, in particular with the electronic health record (EHR). However, despite decades of developments, most CDSSs lack interoperability features. We deal with the interoperability problem of CDSSs and EHRs by exploiting the dual-model methodology. This methodology distinguishes a reference model and archetypes. A reference model is represented by a stable and small object-oriented model that describes the generic properties of health record information. For their part, archetypes are reusable and domain-specific definitions of clinical concepts in the form of structured and constrained combinations of the entities of the reference model. We rely on archetypes to make the CDSS compatible with EHRs from different institutions. Concretely, we use archetypes for modelling the clinical concepts that the CDSS requires, in conjunction with a series of knowledge-intensive mappings relating the archetypes to the data sources (EHR and/or other archetypes) they depend on. We introduce a comprehensive approach, including a set of tools as well as methodological guidelines, to deal with the interoperability of CDSSs and EHRs based on archetypes. Archetypes are used to build a conceptual layer of the kind of a virtual health record (VHR) over the EHR whose contents need to be integrated and used in the CDSS, associating them with structural and terminology-based semantics. Subsequently, the archetypes are mapped to the EHR by means of an expressive mapping language and specific-purpose tools. We also describe a case study where the tools and methodology have been employed in a CDSS to support patient recruitment in the framework of a clinical trial for colorectal cancer screening. The utilisation of archetypes not only has proved satisfactory to achieve interoperability between CDSSs and EHRs but also offers various advantages, in particular from a data model perspective. First, the VHR/data models we work with are of a high level of abstraction and can incorporate semantic descriptions. Second, archetypes can potentially deal with different EHR architectures, due to their deliberate independence of the reference model. Third, the archetype instances we obtain are valid instances of the underlying reference model, which would enable e.g. feeding back the EHR with data derived by abstraction mechanisms. Lastly, the medical and technical validity of archetype models would be assured, since in principle clinicians should be the main actors in their development.This research has been supported by the Spanish Ministry of Education through Grant PR2010-0279, and by Universitat Jaume I through Project P1182009-38. Additionally, this research has been supported by the Spanish Ministry of Science and Innovation under Grant TIN2010-21388-C02-01, and by the Spanish Ministry of Economy and Competitiveness under grant PTQ-11-04987.Marcos, M.; Maldonado Segura, JA.; Martinez-Salvador, B.; Boscá Tomás, D.; Robles Viejo, M. (2013). Interoperability of clinical decision-support systems and electronic health records using archetypes: a case study in clinical trial eligibility. Journal of Biomedical Informatics. 46(4):676-689. https://doi.org/10.1016/j.jbi.2013.05.004S67668946

Biochemical and Mutational Characterization of N-Succinyl-Amino Acid Racemase from Geobacillus stearothermophilus CECT49.

N-Succinyl-amino acid racemase (NSAAR), long referred to as N-acyl- or N-acetyl-amino acid racemase, is an enolase superfamily member whose biotechnological potential was discovered decades ago, due to its use in the industrial dynamic kinetic resolution methodology first known as “Acylase Process”. In previous works, an extended and enhanced substrate spectrum of the NSAAR from Geobacillus kaustophilus CECT4264 toward different N-substituted amino acids was reported. In this work, we describe the cloning, purification, and characterization of the NSAAR from Geobacillus stearothermophilus CECT49 (GstNSAAR). The enzyme has been extensively characterized, showing a higher preference toward N-formyl-amino acids than to N-acetyl-amino acids, thus confirming that the use of the former substrates is more appropriate for a biotechnological application of the enzyme. The enzyme showed an apparent thermal denaturation midpoint of 77.0 ± 0.1 °C and an apparent molecular mass of 184 ± 5 kDa, suggesting a tetrameric species. Optimal parameters for the enzyme activity were pH 8.0 and 55–65 °C, with Co2+ as the most effective cofactor. Mutagenesis and binding experiments confirmed K166, D191, E216, D241, and K265 as key residues in the activity of GstNSAAR, but not indispensable for substrate binding.pre-print784 K

LinkEHR-Ed: A multi-reference model archetype editor based on formal semantics

Purpose To develop a powerful archetype editing framework capable of handling multiple reference models and oriented towards the semantic description and standardization of legacy data. Methods The main prerequisite for implementing tools providing enhanced support for archetypes is the clear specification of archetype semantics. We propose a formalization of the definition section of archetypes based on types over tree-structured data. It covers the specialization of archetypes, the relationship between reference models and archetypes and conformance of data instances to archetypes. Results LinkEHR-Ed, a visual archetype editor based on the former formalization with advanced processing capabilities that supports multiple reference models, the editing and semantic validation of archetypes, the specification of mappings to data sources, and the automatic generation of data transformation scripts, is developed. Conclusions LinkEHR-Ed is a useful tool for building, processing and validating archetypes based on any reference model.This work was supported in part by the Spanish Ministry of Education and Science under grant TS12007-66S7S-C02; by the Generalitat Valenciana under grant APOSTD/2007/055 and by the program PAID-06-07 de la Universidad Politecnica de Valencia.Maldonado Segura, JA.; Moner Cano, D.; Boscá Tomás, D.; Fernandez Breis, JT.; Angulo Fernández, C.; Robles Viejo, M. (2009). LinkEHR-Ed: A multi-reference model archetype editor based on formal semantics. International Journal of Medical Informatics. 78(8):559-570. https://doi.org/10.1016/j.ijmedinf.2009.03.006S55957078

Single Nucleotide Polymorphisms of Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) and Susceptibility to Chronic Viral Hepatitis B and C Infections

The cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is a negative regulator of T-lymphocyte activation and proliferation. Single nucleotide polymorphisms (SNPs) occurring on the CTLA-4 gene can modify the ability to control the proliferation of T-lymphocytes, thereby impacting the clearance of hepatitis B (HBV) and hepatitis C (HCV) virus infections. The −319C/T and +49A/G SNPs of CTLA-4 gene have been associated with autoimmune disorders and liver infections. Studies show that the +49G allele confers susceptibility to HBV and HCV infections in chronic disease (without cirrhosis), associates with the risk of chronic HCV infection in males, confers protective effect against the development of hepatocellular carcinoma, and favors viral elimination. Furthermore, the +49G allele alone or in haplotype with the −319C favors chronic infection with genotype 3 HCV, has an inverse association with HCV genotype 1, and decreases viral load in chronic hepatitis C associated with sustained virological response (SVR). These findings support an important role of the SNPs of CTLA-4 gene in viral hepatitis; however, the mechanisms by which they influence immune response against viral infections are not fully understood. This review gives an overview of the current understanding of the association between CTLA4 SNPs and HBV/HCV infections

Usefulness of Muscle Ultrasonography in the Nutritional Assessment of Adult Patients with Cystic Fibrosis

Muscle ultrasonography of the quadriceps rectus femoris (QRF) is a technique on the rise in the assessment of muscle mass in application of nutritional assessment. The aim of the present study is to assess the usefulness of muscle ultrasonography in patients with cystic fibrosis, comparing the results with other body composition techniques such as anthropometry, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and handgrip strength (HGS). At the same time, we intend to assess the possible association with the nutritional and respiratory status. Methods: This was a prospective observational study in adult patients with cystic fibrosis in a clinically stable situation. Muscle ultrasonography of the QRF was performed, and the results were compared with other measures of body composition: anthropometry, BIA, and DXA. HGS was used to assess muscle function. Respiratory parameters were collected, and nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: A total of 48 patients were included, with a mean age of 34.1 ± 8.8 years. In total, 24 patients were men, and 24 patients were women. Mean BMI was 22.5 ± 3.8 kg/m2. Mean muscular area rectus anterior (MARA) was 4.09 ± 1.5 cm2, and mean muscular circumference rectus was 8.86 ± 1.61 cm. A positive correlation was observed between the MARA and fat-free mass index (FFMI) determined by anthropometry (r = 0.747; p < 0.001), BIA (r = 0.780; p < 0.001), and DXA (r = 0.678; p < 0.001), as well as muscle function (HGS: r = 0.790; p < 0.001) and respiratory parameters (FEV1; r = 0.445, p = 0.005; FVC: r = 0.376, p = 0.02; FEV1/FVC: r = 0.344, p = 0.037). A total of 25 patients (52.1%) were diagnosed with malnutrition according to GLIM criteria. Differences were observed when comparing the MARA based on the diagnosis of malnutrition (4.75 ± 1.65 cm2 in normo-nourished vs. 3.37 ± 1.04 in malnourished; p = 0.014). (...)This study was partially funded by an unrestricted grant from Vegenat Laboratories (Spain) and the Fundación SEEN-Nutricia 2021 Grant for the assessment of body composition by ultrasound. Partial funding for open access charge: Universidad de Málag

Non-invasive lightweight integration engine for building EHR from autonomous distributed systems

[EN] In this paper we describe Pangea-LE, a message-oriented lightweight data integration engine that allows homogeneous and concurrent access to clinical information from disperse and heterogeneous data sources. The engine extracts the information and passes it to the requesting client applications in a flexible XML format. The XML response message can be formatted on demand by appropriate Extensible Stylesheet Language (XSL) transformations in order to meet the needs of client applications. We also present a real deployment in a hospital where Pangea-LE collects and generates an XML view of all the available patient clinical information. The information is presented to healthcare professionals in an Electronic Health Record (EHR) viewer Web application with patient search and EHR browsing capabilities. Implantation in a real setting has been a success due to the non-invasive nature of Pangea-LE which respects the existing information systems.This work was partially funded by the Spanish Ministry of Science and Technology (MEC-TSI2004-06475-102-01) and the Spanish Ministry of Health (PI052245)Angulo Fernández, C.; Crespo Molina, PM.; Maldonado Segura, JA.; Moner Cano, D.; Perez Cuesta, D.; Abad, I.; Mandingorra Gimenez, J.... (2007). Non-invasive lightweight integration engine for building EHR from autonomous distributed systems. International Journal of Medical Informatics. 76(Supplement 3):417-424. https://doi.org/10.1016/j.ijmedinf.2007.05.002S41742476Supplement