Can OpenEHR, ISO 13606, and HL7 FHIR Work Together? An Agnostic Approach for the Selection and Application of Electronic Health Record Standards to the Next-Generation Health Data Spaces.

In order to maximize the value of electronic health records (EHRs) for both health care and secondary use, it is necessary for the data to be interoperable and reusable without loss of the original meaning and context, in accordance with the findable, accessible, interoperable, and reusable (FAIR) principles. To achieve this, it is essential for health data platforms to incorporate standards that facilitate addressing needs such as formal modeling of clinical knowledge (health domain concepts) as well as the harmonized persistence, query, and exchange of data across different information systems and organizations. However, the selection of these specifications has not been consistent across the different health data initiatives, often applying standards to address needs for which they were not originally designed. This issue is essential in the current scenario of implementing the European Health Data Space, which advocates harmonization, interoperability, and reuse of data without regulating the specific standards to be applied for this purpose. Therefore, this viewpoint aims to establish a coherent, agnostic, and homogeneous framework for the use of the most impactful EHR standards in the new-generation health data spaces: OpenEHR, International Organization for Standardization (ISO) 13606, and Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR). Thus, a panel of EHR standards experts has discussed several critical points to reach a consensus that will serve decision-making teams in health data platform projects who may not be experts in these EHR standards. It was concluded that these specifications possess different capabilities related to modeling, flexibility, and implementation resources. Because of this, in the design of future data platforms, these standards must be applied based on the specific needs they were designed for, being likewise fully compatible with their combined functional and technical implementation.

Halogen bonding in solution: thermodynamics and applications.

Halogen bonds are noncovalent interactions in which covalently bound halogens act as electrophilic species. The utility of halogen bonding for controlling self-assembly in the solid state is evident from a broad spectrum of applications in crystal engineering and materials science. Until recently, it has been less clear whether, and to what extent, halogen bonding could be employed to influence conformation, binding or reactivity in the solution phase. This tutorial review summarizes and interprets solution-phase thermodynamic data for halogen bonding interactions obtained over the past six decades and highlights emerging applications in molecular recognition, medicinal chemistry and catalysis.

Improving the Quality and Utility of Electronic Health Record Data through Ontologies.

The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors' rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs.

Increased endothelial cell selectivity of triazole-bridged dihalogenated A-ring analogues of combretastatin A-1.

The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G(2)/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells.

OpenEHR Implementation Guide: Towards Standard Low-Code Healthcare Systems.

Several open source components have been made available in recent years to help develop full openEHR systems. Still doubts exist if these are sufficient. This paper presents a case study of implementing a low-code openEHR system, investigating the feasibility and challenges of developing a system using these components for each step. The method used consisted in selecting successful examples of implementation case studies, identifying key development steps, and for each step searching for possible open source options. As a result, we had a working low-code openEHR powered EHR, successfully demonstrating the feasibility of the proposed implementation guide. The main available free or open source components used were ArchetypeDesigner and EHRbase, developed by Better and Vita/HighMed respectively. In our opinion, it is possible to build EHR systems using the available open source components, but support is still missing in the front end, specifically for form generation and screen representation.

Archetype-based knowledge management for semantic interoperability of electronic health records.

Formal modeling of clinical content that can be made available internationally is one of the most promising pathways to semantic interoperability of health information. Drawing on the extensive experience from openEHR archetype research and implementation work, we present the latest research and development in this area to improve semantic interoperability of Electronic Health Records (EHRs) using openEHR (ISO 13606) archetypes. Archetypes as the formal definition of clinical content need to be of high technical and clinical quality. We will start with a brief introduction of the openEHR architecture followed by presentations on specific topics related to the management of a wide range of clinical knowledge artefacts. We will describe a web-based review process for archetypes that enables international involvement and ensures that released archetypes are technically and clinically correct. Tools for validation of archetypes will be presented, along with templates and compliance templates. All this in combination enables the openEHR computing platform to be the foundation for safely sharing the information clinicians need, using this information within computerized clinical guidelines, for decision support as well as migrating legacy data.

OpenEHR and General Data Protection Regulation: Evaluation of Principles and Requirements.

BACKGROUND: Concerns about privacy and personal data protection resulted in reforms of the existing legislation in the European Union (EU). The General Data Protection Regulation (GDPR) aims to reform the existing directive on the topic of personal data protection of EU citizens with a strong emphasis on more control of the citizens over their data and in the establishment of rules for the processing of personal data. OpenEHR is a standard that embodies many principles of interoperable and secure software for electronic health records (EHRs) and has been advocated as the best approach for the development of hospital information systems. OBJECTIVE: This study aimed to understand to what extent the openEHR standard can help in the compliance of EHR systems to the GDPR requirements. METHODS: A list of requirements for an EHR to support GDPR compliance and also a list of the openEHR design principles were made. The requirements were categorized and compared with the principles by experts on openEHR and GDPR. RESULTS: A total of 50 GDPR requirements and 8 openEHR design principles were identified. The openEHR principles conformed to 30% (15/50) of GDPR requirements. All the openEHR principles were aligned with GDPR requirements. CONCLUSIONS: This study showed that the openEHR principles conform well to GDPR, underlining the common wisdom that truly realizing security and privacy requires it to be built in from the start. By using an openEHR-based EHR, the institutions are closer to becoming compliant with GDPR while safeguarding the medical data.

Can openEHR Represent the Clinical Concepts of an Obstetric-Specific EHR - ObsCare Software?

ObsCare is an obstetric-specific Electronic Health Record in use in nine Portuguese obstetric departments. Like other EHRs, it faces major challenges related to semantic interoperability and data quality. openEHR is proposed to address those needs. This study aimed to describe a summary representation of Obscare workflow and to validate whether archetypes in the openEHR Clinical Knowledge Manager repository can represent ObsCare clinical concepts. The study included the phases: a) ObsCare form selection; b) Description of the workflow care process; c) Detailed data extraction; and d) CKM models analysis. 379 variables were analyzed: 219 were fully represented in CKM repository; 99 were partially represented and needed archetype modification; and 61 were not represented and need new archetypes. To conclude, our study showed that the openEHR CKM repository requires further enhancements to be able to fully answer to the needs of an obstetric-specific EHR, the ObsCare software.

An archetype-based testing framework.

With the introduction of EHR two-level modelling and archetype methodologies pioneered by openEHR and standardized by CEN/ISO, we are one step closer to semantic interoperability and future-proof adaptive healthcare information systems. Along with the opportunities, there are also challenges. Archetypes provide the full semantics of EHR data explicitly to surrounding systems in a platform-independent way, yet it is up to the receiving system to interpret the semantics and process the data accordingly. In this paper we propose a design of an archetype-based platform-independent testing framework for validating implementations of the openEHR archetype formalism as a means of improving quality and interoperability of EHRs.

Novel Signal Noise Reduction Method through Cluster Analysis, Applied to Photoplethysmography.

Physiological signals can often become contaminated by noise from a variety of origins. In this paper, an algorithm is described for the reduction of sporadic noise from a continuous periodic signal. The design can be used where a sample of a periodic signal is required, for example, when an average pulse is needed for pulse wave analysis and characterization. The algorithm is based on cluster analysis for selecting similar repetitions or pulses from a periodic single. This method selects individual pulses without noise, returns a clean pulse signal, and terminates when a sufficiently clean and representative signal is received. The algorithm is designed to be sufficiently compact to be implemented on a microcontroller embedded within a medical device. It has been validated through the removal of noise from an exemplar photoplethysmography (PPG) signal, showing increasing benefit as the noise contamination of the signal increases. The algorithm design is generalised to be applicable for a wide range of physiological (physical) signals.

An ontology-based model of clinical information.

In this paper we describe a model of clinical information designed to make health information systems properly interoperable and safely computable. The model is a response to a number of categories of requirements, ranging from the semantic to the performance of software at runtime. We argue that the starting point of a successful model must be an ontological analysis of the process of clinical care delivery, seen as a scientific problem-solving process. From this approach we develop a classification of types of clinical information called the Clinical Investigator Record (CIR) ontology.

EHR query language (EQL)--a query language for archetype-based health records.

OpenEHR specifications have been developed to standardise the representation of an international electronic health record (EHR). The language used for querying EHR data is not as yet part of the specification. To fill in this gap, Ocean Informatics has developed a query language currently known as EHR Query Language (EQL), a declarative language supporting queries on EHR data. EQL is neutral to EHR systems, programming languages and system environments and depends only on the openEHR archetype model and semantics. Thus, in principle, EQL can be used in any archetype-based computational context. In the EHR context described here, particular queries mention concepts from the openEHR EHR Reference Model (RM). EQL can be used as a common query language for disparate archetype-based applications. The use of a common RM, archetypes, and a companion query language, such as EQL, semantic interoperability of EHR information is much closer. This paper introduces the EQL syntax and provides example clinical queries to illustrate the syntax. Finally, current implementations and future directions are outlined.

Towards automatically generating graphical user interfaces from openEHR archetypes.

One of the main challenges in the field of Electronic Health Records (EHRs) is semantic interoperability. To utilise the full potential of interoperable EHR systems they have to be accepted by their users, the health care providers. Good Graphical User Interfaces (GUIs) that support customisation and data validation play a decisive role for user acceptance and data quality. This study investigates the use of openEHR archetypes to automatically generate coherent, customizable, data-validating GUIs. Using the Mozilla XML User Interface Language (XUL) a series of prototypes has been developed. The results show that the automatic generation of GUIs from openEHR archetypes is feasible in principle. Although XUL revealed some problems, the advantages of XML-based GUI languages are evident.

The openEHR Foundation.

The openEHR Foundation is an independent, not-for-profit organisation and community, facilitating the creation and sharing of health records by consumers and clinicians via open-source, standards-based implementations. It was formed as a union of ten-year international R&D efforts in specifying the requirements, information models and implementation of comprehensive and ethico-legally sound electronic health record systems. Between 2000 and 2004 it has grown to having an on-line membership of over 300, published a wide range of EHR information viewpoint specifications. Several groups have now begun collaborative software development, within an open source framework. This chapter summarises the formation of openEHR, its research underpinning, practical demonstrators, the principle design concepts, and the roles openEHR members are playing in international standards.

Unified EHR standards--is convergence possible?

This paper examines the current state of the art in standards for the electronic health record (EHR) and messaging, and proposes a theoretical design basis for the EHR which is formal yet flexible, and which takes into account many of the difficulties experienced in the past. Recommendations are given for how convergence of EHR specifications might occur, in order to achieve a unified standard suitable for all clinical and cultural contexts.

Archetypes and the EHR.

The health information systems of today lack many of the desirable characteristics for clinical care or cost-effective data management which are required for shared care in an ever-changing domain. One of the most important aspects of the clinical information environment is knowledge, as distinct from information. This paper describes how small constraint models of domain concepts, known as archetypes, can be added to the knowledge environment, significantly improving interoperability, software economics and quality of care.

Organoboron-catalyzed regio- and stereoselective formation of ß-2-deoxyglycosidic linkages.

A borinic acid derived catalyst enables regioselective and ß-selective reactions of 2-deoxy- and 2,6-dideoxyglycosyl chloride donors with pyranoside-derived acceptors having unprotected cis-1,2- and 1,3-diol groups. The use of catalysis to promote a ß-selective pathway by enhancement of acceptor nucleophilicity constitutes a distinct approach from previous work, which has been aimed at modulating donor reactivity by variation of protective and/or leaving groups.

Synthesis of cardiac glycoside analogs by catalyst-controlled, regioselective glycosylation of digitoxin.

The cardiac glycoside natural product digitoxin was selectively glycosylated at one of its five hydroxyl groups using a borinic acid derived catalyst. This method provided access to the glycosylation pattern characteristic of a subclass of natural products from Digitalis purpurea. Variation of the glycosyl donor was tolerated, enabling the synthesis of novel cardiac glycoside analogs from readily available materials.

A-ring dihalogenation increases the cellular activity of combretastatin-templated tetrazoles.

The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32-34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G2/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity.