The European Institute for Innovation through Health Data.

The European Institute for Innovation through Health Data (i~HD, www.i-hd.eu) has been formed as one of the key sustainable entities arising from the Electronic Health Records for Clinical Research (IMI-JU-115189) and SemanticHealthNet (FP7-288408) projects, in collaboration with several other European projects and initiatives supported by the European Commission. i~HD is a European not-for-profit body, registered in Belgium through Royal Assent. i~HD has been established to tackle areas of challenge in the successful scaling up of innovations that critically rely on high-quality and interoperable health data. It will specifically address obstacles and opportunities to using health data by collating, developing, and promoting best practices in information governance and in semantic interoperability. It will help to sustain and propagate the results of health information and communication technology (ICT) research that enables better use of health data, assessing and optimizing their novel value wherever possible. i~HD has been formed after wide consultation and engagement of many stakeholders to develop methods, solutions, and services that can help to maximize the value obtained by all stakeholders from health data. It will support innovations in health maintenance, health care delivery, and knowledge discovery while ensuring compliance with all legal prerequisites, especially regarding the insurance of patient's privacy protection. It is bringing multiple stakeholder groups together so as to ensure that future solutions serve their collective needs and can be readily adopted affordably and at scale.

Discussion of "Combining Health Data Uses to Ignite Health System Learning".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Combining Health Data Uses to Ignite Health System Learning" written by John D. Ainsworth and Iain E. Buchan [1]. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Ainsworth and Buchan. In subsequent issues the discussion can continue through letters to the editor. With these comments on the paper "Combining Health Data Uses to Ignite Health System Learning", written by John D. Ainsworth and Iain E. Buchan [1], the journal seeks to stimulate a broad discussion on new ways for combining data sources for the reuse of health data in order to identify new opportunities for health system learning. An international group of experts has been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.

On moving targets and magic bullets: Can the UK lead the way with responsible data linkage for health research?

PURPOSE: To provide an overview of essential elements of good governance of data linkage for health-related research, to consider lessons learned so far and to examine key factors currently impeding the delivery of good governance in this area. Given the considerable hurdles which must be overcome and the changing landscape of health research and data linkage, a principled, proportionate, risk-based approach to governance is advocated. DISCUSSION: In light of the considerable value of data linkage to health and well-being, the United Kingdom aspires to design and deliver good governance in health-related research. A string of projects have been asking: what does good governance look like in data linkage for health research? It is argued here that considerable progress can and must be made in order to develop the UK's contribution to future health and wealth economies, particularly in light of mis-start initiatives such as care.data in NHS England. Discussion centres around lessons learned from previous successful health research initiatives, identifying those governance mechanisms which are essential to achieving good governance. CONCLUSION: This article suggests that a crucial element in any step-increase of research capability will be the adoption of adaptive governance models. These must recognise a range of approaches to delivering safe and effective data linkage, while remaining responsive to public and research user expectations and needs as these shift and change with time and experience. The targets are multiple and constantly moving. There is not--nor should we seek--a single magic bullet in delivering good governance in health research.

Electronic health records: new opportunities for clinical research.

Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.

A review of the empirical evidence of the healthcare benefits of personal health records.

OBJECTIVES: This literature review sought to identify the established evidence of the health and healthcare benefits (or harms) from the use of electronic personal health records (PHRs) and PHR systems. METHODS: The definition of a PHR published in ISO 14292 was used to scope this review and the search strategy. Publications were included if the introduction of a PHR was the primary intervention, and if its evaluation met one of the Cochrane EPOC Group criteria. Studies were excluded if they only reported the design or basic user acceptance of a PHR system without an assessment of its impact on individuals and/or their health care. The impacts were classified according to the six aims of 21st-century health care defined by the US Institute of Medicine. RESULTS: Searches were conducted in PubMed in December 2012. Out of 741 papers that met our initial search criteria, 31 were retained after title and abstract screening. After full paper review 5 studies were found to report original evidence of impact. Of these, three reported beneficial impacts on effectiveness, one on patient centredness, and one study reported impact on both aims. No harmful effects were reported. CONCLUSIONS: Although this literature review did identify some evidenced benefits from the use of PHRs and systems, our main observation is that there are very few studies published that seek to formally evaluate impact. The majority of publications we screened documented designs or basic user acceptance. Further investment in evaluation is needed to inform the evolution of this field.

Dealing with the archetypes development process for a regional EHR system.

OBJECTIVES: This paper aims to present the archetype modelling process used for the Health Department of Minas Gerais State, Brazil (SES/MG), to support building its regional EHR system, and the lessons learned during this process. METHODS: This study was undertaken within the Minas Gerais project. The EHR system architecture was built assuming the reference model from the ISO 13606 norm. The whole archetype development process took about ten months, coordinated by a clinical team co-ordinated by three health professionals and one systems analyst from the SES/MG. They were supported by around 30 health professionals from the internal SES/MG areas, and 5 systems analysts from the PRODEMGE. Based on a bottom-up approach, the project team used technical interviews and brainstorming sessions to conduct the modelling process. RESULTS: The main steps of the archetype modelling process were identified and described, and 20 archetypes were created. LESSONS LEARNED: -The set of principles established during the selection of PCS elements helped the clinical team to keep the focus in their objectives;-The initial focus on the archetype structural organization aspects was important;-The data elements identified were subjected to a rigorous analysis aimed at determining the most suitable clinical domain;-Levelling the concepts to accommodate them within the hierarchical levels in the reference model was definitely no easy task, and the use of a mind mapping tool facilitated the modelling process;-Part of the difficulty experienced by the clinical team was related to a view focused on the original forms previously used;-The use of worksheets facilitated the modelling process by health professionals;-It was important to have a health professional that knew about the domain tables and health classifications from the Brazilian Federal Government as member in the clinical team. CONCLUSION: The archetypes (referencing terminology, domain tables and term lists) provided a favorable condition for the use of a controlled vocabulary between the central repository and the EMR systems and, probably, will increase the chances of preserving the semantics from the knowledge domain. Finally, the reference model from the ISO 13606 norm, along with the archetypes, proved sufficient to meet the specificities for the creation of an EHR system for basic healthcare in a Brazilian state.

Transient pseudohypoaldosteronism masquerading as congenital adrenal hyperplasia.

We report a six-week-old boy with genitourinary structural abnormalities who presented with profound hyponatraemia and hyperkalaemia due to transient type 1 pseudohypoaldosteronism (PHA) precipitated by a urinary tract infection (UTI), which responded rapidly to intravenous saline and antibiotics. In infants with structural abnormalities of the urinary tract, we wish to highlight the importance of recognizing type 1 PHA and its association with a UTI since prompt and appropriate treatment rapidly corrects the associated metabolic abnormalities. Conversely, the identification of type 1 PHA in an infant should precipitate a search for a UTI and structural abnormalities of the urinary tract.

Analysis of Clinical Record Data for Anticoagulation Management within an EHR System.

OBJECTIVES: This paper reports an evaluation of the properties of a generic electronic health record information model that were actually required and used when importing an existing clinical application into a generic EHR repository. METHOD: A generic EHR repository and system were developed as part of the EU Projects Synapses and SynEx. A Web application to support the management of anticoagulation therapy was developed to interface to the EHR system, and deployed within a north London hospital with five years of cumulative clinical data from the previous existing anticoagulation management application. This offered the opportunity to critique those parts of the generic EHR that were actually needed to represent the legacy data. RESULTS: The anticoagulation records from 3,226 patients were imported and represented using over 900,000 Record Components (i.e. each patient's record contained on average 289 nodes), of which around two thirds were Element Items (i.e. value-containing leaf nodes), the remainder being container nodes (i.e. headings and sub-headings). Each node is capable of incorporating a rich set of context properties, but in reality it was found that many properties were not used at all, and some infrequently (e.g. only around 0.5% of Record Components had ever been revised). CONCLUSIONS: The process of developing generic EHR information models, arising from research and embodied within new-generation interoperability standards and specifications, has been strongly driven by requirements. These requirements have been gathered primarily by collecting use cases and examples from clinical communities, and been added to successive generations of these models. A priority setting approach has not to date been pursued - all requirements have been received and almost invariably met. This work has shown how little of the resulting model is actually needed to represent useful and usable clinical data. A wider range of such evaluations, looking at different kinds of existing clinical system, is needed to balance the theoretical requirements gathering processes, in order to result in EHR information models of an ideal level of complexity.

Medical and Surgical Management of Keratomycosis.

BACKGROUND: Fungal keratitis is a diagnostic and therapeutic challenge to the ophthalmologist. If not treated energetically it results in marked ocular morbidity and permanent visual loss. METHODS: Twenty five patients of fungal keratitis were studied for their response to management and final visual outcome. RESULT: Males outnumbered females. Medical treatment was successful in 72% cases, while 28% required surgical intervention. Keratoplasty was done in five patients out of which graft was clear in four after one year of follow up. Three of these underwent optical keratoplasty since therapeutic grafts became opaque. CONCLUSION: Early recognition of the disease and institution of prompt therapy is the key to successful management in fungal keratitis. Occasionally surgical management is required to preserve anatomical integrity of the globe and to salvage useful vision.

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

OBJECTIVES: To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. DESIGN: Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. SETTING: Six UK paediatric departments. PARTICIPANTS: 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as < or =2 complete bowel movements per week and one of the following: pain on defaecation on 25% of days; > or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. MAIN OUTCOME MEASURES: Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. RESULTS: The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; p<0.001). Further significant differences in favour of PEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (p<0.001), stool consistency (p<0.001) and percentage of hard stools (p = 0.001). Treatment related adverse events (all mild or moderate) occurred in similar numbers of children on PEG+E (41%) and placebo during treatment (45%). CONCLUSIONS: PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

Electronic health record standards.

OBJECTIVES: This paper seeks to provide an overview of the initiatives that are proceeding internationally to develop standards for the exchange of electronic health record (EHR) information between EHR systems. METHODS: The paper reviews the clinical and ethico-legal requirements and research background on the representation and communication of EHR data, which primarily originates from Europe through a series of EU funded Health Telematics projects over the past thirteen years. The major concepts that underpin the information models and knowledge models are summarised. These provide the requirements and the best evidential basis from which HER communications standards should be developed. RESULTS: The main focus of EHR communications standardisation is presently occurring at a European level, through the Committee for European Normalisation (CEN). The major constructs of the CEN 13606 model are outlined. Complementary activity is taking place in ISO and in HL7, and some of these efforts are also summarised. CONCLUSION: There is a strong prospect that a generic EHR interoperability standard can be agreed at a European (and hopefully international) level. Parts of the challenge of EHR interoperability cannot yet be standardised, because good solutions to the preservation of clinical meaning across heterogeneous systems remain to be explored. Further research and empirical projects are therefore also needed.

Security and confidentiality approach for the Clinical E-Science Framework (CLEF).

OBJECTIVES: CLEF is an MRC sponsored project in the E-Science programme that aims to establish methodologies and a technical infrastructure for the next generation of integrated clinical and bioscience research. METHODS: The heart of the CLEF approach to this challenge is to design and develop a pseudonymised repository of histories of cancer patients that can be accessed by researchers. Robust mechanisms and policies have been developed to ensure that patient privacy and confidentiality are preserved while delivering a repository of such medically rich information for the purposes of scientific research. RESULTS: This paper summarises the overall approach adopted by CLEF to meet data protection requirements, including the data flows, pseudonymisation measures and additional monitoring policies that are currently being developed. CONCLUSION: Once evaluated, it is hoped that the CLEF approach can serve as a model for other distributed electronic health record repositories to be accessed for research.

Health care seeking pattern of tuberculosis patients attending an urban TB clinic in Delhi.

The study of pattern of health care seeking of tuberculosis patients is important for identification of factors which might influence delayed reporting of tuberculosis cases, especially the open pulmonary cases. Consecutive 301 pulmonary TB patients, belonging to any of the categories under RNTCP, diagnosed at New Delhi Tuberculosis Centre or its sub-centres over a six-month period were assessed for health care seeking pattern. "Delay" was defined as the time over 3 weeks that a case took to report to the area TB facility. 43.2% patients reported to the TB health facility on their own and others were referred by government hospitals (34.9%) and general practitioners (21.9%). Median delay over 3 weeks was 2.69 weeks for all three categories combined, with a significantly higher delay (3.41 weeks) for retreatment cases as compared to new cases (2.13 weeks). No significant differences were observed in health seeking delay in relation to sex, income, literacy status and source of referral and sputum status. Extensive health education activities can reduce this period of delay in health seeking and result in reduction of transmission of tuberculosis to healthy members of the family and community.

Information architecture for a federated health record server.

This paper describes the information models that have been used to implement a federated health record server and to deploy it in a live clinical setting. The authors, working at the Centre for Health Informatics and Multiprofessional Education (University College London), have built up over a decade of experience within Europe on the requirements and information models that are needed to underpin comprehensive multi-professional electronic health records. This work has involved collaboration with a wide range of health care and informatics organisations and partners in the healthcare computing industry across Europe though the EU Health Telematics projects GEHR, Synapses, EHCR-SupA, SynEx and Medicate. The resulting architecture models have fed into recent European standardisation work in this area, such as CEN TC/251 ENV 13606. UCL has implemented a federated health record server based on these models which is now running in the Department of Cardiovascular Medicine at the Whittington Hospital in North London. The information models described in this paper reflect a refinement based on this implementation experience.

Experimental options in the treatment of heart failure: the role of cytokine antagonism.

Recent studies have identified the importance of biologically active molecules, such as neurohormones, as mediators of disease progression in heart failure. More recently, it has become apparent that, in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article will review recent clinical material that suggests that tumor necrosis factor, a pro-inflammatory cytokine, may contribute to disease progression in heart failure by virtue of the direct toxic effects that this molecule exerts on the heart and circulation. In addition, this article reviews the existing clinical literature, which suggests that cytokine antagonism is safe and potentially effective in patients with heart failure.

Nitric oxide provokes tumor necrosis factor-alpha expression in adult feline myocardium through a cGMP-dependent pathway.

BACKGROUND: The mechanism(s) responsible for the persistent coexpression of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the failing heart is unknown. METHODS AND RESULTS: To determine whether NO was sufficient to provoke TNF-alpha biosynthesis, we examined the effects of an NO donor, S-nitroso-N-acetyl penicillamine (SNAP), in buffer-perfused Langendorff hearts. SNAP (1 micromol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF-alpha mRNA and protein biosynthesis in adult cat hearts. The effects of SNAP were completely abrogated by a NO quenching agent, 2-(4-carboxyphenyl)-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (C-PTIO), and mimicked by sodium nitroprusside. Electrophoretic mobility shift assays demonstrated that SNAP treatment led to the rapid induction of nuclear factor kappa-beta (NF-kappaB) but not AP-1. The importance of the cGMP pathway in terms of mediating NO-induced TNF-alpha biosynthesis was shown by studies that demonstrated that 8-bromo-cGMP mimicked the effects of SNAP and that the effects of SNAP could be completely abrogated using a cGMP antagonist, 1H-(1,2, 4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or protein kinase G antagonist (Rp-8-Br-cGMPS). SNAP and 8-Br-cGMP were both sufficient to lead to the site-specific phosphorylation (serine 32) and degradation of IkappaBalpha in isolated cardiac myocytes. Finally, protein kinase G was sufficient to directly phosphorylate IkappaBalpha on serine 32, a critical step in the activation of NF-kappaB. CONCLUSIONS: These studies show that NO provokes TNF-alpha biosynthesis through a cGMP-dependent pathway, which suggests that the coincident expression of TNF-alpha and NO may foster self-sustaining positive autocrine/paracrine feedback inflammatory circuits within the failing heart.