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.

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.

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.

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.

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.

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.

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.

Stress and unaided smoking cessation: a prospective investigation.

A prospective design was used to determine the outcomes associated with unaided smoking cessation and the influence of stress on cessation. Heavy smokers (N = 308) completed stress-related measures and were then recontacted at 1, 6, and 12 months. At each follow-up, they indicated their smoking status (which was confirmed by collateral report and biochemical tests) and completed several stress-related questionnaires. Results indicated that 33% of subjects smoked continuously throughout the year, 39% quit briefly but subsequently relapsed, and 15% quit (confirmed biochemically). An additional 7% reported that they had quit, but this could not be confirmed, and 6% were lost to follow-up. Compared with nonquiters, quitters reported less perceived stress, greater self-efficacy, greater use of problem solving and cognitive restructuring, and less reliance on wishful thinking, self-criticism, and social withdrawal. A model to forecast quitting was built and cross-validated.

The role of cytokines in the failing human heart.

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure, no single conceptual paradigm has withstood the test of time. In this regard, recent studies have shown that a class of biologically active molecules, generically referred to as cytokines, are overexposed in heart failure. This article will review recent clinical and experimental material that suggest proinflammatory (stress activated) cytokines such as tumor necrosis factor-alpha (TFN-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) may play a role in the pathogenesis of congestive heart failure. The scope of this article includes an overview of the biology of cytokines in the heart, as well as review of the clinical studies that have documented elevated levels of cytokines and cytokine receptors in patients with heart failure.

Degnala disease in buffaloes and cattle: epidemiological investigations.

An attempt was made to identify the epizootiological features associated with Degnala disease occurring in the rice-growing areas of the Indian subcontinent and believed to be associated with mycotoxins. Epizootiological studies were made on disease outbreaks involving 370 herds from 136 villages of Haryana, India, during the years 1968 to 1978. They revealed that the disease, besides being seasonal and regional in occurrence, has a tendency to confine itself to a particular herd or field. All the disease outbreaks occurred during the winter and were associated with the feeding of rice straw. The incidence of the disease, varied from year to year, assuming serious proportions in certain years. The morbidity and mortality rates were 61.61% and 13.93%, respectively, in buffaloes and 13.49% and 2.41% in cattle, with no sex and age differences. Factors such as housing conditions of animals, shape of rice straw stacks, feeding practices, and use of pesticides and fertilizers had no bearing on the occurrence of the disease. Inadequate postharvest drying of rice plants before stacking and stacking at low-lying places or near water channels were the factors identified with occurrence of the disease. In the case of affected herds, 72.07% of the owners stacked rice straw immediately after harvesting, without allowing the plants to dry adequately, versus 10.60% of the owners of unaffected herds. Similarly, 72.97% of the farmers owning affected herds were found to stack rice straw either in low-lying areas or near canals and other water channels, versus 22.73% of the farmers of control herds.

Cardiac remodeling as a consequence and cause of progressive heart failure.

Natural history studies in heart failure have shown that increases in left ventricular (LV) volume and LV mass are directly related to future deterioration in LV performance and a less favorable clinical course. Despite the recognized importance of remodeling in heart failure, very little is known about the basic mechanisms that lead to cardiac remodeling. In this review, we will summarize recent clinical and experimental studies that highlight the importance of the remodeling process during the progression of heart failure. The intent of this review is to provide an integrated view of the mechanisms that contribute to LV remodeling at the cellular level, the myocardial level, and the level of the chamber.

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.

A CORBA-based integration of distributed electronic healthcare records using the synapses approach.

The ability to exchange in a meaningful, secure, and simple fashion relevant healthcare data about patients is seen as vital in the context of efficient and cost-effective shared or team-based care. The electronic healthcare record (EHCR) lies at the heart of this information exchange, and it follows that there is an urgent need to address the ability to share EHCR's or parts of records between carers and across distributed health information systems. This paper presents the Synapses approach to sharing based on a standardized shared record, the Federated Healthcare Record, which is implemented in an open and flexible manner using the Common Object Request Broker Architecture (CORBA). The architecture of the Federated Healthcare Record is based on the architecture proposed by the Technical Committee 251 of the European Committee for Standardization.

Thymus derived rosette forming cell counts and lymphocyte response to phytohaemagglutinin in animals affected with squamous cell carcinoma of horn.

A non-immune erythrocyte rosette test was used to examine the levels of thymus derived lymphocytes in the peripheral blood of 12 bovine horn cancer patients and an equal number of age-matched unaffected controls. The proportion of rosette forming cells (RFC) in horn cancer affected animals was found to be approximately half that of unaffected controls. Phytohaemagglutinin was used to examine lymphocyte transformation (LT), in vitro, of lymphocytes from the peripheral blood of six horn cancer affected animals as well as unaffected controls. Transformation values in affected animals were found to be much lower than in age-matched controls. Lower values of RFC as well as LT in the horn cancer affected animals compared with unaffected controls are suggestive of depression of cell mediated immunity in this condition.

Electronic health records: the European scene.

Caring for patients' health problems relies increasingly on sharing information between clinical departments and disciplines and with managers. The medical record of the future will need to provide a flexible and shareable framework for recording and analysing the consultation process. The advanced informatics in medicine (AIM) programme seeks to encourage research and development in telemedicine in areas that are beyond the scope of any one country. It includes many European projects attempting to define the best storage and transmission formats for such diverse data types as laboratory results, biosignals, x ray images, and photographs, and in clinical specialties varying from intensive care to medicine for elderly people. One example, the good European health record project, is developing a model architecture for computerised health records across Europe that is capable of operating on a wide variety of computer hardwares and will also be able to communicate with many different information systems. The ultimate European health record will be comprehensive and medicolegally acceptable across clinical domains, hold all data types, and be automatically translated between languages.

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.

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.

Development and psychometric evaluation of the Primary Appraisal of Smoking Cessation Inventory.

For this study, we developed and evaluated the psychometric properties of the Primary Appraisal of Smoking Cessation Inventory (PASCI), a self-report measure designed to assess the perceived gains and losses associated with quitting smoking based on the theoretical model of stress described by Lazarus and Folkman (1984). We administered the 26-item PASCI and two other questionnaires to 244 current smokers and to 30 ex-smokers. Item analyses indicated that two items on the PASCI should be deleted due to low item-total correlations. A principal components analysis of the remaining 24 items identified two separate and independent factors, Losses and Gains, and scores on the subscales of both factors were internally consistent and stable over repeated administrations. The validity of the PASCI was established by examining the relationship between smoking status and scores on the PASCI subscales and by finding significant correlations between the PASCI and the Decisional Balance Scale (Velicer, DiClemente, Prochaska, & Brandenburg, 1985), a measure conceptually similar to the construct measured by the PASCI. We concluded that the PASCI is reliable and valid and can be used to investigate the relationship between primary appraisal and smoking cessation.