Using electronic health records to support clinical trials: a report on stakeholder engagement for EHR4CR

Background. The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. Methods. Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. Results. 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. Conclusions. There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform

Effect of selected plant species within biodiverse pasture on in vitro fatty acid biohydrogenation and tissue fatty acid composition of lamb

The effect of botanical diversity on supply of polyunsaturated fatty acids (PUFA) to ruminants in vitro, and the fatty acid (FA) composition of muscle in lambs was investigated. Six plant species, commonly grown as part of UK herbal ley mixtures (Trifolium pratense, Lotus corniculatus, Achillea millefolium, Centaurea nigra, Plantago lanceolata and Prunella vulgaris), were assessed for FA profile, and in vitro biohydrogenation of constituent PUFA, to estimate intestinal supply of PUFA available for absorption by ruminants. Modelling the in vitro data suggested that L. Corniculatus and P. Vulgaris had the greatest potential to increase 18:3 n-3 supply to ruminants, having the highest amounts escaping in vitro biohydrogenation . Biodiverse pastures were established using the six selected species, under-sown in a perennial ryegrass-based sward. Lambs were grazed (~50 days) on biodiverse or control pastures and the effects on the FA composition of m. longissimus thoracis (lean and subcutaneous fat) and m. semimembranosus (lean) were determined. Biodiverse pasture increased 18:2 n-6 and 18:3 n-3 contents of m. semimembranosus (+14.8 and +7.2 mg/100g tissue respectively) and the subcutaneous fat of m. l. thoracis (+158 and +166 mg/100g tissue respectively) relative to feeding a perennial ryegrass pasture. However, there was no effect on total concentrations of saturated FA in the tissues studied. It was concluded that enhancing biodiversity had a positive impact on muscle FA profile reflected by increased levels of total PUFA

Study of diffusion weighted MRI as a predictive biomarker of response during radiotherapy for high and intermediate risk squamous cell cancer of the oropharynx: The MeRInO study

Introduction and background: A significant proportion of patients with intermediate and high risk squamous cell cancer of the oropharynx (OPSCC) continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity of the current combination of intensified dose per fraction radiotherapy and platinum based chemotherapy limits further uniform intensification. If a predictive biomarker for outcomes from CRT can be identified during treatment then individualised and adaptive treatment strategies may be employed. Methods/design: The MeRInO study is a prospective observational imaging study of patients with intermediate and high risk, locally advanced OPSCC receiving radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion coefficient (ADC) measurements will be made on each scan for previously specified target lesions (primary and lymph nodes) and change in ADC calculated. Patients will be followed up and disease status for each target lesion noted. The primary aim of the MeRInO study is to determine the threshold change in ADC from baseline to week 3 of RT that may identify the sub-group of non-responders during treatment. Discussion: The use of DW-MRI as a predictive biomarker during RT for SCC H&N is in its infancy but studies to date have found that response to treatment may indeed be predicted by comparison of DW-MRI carried out before and during treatment. However, previous studies have included all sub-sites and biological sub-types. Establishing ADC thresholds that predict for local failure is an essential step towards using DW-MRI to improve the therapeutic ratio in treating SCC H&N. This would be done most robustly in a specific H&N sub-site and in sub-types with similar biological behaviour. The MeRInO study will help establish these thresholds in OPSCC

Complete Genome Sequence and Comparative Metabolic Profiling of the Prototypical Enteroaggregative Escherichia coli Strain 042

Background \ud Escherichia coli can experience a multifaceted life, in some cases acting as a commensal while in other cases causing intestinal and/or extraintestinal disease. Several studies suggest enteroaggregative E. coli are the predominant cause of E. coli-mediated diarrhea in the developed world and are second only to Campylobacter sp. as a cause of bacterial-mediated diarrhea. Furthermore, enteroaggregative E. coli are a predominant cause of persistent diarrhea in the developing world where infection has been associated with malnourishment and growth retardation. \ud \ud Methods \ud In this study we determined the complete genomic sequence of E. coli 042, the prototypical member of the enteroaggregative E. coli, which has been shown to cause disease in volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains revealing previously uncharacterised virulence factors including a variety of secreted proteins and a capsular polysaccharide biosynthetic locus. In addition, by using Biolog™ Phenotype Microarrays we have provided a full metabolic profiling of E. coli 042 and the non-pathogenic lab strain E. coli K-12. We have highlighted the genetic basis for many of the metabolic differences between E. coli 042 and E. coli K-12. \ud \ud Conclusion \ud This study provides a genetic context for the vast amount of experimental and epidemiological data published thus far and provides a template for future diagnostic and intervention strategies

Using electronic health records to support clinical trials : a report on stakeholder engagement for EHR4CR

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115189, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution.BACKGROUND: The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. METHODS: Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. RESULTS: 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. CONCLUSIONS: There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform.Publisher PDFPeer reviewe

Displays and claims of understanding in conversation by people with aphasia

Background: There is scope for additional research into the specific linguistic and sequential structures used in speech and language therapist (SLT)-led therapeutic conversations with people with aphasia (PWA). Whilst there is some evidence that SLTs use different conversational strategies than the partners of PWA, research to date has focussed mainly on measuring the effects of conversation-based therapies—not on analysing therapeutic conversations taking place between SLTs and PWA. Aims: This paper presents an analysis of the use of oh-prefacing by some PWA during therapeutic supported conversations with SLTs. Methods & Procedures: Normally occurring therapeutic conversations between SLTs and PWA after stroke were qualitatively analysed using Conversation Analysis. Interactions with five PWA were video-recorded, involving three different specialist stroke SLTs. Outcomes & Results: The analysis revealed a difference in the way some PWA use turns that display understanding (e.g., oh right) versus those that continue the conversation, merely claiming understanding (e.g., right). This use of oh-prefacing is similar to that described in the literature on typical conversations. In our data, SLTs are shown to treat oh-prefaced turns differently from non-oh-prefaced turns, by pursuing the topic in the latter, and progressing on to a new topic in the former. Conclusions: At least some PWA use oh-prefacing in the same way as non-language-impaired adults to display understanding of information versus merely claiming to understand. The SLTs in our data are shown to treat non-oh-prefaced turns as mere claims of understanding by providing the PWA with additional information, using supported conversation techniques, and pursuing additional same-topic talk, whereas oh-prefaced turns are treated as displays of understanding by being confirmed, and leading to changes of topic. This study is a first step in providing SLTs with a clearer understanding of the ways in which they are assessing the understanding of PWA, which may in turn help them better support non-therapy staff

Long-term prognostic value of dobutamine stress echocardiography in patients with atrial fibrillation

STUDY OBJECTIVE: To assess the long-term prognostic value of dobutamine stress echocardiography (DSE) for cardiac events (cardiac death, myocardial infarction, and late revascularization) in patients with atrial fibrillation (AF). METHODS: Baseline ECGs were studied in patients undergoing DSE between 1989 and 1998. Sixty-nine patients had AF before DSE. Prognostic value of DSE in these patients was compared with a control group who had sinus rhythm (n = 1,664). The presence of stress-induced ischemia was noted for every patient. The mean follow-up period was 35 months (range, 6 to 84 months). Data are presented as hazards ratio (HR) with 95% confidence interval (CI). RESULTS: Heart rate at rest was higher in patients with AF (77 +/- 15 beats/min vs 73 +/- 14 beats/min; p = 0.04); however, double product at peak stress was not different between patients with AF and sinus rhythm (17,602 vs 17,169, respectively; p = 0.46). In patients with AF, target heart rate was achieved at a lower dobutamine dose (33 +/- 8 microg/kg/min vs 35 +/- 9 microg/kg/min; p = 0.01). Cardiac arrhythmias occurred more frequently (12% vs 5%; p = 0.001) in patients with AF during DSE. During a follow-up period of 7 years, cardiac death occurred in 5 patients, myocardial infarction in 2 patients, and late revascularization in 10 patients. Prognostic value of DSE for all late cardiac events was similar in patients with AF (HR, 3.0; 95% CI, 0.9 to 9.5) and sinus rhythm (HR, 3.4; 95% CI, 2.7 to 4.3; p = 0.85). CONCLUSION: The prognostic value of DSE for late cardiac events is maintained in patients with AF

Development of a lightweight camera for high altitude platform systems

We describe the development of a lightweight, high-resolution surveillance camera for deployment on high altitude platform systems. The instrument is designed to operate at an altitude of ∼20 km and has an expected ground resolution of better than 120 mm with an appropriate sensor. While designed specifically for imaging at visible wavelengths, it is shown that the design is capable of diffraction-limited imaging at NIR and SWIR wavelengths up to 2.5 μm. We have combined a range of materials from aluminum and titanium alloys through to carbon fiber reinforced plastic to produce an instrument with structural components that match the thermal expansion of the optical glasses used. The use of these materials has resulted in an instrument that weighs <2 kg, including a sensor package, and is designed to weigh <3 kg once integrated with an enclosure and actuated gimbal. The successful testing of two prototype systems is described, including several design outcomes from the program intended for implementation in advance of flight trials

The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961–/– mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood