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1. The European medical information framework: A novel ecosystem for sharing healthcare data across Europe

Author

Lovestone, S, Vannieuwenhuyse, B, Visser, PJ, van den Bos, I, Vos, S, Streffer, J, Smith, U, Waterworth, D, Lei, Johan, Rijnbeek, Peter, Oliveira, JL, Van Speybroeck, M, Verbeeck, R, Kalra, D, Nathan, L, Molero, E, Lewi, M, Alexander, M, James, G, Sage, C, Praet, J, Egger, P, Singh, G, Hughes, N, Otorhinolaryngology and Head and Neck Surgery, Medical Informatics, Psychiatrie & Neuropsychologie, and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
MILD COGNITIVE IMPAIRMENT, Medicine (General), Knowledge management, Computer science, BIOMARKERS, Population, EMIF‐AD, Health Informatics, Translational research, DATABASES, Data Protection Directive, R5-920, Health Information Management, SUPPORT, Data Protection Act 1998, media_common.cataloged_instance, EMIF‐MET, European union, education, Experience Report, EMIF-MET, FATTY LIVER-DISEASE, media_common, Ethical code, use case, education.field_of_study, business.industry, DEMENTIA, TRANSLATIONAL RESEARCH, Public Health, Environmental and Occupational Health, EMIF-AD, PLATFORM, Data discovery, PREVALENCE, Sustainability, CLINICAL-RESEARCH, catalogue, Public aspects of medicine, RA1-1270, business, EMIF
Abstract

Introduction The European medical information framework (EMIF) was an Innovative Medicines Initiative project jointly supported by the European Union and the European Federation of Pharmaceutical Industries and Associations, that generated a common technology and governance framework to identify, assess and (re)use healthcare data, to facilitate real‐world data research. The objectives of EMIF included providing a unified platform to support a wide range of studies within two verification programmes—Alzheimer's disease (EMIF‐AD), and metabolic consequences of obesity (EMIF‐MET). Methods The EMIF platform was built around two main data‐types: electronic health record data and research cohort data, and the platform architecture composed of a set of tools designed to enable data discovery and characterisation. This included the EMIF catalogue, which allowed users to find relevant data sources, including the data‐types collected. Data harmonisation via a common data model were central to the project especially for population data sources. EMIF also developed an ethical code of practice to ensure data protection, patient confidentiality and compliance with the European Data Protection Directive, and GDPR. Results Currently 18 population‐based disease agnostic and 60 cohort‐based Alzheimer's data partners from across 14 countries are contained within the catalogue, and this will continue to expand. The work conducted in EMIF‐AD and EMIF‐MET includes standardizing cohorts, summarising baseline characteristics of patients, developing diagnostic algorithms, epidemiological studies, identifying and validating novel biomarkers and selecting potential patient samples for pharmacological intervention. Conclusions EMIF was designed to provide a sustainable model as demonstrated by the sustainability plans for EMIF‐AD. Although network‐wide studies using EMIF were not conducted during this project to evaluate its sustainability, learning from EMIF will be used in the follow‐on IMI‐2 project, European Health Data and Evidence Network (EHDEN). Furthermore, EMIF has facilitated collaborations between partners and continues to promote a wider adoption of principles, technology and architecture through some of its continued work.

Published
2020

2. Executive function mediates the prospective association between neurostructural differences within the central executive network and anti-social behavior after childhood traumatic brain injury

Author

Ryan, NP, Catroppa, C, Hughes, N, Painter, FL, Hearps, S, Beauchamp, MH, Anderson, VA, Ryan, NP, Catroppa, C, Hughes, N, Painter, FL, Hearps, S, Beauchamp, MH, and Anderson, VA

Abstract

BACKGROUND: Despite increasing evidence of a link between early life brain injury and anti-social behavior, very few studies have assessed factors that explain this association in children with traumatic brain injury (TBI). One hypothesis suggests that childhood TBI elevates risk for anti-social behavior via disruption to anatomically distributed neural networks implicated in executive functioning (EF). In this longitudinal prospective study, we employed high-resolution structural neuroimaging to (a) evaluate the impact of childhood TBI on regional morphometry of the central executive network (CEN) and (b) evaluate the prediction that lower EF mediates the prospective relationship between structural differences within the CEN and postinjury anti-social behaviors. METHODS: This study involved 155 children, including 112 consecutively recruited, hospital-confirmed cases of mild-severe TBI and 43 typically developing control (TDC) children. T1-weighted brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 137 children [TBI: n = 103; TDC: n = 34]. All participants were evaluated using direct assessment of EF 6 months postinjury, and parents provided ratings of anti-social behavior 12 months postinjury. RESULTS: Severe TBI was associated with postinjury volumetric differences within the CEN and its putative hub regions. When compared with TD controls, the TBI group had significantly worse EF, which was associated with more frequent anti-social behaviors and abnormal CEN morphometry. Mediation analysis indicated that reduced EF mediated the prospective association between postinjury volumetric differences within the CEN and more frequent anti-social behavior. CONCLUSIONS: Our longitudinal prospective findings suggest that detection of neurostructural abnormalities within the CEN may aid in the early identification of children at elevated risk for postinjury executive dysfunction, which may in turn contribute to chronic anti-social behav

Published
2021

4. Language impairment and comorbid vulnerabilities among young people in custody

Author

Hughes, N, Chitsabesan, P, Bryan, K, Borschmann, R, Swain, N, Lennox, C, Shaw, J, Hughes, N, Chitsabesan, P, Bryan, K, Borschmann, R, Swain, N, Lennox, C, and Shaw, J

Abstract

BACKGROUND: While the prevalence of language and communication difficulties among young people in custody is well established, holistic understanding of the complexity and co-occurrence of additional vulnerabilities among this population are rare. METHODS: Ninety-three young people in a young offenders institution in England were assessed using the Comprehensive Health Assessment Tool, the Test of Word Knowledge, and a range of additional assessments of communication, cognition, and neurodevelopmental difficulties. RESULTS: Forty-seven percent of the young people demonstrated an aspect of language skills significantly below the population average, with more than one in four identified as having impairment. Only one in four of those with an impairment had previously accessed speech and language services. Language needs were associated with difficulties with social communication and nonverbal cognition, as well as higher risk of self-harm and substance misuse. CONCLUSIONS: Earlier identification of language difficulties requires routine assessment of young people at risk of engagement in offending behavior. Where language difficulties are identified, holistic assessments of needs should be undertaken. There is a need for speech and language therapy provision within youth justice services, as well as in other services accessed by young people at risk of engagement in offending.

Published
2017

8. Hypoxia modulates the activity of a series of clinically approved tyrosine kinase inhibitors

Author

Ahmadi, M, Ahmadihosseini, Z, Allison, S J, Begum, S, Rockley, K, Sadiq, M, Chintamaneni, S, Lokwani, R, Hughes, N, and Phillips, R M

Subjects
RM, Dose-Response Relationship, Drug, Cell Survival, Antineoplastic Agents, Apoptosis, Protein-Tyrosine Kinases, MAP Kinase Kinase Kinases, Research Papers, Cell Hypoxia, ErbB Receptors, Oxygen, Inhibitory Concentration 50, src-Family Kinases, Drug Resistance, Neoplasm, Neoplasms, MCF-7 Cells, Humans, raf Kinases, Molecular Targeted Therapy, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Protein Kinase Inhibitors, Signal Transduction
Abstract

BACKGROUND AND PURPOSE\ud Hypoxia in tumours is known to cause resistance to conventional chemotherapeutic drugs. In contrast, little is known about the effects of hypoxia on targeted anti-cancer drugs. This study evaluated the effect of hypoxia on a series of clinically approved tyrosine kinase inhibitors (TKIs).\ud \ud EXPERIMENTAL APPROACH\ud The effect of hypoxia (0.1% oxygen) on the activity of conventional cytotoxic drugs (5-fluorouracil, doxorubicin and vinblastine), the hypoxia-activated prodrug tirapazamine and 9 TKIs was determined in a panel of cell lines. Where hypoxia had a marked effect on chemosensitivity, Western blot analysis was conducted to determine the effect of hypoxia on target expression and the effect of TKIs on cell signalling response under aerobic and hypoxic conditions.\ud \ud KEY RESULTS\ud Three patterns of chemosensitivity were observed: resistance under hypoxia, equitoxic activity against hypoxic and aerobic cells, and preferential cytotoxicity to hypoxic cells. Significant hypoxia selectivity (independent of HIF1) was observed in the case of dasatinib and this correlated with the ability of dasatinib to inhibit phosphorylation of Src at tyrosine 530. Sorafenib was significantly less effective under hypoxic conditions but resistance did not correlate with hypoxia-induced changes in Raf/MEK/ERK signalling.\ud \ud CONCLUSIONS AND IMPLICATIONS\ud Hypoxia influences the activity of TKIs but in contrast to conventional cytotoxic drugs, preferential activity against hypoxic cells can occur. The search for hypoxia-targeted therapies has been long and fruitless and this study suggests that some clinically approved TKIs could preferentially target the hypoxic fraction of some tumour types.

Published
2014

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