News Article | May 4, 2017
Prosthetic implants with enhanced resistance to bacterial infection could improve patient safety while reducing the use of antibiotics. Most prosthetics carry a low risk of infection of below one per cent. But where implants are inserted following an accident, or must be produced at the hospital, the risk of infection can increase significantly, to up to 50 per cent. Treating an infection involves removing the prosthetic and implanting a material that releases high levels of antibiotics to the site. This not only threatens the health of the patient, but risks adding to the rise of antibiotic-resistant bacteria. Now, in an EPSRC-funded project, researchers at Birmingham University are developing implant designs and 3D printing techniques to produce surfaces that are resistant to bacterial contamination. The team will combine technology to embed silver into the material used to build implants, with additive layer manufacturing to produce the prosthetics, according to Birmingham’s Prof. Liam Grover. Using selective laser melting, they will use lasers to fuse powders together layer by layer, creating a porous structure to which the bacterial-resistant silver can be added. Their first target for the technology will be to reduce infections following the implantation of metal plates into the skull. These cranial implants must be refined to fit the patient. As a result, they are typically produced in hospital by bending a titanium sheet over a 3D printed model of the defect. They are then polished and dipped in acid, before being sterilised at over 100 degrees Celsius. While this process typically kills most bacteria, the plates still carry a much higher risk of infection than other implants produced off-site. “Obviously, if you have an infection near the brain, it can be really dangerous,” said Grover. “We think we can have a significant impact into reducing infection in this particular class of patients.” The researchers also aim to alter the structure of the implants to allow them to be imaged by MRI scanners. They will use a technique known as topological optimisation to minimise the mass of titanium used while maintaining its mechanical properties. The researchers will be working with clinicians at University Hospitals Birmingham and the Royal Orthopaedic Hospital NHS Foundation Trust, as well as companies such as Accentus Medical and Johnson Matthey, to develop the technology.
News Article | May 5, 2017
BRISTOL, 05-May-2017 — /EuropaWire/ — A new drug combination that could help thousands of children with arthritis and prevent them from serious complications, including blindness, has been discovered by researchers and thanks to a trial funded by Arthritis Research UK and the National Institute for Health Research (NIHR). Over 5,000 children and adolescents with juvenile idiopathic arthritis (JIA) in the UK are likely to develop uveitis, a condition that causes inflammation in the middle layer of the eye. The trial, the first of its kind in the world, and the findings are a major step forward for children with JIA. The drug therapy has already been approved for use and the study is published in The New England Journal of Medicine. The trial’s co-chief investigators, Professors A. V. Ramanan from the University of Bristol’s School of Clinical Sciences and Michael Beresford from the University of Liverpool and Alder Hey Children’s NHS Foundation Trust, and colleagues from across the UK, found that a drug called adalimumab, in combination with methotrexate, was an effective therapy in children and adolescents with JIA-associated uveitis. The majority (75 per cent) of those children treated with adalimumab experienced a significant reduction in eye inflammation. An early analysis of the data was so convincing that the trial was stopped early. In this randomised, placebo-controlled trial on review of 90 of the target 149 patients with JIA-associated uveitis, the data and safety monitoring committee noted that the adalimumab group had evidence of a significantly lower risk of treatment failure than the placebo group. This multi-centre trial involved extremely close collaboration between paediatric rheumatology and ophthalmology colleagues across the country and was sponsored by University Hospitals Bristol NHS Foundation Trust, and co-ordinated by the Clinical Trials Research Centre at the University of Liverpool. The trial outcomes directly led to the changes in commissioning guidelines and resulted in NHS England approving the use of adalimumab in children with uveitis that threatens their sight, and for whom other treatments have proven ineffective. Professor Ramanan from University Hospitals Bristol NHS Foundation Trust and University of Bristol said: “Uveitis in children is an important cause of loss of vision. This study demonstrates the benefit of adalimumab in children with uveitis. This is the first randomised trial of its kind worldwide and the results will have a major impact in children with uveitis all around the world.” Professor Beresford from University of Liverpool and Alder Hey Children’s NHS Foundation Trust said: “This landmark trial has demonstrated the commitment and leadership of colleagues across the UK in working closely with patients and parents in tackling a key priority of finding the very best way of caring for children with arthritis and this serious problem of uveitis. “It has shown the UK to be extremely well placed to deliver challenging trials in children, with the support of the NIHR Clinical Research Network and other research networks that are in place across the UK.” There are 15,000 children and adolescents in the UK with the auto-immune disease JIA. One third of those are likely to develop uveitis, leading to more serious visual impairments and may be registered as blind. Stephen Simpson, director of research and programmes at Arthritis Research UK, said: “We’re thrilled of the outcome of this trial and the huge promise it heralds for transforming the quality of life for the large numbers of children with JIA-associated uveitis. “This trial is an impressive example of how investing in exceptional science can ultimately help change how treatment is delivered with direct and immediate benefit for patients.” Further informatio Paper ‘Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis’ by Athimalaipet V. Ramanan et al in The New England Journal of Medicine.
News Article | May 4, 2017
Research could lead to new genetic testing strategies for syndromes involving larger size and intellectual disability Researchers have undertaken the world's largest genetic study of childhood overgrowth syndromes - providing new insights into their causes, and new recommendations for genetic testing. Overgrowth syndromes describe conditions that cause children to be taller and to have a bigger head size than expected for their age, and also to have an intellectual disability or other medical problems. Scientists at The Institute of Cancer Research, London, found many of the children with overgrowth syndromes had mutations in one of 14 different genes. They also showed that many of the overgrowth genes are also involved in driving cancer growth, though intriguingly, the types of mutations involved in promoting human growth and cancer growth are often different. The researchers collected samples and information from 710 children with an overgrowth syndrome through an international study, funded by Wellcome. They used a technique called exome sequencing to analyse the DNA of all the genes in each child and discovered a genetic cause for their overgrowth syndrome in 50 per cent of the children. These children had genetic mutations in one of the 14 genes, and usually the mutation started in the child with the overgrowth syndrome and was not inherited from either parent. Amongst the 14 genes was HIST1H1E, which has not been previously linked to a human disorder. The other genes have been linked with human disorders before, but their contribution to overgrowth syndromes was not known. Importantly, the study showed that the major genes causing overgrowth syndromes are involved in epigenetic regulation, which means they control how and when other genes will be switched on and off. Mutations in epigenetic regulation genes were the cause of overgrowth in 44 per cent of the children in the study, which is published today (Thursday) in the American Journal of Human Genetics. Study leader, Professor Nazneen Rahman, Head of Genetics at The Institute of Cancer Research, London, and The Royal Marsden Hospital NHS Foundation Trust, said: "The control of growth is a fundamental process important in development and many diseases, including cancer. We are pleased our work has provided both new insights into the mechanisms that control growth and new strategies by which genetic testing can be used efficiently to diagnose children with overgrowth syndromes." Co-study lead Dr Katrina Tatton-Brown, Reader in Clinical Genetics at St George's, University of London, Consultant Geneticist at The Institute of Cancer Research, London, and the South West Thames Regional Genetics Service, St Georges University Hospitals NHS Foundation Trust, said: "Our study suggests that offering an exome sequencing genetic test to children with overgrowth and intellectual disability would be a practical and worthwhile way to try to identify the cause of their problems. This would allow us to provide children with more personalised management and to give better information to families about risks to other members of the family."
News Article | April 27, 2017
A clinical trial funded by Arthritis Research UK and the National Institute for Health Research (NIHR) led by professors from the Universities of Liverpool and Bristol has discovered a drug combination that could help thousands of children with arthritis. Over 5,000 children and adolescents with Juvenile Idiopathic Arthritis (JIA) in the UK are likely to develop uveitis, a condition that causes inflammation in the middle layer of the eye. The drug combination discovery will help preventing them from serious complications, including blindness. The trial was first of its kind in the world and the findings are a major step forward for children with JIA. The drug therapy has already been approved for use and the study is published today in The New England Journal of Medicine. The trial's Co-Chief Investigators, Professors Michael Beresford and A. V. Ramanan, and colleagues from across the UK, found that a drug called Adalimumab, in combination with Methotrexate, was an effective therapy in children and adolescents with JIA-associated uveitis. The majority (75 per cent) of those children treated with Adalimumab experienced a significant reduction in eye inflammation. An early analysis of the data was so convincing that the trial was stopped early. In this randomised, placebo controlled trial on review of 90 of the target 149 patients with JIA-associated uveitis, the data and safety monitoring committee noted that the Adalimumab group had evidence of a significantly lower risk of treatment failure than the placebo group. This multi-centre trial involved extremely close collaboration between paediatric rheumatology and ophthalmology colleagues across the country and was sponsored by University Hospitals Bristol NHS Foundation Trust, and co-ordinated by the Clinical Trials Research Centre at the University of Liverpool. The trial outcomes directly led to the changes in commissioning guidelines and resulted NHS England approving the use of Adalimumab in children with uveitis that threatens their sight, and for whom other treatments have proven ineffective. Professor Beresford from University of Liverpool's Institute of Translational Medicine and Alder Hey Children's NHS Foundation Trust said: "This landmark trial has demonstrated the commitment and leadership of colleagues across the UK in working closely with patients and parents in tackling a key priority of finding the very best way of caring for children with arthritis and this serious problem of uveitis. "It has shown the UK to be extremely well placed to deliver challenging trials in children, with the support of the NIHR Clinical Research Network and networks that are in place across the UK." Professor Ramanan from University Hospitals Bristol NHS Foundation Trust and University of Bristol said, "Uveitis in children is an important cause of loss of vision. This study demonstrates the benefit of Adalimumab in children with uveitis. This is the first randomised trial of its kind worldwide and the results will have a major impact in children with uveitis all around the world." There are 15,000 children and adolescents in the UK with the auto-immune disease JIA. One third of those are likely to develop uveitis, leading to more serious visual impairments and may be registered as blind. Stephen Simpson, director of research and programmes at Arthritis Research UK, said: "We are thrilled of the outcome of this trial and the huge promise it heralds for transforming the quality of life for the large numbers of children with JIA-associated uveitis. "This trial is an impressive example of how investing in exceptional science can ultimately help change how treatment is delivered with direct and immediate benefit for patients." The full study, entitled 'Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis' can be found here http://www.
News Article | May 5, 2017
Scientists at the University of Warwick's Tissue Image Analytics (TIA) Laboratory—led by Professor Nasir Rajpoot from the Department of Computer Science—are creating a large, digital repository of a variety of tumour and immune cells found in thousands of human tissue samples, and are developing algorithms to recognize these cells automatically. "We are very excited about working with Intel under the auspices of the strategic relationship between Intel and the Alan Turing Institute," said Professor Rajpoot, who is also an Honorary Scientist at University Hospitals Coventry & Warwickshire NHS Trust (UHCW). "The collaboration will enable us to benefit from world-class computer science expertise at Intel with the aim of optimising our digital pathology image analysis software pipeline and deploying some of the latest cutting-edge technologies developed in our lab for computer-assisted diagnosis and grading of cancer." The digital pathology imaging solution aims to enable pathologists to increase their accuracy and reliability in analysing cancerous tissue specimens over what can be achieved with existing methods. "We have long known that important aspects of cellular pathology can be done faster with computers than by humans," said Professor David Snead, clinical lead for cellular pathology and director of the UHCW Centre of Excellence. "With this collaboration, we finally see a pathway toward bringing this science into practice. The successful adoption of these tools will stimulate better organisation of services, gains in efficiency, and above all, better care for patients, especially those with cancer." The initial work focuses on lung cancer. The University of Warwick and Intel are collaborating to improve a model for computers to recognize cellular distinctions associated with various grades and types of lung cancer by using artificial intelligence frameworks such as TensorFlow running on Intel Xeon processors. UHCW is annotating the digital pathology images to help inform the model. The aim is to create a model that will eventually be useful in many types of cancer—creating more objective results, lowering the risk of human errors, and aiding oncologists and patients in their selection of treatments. The TIA lab at Warwick and the Pathology Department at the UHCW have established the UHCW Centre of Excellence for Digital Pathology and begun digitising their histopathology service. This digital pathology imaging solution will be the next step in revolutionising traditional healthcare with computerised systems and could be placed in any pathology department, in any hospital. The project has been launched in collaboration with Intel and the Alan Turing Institute—the latter being the UK's national centre for data science, founded in 2015 in a joint venture between the University of Warwick and other top UK universities. "This project is an excellent example of data science's potential to underpin critical improvements in health and well-being, an area of great importance to the Alan Turing Institute," said Dr. Anthony Lee, the Strategic Programme Director at the Alan Turing Institute for the collaboration between the Institute and Intel. Rick Cnossen, general manager of HIT-Imaging Analytics in Intel's Data Center Group, commented, "This project has massive potential benefit for cellular pathology, and Intel technologies are the foundation for enabling this transformation. "We've seen what has happened over recent years with the digitisation of X-rays (PACS). The opportunity to transform the way pathology images are handled and analysed, building on experience with PACS and combining data with other sources, could be truly ground-breaking. "This collaboration could not only improve service efficiency, but also open up new and exciting analytical techniques for more personalised precision care." Explore further: New advances in cancer diagnosis
Hoit B.D.,Case Western Reserve University |
Hoit B.D.,University Hospitals
Journal of the American College of Cardiology | Year: 2014
The author examines the ability of left atrial size and function to predict cardiovascular outcomes. Data are sufficient to recommend evaluation of left atrial volume in certain populations, and although analysis of atrial reservoir, conduit, and booster pump function trails in that regard, the gap is rapidly closing. In this state-of-the-art paper, the author reviews the methods used to assess left atrial size and function and discusses their role in predicting cardiovascular events in general and referral populations and in patients with atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart disease. © 2014 by the American College of Cardiology Foundation.
Van Gerven L.,University Hospitals
Rhinology | Year: 2012
Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or allergen-specific IgE measurements in the serum, whereas NAR patients form a heterogeneous group and are difficult to diagnose because of an extensive list of different phenotypes, all varying in severity, underlying etiology and type of inflammation. Characterization of those phenotypes, mechanisms and management of NAR represents one of the major unmet needs in the field of allergic and non-allergic diseases. This review aims at providing a comprehensive overview of the state of the art in classifying the NAR patients and focuses on the neuro-immune mechanisms involved in allergic and non-allergic rhinitis, including reflections on the pathophysiology and the currently available treatment options.
Samama C.M.,University Hospitals
Seminars in Thrombosis and Hemostasis | Year: 2016
Surgical bleeding has been decreasing steadily for the last 20 years, but there are still some hemorrhagic procedures occurring in scheduled surgical settings and emergency procedures. The interest in potent hemostatic agents has recently focused on fibrinogen concentrates. A weak historical rationale based on the rapid decrease in fibrinogen concentration in the bleeding patient and several uncontrolled studies have prompted the use of fibrinogen concentrates in emergency units and in operating theaters. Very few positive randomized studies are available to confirm the usefulness of fibrinogen concentrates. The largest most recent double-blind studies are even negative. As recent guidelines recommend early and liberal use of fibrinogen concentrates in massive bleeding patients, this review reports the most important facts and studies on efficacy and raises some questions about safety. © 2016 by Thieme Medical Publishers, Inc.
Vergote I.,University Hospitals
Expert Opinion on Investigational Drugs | Year: 2014
Introduction: Despite primary cytoreductive surgery followed by standard-of-care treatment, at least 60% of patients with ovarian cancer ultimately develop recurrent disease. There is an urgent unmet medical need to develop more effective treatments for ovarian cancer. Areas covered: This article provides a summary of the novel targeted therapeutics currently in development for the treatment of ovarian cancer. Expert opinion: The goal of first-line therapy is to increase progression-free survival and overall survival in women with ovarian cancer. Women with advanced disease frequently experience disease relapse following standard cytotoxic therapy, so new treatments are being explored. Using a molecular approach, targeted drugs are now being tested in clinical trials. These studies have investigated angiogenesis inhibitors (that target VEGF and other tyrosine kinases), angiopoietin inhibitors, poly(ADP-ribose) polymerase inhibitors, folate receptor blockers, MEK inhibitors and a protein kinase Cβ inhibitor (enzastaurin) in ovarian cancer. Of these, antiangiogenic agents (bevacizumab, pazopanib, nintedanib and trebananib) are furthest in development, having positive Phase III data. It is hoped that more effective agents are on the horizon and that the use of these agents can eventually be combined and tailored to the individual with ovarian cancer. © 2014 Informa UK, Ltd.
University Hospitals | Date: 2015-01-28
An intrathecal delivery system for a pharmaceutical includes a reservoir containing a volume of the pharmaceutical agent, and a pump configured to deliver a portion of the pharmaceutical agent contained in the reservoir. A controller is configured to receive biological cycle information pertaining to a biological cycle (e.g., cardiac cycle), and configured, based on the received biological cycle information, to control the pump to deliver the pharmaceutical agent into a patients intrathecal space as a high-speed bolus at a time corresponding to a time determined based on Processing the biological cycle information. The high-speed bolus may be delivered at a rate of 10-100 L per second. The timing of such delivery corresponds to a time within the biological cycle when cerebrospinal fluid flow is optimal for intrathecal delivery of the pharmaceutical agent. Conditions for which treatment is enhanced by the intrathecal delivery system include refractory hypertension, spasticity and chronic pain management.