Patients with atrial fibrillation (AF) – a common heart arrhythmia – could have one blood test to assess their risk of cardiovascular events in the following five years, new research has found.
Published in Cardiovascular Research and presented at the Frontiers in CardioVascular BIology Congress 2024 conference in Amsterdam, the research suggests that a blood-based biomolecule test alone could assess the risk of having a cardiovascular event in the next five years.
The study of 1,586 AF patients found that a cluster of high-risk patients who recorded high levels of 13 biomolecules had five times more cardiovascular events than those in the low-risk cluster.
Professor Larissa Fabritz, from the Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg Eppendorf and an Honorary Professor at BHP founder-member the University of Birmingham said: “These validated findings show that one blood test could be used to help predict the risk of cardiovascular events for patients with atrial fibrillation, helping to differentiate healthcare where it’s most needed. Through a further validation study carried out in Birmingham, we are confident that the blood test can give a useful understanding of those in greatest need of interventions to avoid strokes, acute heart failure and death.”
The international team developed a profile of 13 specific biomarkers that were used to differentiate risk in atrial fibrillation. Using samples from AF patients, they analysed likely target biomarkers and through the trial and validation in the Birmingham BBC-AF registry found that a combination of elevated biomarkers corresponded with risk variation in patients.
The findings are taken from a subset of the EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial which demonstrated that early rhythm control – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes in 2,789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.
Pregnant women with epilepsy could see a major improvement in the care they receive through a new cross-BHP project led by the University of Birmingham with Birmingham Women’s and Children’s Hospitals NHS Foundation Trust (BWC), which also aims to reduce maternal mortality risk.
The EpiSafe project, funded by the National Institute for Health and Care Research over five years, will create and trial an evidence-based, personalised care bundle specifically designed for pregnant women with epilepsy.
The team of researchers, led by Professor Shakila Thangaratinam from the University of Birmingham and BWC, will provide healthcare professionals with the tools and guidance they need to streamline the care they provide and allow for shared decision-making with women regarding their epilepsy and pregnancy.
The EpiSafe project will also study the long-term effects of newer anti-epileptic drugs (AEDs) on children’s development. Many mothers are prescribed these newer AEDs due to concerns with older medications, yet they often discontinue them out of fear of potential harm to their baby.
As part of this study, the researchers across BHP will bridge the knowledge gap by assessing the long-term neurodevelopmental outcomes of children exposed to newer AEDs during pregnancy. This research will empower pregnant women with epilepsy, enabling them to make informed decisions about the safe use of AEDs.
“Epilepsy continues to be one of the main causes of mothers dying in pregnancy and postpartum period. Sadly, we are not observing a fall in maternal deaths. On the contrary, there has been a doubling of the rates of Sudden Unexpected Death in Epilepsy (SUDEP) in mothers between 2013-15 and 2019-21 in UK and Ireland.
“We know that the primary factors contributing to these poor maternal outcomes are the lack of specialist antenatal care and reduced compliance with anti-seizure medication. The EpiSafe programme of work has the potential to improve the care these women receive and save lives within this high-risk group.”
At the core of the EpiSafe programme are mothers with lived experiences of epilepsy from diverse backgrounds. They will play a pivotal role throughout the lifetime of the programme in shaping the development and roll-out of the EpiSafe bundle. Charity partners on the programme include Epilepsy Research Institute and Epilepsy Action, who will provide invaluable insight and guidance.
Dr John Allotey, Associate Professor in Epidemiology and Women’s Health at the University of Birmingham and project leader said: “By working with diverse groups of women with epilepsy and their families, professional bodies, organisations providing care for pregnant women with epilepsy, as well as dedicated epilepsy charities, we will develop an acceptable, relevant and accessible tool which identifies pregnant women with epilepsy who are at high risk and promotes safe use of AED.”
The project consists of six work packages to create the EpiSafe risk assessment and treatment pathway, that will facilitate early specialist epilepsy care for high-risk women. The team will also evaluate whether EpiSafe will help more women at high-risk access specialist epilepsy care early in pregnancy.
The Epilepsy Research Institute’s Director of Research Partnerships, Dr Caoimhe Twohig-Bennett, said: “The Institute launched last month with Reproduction & Hormones as one of our overarching strategic research theme. We are delighted to be collaborating on the EpiSafe project, to ensure safer care and reduced risks for pregnant women with epilepsy.“Central to the work of the Epilepsy Research Institute is a culture of advocating and actioning the research priorities of people affected by epilepsy through our Shape Network PPIE group. Members of the network have been pivotal in the development of this programme of research, and we look forward to their continued involvement as this important project progresses.”
Rajinder Flora, Assistant Director of NIHR’s Programme Grants for Applied Research (PGfAR), which funds the research, said: “Epilepsy causes 1 in 10 of all deaths during pregnancy in the UK, this new project aims to identify women with epilepsy who are at highest risk of seizures and create a treatment pathway for them.
“Funding research like this is vital to provide evidence-based personalised care for pregnant women with epilepsy”
The EpiSafe team also includes co-applicants from University of Liverpool, University of Manchester, Birmingham City University, University of Aberdeen and Belfast Health and Social Care trust, as well as partnerships with Kings Health Partnership and Murdoch Children’s Research initiative.
The EpiSafe work streams consist of:
Gathering all evidence needed to design the EpiSafe bundle,
Co-designing and testing the EpiSafe bundle by working with women and healthcare professionals,
A randomised controlled trial to see if using the EpiSafe bundle improves care, reduces seizures and complications in mother and baby,
Studying the longer-term development of children aged 7-11 exposed to AEDs before birth,
Studying the cost of using EpiSafe and its long-term impact, and
Planning appropriate involvement and engagement with women with epilepsy and their support networks.
Parliamentary event
At a parliamentary event to launch the project hosted by former Health Minister Baroness Cumberlege – who chaired key report on harmful side effects of some medicine – patients and researchers explained about how important this project is for ensuring that women across the UK get a say in managing epilepsy during pregnancy.
Addressing the event, Baroness Cumberlege said: “Being pregnant is a very important stage for every woman, conscious that if all goes well she is bringing new life into the world. The EpiSafe programme is crucial in creating evidenced based pathways which must ensure the voices and experience of women directly shape solutions. The success of this programme will only be realised if there is meaningful collaboration between researchers, clinicians, and women with epilepsy and their families. Cooperation is vital to spur change.
“All those involved in the care of pregnant women have a duty to safeguard the wellbeing of all mothers with chronic health needs. I will follow the progress of innovations borne from initiatives such as this closely, and with the help of others advocate tirelessly for their swift translation into enhanced standards of care.”
Increased funding for the renewed NIHR Birmingham Biomedical Research Centre will enable continuation of major developments around inflammatory diseases and new technologies and systems
The NIHR Birmingham Biomedical Research Centre (BRC) has been awarded more than £30 million in funding from the National Institute for Health and Care Research, a major funder of global health research and training, to support world-leading research into inflammation – including the development of new diagnostic tools and treatments for those with cancer, liver and heart disease, and many more illnesses.
The centre brings together multiple BHP members – including leading NHS providers led by the University Hospitals Birmingham NHS Foundation Trust and academic institutions led by the University of Birmingham – as well as other organisations working closely with charities and businesses. Its aim is to support research into inflammation which causes or worsens many common long-term illnesses including arthritis, liver disease and cancer.
This new investment represents an almost threefold increase in funding for the NIHR Birmingham BRC and will enable researchers to focus on eight areas of illness including heart disease, women’s health, and common complications from inflammation. Researchers will also be empowered to consider new tests and biomarkers for disease, health technologies including stem cells and gene therapy, patient experiences and data science.
Professor Phil Newsome, Director of the NIHR Birmingham BRC, said: “Inflammation plays a central role in many health conditions, with millions of people in the UK alone experiencing inflammatory diseases such as arthritis and bronchitis. This significant increase in funding will enable us to provide an outstanding environment for world-leading clinical research and allow us to make a step-change in our work tackling different forms of cancer, trialling new drugs for liver disease, and dealing with antimicrobial resistance.”
Patients will benefit from the increased funding thanks to the BRC’s collaborative research that has seen nearly 1,000 clinical trials and informed UK clinical guidelines.
Researchers will look at eight themes to continue to understand and help patients manage inflammation-based diseases including cancer, arthritis, and liver disease. The investment of the NIHR funding in biomedical research will enable clinicians, researchers, patients and supporters to find new treatments such as the development of new immunotherapies, which are types of cancer treatments to support the body to fight cancer.
Professor David Adams, Director of BHP, commented: “The investment from NIHR is hugely important for researchers working across the BRC partner institutions, to continue to tackle some of the critical health themes that affect our region. The funding will allow us to deliver new therapies and diagnostic tests for a range of chronic inflammatory diseases for which we currently have few effective treatments.”
Professor Lucy Chappell, Chief Executive of the NIHR, said: “Research by NIHR Biomedical Research Centres has led to a number of ground-breaking new treatments, such as new gene therapies for haemophilia and motor neurone disease, the world-first treatment for Creutzfeldt–Jakob disease, a nose-drop vaccine for whooping cough, and the first UK-wide study into the long-term impact of COVID-19.
“This latest round of funding recognises the strength of expertise underpinning health and care research across the country and gives our nation’s best researchers more opportunities to develop innovative new treatments for patients.”
The Birmingham Biomedical Research Centre is made up of the following BHP member organisations:
University Hospitals Birmingham NHS Foundation Trust
University of Birmingham
Sandwell and West Birmingham NHS Trust
Birmingham Women’s and Children’s NHS Foundation Trust
Aston University
Working closely with partners:
Birmingham Community Healthcare NHS Foundation Trust
BHP members Birmingham Women’s and Children’s Hospitals have initiated a new study which could potentially revolutionise care for young people with asthma using artificial intelligence technology.
Over the next two years, 50 children and families will take part in the Childhood Home Asthma Monitoring Study (CHAMP), which uses a small table-top electronic device designed by Albus Health, not dissimilar in size to an Amazon ‘Alexa’ virtual assistant, to personally monitor a child’s symptoms and breathing while they sleep.
Using sensors and a microphone, it measures breathing and heart rate by analysing coughs, wheezing and other noises, while also assessing environmental factors, such as humidity and air pollution levels. The data collected over a period of months will help form a unique and personalised set of triggers which is able to warn of a future asthma attack days before it potentially happens, allowing for action to be taken.
Around one in 11 children in the UK has asthma and it’s one of the most common chronic conditions which causes hospitalisations. The potential of this AI technology is potentially huge; positively impacting thousands in the future.
Dr Prasad Nagakumar, Respiratory Consultant, is the Chief Investigator leading this exciting £1.6million CHAMP study, funded by the National Institute for Health Research. He’s looking forward to working alongside partners including Asthma UK, Imperial College London, Oxford Academic Health Science Network and Royal Brompton Hospital, where patients are also being recruited to take part.
Dr Nagakumar said: “I’m delighted that we’ve now started this exciting study, which has such a huge potential. Over the next two years we’ll be working hard to further understand and develop the use of this innovative monitoring and, importantly, prediction technology.
“Our aim is to build algorithms and clinical-supporting tools for the early detection of asthma attacks in children by capturing warning signs before patients or those giving care perceive them.”
Professor Jeremy Kirk, Clinical Director NIHR Clinical Research Network (West Midlands) and Research and Innovation Director at our Children’s Hospital, said: “Asthma is the most common chronic disease in childhood and blights many lives. This project utilises the very newest cutting-edge technologies to give us further understanding of this condition, hopefully enabling better monitoring, optimal care and a reduction in hospital admissions.
“Dr Nagakumar and the team are to be congratulated on being awarded this highly competitive and prestigious grant.”
A potential link between inflammation and the structure of specific regions of the brain has been identified by researchers at BHP founder-members the University of Birmingham.
The study, published today in JAMA Psychiatry, may be particularly relevant for neurodevelopmental psychiatric disorders including autism spectrum and schizophrenia.
Researchers say the findings could open up a completely new target for the pharmacological treatment of these disorders, which has not significantly changed since the identification of antipsychotic medications in the mid-late 20th century.
The research was carried out by a team based in the University’s Institute for Mental Health and Institute and Institute of Cancer and Genomic Sciences, with collaborators from the University of Cambridge, Manchester and Bristol. It showed that genes associated with inflammation, particularly interleukin (IL) 6, are linked to a reduction in grey matter volume in certain areas of the brain known to be implicated in neuropsychiatric disorders.
Using records from the UK Biobank, a large-scale biomedical database, the team was able to compare genetic variants which affect levels of IL-6, and other inflammatory genes in more than 20,000 patients with changes in grey matter volume in specific areas of the brain.
They were able to show strong links between IL-6 and brain structure particularly in the temporal and frontal regions. Further analysis using the Allen Human Brain Atlas, showed that genes overexpressed in these areas are associated with conditions such as epilepsy, cognitive dysfunction, and schizophrenia.
Professor Rachel Upthegrove of the University of Birmingham Institute for Mental Health, explained: “This study shows that the IL-6 gene, which we know to be linked to systemic inflammation, also affects brain structure in areas associated with these neuropsychiatric disorders. Understanding these links offers an exciting opportunity to explore new treatments which target IL-6. This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years.”
Dr John Williams, of the Institute for Cancer and Genomic Sciences at the University, a first author on the paper, said: “Current treatments for these illnesses act on dopamine, a chemical messenger in the brain associated with mood and attention. These drugs can have side effects, however, and they are not effective in all patients.
“There are drugs already on the market which target inflammation as well as the opportunity to screen potential new compounds. Finding a new avenue for exploring the links between inflammation, brain structure and neuropsychiatric disorders is really exciting.”
The work is part of the PIMS (Psychosis Immune Mechanism Stratified Medicine Study) programme, led by the University of Birmingham and set up to investigate the links between inflammation and psychosis. In the next phase of the research, the group will carry out experimental studies to knock out IL-6, as well as replicating the Biobank research in more diverse patient cohorts.
BHP founder-member the University of Birmingham has announced the launch of five new major studies aimed at improving the prevention, treatment and management of type 1 diabetes – with a particular focus on children and young adults.
The new studies include:
The ELSA Study: Led by Professor Parth Narendran, the ELSA Study (EarLy Surveillance for Autoimmune diabetes) will see researchers interviewing families, doctors, nurses and schools, to determine if, and how, the UK should develop a testing and monitoring programme that will identify children at risk of type 1 diabetes. The ELSA Study is being funded by the National Institute for Health Research (NIHR), and is being carried out in collaboration with Birmingham Health Partners, Birmingham Community Healthcare NHS Foundation Trust and the Department of Health and Social Care, as well as the Universities of Cardiff, Warwick, Oxford and Imperial College London.
Diabetes and health inequalities: Through £1.9m funding from NIHR, Professor Tim Barrett’s team will ask children and young people with diabetes and their families from poorer and/ or ethnic minority backgrounds how language issues, feelings, income, living conditions and food availability affect how they manage diabetes. They will identify new ways to make diabetes management easier and more successful, and will test these systems in trials involving NHS hospitals.
Immunotherapies for diabetes: The greatest barrier to the development of specific immunotherapies for type 1 diabetes is that we currently do not understand the mechanism of how immunotherapies switch off the immune response to our own proteins. A clinical study led by Professor David Wraith, and funded by $735,000 from The Leona M. and Harry B. Helmsley Charitable Trust, will be carried out in collaboration with Cardiff University. It will test a new peptide developed by the University of Birmingham, work which was also funded by the Helmsley Charitable Trust with a $610,000 grant. The new peptide has the potential to control the T-cell immune response in people who are either at risk of developing type 1 diabetes or are newly diagnosed. In this study, the team will assess the changes in immune cells from the site of injection, the draining lymph nodes and peripheral blood. This will be the first in-depth analysis of the molecular changes responsible for antigen-specific immunotherapy in type 1 diabetes.
Sight loss and diabetes: Two separate projects led by Dr Jose Romero Hombrebueno will explore the function of membrane-bound cell organelles, known as mitochondria, which generate most of the chemical energy needed to power the cell’s biochemical reactions. The researchers will examine the role of mitochondrial function in both the development of multiple health conditions as the consequence of type 1 diabetes, and also the role it plays in developing diabetic retinopathy – an eye condition that can cause sight loss and blindness in people who have diabetes. The latter research is being funded by Diabetes UK, while the former is being funded by the European Foundation for the Study of Diabetes.
Exercise and type 1 diabetes: Led by Dr Alex Wadley and funded by the Rosetrees Trust, this research will examine how a home-based exercise programme impacts autoimmunity in patients with newly diagnosed type 1 diabetes. The project will evaluate whether exercise slows the progression of type 1 diabetes by altering the number and activity of white blood cells in the circulation that have the potential to attach to, enter and degrade the pancreas. Although evidence supports a role for exercise to promote general health and wellbeing in patients with type 1 diabetes, this project aims to provide novel evidence that exercise can directly slow the progression of the disease upon diagnosis.
Parth Narendran, Professor of Diabetes Medicine at the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “The UK has one of the highest incidences of type 1 diabetes in the developed world, at 25 per 100,000 per year, and type 1 diabetes is the most common form of diabetes in children. It occurs when cells that make insulin don’t work as they should, and people with the condition have to self-inject insulin for their entire lives. Studies have recently shown that some medicines can safely delay people getting type 1 diabetes. Some countries, such as the US and Australia, already have surveillance systems to identify people at risk of developing type 1 diabetes and to offer them participation in prevention trials and also to reduce their chances of developing type 1 diabetes as an unexpected emergency. The UK does not have such a system in place. Until now, nobody in the UK has explored whether parents and children would welcome such a system, and how it would work. Through ELSA we will potentially be able to change NHS healthcare policy which would result in the early detection and prevention of this condition and its associated long-term complications.”
Timothy Barrett, Professor of Paediatrics and Child Health at the University of Birmingham’s Institute of Cancer and Genomic Sciences, said:“Diabetes causes high blood sugar levels, which can lead to eye and kidney damage if the condition is not well managed. We know that better sugar control reduces this risk, however, children with diabetes from poorer and/ or ethnic minority groups, often have worse sugar control, while these complications often develop when they are young adults who are working and starting families. There is little evidence to show any previous interventions have helped in reducing health inequalities for children with diabetes in different groups. We will work with young people, their families, and diabetes clinicians to develop an action plan that families feel comfortable with and that will support them to improve their self-management.”
Professor David Wraith, Director of the University of Birmingham’s Institute of Immunology and Immunotherapy, said:“Studies have shown that immunotherapies could play a vital role in treating type 1 diabetes, and it’s essential that we can develop new drugs that could specifically target cells that cause the body’s immune response to behave the wrong way in a person with type 1 diabetes. Our project will help improve our understanding of how the human body’s immune system responds to therapies, which in turn will help the development of new treatments.”
Dr Jose Romero Hombrebueno, Hale-Rudd Lecturer in Experimental Ophthalmology at the University of Birmingham’s Institute of Inflammation and Ageing, said:“It is estimated that 224 million people will have diabetic retinopathy and 70 million will have sight-threatening diabetic retinopathy by 2040. Nearly 90-95% of patients with type 1 diabetes and 78% with type 2 diabetes are expected to develop minimal retinal damage after having diabetes for more than 15 years. Therefore it’s essential that we carry our research that will help advance our knowledge of the underlying causes and potential ways to treat or prevent vision loss in those with diabetes.”
Dr Alex Wadley, of the University of Birmingham’s School of Sport, Exercise and Rehabilitation Sciences, said: “It’s estimated that around 70% of patients with type 1 diabetes do not meet the current recommended exercise guidelines of 150 minutes per week. We are using a home-based exercise programme, which has proven highly popular and safe for individuals with type 1 diabetes, to evaluate how regular exercise impacts the immune system of newly diagnosed patients. Type 1 diabetes is a disease where the body’s own white blood cells attack the pancreas and stop insulin production, resulting in high blood sugar. Regular participation in exercise is key to supporting health and wellbeing in people with type 1 diabetes, but we don’t know how exercise directly impacts these white blood cells that do the damage. With limited therapies available for patients currently, we hope that our findings can promote the use of exercise as an important lifestyle choice for patients and impact standard treatment approaches for type 1 diabetes nationally.’’
