Skip to main content

Author: Louise Stanley

Expanded membership signifies ambition for Birmingham Health Partners

Written by Louise Stanley on . Posted in Birmingham Health Partners.

The second city’s University-NHS partnership Birmingham Health Partners (BHP) has expanded its membership by welcoming Sandwell and West Birmingham Hospitals NHS Trust (SWBH) on board, joining the University of Birmingham, University Hospitals Birmingham NHS Foundation Trust (UHB), Birmingham Women’s and Children’s Hospitals NHS Foundation Trust (BWC), and West Midlands Academic Health Sciences Network (WMAHSN).

SWBH’s inclusion extends BHP’s research and education capabilities, and builds on many years of successful collaboration between the Trust and BHP members, working on studies and trials in specialties as diverse as cancer immunotherapy, rheumatology and heart disease. The Trust provides acute hospitals and community healthcare services to a population of around 500,000 people across Sandwell, City and Rowley Regis Hospitals, as well as operates the Birmingham and Midland Eye Centre, the regional Sickle Cell and Thalassaemia Centre, and is the regional base for the National Poisons Information Service. It is also currently developing the Midland Metropolitan University Hospital, which will provide acute care services when it opens.

The news also follows publication of a joint report from BHP, Association of the British Pharmaceutical Industry (ABPI) and the Confederation of British Industry (CBI) which showcased the huge potential of the West Midlands’ life science ecosystem and recommended a joined-up approach to regional leadership and collaboration, in order to tackle the specific health burdens of the West Midlands and beyond.

BHP Director Professor David Adams, who is Head of the University of Birmingham’s College of Medical and Dental Sciences, explained: “Our city and region is home to a concentration of multidisciplinary health and life sciences excellence, and has the potential to strengthen the UK’s position as a world leader in the sector. This can only happen if we work inclusively and collaboratively across the Midlands. With a strong track record of research partnership between BHP’s founder-members and SWBH already in place, it is a natural next step to bring the Trust on board as a full member – demonstrating BHP’s regional leadership, commitment to delivering on our recommendations, and dedication to improving the health of our diverse population.”

Professor David Carruthers, Medical Director of SWBH, commented: “We are delighted to be part of BHP and contribute to the development of research in the West Midlands. This will build on the strong track record that SWBH has in delivering research that involves and is relevant to our patients. This partnership will reinforce our commitment to the development of our staff as well as improving the health of our local population through high quality research opportunities.”

BHP is committed to achieving health and economic impact through harnessing the combined strength and expertise of its members.

New study explores unique approach to treat a rare liver disease

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine.

A UK research study looking into a new approach to treat primary sclerosing cholangitis (PSC), a rare disease where the body’s immune attacks its own liver, has been given the green light thanks to vital funding from LifeArc and the patient-led organisation PSC Support.

The FARGO trial, led by Dr Palak Trivedi at the University of Birmingham, will find out if a new treatment can slow PSC progression and improve quality of life for patients.

What is PSC?

PSC is a rare liver disease which affects around 3,600 people in the UK. People can develop the condition at any age, but most commonly those under the age of 40.

In PSC, the body’s immune system attacks the liver, causing inflammation and scarring of the bile ducts. This causes bile to stop flowing properly, and patients experience repeated infections, develop liver failure and, in some cases, cancer. In four out of five people, the body’s immune system will also attack the bowel, leading to inflammatory bowel disease (IBD) as well as liver disease. The combination of PSC and IBD can lead to around a third of all patients developing bowel cancer and patients require a colonoscopy every year to screen for it.

Currently, doctors treat PSC by managing symptoms only. We don’t fully understand what causes PSC, and there is no cure. A liver transplant is the only life-saving treatment. Although a very rare disease, PSC accounts for 1 in 10 of all liver transplants in the UK and is now the leading reason for liver transplantation in several European countries.

While it is life saving, liver transplantation is also risky and costly to the NHS. People who have had a transplant must take a cocktail of drugs to prevent their new liver being rejected. PSC can still return in around a third of people who have had a liver transplant.

Imbalance of gut microorganisms – and a new approach

We know that the microbes present in the gut of people with PSC are different to those in people without liver and bowel inflammation. This gut microbe imbalance is linked with many abnormal immune functions, which may drive development of the condition.

In the FARGO study, the research team will find out if taking stools containing natural microbes from the gut of healthy donors, refining it in a lab, and transferring it to the bowel of people with PSC, could reverse the imbalance of gut microorganisms. This treatment is called faecal microbiota transplantation, or FMT. Early research has also shown that it can treat IBD.

Bespoke clinical trial

The Birmingham team, together with teams at the Royal Free London, St Mark’s Hospital, Imperial College London, and Norfolk and Norwich University Hospitals NHS Foundation Trust, will carry out a clinical trial to test this new treatment approach. People with PSC taking part in the study will receive either FMT once a week for eight weeks, or placebo (an inactive FMT equivalent). Each group will continue to receive their usual routine standard of care for their IBD.

The teams will observe both groups for another 40 weeks. The team will then measure how successful the treatment has been in improving liver blood tests, reduce scarring of the liver, lessen the severity of their IBD, and improving symptoms and quality of life.

Dr Palak, who is leading the trial at the NIHR Birmingham Biomedical Research Centre, said: “I am delighted that LifeArc has chosen to support such a novel, bespoke and distinctive clinical trial, and to enable us to the necessary ground work needed to better understand how PSC develops and progresses.

“This study will really help us to understand which gut microbes are most important, and how this potential treatment could be scaled up to treat more people.

“Our study will lay the foundation for future work on a larger scale, with a view to making FMT available across the world.

“Should our trial show that FMT works well, PSC Support will be advocating for patients to access FMT as early as possible. We hope this means it will be making a difference to patients within five years after we’ve completed this work.”

LifeArc’s Dr Catriona Crombie said: “Our approach to funding is to work with others, to uncover the potential of promising research that could solve complex healthcare problems that patients face.”

She continued: “We’re delighted to be jointly funding this project with PSC Support, where Dr Trivedi’s team aim to reveal more information about PSC and help to translate this experimental treatment, from lab idea towards the clinic, where it could offer hope to patients with PSC.”

Martine Walmsley, Chair of Trustees at PSC Support, said: “Although we welcome clinical trials that test brand new drugs for PSC, progress is painfully slow. People with PSC don’t have the luxury of time and we must look at quicker medicine development routes.”

£7m funding boost for world-leading surgical research team

Written by Louise Stanley on . Posted in Health inequalities.

A world-leading global surgical research team led from BHP founder member the University of Birmingham has received £7 million of funding to continue its life-saving work in developing countries – finding ways of increasing surgical capacity and preventing post-operative complications.

The NIHR Global Health Research Unit on Global Surgery (NIHR GSU) will focus on training non-surgeons to perform essential hernia operations – hernias posing a major problem with five million patients awaiting surgery in sub-Saharan Africa, stopping young men from providing for their families.

The team will also continue its work in boosting post-operative recovery in Low- and Middle-income Countries (LMICs) – testing simple innovations such as the use of high-dose oxygen, mouthwashes and inhalers.

Researchers are also looking to bring innovation back into the health systems of high-income countries by piloting innovative practices in LMICs – proving their worth ahead of wider roll-out.

Established in 2017, the new NIHR funding will allow the GSU to continue its global research for at least a further five years. The Unit co-ordinates a global network of surgeons that includes over 20,000 clinicians from over 100 countries.

Based at the University of Birmingham, it is co-directed by Professor Dion Morton OBE, Barling Chair of Surgery and Professor Stephen Tabiri, Dean of the Medical School at University for Development Studies in Tamale, Ghana.

Professor Dion Morton commented: “Delivering safe and effective surgical care across the world is one of the greatest challenges facing global health today. Our work impacts the most disadvantaged and vulnerable populations of the world – we are training surgeons in these countries to continue the research drive that is helping to save lives.

“Surgical capacity is a critical issue – a matter of life and death. In many developing countries, there are simply not enough surgeons to deliver the operations that are needed – there are less than 100 general surgeons working in the Benin health service to serve a population of 12 million people.

“Equally, it’s no use performing more operations if patients are at risk of dying from post-operative complications. Simple but effective steps in reducing risks such as surgical site infection (SSI) – the most common post-surgical complication – will be vital in ensuring improved health outcomes for people living in LMICs.”

The GSU’s international cohort studies are open to all collaborators – whether medical students, clinical officers, doctors, nurses or researchers. The team works across clinical disciplines with healthcare professionals, policy makers, epidemiologists, economists, patients and community members.

The GSU provides the tools and infrastructure to help surgeons around the world to sustain the research drive that will increase surgical capacity in LMICs.

A ‘hub and spoke model’ helps the GSU co-ordinate surgical research globally in seven LMICs: India, South Africa, Rwanda, Nigeria, Benin, Ghana and Mexico. Each hub acts as an independent research centre for conducting clinical trials and cohort studies, as well as supporting local and international research training and education. The network consists of more than 100 urban and rural hospitals in these seven countries, some in the most remote parts of the world.

The GSU runs a range of cohort studies, qualitative research and clinical trials aimed at:

3d rendering of red blood cells in vein

New blood cancer gene defect can be treated with existing drugs

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

A defective gene normally found in blood cancers could be treated with drugs already available for cancers with similar gene defects, scientists at BHP founder-member the University of Birmingham and Queen’s University Belfast have revealed.

The research team, funded mainly by Cancer Research UK and the Medical Research Council, found that tumours with mutations in the SF3B1 gene respond to PARP inhibitors – a type of drug used to treat cancers which have similar mutations in the BRCA1 and BRCA2 genes.

The researchers believe that PARP inhibitors could be used to treat patients with tumours carrying the defective SF3B1 gene. This mutation is most often found in blood cancers, including chronic lymphocytic leukaemia, as well as some rare cancers like uveal melanoma.

Co-author Professor Grant Stewart, of the University of Birmingham, said: “Our work demonstrates that a molecular understanding of how a specific gene mutation affects a cancer cell’s ability to repair damaged DNA can be exploited clinically to specifically tailor the anti-cancer therapy used to treat an individual’s tumour. This will increase the effectiveness of the therapy and hopefully, reduce the chances of re-occurrence.”

Dr Kienan Savage, lead author and Reader at Queen’s University Belfast, said: “Our findings have clinical implications for the treatment of many cancers. We specifically focused on this genetic mutation as it is found in several difficult to treat leukaemias and other cancers, and it affects so many cancer patients. By deepening our understanding of this gene mutation, we have identified new ways of treating these cancers that could improve survival rates.”

PARP inhibitors, which include olaparib and rucaparib, are used to treat some patients with ovarian, breast, prostate and pancreatic cancers – usually patients who have inherited a faulty BRCA1 or BRCA2 gene. Around 1 in 400 people have a faulty BRCA1 or BRCA2 gene.

The research – published in Cancer Research, a journal of the American Association for Cancer Research – found that the SF3B1 mutation produces similar effects to the faulty BRCA1 gene by damaging DNA, preventing it from being repaired properly, and stopping it from making normal copies of itself. PARP inhibitors target the cell’s DNA repair tools by locking them in place on the DNA. This stops DNA repair, causing the cancer cells to die.

The scientists found that cancer cells with the SF3B1 mutation were sensitive to olaparib, the most common PARP inhibitor, some specific chemotherapies and to radiotherapy. The scientists believe that the SF3B1 mutation disrupts the cell’s ability to make DNA repair proteins, leaving it vulnerable to drugs which target these proteins.

The SF3B1 mutation occurs in up to 30% of blood cancers called myelodysplastic syndromes, where blood cells don’t form properly. They are difficult to treat as they occur predominantly in older patients who may not be considered fit for treatment. The mutation is also common among uveal melanoma or cancers of the eye, which currently have limited treatment options.

Dr Katrina Lappin, of Queen’s Univesity Belfast and first author of the study, added: “Our research shows that cancers with these specific mutations, may be treated effectively with PARP inhibitor therapy drugs, which are less toxic, better at killing cancer cells with these mutations and can be taken at home in tablet form. This could have huge implications for improving outcomes and quality of life of people with these cancers. This work will pave the way for clinical trials using PARP inhibitors for the treatment of patients with this commonly associated cancer mutation, allowing a more personalised approach to the treatment of these cancers.”

The researchers now want to test PARP inhibitors in clinical trials with patients who have the SF3B1 mutation to see if they can stop their cancer from spreading.

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Our scientists helped to discover the BRCA gene over 25 years ago and since then we’ve led the way in developing PARP inhibitors to treat cancers with BRCA gene faults. It’s really exciting to hear about a new mutation, which behaves like the BRCA1 mutation and could in the future be treated in the same way. With PARP inhibitors already widely available, there is huge potential to help people with some of the rarest and most difficult-to-treat cancers known to us. Over the past two decades, PARP inhibitors have saved thousands of lives worldwide, and it will be interesting to see if this research in the future could lead to a similar impact for people with rarer cancers.”

The research was funded by the UK Medical Research Council, Cancer Research UK, Blood Cancer UK, Leukaemia and Lymphoma NI and Great Ormond Street Hospital Children’s Charity.

a woman injects insulin into her abdomen

Diabetes: Birmingham launches five new research studies

Written by Louise Stanley on . Posted in Clinical trials, Health inequalities, Inflammation and chronic disease.

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.’’

an infact lies in a hospital bed after open heart surgery

New clinical trial aims to improve heart protection during surgery in children

Written by Louise Stanley on . Posted in Clinical trials.

A new clinical trial being led by BHP founder-member the University of Birmingham and funded by the British Heart Foundation could help improve the recovery of children who undergo life-saving heart surgery.

The £570,000 study will compare two ways of protecting the heart when children require open heart surgery to repair congenital heart defects, to find which is most effective.

Congenital heart disease is a heart defect that develops in the womb before a baby is born. Each day in the UK, around 13 babies are diagnosed with a congenital heart condition, with more diagnoses later in life.

In severe cases, and often at a young age, open heart surgery is required to repair the defect to help improve the child’s survival and quality of life. Some children require multiple operations, and recovery from open heart surgery can take several weeks or even months.

During open heart surgery, a fluid called cardioplegia is commonly used to stop the heart beating so that the surgeon can repair it safely. Although the technique is safe, cardioplegia stops the blood flow to the heart and may cause damage to the heart muscle when the blood flow is restored, which can affect the child’s recovery.

There are many different types of cardioplegia solutions available, which work in slightly different ways – and it is not currently known which fluid works best in children of different ages.

In the United States, the most commonly used solution is called del Nido cardioplegia, which was designed specifically for use in children’s heart surgery but has not previously been available in the UK.

The new trial will compare del Nido cardioplegia with St Thomas’ cardioplegia, which has been used for many years in both adults and children and is currently the standard of care in the UK.

It will involve 220 children undergoing open heart surgery at four hospitals across the UK – Birmingham Children’s Hospital, Bristol Royal Hospital for Children, Great Ormond Street Hospital and Leeds Children’s Hospital.

Half of the patients will be assigned to receive del Nido, with the other half receiving St Thomas’ cardioplegia. Researchers will then compare the two groups by assessing how well the children recover from surgery and determining the extent of any heart damage.

The study will help to reveal whether one solution is potentially more effective than the other for children during surgery.

The research will be led by Nigel Drury, Consultant in Paediatric Cardiac Surgery at BHP member Birmingham Children’s Hospital and Hunterian Professor in the Institute of Cardiovascular Sciences at the University of Birmingham.

Mr Drury, who is also a British Heart Foundation (BHF) Intermediate Fellow, said: “By improving the way in which we protect the heart during surgery, we expect that children will recover from surgery faster and with fewer complications.

“These early benefits may also lead to better long-term outcomes, with less injury and scarring to the heart muscle. As children with severe heart defects often need multiple operations, they will have the most to gain from improving how we protect the heart during each surgery.

“If our trial is successful, this will support the need for a larger, definitive study, which could have the potential to change the way children are treated around the world.”

Dr Shannon Amoils, Senior Research Advisor at the British Heart Foundation, said: “Heart defects are the most common congenital anomaly in babies born in the UK, so it’s important that we continue to refine treatments for these conditions to help improve the lives of young patients.

“This multi-centre trial, held at four leading UK children’s hospitals, will compare how well these two solutions can protect the hearts of children undergoing open heart surgery. If the study reveals important differences between the two solutions, a larger clinical trial would be needed to further investigate the findings. Ultimately, this important research could result in heart surgery becoming even safer for children.

“The BHF can only fund vital research like this thanks to the generous support of the public, in driving forward our mission to beat heartbreak forever.”

Alfie Donnelly, aged nine and from Erdington, was born with various complex congenital heart diseases and has had to undergo three open heart surgeries at Birmingham Children’s Hospital.

Mum Claire Donnelly, aged 43, said: “When Alfie was a new-born, we noticed that he wasn’t feeding well, was cold all the time and wouldn’t cry. We struggled to wake him one morning and he was making a grunting noise when he was breathing, so I rang the hospital who told us to bring him in.

“Alfie became so ill that he was put on a life support machine. After several tests and scans, we were told that Alfie’s heart condition was rare and complex and that he needed open heart surgery. We were also told that if a procedure did go ahead, it was unlikely he would survive past his first birthday. The whole situation felt so bizarre, I remember feeling frozen to the spot.

“Alfie was just one week old when he had his first operation, and he was a little fighter. He has since had two more open heart surgeries, which included replacing the damaged valve in his heart with a donor valve.

“Alfie’s recovery after surgery has been slow and he has had further complications. Following his first and second surgery, Alfie had a build up of fluid in his lungs and this required several chest drains, which meant spending further time in hospital.

“With what Alfie has been through, it has made us a solid family and we all appreciate life even more. For us as a family, the research that the BHF is funding gives us hope that children and babies with congenital heart disease, like Alfie, aren’t being forgotten. So much more is needed to raise awareness of heart defects in children.”