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Author: Louise Stanley

Genetically-determined levels of inflammation linked to neuropsychiatric illness

Written by Louise Stanley on . Posted in Inflammation and chronic disease, Mental health.

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.

Funding boost to help improve ovarian cancer survival rates

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection, Health inequalities.

BHP’s newest member NHS Trust has been given a charity grant of £100,000 to help improve survival rates of women with ovarian cancer.

The Pan-Birmingham Gynaecological Cancer Centre, based at SWBH’s City Hospital, is working jointly with University of Cambridge to boost the uptake in genetic testing, especially in Black, Asian and Minority Ethnic communities (BAME) where survival rates are low.

The project, called the Demonstration of Improvement for Molecular Ovarian cancer testing (DEMO), will create information about genetic testing in various languages both in leaflet and video format. The project will also improve the quality of the sample taken to aid diagnosis when there is suspicion of ovarian cancer by establishing a guidance document for all healthcare professionals involved in the process.

Dr Elaine Leung, Clinical Lecturer and Specialist Registrar at the Pan-Birmingham Gynaecological Centre which is run by Sandwell and West Birmingham NHS Trust, said: “This is a much-needed project reaching those diverse communities in the area.

“With the support of our patient representatives, the materials we co-create will be in an easy-to-understand format in both written and video form, which will give women a better understanding of the link between cancer and genetic testing.

“It’s important to ensure women know that genetic testing is similar to early detection and can help prolong life – we have already seen evidence of this through other studies.

“It helps to provide tailored treatments for patients and ultimately can mean surviving an ovarian cancer diagnosis.

“The lack of informed decision-making resources for women whose first language is not English could be a contributor to the low rates of testing within these communities. The team will co-produce information in multiple languages, as well as exploring why some groups of women are more likely to decline genetic testing.”

The project has been funded by health charity Ovarian Cancer Action and is part of a wider national initiative which includes funding for five other NHS cancer centres.

The Pan-Birmingham Gynaecological Cancer Network delivers cancer care to more than two million people in the West Midlands.

The project also builds on the team’s previous experience with the genetic testing studies, looking at BRCA testing in women with a new diagnosis of ovarian cancer before it became mainstream practice.

Lisa Bird, a former cancer patient who is part of the project, said: “When I was in my thirties I was diagnosed with ovarian cancer, which was a large shock.  My first line treatment successfully got me into remission but I wanted to know what options would be available to me if I came out of remission.

“I investigated treatment options and found that there were some treatments only available to those that have the BRCA 1 and 2 genes.  I also wanted to know if other family members were at an increased genetic risk of also getting ovarian cancer, so that I could warn them of the symptoms and ensure that they received better monitoring by their GPs.

“I’m really pleased to be part of the DEMO project team that will encourage more patients to have these same tests. I’m passionate that anyone affected by ovarian cancer should be able to have this genetic knowledge so that their healthcare teams can give them the best treatments available to them as quickly as possible. I really believe that the results of this project will help to provide patients with ovarian cancer, with a greater chance of an extended life.”

Continuation of funding secures Birmingham’s Clinical Research Facility

Written by Louise Stanley on . Posted in Experimental medicine.

The Birmingham Health Partners NIHR Wellcome Trust Clinical Research Facility (CRF) has been successful in its renewal funding bid from the National Institute for Health Research.music

The NIHR Wellcome Trust CRF was established in 2000 as one of the original 5 ‘millennium’ facilities, based at Queen Elizabeth Hospital Birmingham. It incorporated a facility at Birmingham Women’s and Children’s hospital in 2008.  This new award of £12.9million will continue to allow BHP founder-members UHB and BWC NHS Foundation Trusts to provide patients with opportunities to participate in experimental medicine research projects alongside their routine clinical care, in our ageless approach to care – from newborns through childhood, adulthood, maternity to old age.  In addition to this, the CRF is a vital facility enabling healthy volunteer studies and first in human trials for the advancement of new treatments and will continue to deliver this important work over the next five years.

The CRF supports both research and education, ensuring it maximises opportunities for staff development including all learners whether students on placement or healthcare professionals pursuing a clinical academic career.

Joanne Gray, CRF Clinical Manager said: “This is fantastic news for UHB and BWC patients and staff, allowing continuation of an established research facility leading to direct patient benefits and new technologies supporting patient care pathways.

“I am so happy to have received this news following our bid for funding at a time of such challenging times for the NHS.  It is great news for not only the CRF team but for the whole of the Birmingham region as we continue to offer research to Birmingham patients in an area the size of Scotland with the diversity of the world.”

Dr Dhruv Parekh, Programme Director, explained: “Experimental research is crucial and the stepping-stone to finding new treatments that may benefit patients. We are grateful for the on-going funding from the NIHR for the next 5 years to ensure the Birmingham Clinical Research Facility continues its excellent track record of ensuring new discoveries are translated to benefit our diverse populations across a wide range of diseases and ages.”

Professor Jeremy Kirk, Research and Innovation Director at Birmingham Children’s Hospital, said:

“We are delighted that the funding of the Birmingham Clinical Research Facilities has been renewed. This continued funding is a reflection of the very high-quality research being performed within Birmingham, including at the Children’s Hospital, the first paediatric unit of its kind in the UK.

“The early phase studies being performed within the CRF will ensure that our patients have access to the best and most promising therapies both now and in the future.”

Prof Simon Ball, UHB Chief Medical Officer added: “We are delighted to receive ongoing support for the Birmingham Clinical Research Facility from NIHR. It is a testament to our world-class facilities and professionals, the strength of the Birmingham Health Partners strategic alliance, and the relationship we have with our patients and population. We look forward to ensuring early phase clinical research is accessible to all the communities we serve.”

Matthew Boazman, Chief Officer for Strategy and Innovation at BWC said: “We are absolutely delighted to have received confirmation of funding and the ongoing support of the NIHR for the Birmingham Clinical Research Facility.

“This recognition is testament to the outstanding track record and expertise we have across the whole of our partnership for the delivery of early phase clinical trials and will enable us to continue to support experimental medicine and the advancement of new treatments from childhood through to old age over the next five years.”

Professor Lorraine Harper, Director of the CRF, added: “We are absolutely delighted to receive this funding award which reflects the world-class staff and facilities we have within our CRF.

We now look forward to offering opportunities to take part in early phase clinical research to a broader range of our diverse communities reflected within our Birmingham Health partnership”

Christopher Hodson, CRF patient/public representative, commented: “The CRF is a centre of excellence, providing vital input into early clinical and medical trials from a wide range of disciplines both from UHB and Birmingham Children’s Hospital. It is supported by a first class medical, nursing and laboratory team with a can-do ethic.  It is a privilege to be associated with it.”

Sandra Haynes, also a patient representative, added: “Involvement in the CRF and the funding means that patients get the very real opportunity to influence how research impacts on them, and make it relevant for all of us without medical backgrounds to have a say. We are the voice of those with lived experience, helping to guide researchers and experts to put patients at the centre of all they do.”

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: