How the University of Bristol’s research and teaching has helped shape the NHS and save lives

 

Press release issued: 5 July 2023

Today [Wednesday 5 July] we celebrate 75 years of the NHS – the first universal health care system to be established anywhere in the world.

Since it was established in 1948, the National Health Service (NHS) has become one of the nation’s most-loved institutions, playing a vital role in our lives.

We are proud to work closely with the NHS, from training the doctors, specialist surgeons and dentists of tomorrow, to research breakthroughs today.

We’re also shining a spotlight on how, by working closely with colleagues in Bristol’s two large NHS hospitals – North Bristol NHS Trust (NBT) and University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) – our research and teaching has helped to shape the NHS and improve people’s health:

1. Bristol Medical School

Bristol had a medical school long before the current University received its Royal Charter in 1909. Founded in 1833, Bristol Medical School educated scholars from the city and beyond, including the famous cricketer W.G. Grace, who enrolled at the Medical School in 1868. In 1893, the Medical School was incorporated into what was, for a short time, University College, Bristol.

Medicine has been taught at Bristol on a continuous basis since the first Medical School. It now comprises around 1,327 students and around 900 staff, who through research and teaching improve the health of individuals and populations locally, nationally and internationally. Nearly 6,000 students have graduated in medicine over the past 30 years.

2. Cutting cot death by 80%

Thirty-one years ago, Professor Peter Fleming pioneered research which showed lives could be saved if babies were placed on their backs – and not their fronts – to sleep. It is estimated his research has saved the lives of more than 20,000 babies in the UK alone and has changed official advice about safer sleeping for babies the world over.

3. Cooling baby treatment one of ‘Nation’s Lifesavers

Marianne Thoresen, Professor of Neonatal Neuroscience, discovered that cooling babies who have suffered a lack of oxygen at birth improves their survival without brain damage in later childhood. Professor Thoresen was named by Universities UK as one of the ‘Nation’s Lifesavers’.  This approach has already saved 1,500 babies from death and disability each year.

4. Largest ever pneumonia trial to be carried out

Over 22,000 participants will be recruited in the largest ever trial to investigate whether aspirin can reduce the risk of a heart attack or stroke in patients who are admitted to hospital with pneumonia. Led by Bristol, sponsored by NBT and supported by the Bristol Trials Centre, the  ‘Aspirin after hospitalisation with Pneumonia to prevent cardiovascular Events randomised Controlled Trial’ (ASPECT) will invite adults over 50 who have been admitted to hospital with pneumonia to take part over the next four years.

5. New guidance on hip fracture services will improve recovery for thousands of patients

A new ‘toolkit’ for senior doctors and hospital managers, that will help make changes to their organisational arrangements and improve the quality of hip fracture care across the UK, has been launched by The Royal Osteoporosis Society (ROS) in collaboration with University researchers.

The guidance was developed after the REDUCE study, carried out by the University, found how well patients recover after a hip fracture varies enormously between NHS hospitals in England and Wales.

6. Bristol Network awarded Tessa Jowell Centre of Excellence status for brain tumour research

With 12,000 people diagnosed with a brain tumour every year in the UK, there has never been a more important time to recognise the efforts of NHS staff committed to developing and improving brain tumour treatment and care.

The Bristol Network, which includes NBT, UHBW, Gloucestershire Hospitals NHS Foundation Trust and Royal United Hospitals Bath NHS Foundation Trust, was recognised for its commitment to service development, in particular the further development of its rehabilitation pathways.

It is hoped that for the 88,000 British people currently living with a brain tumour, the Excellence status provides reassurance about the availability of excellent care and commitment to improvement in the NHS across the UK

7. Bristol childhood obesity clinic forms blueprint for national NHS pilot

The Care of Childhood Obesity (CoCo) at the Bristol Royal Hospital for Children is led by clinicians and researchers from the University, UHBW and the National Institute for Health Research Bristol Biomedical Research Centre (NIHR Bristol BRC). It treats children experiencing health complications related to severe obesity, and offers children specialist treatment tailored care packages developed with their family, which could include diet plans, mental health treatment and coaching. In 2021, 15 new specialist NHS services were created, based on the Bristol clinic.

8. Bristol’s research plays a key role in the world’s response to COVID-19

Collaborating with colleagues at UHBW and NBT, Bristol researchers carried out clinical trials to assess how well certain vaccines worked to prevent people from becoming infected with COVID-19.

Longitudinal studies, also carried out by University and NHS teams, explored the impact of lockdowns and the pandemic on mental health and antibody testing.

9. Pfizer’s Vaccine Centre of Excellence launches at the University of Bristol

In 2021, a new Pfizer Centre of Excellence for Epidemiology of Vaccine-preventable Diseases was launched at the University.

The centre conducts real-world population-based surveillance studies in hospitals and the community to identify and measure the burden of specific vaccine-preventable infectious diseases affecting adults, including the elderly, as well as children.  Research will also be undertaken to support the design, development and use of next-generation vaccines.

10. How the University of Bristol supported NHS staff and volunteers during the pandemic

During the Covid pandemic, 100 rooms in the University’s student accommodation were given to NHS workers and volunteers. The University also made two of its biggest car parks available to NHS staff at UHBW, and donated personal protective equipment, such as suits, goggles, gloves and masks to the South Western Ambulance Service and NHS workers.

Almost 300 fifth year medical students joined the frontline prior to their graduation to help the NHS.

11. Intervention to help GPs identify, assess and treat patients with hepatitis C found to be effective

The University led the first clinical trial to increase the identification and treatment of hepatitis C virus (HCV) patients in primary care, which was found to be effective, acceptable to staff and highly-cost effective for the NHS.

Around 143,000 people in the UK have chronic HCV infection. As symptoms do not appear for several years, less than half of people infected are aware they have HCV and many more are not receiving treatment, increasing the risk of liver damage and passing the virus to others.

Looking to the future, the University of Bristol is working on dozens of research projects which could revolutionise NHS healthcare:

12. First ever clinical trial of laboratory grown red blood cells being transfused into another person underway

Red blood cells grown in a laboratory have now been transfused into another person in a world first clinical trial led by a UK team including Bristol researchers.  If proved safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders such as sickle cell and rare blood types.

13. Mesenchymal cell plasters to stop children needing repeated heart surgeries

University researchers, funded by the British Heart Foundation (BHF), have developed ‘mesenchymal cell plasters’ to revolutionise the way surgeons treat children living with congenital heart disease, so they don’t need as many open-heart operations.

There are around 200 repeat operations for people living with congenital heart disease every year in the UK. The technology could save the NHS an estimated £30,000 for every operation no longer needed, saving millions of pounds each year.

 

Fostering collaboration and supporting early career researchers

Bristol Heart Institute installation in Royal fort Gardens, Bristol

Eighty Bristol Heart Institute researchers joined ‘Fostering collaboration and supporting early career researchers’, our 5th Annual Meeting on 19 November 2021. The day was an opportunity not only to get to know some of the research taking place in the University’s Specialist Research Institute, but also the researchers driving it forward.

BHI researcher talks

In the first session on cardiac surgery, Massimo Caputo looked at tissue engineering, combining surgical facilities and imaging technologies in ‘hybrid’ theatre, cardiac 3D printing to help plan operations and how advances in VR technology are taking this to the next level.

Next, Tom Johnson, Consultant Cardiologist and recently appointed Associate Professor, examined a range of cardiovascular research priorities, from intracoronary imaging to industry collaboration, AV Cath lab broadcasting to encourage collaboration and the potential for system-wide datasets to enhance patient outcomes.

Jules Hancox from the School of Physiology, Pharmacology and Neuroscience shared some thoughts on career progression for early career researchers, including memorable advice about choosing a research project: “Interesting is not equivalent to important” – a trap that all researchers fall into from time to time, he acknowledged!

To wrap up the morning’s talks, Deborah Lawlor discussed Bristol’s epidemiological research in the BHI.

Plenary

For the plenary we welcomed Professor Andrew Taylor, Director of Innovation at Great Ormond Street Hospital and Head of Cardiovascular Imaging at UCL Institute of Cardiovascular Science, to talk about innovating in cardiovascular research. Using examples such as fast imaging protocols and the potential for delivering precision medicine via AI, he looked at why putting innovations into clinical practice at pace remains challenging, and how ongoing interaction between researchers and clinical teams is vital.

Quickfire presentations

BHI PhD students and early career researchers were invited to present their work in five minutes in three themed sessions covering epidemiology, basic science and clinical research. Attendees voted for the best presentation in each session – well done to:

  • Lucy Goudswaard: “Combining Mendelian randomisation and randomised control trial study designs to determine effects of adiposity on the plasma proteome”
  • Stanley Buffonge: “The battle to protect the coronary microvascular endothelial glycocalyx in diabetes”
  • Monica Gamez: “Endothelial glycocalyx heparan sulfate contributes to the integrity of the blood-retina-barrier and can be therapeutically targeted in diabetes mellitus”

Thank you

Thanks to everyone who took part in the meeting and especially to the organising committee, without whom the day wouldn’t have been possible: Alexander Carpenter, Alba Fernandez-Sanles, Laura Pannell, Eva Sammut and Andrew Shearn, along with Giovanni Biglino and Stuart Mundell.

Laura says:

“It was a fantastic day showcasing research the BHI can be proud of, and will enable the development of collaborative relationships for many years to come!”

 

The beating heart of Royal Fort Garden

Bristol Heart Institute interpretation sign

The new interpretation sign for the University of Bristol brings a whole new meaning to the phrase ‘living statue’.

The solid oak monolith is the third instalment in a series of iconic totems dedicated to the University’s research institutes. This sign embodies the work of the Bristol Heart Institute and has been designed to reflect the relationship between human life and nature. Joining many other works of art in the Royal Fort Garden this piece stands proud at three metres high, and if you get close enough you can hear the low thud of a heartbeat coming from deep within the structure day and night.

Previous designs highlighted the work of the Bristol Population Health and the Bristol Bio Design Institutes.

The new monolith is built from four solid oak panels which have been laser cut and hand painted to represent a human cardiovascular system. Following a couple of years of pandemic enforced hiatus, it’s great to add to the collection and celebrate the work of the Bristol Heart Institute in such a creative way.  

(Photo by Green Hat. Words adapted from text supplied by Green Hat)

MINOCA study recruitment wraps up

Principal Investigator Matt Williams on the MINOCA study, which completed its recruitment phase at UHBW in March.

One in 10 patients who suffer a suspected heart attack do not have a blocked or narrowed heart artery. These patients are classified as having a myocardial infarction with non-obstructive coronary arteries (MINOCA).

Previously thought to be low risk, MINOCA patients were often discharged with no treatment or follow up. However, research shows that these patients have mortality of nearly five per cent at only 12 months.

MINOCA patients are more likely to have had a stressful event prior to admission and a history of anxiety or depression. Previous research has even suggested that people with a stress cardiomyopathy – a common cause of MINOCA – have structural and functional differences in their brain, which may lead to differences in emotional processing and increased sympathetic drive  compared to people who do not develop this condition in response to stress.

The MINOCA study is investigating for the first time this link between the heart and the brain in MINOCA patients.

Over the last two years, our team has conducted a functional brain MRI and a cardiac MRI, as well as blood tests, ECGs and questionnaires, on 100 participants within two weeks of being admitted to hospital, with follow up MRI scans at six weeks and six months.

We are looking to see if patients with MINOCA have specific functional and anatomical changes in their brain which might explain why they develop this condition. Ultimately, it may be possible to target increased stress related brain activity to reduce the risk of this condition and improve patient outcomes.

Our study has been funded by grants from Above and Beyond, the James Tudor Foundation and the Rosetrees Trust.

This post first appeared in the March 2021 BHI Newsletter

Restoring respiratory sinus arrhythmia in heart failure

A CiC award will enable Eva Sammut to test the safety and feasibility of a novel device to reinstate RSA in dyssynchronous heart failure.

Confidence in Concept (CiC) awards fund proof of concept studies, which provide robust evidence of the feasibility of a proposed solution to a clinical need.

Dr Eva Sammut, NIHR-funded academic clinical lecturer in Cardiology at the BHI, received a £100K Elizabeth Blackwell Institute MRC CiC award in January to look at the feasibility, safety and effectiveness of a novel device to restore respiratory sinus arrhythmia in patients with heart failure.

Q: Why is your research significant?

Heart failure is a global clinical pandemic with clear unmet clinical need. Despite some advancements in therapy, prognosis remains poor with a 50 per cent five-year mortality representing a significant societal and healthcare burden.

Respiratory sinus arrhythmia (RSA) is a physiological phenomenon of a subtle increase of heart rate during inspiration and the converse during expiration. RSA is a major component of physiological heart rate  variability, a sign of good cardiac health, and is known to be lost in patients with heart failure. Loss of RSA is associated with increased ventricular  arrhythmia and sudden cardiac death. Restoring RSA in heart failure patients could improve their life  expectancy and markedly reduce hospitalisation costs. Existing preclinical models are inadequate to validate the safety of new treatments in this priority area.

Q: What are you developing?

Our group have developed a novel device which is able to reinstate RSA. Our preliminary results are very promising and demonstrate feasibility. Further proof of concept data from an advanced preclinical model is now pivotal to ensure the safety, feasibility and applicability of the new device to  progress it toward bedside to benefit patients.

This project will test the safety and feasibility of this new technology in the setting of dyssynchronous HF. This is a complex form of heart failure that responds poorly to the best available current treatment –  a specialised pacemaker named cardiac  resynchronisation therapy.

This study will be performed at the University’s Translational Biomedical Research Centre facility. We will develop an advanced preclinical model of dyssynchronous heart failure with balloon catheter myocardial infarction and superimposed pacemaker-induced ventricular dyssynchrony. Next, we will use this model to test this novel pacemaker approach to reinstating respiratory sinus arrhythmia in addition to cardiac resynchronisation therapy.

Q: Who are you working with?

A unique multidisciplinary team has been assembled including Professors Julian Paton, Raimondo Ascione and Alain Nogaret, and Drs Tom Johnson, Ed Duncan and Vito Domenico Bruno, who are co-applicants supporting this project.

We are also working in collaboration with Ceryx Medical, a spin out company formed by the universities of Bristol, Bath and Auckland.

Q: What next?

We are delighted to receive this funding to be able to take this exciting new technology to the next  developmental stage. This project is critical to ensure safety, feasibility and applicability of the new device in this setting. If positive results are demonstrated this would pave the way for larger, efficacy translational studies, with a view to reach patients in the NHS  within the next five to six years.

This post first appeared in the March 2021 BHI Newsletter

Preventing vascular damage associated with protein in urine

Becky Foster and Simon Satchell received a three-year BHF grant to investigate endothelial glycocalyx restoration. Principal Investigator Becky explains:

Proteinuria (protein within the urine) is an independent risk factor for cardiovascular disease. This is not only relevant for patients with kidney disease, but also for five per cent of the general population who have low-level proteinuria. A twofold increase in proteinuria increases risk of  cardiovascular mortality by 30 per cent.

If we knew how proteinuria is linked to vascular damage, we would potentially be able to treat these patients to prevent vascular disease.

Proteinuria begins in the filtering microvessels that form the glomerulus in the kidney. The microvessel wall is a specialised filtration barrier made up of  endothelial cells, a glomerular basement  membrane and epithelial cells (podocytes). Podocyte damage is often key to major glomerular protein leakage. A proteoglycan-rich endothelial glycocalyx (eGlx) layer lines all blood vessels. Damage to eGlx leads to increased vascular  leakage around the body, which can progress to vascular disease.

We have also shown that, in conditions of  proteinuria, eGlx is also damaged in non-kidney blood vessels, and that this is associated with increased vascular leak. Heparanase is an enzyme that is upregulated in conditions of proteinuria by  podocytes and also induces eGlx damage.

Our study will address our novel research  question, that podocyte-induced heparanase  expression causes vascular eGlx damage in  proteinuric disease.

From this project, we will know whether  heparanase upregulation by podocytes induces vascular damage, whether podocyte damage in proteinuria causes eGlx vascular damage and whether this is dependent upon heparanase. We will also use a clinically relevant heparanase  inhibitor, which can be used to drive translatProteinuria diagramion  into the clinic for these patients.

 

 

 

 

 

 

 

This post first appeared in the March 2021 BHI Newsletter

First use of ROB2 in Cochrane Review of Exercise Interventions for CHD

Graham Stuart and Guido Pieles collaborated with Craig Williams at the University of Exeter to publish a Cochrane Review, which gathered evidence for the effectiveness of physical activity interventions for people with congenital heart disease.

The Review compared three types of interventions from 15 trials, including programmes designed to increase physical activity, aerobic fitness and health-related quality of life. It found some evidence for increased physical fitness and physical activity, although there are no data yet to suggest this results in fewer hospital visits.

Read the Review in the Cochrane Library

Graham says:

Exercise used to be discouraged in patients with CHD. This was poor advice and led to an increase in cardiovascular and psychosocial morbidity.

Our Cochrane Review has shown that there is a need for further research to demonstrate why  exercise benefits disordered cardiovascular  physiology and to establish whether the  multiple theoretical benefits of exercise training  can translate into improved clinical outcomes.

All authors of Cochrane systematic reviews are now expected to use the Cochrane Risk of Bias tool (ROB2) to assess the risk of bias in any  randomized controlled trials they identify, to help people understand the trustworthiness of the findings. This was the first Cochrane Review to use ROB2 methodology.

Read the Cochrane editorial on ROB2

This post first appeared in the March 2021 BHI Newsletter

Mechanisms of cardiovascular complications in COVID-19

Paolo Madeddu discusses the progress of a timely research project.

Q: Why is this research significant?    

The coronavirus that causes COVID-19 enters the body through the epithelial-endothelial barrier of the lung and then spreads systemically. Its most severe manifestation is severe acute respiratory syndrome, where the epithelial-endothelial barrier is damaged to a level that fluid escapes into the alveoli. This makes it difficult for the lung to expand and allow the physiological exchanges of gases, resulting in severe hypoxia, shock and systemic organ damage. Organ damage is also caused by the virus’ ability to bring about a systemic inflammatory response and evade the immune system’s defences.

Pericytes – cells surrounding the vasculature – are essential to maintain vascular stability. We think that they can be damaged by the virus, which contributes to pulmonary and systemic damage.  We also think that the damage starts very early, when the viral S protein engages with the entry receptors expressed on cells. This is sufficient to activate detrimental signals in the pericytes and eventually prepare the ground for the virus to spread.

Q: What do you aim to do?

Our research aims to determine which receptors are expressed by human cardiac pericytes (ACE2 and also CD147, which is a more controversial receptor); determine if the S protein alone can induce signalling in exposed pericytes in culture; understand the functional consequences; and verify whether we can shield pericytes by blocking the interaction between S protein and receptors.

Q: How are you progressing?

The data we have gathered confirm the entry  receptor CD147 is expressed in pericytes. However, the expression of ACE2 receptors was low.

The S protein induces the phosphorylation of ERK1/2. This is a kinase enzyme involved in various cellular functions, but also used by the virus to activate RNA polymerase (the enzyme that makes copies of RNA and is used by the virus to make copies of itself). This reaction makes the pericytes less able to support the vascular network and also induces them to secrete inflammatory molecules typical of the cytokine storm. The instability is more evident in adult cells compared with young cells.

We can inhibit these reactions with an antibody  directed to the CD147 receptor, which suggests this is a viable method to shield human pericytes.

Our pre-prints in BioRXiv and the Lancet have received a lot of attention to date.

Q: What’s next?

Because cardiovascular patients are more  susceptible to complications from COVID-19, we  want to integrate the shielding approach of vascular cells within a more general strategy to protect the human body at the early stages of the disease.

A BHF grant is funding our work for one year. This work is carried out by Dr Elisa Avolio on cardiac pericytes provided by Professor Massimo Caputo, both acting as co-PIs.

As part of Bristol’s collective research effort into  COVID-19, we are seeking an additional  contribution from other charities and funding  agencies to work with fellow Bristol researchers  to generate an aerosol containing blockers of  entrance and attachment receptors.

This post first appeared in the March 2021 BHI Newsletter

BHF PhD programme funding renewed

BHI Deputy Director Alastair Poole explains the impact for our PhD in Integrative Cardiovascular Sciences.

In December 2020, the British Heart Foundation (BHF) announced new funding for its flagship four-year PhD programmes at 12 universities, aimed at nurturing the next generation of cardiovascular research leaders.

At the University of Bristol, we have been running the popular PhD programme in Integrative Cardiovascular Sciences since 2017, with tuition fees and research costs fully-funded by the BHF.

Understanding the biology and medicine of the cardiovascular system now requires approaches that cross-bridge disciplines, with our current cohort of students working across fundamental bioscience, clinical science and population health.

In this renewal, we aim to build on this successful strategy, introducing new disciplinary strands, supervisors and training in digital health, data analytics, coding and bioengineering. This aligns to the BHF strategy in aiming to prevent disease, identify and manage risk factors, through large scale genomics, data science, AI and multiparameter monitoring of environmental and medical measurements using novel personal and environmental devices. Bioengineering is now seen as an important component of regenerative medicine, and capitalizing on our broad base of expertise in Bristol, we have incorporated several new supervisors into this element. These will provide additional depth and breadth to the training for our students and further opportunities for innovative cardiovascular discovery.

When the funding was announced, Professor Metin Avkiran, the BHF’s Associate Medical Director, said:

“Today’s PhD students are tomorrow’s leaders in cardiovascular research. At this difficult time, it is more important than ever to maintain that pipeline of scientific talent and discovery towards future advances in the prevention, detection and treatment of heart and circulatory diseases.”

We look forward to welcoming our newest BHF PhD students in 2021.

PhD student Ffion Jones talks about what she enjoys about the programme:

This post first appeared in the March 2021 BHI Newsletter

The future may be on hold, but it has not been cancelled

BHI Director Gianni Angelini reflects on a turbulent year.

The COVID-19 pandemic made 2020 a year like no other.

It caused major disruption to our  cardiovascular research and teaching, which is continuing into 2021. Clinical translation research has virtually stopped, and basic science work has been significantly curtailed by the limited access to laboratories.

Charities, which are the backbone funders of our work, are experiencing unprecedented difficulties and this translates to reduced grant awards.  However, the renewal award of our BHF-funded PhD programme in Integrative Cardiovasular Science is excellent news.

And, at the same time, the use of  virtual platforms has transformed our work and opened avenues which were unthinkable a year ago. So, despite the gloom and doom, the pandemic is giving us a unique opportunity to regroup and reflect on what we did in the past, and what we can do better in the future.

These are the things that have not changed:

  • Our determination to continue to stand out as the leading academic cardiovascular centre in the UK, and amongst the foremost worldwide.
  • Our ability to turn innovations into benefit for adult and paediatric patients, and the health system.
  • Our creation of an environment where  clinicians, basic scientists and clinical research  methodologists can thrive, attract the most talented individuals and produce world-leading research.
  • Our resolve to facilitate a smooth and timely transition to the next generation of  cardiovascular clinicians and researchers.

This last point is possibly the most relevant for somebody heading towards the twilight of his career! We have an obligation to nurture and mentor our future research leaders by encouraging them to build the confidence to lead. We must pay more attention to our early- and mid-career  researchers and encourage them to play a  major role at the heart of our activities. They are the next generation who will guarantee our  continued success.

The future is still there for you to grab: it has not been cancelled.

This post first appeared in the March 2021 BHI Newsletter