Medicine

Addressing the urgent clinical challenges of an ageing population | by University of Leeds | University of Leeds | Nov, 2021

By 2050, one in four people in the UK will be 65 and over — an increase from one in five in 2019. This is due to declining fertility rates and people living longer. With fewer births and later deaths, the overall age structure has become gradually older.

This shift has created urgent clinical challenges as more people suffer from chronic diseases or are living with multiple diseases or medical conditions (co-morbidities).

Researchers at the University of Leeds are using their expertise in cancer, cardiovascular disease, musculoskeletal disorders, and infectious disease to address health inequalities and improve patient outcomes.

University of Leeds research into early treatment of rheumatoid arthritis has already benefited 11 million people worldwide

Rheumatoid arthritis is the largest cause of treatable disability in the Western world, costing the NHS around £560 million a year and the UK economy £1.8 billion a year.

Professor Paul Emery at the University of Leeds was the first to propose rheumatoid arthritis should be treated immediately and aggressively to control inflammation and prevent joint damage.

His research showed poor control of inflammation in early rheumatoid arthritis caused disability, bone-thinning and joint damage. Further, if joint inflammation can be completely suppressed for people with rheumatoid arthritis early, joint damage can be prevented.

Alongside other researchers, he showed early use of emerging biological medicines improves remission rates and long-term outcomes. This revealed early intervention allows many people to eventually reduce or stop treatment altogether.

These findings have gone on to inform clinical guidance internationally and directly influence the care of over 11 million people.

The early phase of rheumatoid arthritis is of unique importance as, early in disease, the symptoms and signs can be rapidly reversed by appropriate treatments. Early, aggressive treatment improves patients’ quality of life by reducing pain and increasing functional ability and participation in valued activities, including work.

— Professor Paul Emery

Professor John Greenwood’s research has the potential to change how ischaemic heart disease is detected around the world

Coronary heart disease is a significant cause of death and disability worldwide, and the leading single cause of mortality in Europe.

In the UK, there are around 1.8 million people suffering with symptoms of angina (chest pain caused by reduced blood flow to the heart muscles) and heart disease costs the UK £9 billion a year.

Cardiac Magnetic Resonance (CMR) imaging is a medical imaging technology for the non-invasive assessment of the function and structure of the cardiovascular system. It is one of several non-invasive tests used for diagnosing heart disease.

Leeds research, led by Professor John Greenwood, has provided the largest real-world evidence that CMR imaging is more accurate and cost effective at detecting ischaemic heart disease than nuclear perfusion imaging — currently the most widely used test around the world.

As a result, CMR imaging for ischaemic heart disease detection has been rapidly introduced across the NHS, with 24% of all UK CMR referrals now being for an ischaemic heart disease indication.

Not only is CMR imaging more diagnostically accurate and cost effective than alternative tests, it is non-invasive and avoids the health risks that come from using ionising radiation. Its superiority has been recognised through rapid uptake of CMR imaging for heart disease investigation across the NHS.

— Professor John Greenwood

Professors John Fisher and Eileen Ingham have developed a novel processing method to allow human tissue to be used for wound repair

Wounds affect 3.8 million adults in the UK, costing the NHS £8.3 billion a year. Two-thirds of that money is spent on treating wounds that are hard-to-heal with standard therapy (chronic wounds) despite chronic wounds accounting for less than a third of all wounds. New, effective treatments for chronic wounds are therefore an urgent need.

Professors John Fisher and Eileen Ingham at the Institute of Medical and Biological Engineering have developed a novel processing method to remove cells from human and animal tissues so that they can be used to repair chronic wounds.

This technique, called decellularisation, involves washing a specific type of tissue to be used as an implant in a series of mild solutions. This removes cells, then lipid membranes, various other molecules and finally DNA. At this point it has no cellular content and is known as a ‘scaffold’.

When it is implanted in the body, it will not be rejected because the host body’s defences have nothing to react to. Over time the host cells will colonise the implanted tissue which will integrate and grow naturally in the body.

Our decellularisation process has been adapted and used in different tissue types. This has had a direct impact on the care of thousands of patients.

— Professor Eileen Ingham

In collaboration with NHS Blood and Transplant Tissue and Eye Services, decellularised human dermis has been developed and manufactured for chronic wounds and is being used for patient treatment in the UK.

Dr David Russell, a consultant vascular surgeon at Leeds Teaching Hospitals NHS Trust, is leading a trial looking at the effectiveness of decellularised dermis — and other treatments — for diabetic foot ulcers.

We are trying to establish the optimal way to treat chronic diabetic foot ulcers. While a number of treatments are used by the NHS, there is limited evidence on which combination of these works best.

— Dr David Russell

Researchers have developed an in vitro gut model that is helping find ways to use antibiotics more effectively to treat C. difficile infection. Image: Janice Carr, Centers for Disease Control and Prevention.

Antimicrobials have revolutionised the treatment of infectious diseases. Resistance is an inevitable development as microorganisms adapt to antimicrobials, but overuse and misuse of antimicrobials is speeding up resistance. This is reducing our capability to treat infections, and increasing morbidity and mortality.

Within the next 30 years, annual deaths from antimicrobial resistance will outstrip those due to cancer.

Clostridium difficile is a bacterium that can cause bowel infection, typically associated with antibiotic use that damages the healthy gut bacteria. C. difficile infection is a substantial burden on healthcare systems and is likely to remain so given the reliance on antimicrobial therapies to treat bacterial infections, especially in an ageing population in whom multiple co-morbidities are common.

The University of Leeds has a history of partnering with industry in the discovery and development of treatments and prevention approaches for C. difficile infection.

Despite the introduction of the antibiotic fidaxomicin in 2012, treatment options for C. difficile infection are limited and rates of recurrent disease are high.

Dr Jane Freeman and Professor Mark Wilcox’s team developed an in vitro gut model that can mimic the effects of antibiotic exposure on gut bacteria and so C. difficile infection. It has been used to help develop new treatments such as ridinilazole and to evaluate and optimise new dosing strategies for existing treatments.

This gut model demonstrated that by changing antibiotic dosing, the treatment can be just as efficient against C. difficile, but with less damage to the gut bacteria, so reducing the risk of recurrent disease. Gut model results have contributed to the positioning of fidaxomicin in international guidelines, and have directly informed on a new dosing regimen for fidaxomicin with a potential cost saving of £700,000 per year for the NHS.

This has led to new fidaxomicin dosing in international guidelines and a potential cost saving of £700,000 per year for the NHS.

The ridinilazole gut model and early phase clinical trial results showed ridinilazole was better than vancomycin at treating C. difficile infection. This helped ridinilazole achieve Fast Track designation by the FDA — the US body that approves new drugs — for its clinical development.

By accurately simulating gut bacteria, our gut model has allowed us to define which are low versus high risk antibiotics to induce C. difficile or CDI, to identify novel dosing strategies for existing drugs to treat CDI, and to develop potential new treatments. It is particularly pleasing to see the results directly influencing treatment and prevention strategies for CDI internationally.

— Professor Mark Wilcox

With the ageing population trend set to continue well into the 21st century, health services globally are finding themselves under increasing pressure.

To combat this, the University of Leeds is capitalising on today’s technologies to identify disease early, detect changes in the body as a result of disease and use advances in robotics and artificial intelligence to improve patient outcomes and quality of care.


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