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AI identifies patients with heart failure that respond to beta-blocker treatment

Written by Louise Stanley on . Posted in Early diagnosis and detection, Health inequalities, Inflammation and chronic disease.

Researchers at BHP founder-member the University of Birmingham have developed a new way to identify which patients with heart failure will benefit from treatment with beta-blockers.

Heart failure is one of the most common heart conditions, with substantial impact on patient quality of life, and a major driver of hospital admissions and healthcare cost.

The study involved 15,669 patients with heart failure and reduced left ventricular ejection fraction (low function of the heart’s main pumping chamber), 12,823 of which were in normal heart rhythm and 2,837 of which had atrial fibrillation (AF) – a heart rhythm condition commonly associated with heart failure that leads to worse outcomes.

Published in The Lancet, the study used a series of artificial intelligence (AI) techniques to deeply interrogate data from clinical trials.

The research showed that the AI approach could take account of different underlying health conditions for each patient, as well as the interactions of these conditions to isolate response to beta-blocker therapy. This worked in patients with normal heart rhythm, where doctors would normally expect beta-blockers to reduce the risk of death, as well as in patients with AF where previous work has found a lack of effectiveness. In normal heart rhythm, a cluster of patients was identified with reduced benefit from beta-blockers (combination of older age, less severe symptoms and lower heart rate than average). Conversely in patients with AF, the research found a cluster of patients who had a substantial reduction in death with beta-blockers (from 15% to 9% in younger patients with lower rates of prior heart attack but similar heart function to the average AF patient).

The research was led by the cardAIc group, a multi-disciplinary team of clinical and data scientists at the University of Birmingham and fellow BHP founder-member University Hospitals Birmingham, aiming to integrate AI techniques to improve the care of cardiovascular patients. The study uses data collated and harmonized by the Beta-blockers in Heart Failure Collaborative Group, a global consortium dedicated to enhancing treatment for patients with heart failure.

First Author Dr Andreas Karwath, Rutherford Research Fellow at the University of Birmingham and member of the cardAIc group, added: “We hope these important research findings will be used to shape healthcare policy and improve treatment and outcomes for patients with heart failure.”

Corresponding author Georgios Gkoutos, Professor of Clinical Bioinformatics at the University of Birmingham, Associate Director of Health Data Research UK Midlands and co-lead for the cardAIc group, said: “Although tested in our research in trials of beta-blockers, these novel AI approaches have clear potential across the spectrum of therapies in heart failure, and across other cardiovascular and non-cardiovascular conditions.”

Corresponding author Dipak Kotecha, Professor & Consultant in Cardiology at the University of Birmingham, international lead for the Beta-blockers in Heart Failure Collaborative Group and co-lead for the cardAIc group, added: “Development of these new AI approaches is vital to improving the care we can give to our patients; in the future this could lead to personalised treatment for each individual patient, taking account of their particular health circumstances to improve their well-being.”

The research used individual patient data from nine landmark trials in heart failure that randomly assigned patients to either beta-blockers or a placebo. The average age of study participants was 65 years, and 24% were women. The AI-based approach combined neural network-based variational autoencoders and hierarchical clustering within an objective framework, and with detailed assessment of robustness and validation across all the trials.

The research was presented this week at the ESC Congress 2021, hosted by the European Society of Cardiology – a non-profit knowledge-based professional association that facilitates the improvement and harmonisation of standards of diagnosis and treatment of cardiovascular diseases.

radiographer looks at cross sectional MRI images of a human skull

UHB and Cambridge University Hospitals win government funding for ground-breaking AI in radiotherapy

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

A machine learning technology that helps cut the time patients wait for life-saving cancer treatment has been successful in the latest round of the Artificial Intelligence (AI) in Health and Care Award.

BHP founder member University Hospitals Birmingham, working in partnership with Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) is one of 38 organisations singled out for funding.

The AI Award is making £140 million available over four years to accelerate the testing and evaluation of artificial intelligence technologies which meet the aims set out in the NHS Long Term Plan.

Over the next year, UHB will work with CUH to leverage Microsoft Project InnerEye’s open-source AI toolkit to differentiate tumour and healthy tissue on cancer scans (called ‘segmenting’), prior to radiotherapy treatment. The aim of this AI Award project is to evaluate how this could save clinicians’ time, reduce the time between the scan and commencing treatment, and scale this to four NHS Trusts.

Dr Kal Natarajan, UHB consultant clinical scientist, said: “I’m really looking forward to working with colleagues in Birmingham and Cambridge on this project.

“The technology has tremendous potential to transform radiotherapy care, helping patients to be treated quicker and ensure clinicians spend their time as effectively as possible.”

Dr Raj Jena, CUH oncologist and project lead, said: “I am so pleased that our project has been awarded government funding to take it to the next level. AI has the capacity to deliver so much behind-the-scenes routine work, enabling doctors to spend more time face-to-face with patients, and shortening the time that patients have to wait for treatment.

“We believe this is first time an NHS hospital has trained its own medical imaging AI for its own patients and our aim is to assist other radiotherapy departments to use the models for their patients.”

Up to half of the UK population will be diagnosed with cancer at some point in their lives. Of those, half will be treated with radiotherapy, often in combination with other treatments such as surgery, chemotherapy, and increasingly immunotherapy.

Radiotherapy involves focusing high-intensity radiation beams to damage the DNA of hard cancerous tumours while avoiding surrounding healthy organs. This is a critical tool in the fight against cancer, with around 40% of cured patients undergoing precision radiotherapy.

Radiotherapy is most effective when treatment takes place as soon as possible. However, segmenting the tumour targets and healthy tissue on image scans is a key step that is currently performed manually by doctors, taking several hours per patient.

Microsoft’s recent peer-reviewed research paper in JAMA Network Open shows that clinicians could segment prostate and head & neck cancer images up to 13 times faster when using InnerEye machine learning assistance, with an accuracy similar to that of human experts.

Javier Alvarez-Valle, from Microsoft Research Cambridge, said: “We are delighted that CUH and UHB are able to use our open-source software to build their own AI models, for the benefit of their patients. This NHSX AI Award paves the way for more NHS Trusts to reduce cancer treatment times using assistive AI, and to help alleviate the workload of clinicians.”

Already, over 17,000 stroke patients and over 25,000 patients with diabetes or high blood pressure have benefited from the first round of the AI in Health and Care Award since September, where £50 million was given to 42 AI technologies.

The AI Award is one of the programmes that make up the NHS AI Lab, led by NHSX and delivered in partnership with the Accelerated Access Collaborative (AAC) and National Institute for Health Research (NIHR).

Urine test for bladder cancer to be developed by University of Birmingham and Nonacus

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

BHP founder-member the University of Birmingham and Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, have partnered to develop a non-invasive test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.

Bladder cancer is the seventh most common cancer in the developed world1. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria).  The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder.   Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.

Dr Bryan, Director of the Bladder Cancer Research Centre,  commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality.  Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis.  What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”

While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results.  However, researchers at the University started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of fetal DNA in maternal blood samples.  Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.

The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs).  Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients.  This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours.  The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling2.

As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.

Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis.  The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.

Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.

Chris Sale, CEO of Nonacus Ltd, commented:  “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”

Tony Hickson, Chief Business Officer at Cancer Research UK, said: “As funders of much of the world-class, cutting-edge cancer research happening in the UK, we offer unique opportunities to commercial partners looking for early involvement in new discoveries. Having Nonacus on board to help transform promising findings in the lab into a new non-invasive test to diagnosis bladder cancer is a testament to how commercial collaborations have the potential to transform the lives of patients. We are looking forward to seeing the next steps as the test is developed and rolled out to the UK and beyond.”

Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said:  “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not ​accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis.  A urine test that can rapidly determine who needs these tests will be a very welcome development.  Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects.  This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer.”

DNA strands

Young patients with cancer to benefit from £1million investment in genomic testing

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection, Experimental medicine.

Children and young people living with cancer from across the West Midlands, Oxfordshire and parts of Southern England will now benefit from improved genetic testing, thanks to a seven-figure donation to Birmingham Children’s Hospital Charity from Children with Cancer UK, in partnership with Kwik-Fit.

Home to one of the largest children’s cancer centres in the UK, BHP member Birmingham Children’s Hospital cares for over 200 patients with cancer, leukaemia and brain tumours every year, from the West Midlands and beyond.

Genomic testing for patients diagnosed with cancer is incredibly important and over the last decade, large scale sequencing projects have identified pertinent DNA changes, which have enabled scientists to develop new and improved cancer drugs and treatments to specifically target these variations.

Sequencing all possible DNA changes in a single test gives scientists the best possible chance of detecting the genetic changes driving a child’s cancer; and knowing the genetic makeup of a child or young person’s cancer, or tumour, allows clinicians to offer a more tailored treatment.

Targeted therapies have improved the number and different types of treatment offered to children and young people, aimed at saving more lives and improving the quality of life for patients living with cancer.

The UK’s largest genetics laboratory, the West Midlands Regional Genetics Laboratory, based at BHP member Birmingham Women’s and Children’s NHS Foundation Trust, provides cancer genetic services for patients across the West Midlands, Oxfordshire and parts of Southern England, covering a population of 12million.

The NovaSeq 6000 is a state-of-the-art piece of DNA sequencing equipment which has enabled the rapid expansion of cancer genetic testing at the West Midlands Regional Genetics Laboratory.
The NovaSeq 6000 is a state-of-the-art piece of DNA sequencing equipment which has enabled the rapid expansion of cancer genetic testing at the West Midlands Regional Genetics Laboratory.

Now a donation of just over £1million to Birmingham Children’s Hospital Charity has allowed the laboratory to purchase a high-throughput next generation sequencing platform.  This investment is possible thanks to the incredible fundraising efforts of Kwik-Fit’s staff, customers and suppliers who raised the substantial sum after Kwik-Fit employees chose Children with Cancer UK as the company’s national charity partner.

The NovaSeq 6000 is a state-of-the-art piece of DNA sequencing equipment which has enabled the rapid expansion of cancer genetic testing at the West Midlands Regional Genetics Laboratory.

Initial forecasts provided by NHS England and NHS Trusts across the West Midlands, Oxfordshire and parts of Southern England suggest that approximately 560 children and young people per year could benefit from large cancer panel genetic testing following the installation of the NovaSeq.

The significant gift also allowed for the refurbishment of the laboratory in which the NovaSeq will sit.

The Chairman of Birmingham Women’s and Children’s NHS Foundation Trust and its Charity, Professor Sir Bruce Keogh, former Medical Director of the NHS in England, said: “The NovaSeq 6000 has dramatically enhanced our ability to identify diagnostic and prognostic biomarkers for childhood and young people’s cancers, thereby enabling our expert scientists and doctors to quickly optimise and develop more effective and less toxic treatments for children and young people with cancer.

“We’re incredibly thankful to Children with Cancer UK and all the employees at Kwik-Fit for enabling us to expand our cancer genetic testing capability in this way. It really will make a difference to thousands of families living with a cancer diagnosis.”

Children with Cancer UK, the charity dedicated to the fight against childhood cancer, is a long-term supporter of Birmingham Children’s Hospital and is making its second £1million donation to the hospital’s charity. The first helped ensure the opening of a brand new Children’s Cancer Centre in 2018.

Children with Cancer UK Trustee, Nick Goulden, said: “We are delighted the new NovaSeq 6000 has been installed at the West Midlands Regional Genetics Laboratory, ready to serve its young cancer patients across the region. By offering personalised treatments through genetic sequencing, it’s another step towards our ultimate goal of saving the life of every child and young person diagnosed with cancer.

“We are also incredibly grateful for our year-long partnership with Kwik-Fit who shared this vision with us. Through their innovative and dedicated fundraising, Kwik-Fit employees raised £1million to make all of this possible and the legacy of our relationship will benefit the lives of thousands of children and young people in the future.“

Kwik-Fit’s partnership with Children with Cancer UK, which took place before the pandemic, saw its staff participate in events such as the Virgin Money London Marathon and the Simplyhealth Great North Run. It also organised various fundraising activities including bake sales, static bike challenges, car washes and sponsored walks. In addition, staff swapped cars for cycles as part of the company’s first-ever ‘Tour De Branch’ – a nationwide bike ride in which over 80 employees covered 2,500 miles between 120 Kwik-Fit centres.

Mark Slade, managing director of Kwik-Fit, said: “We were delighted to hit our fundraising target of £1million which has enabled Birmingham Children’s Hospital Charity to invest in such an important piece of equipment.

“I would like to congratulate and thank all of the Kwik-Fit staff for their tremendous effort and dedication and all our customers and partners who supported us – we would not have been able to achieve this target without them. We hope that this vital testing equipment will make a massive difference to the outcome for many families in the future.”

Revolutionising diagnosis and treatment of life-threatening post-partum haemorrhage

Written by Louise Stanley on . Posted in Early diagnosis and detection, Maternal health.

Post-partum haemorrhage (PPH) accounts for 27% of all maternal deaths worldwide, according to the World Health Organization (WHO). The burden of PPH disproportionately affects mothers from low- and middle-income countries, which account for 86% of all maternal deaths.

PPH is defined as blood loss from the genital tract of 500 ml or more within 24 hours of birth. PPH usually happens within a day of giving birth, but it can occur up to six weeks after a birth.

To find possible solutions to the terrible problem of PPH, researchers at BHP founder-member the University of Birmingham are conducting the E-MOTIVE trial based on the WHO ‘first response bundle’ in five countries: Kenya, Sri Lanka, South Africa, Tanzania and Nigeria.

Kristie-Marie Mammoliti, one of the lead researchers for the University of Birmingham explained the thinking behind the trial: “Surviving childbirth shouldn’t be a privilege; it should be the norm. Tragically this is not the case for so many women around the world. As PPH is the leading cause of maternal mortality globally, we are working together with our low– and middle-income country partners to find solutions to stop women from bleeding to death after childbirth.”

Professor Hadiza Galadanci, from one of the University’s partners in Nigeria, commented: “One of the most frightening sights in Obstetrics is to see blood pouring from a woman after birth and to try all you can to stop it and you are not able to. If E-MOTIVE strategy is implemented in low- and middle-income countries, the light at the end of the tunnel to reducing maternal deaths due to PPH will be bright.”

The E-MOTIVE trial has the potential to revolutionise how medical institutions diagnose and treat PPH, and remove it from the list of life-threatening conditions facing pregnant women.

As we approach International Mother’s Day on Sunday 9 May, it is important for everyone to care and be aware of the risks that women across the world face when bringing life into the world, and how these risks can be reduced.

a group of rugby players on the pitch, in a scrum formation

Rugby study identifies new method to diagnose concussion using saliva

Written by Louise Stanley on . Posted in Early diagnosis and detection.

A study of top-flight UK rugby players – carried out by BHP founder-member the University of Birmingham in collaboration with the Rugby Football Union (RFU), Premiership Rugby, and Marker Diagnostics – has identified a method of accurately diagnosing concussion using saliva, paving the way for the first non-invasive clinical test for concussion for use in sport and other settings.

Following the team’s previous research, which identified that the concentration of specific molecules  in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these ‘biomarkers’ could be used as a diagnostic test for sport-related concussion.

Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues – the Premiership and Championship.

The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs), published today (March 23) in the British Journal of Sports Medicine, has for the first time shown that specific salivary biomarkers can be used to indicate if a player has been concussed.  Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later.

The scientific breakthrough provides a new laboratory-based non-invasive salivary biological concussion test, which could have wide-reaching use and potential to reduce the risk of missing concussions not only in sport – from grassroots to professional levels – but also in wider settings such as military and healthcare.

In community sport, these biomarkers may provide a diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting.  While, at an elite level of rugby, the concussion test may be used in addition to the existing World Rugby Head Injury Assessment (HIA) protocol.

Marker Diagnostics, a subsidiary of Swiss biotechnology company Marker AG, is in the process of commercialising the patented salivary concussion test as an over-the-counter test for elite male athletes.  It has also obtained a CE Mark for test, which has been named MDx.100.

The team now aims to collect further samples from players in two elite men’s rugby competitions in order to provide additional data to expand the test and develop its use to guide the prognosis and safe return to play after concussion and to further establish how it will work alongside the HIA process.

The team will present their findings and planned next research steps at the World Rugby Laws and Welfare Symposium to be held later this month.

Meanwhile, Marker Diagnostics and the University of Birmingham are also currently carrying out several additional studies to further validate and expand the test for use in different groups that were not included in the SCRUM study, including women, young athletes and community sports players.

The research is part of the REpetitive COncussion in Sport (ReCoS) research programme being led by the University of Birmingham through the National Institute for Health Research’s Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) based at fellow BHP founder-member University Hospitals Birmingham NHS Foundation Trust (UHB).

First author Dr Valentina Di Pietro, of the University of Birmingham and NIHR SRMRC, said: “Concussion can be difficult to diagnose, particularly in settings such as grass roots sports where evaluation by a specialist clinician is not possible. Consequently, some concussions may go undiagnosed.

“There are also concerns regarding the long-term brain health of those exposed to repeated concussions.

“A non-invasive and accurate diagnostic test using saliva is a real game changer and may provide an invaluable tool to help clinicians diagnose concussions more consistently and accurately.

“In professional sports, this diagnostic tool may be used in addition to current head injury assessment protocols and return to play evaluation to ensure the safety of individuals.”

Senior author Antonio Belli, Professor of Trauma Neurosurgery at the University of Birmingham, Consultant Neurosurgeon at UHB, and Director of NIHR SRMRC, added:  “Conducting a study in a professional contact sports setting has meant we have been able to collect invaluable data enabling us to make significant advances in our biological knowledge and understanding of concussion and its diagnosis.

“Crucially, the differences in the salivary concentration of these biomarkers are measurable within minutes of injury, which means we can make rapid diagnoses.

“The ability to rapidly diagnose concussion using biomarkers in addition to existing tools solves a major unmet need in the sporting world as well as in military and healthcare settings, particularly in injuries without significant visible symptoms.”

Author Dr Simon Kemp, RFU’s Medical Services Director, said: “This study is an important part of the portfolio of collaborative research initiatives the RFU undertakes into concussion.

“While still a way from having something that can be used in community rugby, it is extremely encouraging to now be able to start to develop a rapid and non-invasive test which could add real value particularly at a grassroots level of the game.

“We would like to thank all the players and clubs who participated in the study and to World Rugby for granting permission for us to extend the duration of the HIA from 10 to 13 minutes in order for the saliva samples to be captured. We wouldn’t have been able to do it without this support.

“We will now be working with World Rugby to secure further research options in two elite men’s competitions.”

Author Dr Matt Cross, Head of Science and Medical Operations at Premiership Rugby, said: “We would like to thank our clubs and all of the players for volunteering to be part of this very important research project.

“The findings from the study are clearly promising and highlight the potential for salivary biomarkers to further support clinical decision making and the accurate identification and diagnosis of concussion in a range of different sporting and non-sporting settings.

“Premiership Rugby and the Premiership clubs support a number of player welfare focused research projects, and we are looking forward to continuing to collaborate and support further research in the next phase of this specific project from 2021-22 onwards.”

Dr Éanna Falvey, World Rugby Chief Medical Officer, added: “Elite Rugby’s Head Injury Assessment process has proven an invaluable tool in the identification of concussion with an accuracy of over 90 per cent, but we are continually evaluating the latest developments in science and technology to identify potential enhancements.

“This study, its rigour and outcomes demonstrates the value in a targeted, scientific approach and reflects rugby’s progressive commitment to player welfare.”

Tinus Maree, CEO of Marker AG, said: “This ground-breaking validation of the biomarker panel shows that we can use the simple swab collection of saliva to accurately and specifically diagnose concussion.

“It is a biological measure of mild traumatic brain injury and will contribute to a new global standard of care for the injury and a meaningful reduction of the cost and health burden associated with concussion.

“We are grateful to our collaborators, especially to Dr Simon Kemp and the RFU, for their efforts and visionary support of this important work.”

The study, fully supported by The Rugby Players’ Association, saw the team obtaining saliva samples from male professional players in the top two tiers of England’s elite rugby union competition during the 2017-18 and 2018-19 rugby seasons.

Saliva samples were collected pre-season from 1,028 players.  They were also collected from 156 of these players during standardised World Rugby head injury assessments (HIAs) at three time points – in-game, post-game, and 36-48 hours post-game.  The HIA protocol, used by rugby medical staff, includes a neurological examination, a series of cognitive tests and evaluation of gait and balance to determine if a player has been concussed.

‘Control’ samples were also collected from 102 uninjured players and 66 players who were removed from the game due to musculoskeletal injuries.

Using samples collected during the 2017-18 season, the team identified a panel of a combination of 14 salivary biomarkers – known as small non-coding RNAs or sncRNAs – that was highly accurate (96%) at identifying concussed players from all other groups.

This included players with suspicion of mild traumatic brain injury who had a concussion ruled out after a structured HIA; uninjured controls from the same game; and players who had suffered musculoskeletal injuries.

The panel was prospectively tested during the 2018-19 season, and the research showed it could successfully predict whether players would be positive or negative for concussion via the HIA protocol in 94% of cases.

The study was funded by the Midland Neurosciences Teaching and Research Fund, NIHR SRMC, Medical Research Council, Rugby Football Union and Marker AG.