Strong partnership working has led to advances in care for trauma patients – University of Birmingham

Professor Janet Lord, who is Professor of Immune Cell Biology at Birmingham and Director of the collaborative MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, which is led from Birmingham, receives the award for ‘Services to Older People’.

Professor Lord is also a Theme Lead and key linchpin at the NIHR SRMRC .

Follow this link to read more: University of Birmingham healthy-ageing pioneer awarded CBE – University of Birmingham

This result was unexpected as glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. However, previous clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of supplementation with glutamine.

International nutrition guidelines have recommended enteral glutamine for major burn patients but more recent findings in critical illness showing no benefit or even harm from glutamine supplementation warranted better data in the burn setting.

Participants were randomized to double-blind treatment within 72 hours after admission to an ICU or burn unit with glutamine (0.5 g/kg body weight per day) or placebo every 4 hours through a feeding tube or three or four times a day by mouth. Treatment continued until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission.

A key limitation was that the trial was stopped before the planned 2,700-patient accrual because of slow enrollment. Once it became clear the original sample size wasn’t feasible, the protocol was amended to switch the primary and secondary outcomes. Another limitation was attrition of participants to the 6-month survivor questionnaires.

The study’s lead, Dr Daren Heyland (Professor of Medicine at Queen’s University and the Director or the Clinical Evaluation Research Unit, Kingston General Hospital, Canada) noted that “the large number of diverse patients recruited across a large global network of burn units supports broad generalizability of the findings.”

At the University Hospitals Birmingham Foundation Trust the study was led by the Director of the Centre for Conflict Wound Research, Professor Naiem Moiemen. RE-ENERGIZE was supported locally by the Delivery Team under the Trauma, Burns and Critical Care umbrella and recruited 29 patients.

Professor Moiemen added ‘this is the first large scale multi-national randomised clinical trial in Burns. This great work has settled a clinical question that was debated within the burn community for decades. The successful conducting of this trial has established a strong research network, essential for further trials that can provide quality evidence in future.’

Sources

New England Journal of Medicine

Source Reference: Heyland DK, et al “A randomized trial of enteral glutamine for treatment of burn injuries” N Engl J Med 2022; DOI: 10.1056/NEJMoa2203364.

Glutamine for Burn Patients: Time for a Rethink by Crystal Phend, Contributing Editor, MedPage Today September 9, 2022

https://www.medpagetoday.com/hospitalbasedmedicine/generalhospitalpractice/100619

The National Institute for Health Research has changed its name. To emphasise our enduring commitment to social care research, from today the NIHR will officially become the ‘National Institute for Health and Care Research’. The acronym ‘NIHR’ will remain unchanged.

A history of investment

Since its establishment in 2006, the NIHR has invested over £200m in more than 470 social care research projects across its portfolio, with £90m worth of NIHR-funded social care studies starting in the last three years. Of these, over a third have been funded by the NIHR’s dedicated School for Social Care Research.

NIHR-funded research is diverse, exploring a wide range of important issues, and has led to a number of changes to social care practice. In one example, a new approach was developed which reduced challenging behaviours among people with learning disabilities in residential settings by two thirds and was rolled out across 800 residential care sites.

As well as the £200m in direct funding, we have also supported and delivered social care research through our wider infrastructure, in particular the Applied Research Collaborations which worked with local authorities to support over 80 studies in 2020/2021, and the Research Design Service which supports researchers to develop high quality applications.

Additionally, the NIHR has supported those who want to develop their career in social care research, funding internships, career development and senior leaders awards and PhDs through the NIHR Academy and the School for Social Care Research. We have also supported those working in the social care sector through the Local Authority Fellowship Scheme.

Deeper and broader commitments

Tied to today’s announcement are a range of investments and commitments to future work.

These are designed to both deepen and broaden the range of social care research the NIHR supports – through funding, building capacity within our research delivery infrastructure, strengthening the links between academia and practice, and engaging carers and people who need care and support.

An increase in spending of £5m a year has been dedicated to social care research, some of which will go towards funding an additional call run through the Research for Social Care programme. This programme funds research which generates evidence to improve, expand and strengthen the way adult social care is delivered for users of care services, carers, and the public. From today, this work will be accompanied by a commitment to fund much-needed research in the area of social care for children and young people, working in partnership with the Department for Education.

Our Health and Social Care Delivery Research Programme is today launching a ‘Social Care Rapid Evaluation’ funding call, designed to fund new teams to deliver rapid reviews of promising social care innovations identified by the social care sector. This will generate nationally relevant evidence to improve care and outcomes for people who use services and professionals delivering those services. And next week, the NIHR and the Engineering and Physical Sciences Research Council will be announcing the studies funded through a new, jointly-run call focused on transforming care and health at home and enabling independence.

The NIHR’s Health Technology Assessment programme is establishing a social care prioritisation committee with wide representation from social care practice, people with lived experience and others. This aims to examine social care research questions, prioritise them and then oversee commissioning briefs to be advertised.

Prof. Lucy Chappell, Chief Executive of the NIHR, said:

“At NIHR, we believe that funding and supporting research that expands and strengthens the way that social care is provided is one of the most important ways to improve standards of care for people who need it. We want to support the incredible work being done on the ground by both paid and unpaid carers.

“This name change is more than symbolic. Our history of investment in social care research already tells a strong story, and today’s concrete plans to further fund and support such research are a clear affirmation of our commitment to this vital part of the health and care sector.

“It is our hope that today’s name change will inspire not just current and future generations of social care researchers, whose talent and expertise can revolutionise the social care sector, but also people who need care and support, carers, the public and those working in social care. The involvement of all these groups will be key to getting the right research to the right places in the right way.”

Minister for Innovation, Lord Kamall, said:

“We want to see the UK continue to be a catalyst of innovation for health and care research from rapidly creating new vaccines to advancing new research to improve the effectiveness of social care, such as developing best practice for supporting people with learning disabilities.

“NIHR’s name change and this additional funding will ensure we remain at the forefront of ground-breaking research in both health and social care.

“I encourage researchers, social care users and practitioners to get involved with social care research. Research is a key way to identify and address current challenges to improve the lives of carers and people receiving social care.”

How you can get involved

The NIHR is calling on researchers, social care practitioners and users of social care services to undertake and get involved with social care research that identifies and addresses current challenges to improve the lives of carers and people receiving social care.

If you are interested in engaging with the NIHR’s work in this area, you can find out more on our social care home page. You can also learn about the work we’re doing with local authorities and explore the resources provided by the School for Social Care Research.

On 26th April, the NIHR’s School for Social Care Research will be holding its annual conference in London. It provides a great opportunity to hear about new studies as well as emerging evidence from the School’s commissioned studies and its implications for adult social care practice. The conference will feature a message from NIHR CEO Prof Lucy Chappell, and a wide range of contributions from experts and practice colleagues in the adult social care field. For more information and to register for your free ticket, visit our conference registration page.

The study aims to validate a selection of tools identified in an earlier study, BOSS-1, which can objectively assess burn scars for characteristics like thickness, pliability and colour. These tools can then be used to measure how well healing develops following new treatments and therapies in upcoming trials.

BOSS-2 will recruit 60 burn patients over a year and then follow them up for 3, 12, 18 and 24 months. Healing time will be recorded and if the patient is co-enrolled with another study supported by the SRMRC delivery team, SiFTi-2, samples such as skin biopsies and blood will also be taken.

The assessment of a scar following a burn is very subjective and varies based on experiences of both the patient and the clinician. Using a validated scar score, we will be able to more accurately assess the efficacy of future scar treatments.

Along with recruiting patients here at the Queen Elizabeth Hospital, UHB, we are working to open the study at St Andrew’s Burn Centre, Broomfield Hospital, Chelmsford and The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea.

At the end of each financial year, UHB publishes a list of the top 10 Principal Investigators (PIs) and the number of patients they have recruited to these challenging trials. Trial PIs are the individuals responsible for the conduct of the research at a research site. Last year, three of the PIs who work within our delivery team made it onto this list:

4^th place

Dr Dhruv Parekh (Consultant in Critical Care and Respiratory Medicine) for the Covid REMAP-CAP trial.

7^th place

Dr Jaimin Patel (Consultant in Intensive Care Medicine and Anaesthesia) for the VitDalize trial.

10^th place

Col Mark Foster (Consultant in Hand and Plastic Surgery) for the ADaPT trial, which is an NIHR SRMRC core-funded study.

Of course, none of this could have been achieved without the support of the rest of the delivery team and the patients and families who kindly agree to their participation.

NIHR SRMRC Neurotrauma Research Fellow, Mr Andrew Stevens, has been collaborating with a multidisciplinary team which includes NIHR SRMRC Director, Professor Tony Belli, UHB clinicians and researchers from the University of Birmingham, to win a prestigious award for funding in this emerging field of TBI treatment.

The team will work on developing a system which uses light to monitor and treat injured brain cells in the early stages after trauma. Near-infrared light has been shown in laboratory studies to increase survival of brain cells after injury. This special type of light can also be used to monitor the health of injured brain, and measure the effectiveness of the therapy to ensure the correct dose of light is given, using technology called ‘Raman spectroscopy’.

The project is funded by the Wellcome Trust and will be comprised of two parts:

1. Efficacy and safety testing in rats
2. Development of the current prototype to develop a product which can deliver the treatment in humans

The Wellcome Translational Development Fund (TDF) provides funding to address early-stage barriers to translation, enabling projects to progress along the translational development pathway to ultimately achieve impact. The TDF is focused on the first step from discovery research towards identification or initial validation of potential clinical, practical or commercial outcomes.

The grant, which amounts to nearly £30,000 over 6 months, was very competitive, so well done to Andrew and the team.

If this proof of concept project is successful then the next steps would be to apply for more funding to test the product in larger animals and eventually to run a full-scale trial in humans. If proven effective, this device could provide treatment to patients with TBI and potentially also spinal cord injury by enhancing nerve cell survival and therefore improving patient recovery.

The Race Equality Framework was developed by the NIHR Race Equality Public Action Group (REPAG), which is co-chaired and led by Black, African, Asian and Caribbean heritage people. Contributors also included public members with lived experience of the challenges being addressed, public involvement leads and researchers.

Jeremy Taylor, Director of the NIHR Centre for Engagement and Dissemination (CED), which is leading on the pilot, said: “I am very excited that we have reached the stage of testing out our Race Equality Framework. This will be an important tool in creating a more inclusive research culture.”

The NIHR SRMRC is working in partnership with our Patient and Public Involvement (PPI) community to identify and address health inequalities throughout our research.  This Framework will give us the opportunity to reflect on current practice and identify how to further increase the ethnic diversity of people taking part in our research. This will, in turn, better reflect the needs of the population at large.

The results from this pilot will be included in the final version of the Framework which is due to be released nationally in 2022.

This information is taken from the Race Equality Framework page of the NIHR website, please click on the link for more details.

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 on the 23^rd March 2021 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 University Hospitals Birmingham NHS Foundation Trust (UHB). The study was fully supported by The Rugby Players’ Association.

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 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.

Notes to Editors

• Di Pietro et al (March, 2021). ‘British Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)’. British Journal of Sports Medicine. DOI: 10.1136/bjsports-2020-103274
• The study was carried out in collaboration with the Universities of Bath and Cambridge, and London School of Hygiene and Tropical Medicine.
• The University of Birmingham is ranked amongst the world’s top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.
• Marker Diagnosticsis a subsidiary of Marker AG, a Swiss-based diagnostics and therapeutics developer. Marker Diagnostics AG’s MDx.100 test is a patented and CE marked salivary-based concussion test based on sncRNA and qPCR analytical technology. Marker Therapeutics AG also has patented and CE marked the MTx.100 Plasma Adsorption Column for the removal of a broad spectrum of inflammatory cytokines, metabolic waste, toxins and poisons from plasma in the mediation of acute life-threatening inflammatory conditions, including cytokine storms and currently being used in the USA under an FDA Emergency Use Authorization to treat severe COVID-19 patients.
• The National Institute for Health Research(NIHR) is the nation’s largest funder of health and care research. The NIHR:

1. Funds, supports and delivers high quality research that benefits the NHS, public health and social care
2. Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
3. Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
4. Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
5. Partners with other public funders, charities and industry to maximise the value of research to patients and the economy
6. The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

• The Midland Neuroscience Teaching and Research Fundis a charity founded in 1971 with the purpose of supporting research and teaching into disorders of the brain and the nervous system. Over nearly 50 years, it has funded a large number of research projects into a variety of unsolved problems associated with diseases of the nervous system.

Here’s what they have to say in their own words………..

Conor Bentley under supervision of Professors Janet Lord and Carolyn Greig & Col Mark Foster, Leads from the NIHR SRMRC

My PhD was focused upon the endocrine and nutritional response to traumatic injury. With the help of the NIHR SRMRC, we were able to undertake three projects to aid patient benefit. By utilising the Golden Hour Study, we looked at the sex-steroid levels in the blood from male trauma patients within one-hour post-injury, up until 72 hours of their hospital stay. The research nurses and lab staff of the SRMRC were central to the 24/7 nature of sample and data collection. The results show that changes in many sex-steroids occur rapidly. Levels of Dehydroepiandrosterone (DHEA) and its stored form Dehydroepiandrosterone Sulfate (DHEAS) were altered during this important time.

DHEA and DHEAS have previously been shown to be low in trauma patients for many weeks and months after injury. We, therefore, decided that we would supplement trauma patients with DHEA. However, there are no trauma studies suggesting the dose that is needed nor the route that clinical staff will need to utilise to administer the DHEA. A unique study was designed so that patients would not receive an ineffective dose nor be disturbed for a blood or urine sample. Again, research nursing staff have been central to the protocol development, patient enrollment, consenting and recruitment, and the data and sample collection needed for such a complex piece of work.

Additionally, the lab staff have been available seven days per week to process, store and analyse samples. This project is currently ongoing and will hopefully provide answers later this year. These results will yield information to future trauma studies that may enhance the patients’ recovery.

Such projects need immense dedication and commitment. Patients subjected to traumatic injury do not necessarily arrive between the hours of 9-5! However, I know that such work will aid the recovery of trauma patients in the future – which is a great feeling.

Callum Watson under the supervision of Professor Tony Belli (Director of the NIHR SRMRC) and Dr Valentina Di Pietro 

My PhD looked into whether concussion could be monitored using microRNAs as biomarkers in saliva and urine, and whether these molecules could highlight individuals at risk of neurodegenerative disease. The NIHR SRMRC enabled the research to take place thanks to their financial support.

I have taken a new role as a Field Application Specialist for PrimerDesign, which the qPCR skills I gained from my PhD were integral. I will see where this takes me.

“Hard work but a thoroughly enjoyable and rewarding experience overall.”