AI speeds up cancer treatment

Doctors at Addenbrooke’s hospital in Cambridge aim to drastically cut cancer waiting times using artificial intelligence (AI) to automate lengthy radiotherapy preparations.

The AI technology, known as InnerEye, is a result of an eight-year collaboration between Cambridge-based Microsoft Research and Addenbrooke’s. Its aim is to save clinicians many hours of time laboriously marking up patient scans prior to radiotherapy.People who change the world

Now the team have demonstrated how machine learning (ML) models built using the InnerEye open-source technology can cut this preparation time by up to 90% – meaning that waiting times for starting potentially life-saving radiotherapy treatment can be dramatically reduced. Health and Social Care Secretary Matt Hancock said:

New innovations like this can make all the difference to patients and I am proud to see we are once again leading the way in new cancer treatments.Matt Hancock

“Helping people receive treatment faster is incredibly important and will not only improve recovery rates but will save clinicians precious time so they can focus on caring for patients.

“Embracing new technologies will help save lives and is vital for the sustainability of the NHS, and our NHS Long Term Plan will continue to deliver the best possible care for patients so that we can offer faster, more personalised and effective cancer treatment for all.”

Addenbrooke’s oncologist, Cambridge University researcher and InnerEye co-lead Dr Raj Jena said: “These results are a game-changer. To be diagnosed with a tumour of any kind is an incredibly traumatic experience for patients. So as clinicians we want to start radiotherapy promptly to improve survival rates and reduce anxiety.

Using machine learning tools can save time for busy clinicians and help get our patients onto treatment as quickly as possible.Dr Raj Jena

Dr Yvonne Rimmer, oncologist at Addenbrooke’s, said: “There is no doubt that InnerEye is saving me time. It’s very good at understanding where tumours and healthy organs are. It’s speeding up the process so I can concentrate on looking at a patient’s diagnostic images and tailoring treatment to them.

But it’s important for patients to know that the AI is helping me do my job; it’s not replacing me in the process. I double check everything the AI does and can change it if I need to. The key thing is that most of the time, I don’t need to change anything.Dr Yvonne Rimmer

Up to half of the population in the UK 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, with around 40% of successfully treated patients undergoing some form of radiotherapy.

Research published by the team in JAMA Network Open confirms that the InnerEye ML models can accurately and rapidly carry out the otherwise lengthy ‘image segmentation’ requiring hours of expert clinicians’ time.

Head of Health Intelligence at Microsoft Research, Aditya Nori, said:

This is the first time, we believe, that an NHS Trust has implemented its own deep learning solution trained on their own data, so it can be used on their patients.Aditya Nori

“It paves the way for more NHS Trusts to take advantage of open-source AI tools to help reduce cancer treatment times.”

The InnerEye Deep Learning Toolkit has been made freely available as open-source software by Microsoft.

Whilst ML models developed using the tool need to be tested and validated in each individual healthcare setting, doctors at Cambridge University Hospitals (CUH) have demonstrated how the technology can be applied in clinical settings.

Written by Cambridge University Hospitals.

Rhythm and bleughs: how changes in our stomach’s rhythms steer us away from disgusting sights

Does the sight of maggots squirming in rotten food make you look away in disgust? The phrase ‘makes my stomach turn’ takes on a new meaning today as researchers at the University of Cambridge reveal that changes in the rhythm of our stomachs prompt us to look away from disgusting images.

Disgust is a natural response to unpleasant sights, such as rotting food, bodily waste and creepy crawlies, and has evolved to help us survive, encouraging us to avoid things that might spread disease. But for some people, disgust can become pathological, affecting their mental health and quality of life.

In a study published today (24 November) in Current Biology, researchers at the MRC Cognition and Brain Sciences Unit show that domperidone, a commonly-prescribed anti-nausea medicine, can help significantly reduce how much volunteers look away from disgusting images.

Domperidone works by stabilising the rhythm of the electrical signals in our stomach muscles. Normally, these signals help the stomach expand and contract, helping move food through the digestive tract. These rhythms become abnormal when we are nauseous or when we are hungry or full, for example. When they are strongly disrupted – for example, when we feel strong revulsion towards something – they can cause us to throw up the contents of our stomach.

In the study, twenty-five volunteers aged 18-35 were randomly assigned to one of two groups: one group to receive domperidone, the second a placebo.

Before taking their pills, the volunteers were shown a series of unpleasant images along with neutral images, such as a scarf or buttons, while the researchers tracked their eye movements. Thirty minutes after taking their tablets, the volunteers were again shown the images while their eye movements were tracked.

Next, the researchers offered an incentive to the volunteers: for every four to eight seconds that they could look at a disgusting image, they would receive 25p – and hear a ‘kerching!’ sound. The volunteers then viewed the images again for a final round, but this time with no incentive.

The volunteers were also asked to rate how disgusting they found the images at the start and end of the trial.

The researchers found that initially, taking domperidone made little difference to the time the volunteers spent looking at a particular image. As could be expected among both groups, the dwell time increased dramatically when they were paid to look at the images.

In the final condition – when the volunteers were no longer being incentivised – the team found that volunteers who had received domperidone spent significantly longer than the placebo group looking at the disgusting images. By the end, people looked at the neutral image roughly 5.5 seconds more than the disgusting image, but under the influence of domperidone, the difference was only about 2.5 seconds.

Domperidone made no difference to how disgusting the volunteers rated the images to be.

“We’ve known for some time that when you see something disgusting, your stomach muscles’ electrical signals become dysregulated, which in some cases causes people to feel sick or their stomach to turn. You’re then likely to avoid that thing,” said Dr Camilla Nord from the MRC Cognition and Brain Sciences Unit at the University of Cambridge.

“What we’ve shown here is that when we steady the stomach’s electrical signals, people become less avoidant of a disgusting image after engaging with it. Changes in the stomach’s rhythm led to reduced disgust avoidance in our study – and so the stomach’s rhythm must be one cause of disgust avoidance in general.”

“In another recent study, we showed that we do not become immune to looking at disgusting images – a fact supported by the placebo condition in this new study,” said Dr Edwin Dalmaijer, also from the MRC Unit. “This is one reason why treating pathological disgust by exposure is often unsuccessful. Our research suggests domperidone may help.”

“We’ve shown that by calming the rhythms of our stomach muscles using anti-nausea drugs, we can help reduce our instinct to look away from a disgusting image,” added Professor Tim Dalgleish, also from the MRC Unit, “but just using the drug itself isn’t enough: overcoming disgust avoidance requires us to be motivated or incentivised. This could provide us with clues on how we can help people overcome pathological disgust clinically, which occurs in a number of mental health conditions and can be disabling.”

Explaining why the stomach should play a role in our disgust response, Dr Nord added: “When the brain constructs its representation of the environment, it integrates signals from the outside world, such as ‘is it daylight?’ with signals from the inside world, such as ‘am I hungry?’. So your internal environment, and your perception of it, plays a large role in how you experience the world.

“Many studies have shown that the state of our body influences emotion, perception, and action. For example, the timing and your awareness of your heartbeats influences learning, anxiety, and other emotion perception. Our study shows that the state of your stomach also influences your behaviour.”

The research was supported by the Medical Research Council, AXA Research Fund and the National Institute for Health Research Cambridge Biomedical Research Centre.

Paper reference

Nord, CL & Dalmaijer, E, et al. A causal role for gastric rhythm in human disgust avoidance. 
Current Biology; 24 Nov 2020; DOI: 10.1016/j.cub.2020.10.087

Software tool will help doctors identify and prevent hospital transmission of SARS-CoV-2

A new software tool developed in Cambridge will help doctors identify where cases of COVID-19 were caused by transmission within a hospital, helping them to prevent further spread of the disease.

The new software package, A2B-Covid, has been designed by a team of doctors and scientists at Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, NIHR Cambridge Biomedical Research Campus, and the MRC Biostatistics Unit at the University of Cambridge.

Addenbrooke’s cares for coronavirus patients from Cambridge and across the East of England.  As the virus is highly infectious, an important part of care is preventing the spread of the virus within the hospital grounds.  However, with patients coming in and out of the hospital every day it can be hard to tell whether new infections come from the local community or from transmission in the hospital itself. 

The software combines knowledge about infection dynamics, data describing the movements of individuals, and genome sequence data to assess whether or not coronavirus has been transmitted between people in the hospital environment. As the virus replicates and spreads, small changes occur in the viral genome.  Genome sequencing – reading the genomes of a sample of viruses taken from a patient – helps researchers to work out whether cases are linked.  Other factors, such as the difference in time between people reporting symptoms, also inform the analysis.  Knowing where different people stayed or worked in the hospital gives an idea of who was in the same place at the same time so as to potentially transmit the virus.

Dr Chris Illingworth from the MRC Biostatistics Unit, one of the developers of the code, explained, “Doctors collect lots of information to identify cases of transmission.   The dates on which people got sick, and where they were in the hospital, are all useful information.  In addition, new advances in genomics mean that doctors can read the genome sequence of a virus cheaply and easily.  More similar sequences suggest that two cases are more likely to be linked.  Our program combines all of the data in one to identify cases of possible transmission.”

Flagging up possible cases of transmission is a first step in taking action.  Looking at the details of a case, doctors can make a judgement about whether transmission has happened, and if so, how that took place.  Early identification can prevent the spread of coronavirus through a ward.  Where transmission has happened, lessons can be learnt, taking steps to make the hospital a safer place for patients and healthcare workers alike. 

A2B-Covid will be available for free to doctors and clinicians across the UK and worldwide.  Details of the package have been published in a pre-print article in MedRxiv, prior to being peer-reviewed.

Dr Will Hamilton, an infectious diseases clinician at Addenbrooke’s and author of the study said, “Infection control is a vital part of keeping people safe and well in hospital.   In a busy hospital environment this tool will make it simpler and easier to identify cases of concern, so as to minimise incidence of hospital-based viral transmission.”

The project has been funded by the COVID-19 Genomics UK Consortium, a Cambridge-led nationwide initiative to deliver large-scale, rapid sequencing of the cause of the disease and share intelligence with hospitals, regional NHS centres and the Government. It is an example of the increasing use of genomic technologies in a clinical setting. 

Dr Estee Torok, from the Department of Medicine at the University of Cambridge and senior author of the paper, said, “This work is a great example of how genome sequence data, rapidly collected and made available to clinicians, can make a real difference to clinical practice and patient safety.  From the nurses who collected samples, through to the sequencing team, medics and statisticians, this has been a case of experts across multiple disciplines coming together to combat COVID-19.”

Age and pre-existing conditions increase risk of stroke among COVID-19 patients

Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions, according to a report.

COVID-19 has become a global pandemic, affecting millions of people worldwide. In many cases, the symptoms include fever, persistent dry cough and breathing difficulties, and can lead to low blood oxygen. However, the infection can cause disease in other organs, including the brain, and in more severe cases can lead to stroke and brain haemorrhage.

A team of researchers at the Stroke Research Group, University of Cambridge, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. This approach allows researchers to bring together existing – and often contradictory or under-powered – studies to provide more robust conclusions.

In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. The results of their study are published in the International Journal of Stroke.

The researchers found that stroke occurred in 14 out of every 1,000 cases. The most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.  

Age was a risk factor, with COVID-19 patients who developed stroke being on average (median) 4.8 years older than those who did not. COVID-19 patients who experienced a stroke were on average (median) six years younger than non-COVID-19 stroke patients. There was no sex difference and no significant difference in rates of smokers versus non-smokers.

Pre-existing conditions also increased the risk of stroke. Patients with high blood pressure were more likely to experience stroke than patients with normal blood pressure, while both diabetes and coronary artery disease also increased risk. Patients who had a more severe infection with SARS­CoV­2 – the coronavirus that causes COVID-19 – were also more likely to have a stroke.

The researchers found that COVID-19-associated strokes often followed a characteristic pattern, with stroke caused by blockage of a large cerebral artery, and brain imaging showing strokes in more than one cerebral arterial territory. They argue that this pattern suggests cerebral thrombosis and/or thromboembolism are important factors in causing stroke in COVID-19.  COVID-19-associated strokes were also more severe and had a high mortality.

An important question is whether COVID-19 increases the risk of stroke or whether the association is merely a result of COVID-19 infection being widespread in the community.

“The picture is complicated,” explained Dr Stefania Nannoni from the Department of Clinical Neurosciences at the University of Cambridge, the study’s first author. “For example, a number COVID-19 patients are already likely to be at increased risk of stroke, and other factors, such as the mental stress of COVID-19, may contribute to stroke risk.

“On the other hand, we see evidence that COVID-19 may trigger – or at least be a risk factor for – stroke, in some cases. Firstly, SARS­CoV­2 more so than other coronaviruses – and significantly more so than seasonal flu – appears to be associated with stroke. Secondly, we see a particular pattern of stroke in individuals with COVID-19, which suggests a causal relationship in at least a proportion of patients.”

The researchers say there may be several possible mechanisms behind the link between COVID-19 and stroke. One mechanism might be that the virus triggers an inflammatory response that causes thickening of the blood, increasing the risk of thrombosis and stroke. Another relates to ACE2 – a protein ‘receptor’ on the surface of cells that SARS-CoV-2 uses to break into the cell. This receptor is commonly found on cells in the lungs, heart, kidneys, and in the lining of blood vessels – if the virus invades the lining of blood vessels, it could cause inflammation, constricting the blood vessels and restricting blood flow.

A third possible mechanism is the immune system over-reacting to infection, with subsequent excessive release of proteins known as cytokine. This so-called ‘cytokine storm’ could then cause brain damage.

The team say their results may have important clinical implications.

“Even though the incidence of stroke among COVID-19 patients is relatively low, the scale of the pandemic means that many thousands of people could potentially be affected worldwide,” said Professor Hugh Markus, who leads the Stroke Research Group at Cambridge.

“Clinicians will need to look out for signs and symptoms of stroke, particularly among those groups who are at particular risk, while bearing in mind that the profile of an at-risk patient is younger than might be expected.”

While the majority of strokes occurred after a few days of COVID-19 symptoms onset, neurological symptoms represented the reason for hospital admission in more than one third of people with COVID-19 and stroke.

Dr Nannoni added: “Given that patients admitted to hospital with symptoms of stroke might have mild COVID-19-related respiratory symptoms, or be completely asymptomatic, we recommend that all patients admitted with stroke be treated as potential COVID-19 cases until the results of screening in the hospital are negative.”

The research was supported by the Medical Research Council, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the British Heart Foundation.

Paper reference

Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke; 26 Oct 2020; DOI: 10.1177/1747493020972922. Epub ahead of print. PMID: 33103610.

Tiny golden bullets could help tackle asbestos-related cancers

Gold nanotubes – tiny hollow cylinders one thousandth the width of a human hair – could be used to treat mesothelioma, a type of cancer caused by exposure to asbestos, according to a team of researchers at the Universities of Cambridge and Leeds. 

In a study published in journal Small, the researchers demonstrate that once inside the cancer cells, the nanotubes absorb light, causing them to heat up, thereby killing the cells.

More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos. Although the use of asbestos is outlawed in the UK now, the country has the world’s highest levels of mesothelioma because it imported vast amounts of asbestos in the post-war years. The global usage of asbestos remains high, particularly in low- and middle-income countries, which means mesothelioma will become a global problem.

“Mesothelioma is one of the ‘hard-to-treat’ cancers, and the best we can offer people with existing treatments is a few months of extra survival,” said Dr Arsalan Azad from the Cambridge Institute for Medical Research at the University of Cambridge. “There’s an important unmet need for new, effective treatments.”

In 2018, the University of Cambridge was awarded £10million from the Engineering and Physical Sciences Research Council to help develop engineering solutions, including nanotech, to find ways to address hard-to-treat cancers.

In a collaboration between the University of Cambridge and University of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.

The researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.

Professor Stefan Marciniak, also from the Cambridge Institute for Medical Research, added: “The mesothelioma cells ‘eat’ the nanotubes, leaving them susceptible when we shine light on them. Laser light is able to penetrate deep into tissue without causing damage to surrounding tissue. It then gets absorbed by the nanotubes, which heat up and, we hope in the future, could be used to cause localised cancer-cell killing.”

The team will be developing the work further to ensure the nanotubes are targeted to cancer cells with less effect on normal tissue.

The nanotubes are made in a two-step process. First, solid silver nanorods are created of the desired diameter. Gold is then deposited from solution onto the surface of the silver. As the gold builds-up at the surface, the silver dissolves from the inside to leave a hollow nanotube. 

The approach advanced by the Leeds team allows these nanotubes to be developed at room temperature, which should make their manufacture at scale more feasible.

Professor Stephen Evans from the School of Physics and Astronomy at the University of Leeds said: “Having control over the size and shape of the nanotubes allows us to tune them to absorb light where the tissue is transparent and will allow them to be used for both the imaging and treatment of cancers. The next stage will be to load these nanotubes with medicines for enhanced therapies.”

The research was funded by the British Lung Foundation, Victor Dahdaleh Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Royal Papworth Hospital, Alpha1-Foundation, Medical Research Council and the Engineering & Physical Sciences Research Council.

Paper reference

Ye, S & Azad, AA et al. Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells. Small; 25 Oct 2020: DOI: 10.1002/smll.2003793

‘Mini-lungs’ reveal early stages of SARS-CoV-2 infection

To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, the virus that causes COVID-19, especially in patients that develop pneumonia, appear to be alveoli – tiny air sacs in the lungs that take up the oxygen we breathe and exchange it with carbon dioxide to exhale.

To better understand how SARS-CoV-2 infects the lungs and causes disease, a team of scientists from the UK and South Korea turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behaviour of tissue and organs.

The team used tissue donated to tissue banks at the Royal Papworth Hospital NHS Foundation Trust and Addenbrooke’s Hospital, Cambridge University NHS Foundations Trust, UK, and Seoul National University Hospital to extract a type of lung cell known as human lung alveolar type 2 cells. By reprogramming these cells back to their earlier ‘stem cell’ stage, they were able to grow self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue.

Dr Joo-Hyeon Lee, co-senior author, and a Group Leader at the Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, said: “We still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease. Our approach has allowed us to grow 3D models of key lung tissue – in a sense, ‘mini-lungs’ – in the lab and study what happens when they become infected.”

The team infected the organoids with a strain of SARS-CoV-2 taken from a patient in South Korea who was diagnosed with COVID-19 on 26 January 26 2020 after traveling to Wuhan, China. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.

When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue.

Around the same time, the cells began to produce interferons – proteins that act as warning signals to neighbouring cells, telling them to activate their antiviral defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infection.

Sixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.

Although the researchers observed changes to the lung cells within three days of infection, clinical symptoms of COVID-19 rarely occur so quickly and can sometimes take more than ten days after exposure to appear. The team say there are several possible reasons for this. It may take several days from the virus first infiltrating the upper respiratory tract to it reaching the alveoli. It may also require a substantial proportion of alveolar cells to be infected or for further interactions with immune cells resulting in inflammation before a patient displays symptoms.

“Based on our model we can tackle many unanswered key questions, such as understanding genetic susceptibility to SARS-CoV-2, assessing relative infectivity of viral mutants, and revealing the damage processes of the virus in human alveolar cells,” said Dr Young Seok Ju, co-senior author, and an Associate Professor at Korea Advanced Institute of Science and Technology. “Most importantly, it provides the opportunity to develop and screen potential therapeutic agents against SARS-CoV-2 infection.”

“We hope to use our technique to grow these 3D models from cells of patients who are particularly vulnerable to infection, such as the elderly or people with diseased lungs, and find out what happens to their tissue,” added Dr Lee.

The research was a collaboration involving scientists from the University of Cambridge, UK, and the Korea Advanced Institute Science and Technology (KAIST), Korea National Institute of Health, Institute for Basic Science (IBS), Seoul National University Hospital and GENOME INSIGHT Inc. in South Korea.

Funding
The research was supported by: the National Research Foundation of Korea; Research of Korea Centers for Disease Control and Prevention; Ministry of Science and ICT of Korea; Ministry of Health & Welfare, Republic of Korea; Seoul National University College of Medicine Research Foundation; European Research Council; Wellcome; the Royal Society; Biotechnology and Biological Sciences Research; Suh Kyungbae Foundation; the Human Frontier Science Program and supported by the NIHR Cambridge Biomedical Research Centre

Written by the University of Cambridge

Jeonghwan Youk et al. Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2. Cell Stem Cell; 21 Oct 2020; DOI: 10.1016/j.stem.2020.10.004

Supporting research at Cambridge University Hospitals

14 October 2020

As the COVID-19 situation develops, research staff at Cambridge University Hospitals (CUH) continue our support of COVID-19 research studies, including Urgent Public Health Studies (UPH), while maintaining safe recruitment to existing open studies and, where possible, safely restarting research studies that were paused during the initial stages of the pandemic.

To date, we have supported, and continue to support, more than 30 COVID-related research studies, including RECOVERY and the Cambridge-led TACTIC trials, as well as recruiting patient and staff participants to the NIHR COVID-19 BioResource project and participating in vaccine studies.  At the same time, we have re-opened recruitment to more than 300 paused studies and continue to work toward re-opening the remaining studies on our portfolio.

Following NIHR guidance, R&D is closely monitoring the pandemic situation, and will continue to release guidance to research teams as local and national infection levels fluctuate. We will support the provision of safe patient care within CUH while maintaining recruitment to currently open clinical trials and studies where possible. 

Subject to the approval of the COVID-19 Research Oversight board, we will also continue to accept and support new local and nationally prioritised COVID studies; new non-COVID research studies should be submitted to R&D.  All CRN funded staff have been directed to work on UPH-listed studies as their priority.

Questions regarding research restart, COVD-risk assessment, staffing, finance and new COVID- or non-COVID research should direct their enquiries to cuh.research@nhs.net in the first instance.  Enquiries regarding CRN funded staff contact Christian.sparke@addenbrookes.nhs.uk or Tel: 01223 596458

Early care for people with psychosis supports recovery

A study with early intervention mental health service CAMEO at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) has found that sixty percent of people cared for in their first episode of psychosis recovered well.

Psychosis is a mental health condition characterised by problems with perception and thinking, such as hallucinations and strong false beliefs (delusions). The CAMEO team specialises in identifying and treating this condition as early as possible to support people through their first experience, before they are discharged to their GP or CPFT’s community mental health services for further care.

The research team led by consultant psychiatrist and Wellcome Trust Fellow Dr Golam Khandaker used CPFT’s Research Database to review blood markers and health outcomes for CAMEO service users, in a longitudinal study of anonymous patient records between January 2013 and November 2019. The study results have been published in Brain, Behaviour and Immunity.

Lead author CPFT psychiatry registrar Dr Emanuele Osimo (right) said: “We wanted to know how well people do overall, and if demographics, clinical measures and blood tests taken when people develop psychosis can be linked to how well people recover after receiving care for their first episode of psychosis.

“CPFT’s Research Database provides an ethically approved, secure source of anonymous information about service users who have not opted out of their data being used for research.
It enabled us to review 749 people who were cared for by CAMEO between 2013 and 2019 and completed their treatment pathway.

“We found that around sixty percent of people with first episode psychosis recovered well enough to be discharged to their GP. Several blood markers were consistently higher or lower in other people who required long term specialist psychiatric care. These included types of white blood cell (immune markers), and measures of metabolic health.”

This is one of the first studies in the UK to measure these associations in a large group of people, using a broad set of blood tests for biomarkers which can signal physical health issues underlying mental health conditions.

Emanuele added: “Our results suggest that blood tests may help in future to predict outcomes for people experiencing their first episode of psychosis, and help us find more effective treatments for those who don’t recover so well. We now need to replicate our results in other groups, and develop clinically useful tools for predicting long term mental health outcomes and improving care pathways.

“I would like to thank all the CPFT patients who kindly allowed the use of their anonymous data for this important research, and the clinical staff who have collected, processed, and recorded all the samples and information.”

CAMEO clinical lead Professor Jesus Perez said: “This study used real world clinical data to review the impact of care provided by CAMEO. It reveals that a high proportion of our service users, that could have ended up with a chronic disability, now have a good long term clinical outcome after receiving early mental health treatments, including psychological therapies, medication, occupational therapies and general one to one support.”

CPFT’s CAMEO service has also been recognised as one of 26 global centres of excellence for psychosis care, and was recently awarded $1.3 million to join a major international research partnership investigating new treatments for schizophrenia.

This research was funded through Dr Osimo’s National Institute for Health Research (NIHR) Academic Clinical Fellowship and supported by the NIHR Cambridge Biomedical Research Centre. Collaborating authors were also supported through funding from the NIHR, Medical Research Council, Wellcome Trust, and MQ: Transforming Mental Health.

Funding award to develop minimally invasive tools to improve cancer surgery

Cambridge University Hospitals have teamed up with Ablatus Therapeutics Limited to develop a device to help treat tumours in the liver and minimalise the invasive procedure after the Cambridge based company were awarded a £1 million Government grant.

Working with Dr TC See Interventional Radiologist at Cambridge University Hospitals, the award will fund a two-year project to create a new surgical tool to perform ablations – a technique to destroy abnormal tissue, such as tumours. The device will then begin clinical trials at Addenbrooke’s Hospital, supported by the NIHR Cambridge Biomedical Research Centre.

Over 6,000 people are diagnosed with liver cancer in the UK ever year. It can be hard to detect because symptoms often only develop at a late stage. Liver cancer can be treated with surgery to remove the tumour, but this is not always possible. If surgery is not possible, it may be feasible to reduce the tumour through a technique called ablation. This is where needles are inserted into the liver and the cancerous tissue is destroyed through heating.

The new funds will allow Ablatus Therapeutics Limited to develop the new surgical tool with Cambridge University Hospitals, with the hope that this will improve outcomes. The device will use Bimodal Electric Tissue Ablation (BETA), an energy-based alternative to open surgery that offers a novel, cost-effective and efficient approach to destroying abnormal tissue in situ and without major surgery.

Professor John Bradley, Director of Research at Cambridge University Hospitals said: “This partnership between Cambridge University Hospitals and Ablatus Therapeutics, supported by a £1m award from the Government, is a major step forward in treating liver cancer. It builds on our expertise in translating technology into the clinic to provide real benefits for patients.”

Dr Natalie Hayes, Chief Medical Officer and Interim CEO for Ablatus Therapeutics Limited said: “This is an enormous opportunity for Ablatus to build on the important work we have already done to complete development of what could be a game-changing treatment for patients with tumours. We are especially pleased to be able to bring this exciting new technology to local patients here in Cambridge when we start our first clinical study in Addenbrooke’s Hospital.”

Punctured lung affects almost one in a hundred hospitalised COVID-19 patients

Like the inner tube of bicycle or car tyre, damage to the lungs can lead to a puncture. As air leaks out, it builds up in the cavity between the lung and chest wall, causing the lung to collapse. Known as a pneumothorax, this condition typically affects very tall young men or older patients with severe underlying lung disease.

New model predicts oesophageal cancer eight years early for one in two patients

DNA from tissue biopsies taken from patients with Barrett’s oesophagus – a risk factor for oesophageal cancer – could show which patients are most likely to develop the disease eight years before diagnosis. 

Oesophageal cancer is often preceded by Barrett’s oesophagus, a condition in which cells within the lining of the oesophagus begin to change shape and can grow abnormally. The cellular changes are cause by acid and bile reflux – when the stomach juices come back up the gullet.

Barrett’s oesophagus and oesophageal cancer are diagnosed using biopsies, which look for signs of dysplasia, the proliferation of abnormal cancer cells. Between one and five people in every 100 with Barrett’s oesophagus will go on to develop oesophageal cancer in their life-time, but as this type of cancer can be difficult to treat, particularly if not caught early enough, researchers have been trying to identify ways to catch the disease early.

Professor Rebecca Fitzgerald (right) from the MRC Cancer Unit at the University of Cambridge and NIHR Cambridge BRC researcher said: “Early diagnosis of cancer is one of the best strategies to improve patient survival and decrease the side-effects from treatments. However, this strategy can result in overtreatment – patients incorrectly identified as high-risk and given unnecessary treatments. We need to find new ways to accurately spot cancer progression at a very early stage to help us identify those patients at greatest risk.”

A phenomenon commonly seen in the DNA of tumours – but not in healthy tissues – is one whereby whole ‘chunks’ of DNA are either deleted or repeated several times as cells copy and multiply. These are known as ‘copy number alterations’. In a study published today in Nature Medicine, researchers at Cambridge have shown how these DNA ‘signals’ could help diagnose patients earlier.

The team used whole genome sequencing to analyse samples from 88 patients and compared their DNA against that from 777 control samples collected during clinical surveillance for Barrett’s oesophagus. They were looking for differences in the DNA between the patients who were eventually diagnosed with cancer versus those who were not.

The researchers found that the genomes in samples from individual patients who went on to develop cancer tended to have a higher number of copy number alterations, and that the number and complexity of such alterations increased over time. They used this information to develop a statistical model that could predict whether a patient was at a high or low risk of cancer from a single, tiny biopsy sample taken years before. The model was then used to predict and classify risks for individuals in a validation cohort of 76 patients and 213 samples.

The model accurately predicted oesophageal cancer eight years before diagnosis for half of all patients who went on to develop the disease. This increased to more than three-quarters of patients one to two years before a diagnosis.

Equally importantly, the model accurately and consistently predicted patients who were at a low risk of developing cancer over many years of clinical surveillance. This meant that these patients did not need to be subjected to regular, invasive monitoring or treatment.

The researchers found a high degree of variability in copy number alternations even within a single biopsy, but even so, the model provided surprisingly stable predictions of a patient’s risk of progression to cancer.

Dr Sarah Killcoyne from the MRC Cancer Unit at the University of Cambridge and the European Bioinformatics Institute, joint first author, said: “Our research shows the power of genomic medicine for the early detection for cancer. We combined low-cost sequencing of standard tissue biopsies with statistical modelling to identify which patients were at greatest risk of progressing from Barrett’s oesophagus to oesophageal cancer.”

Eleanor Gregson from the MRC Cancer Unit, joint first author, added: “This new approach could allow us to intervene earlier, helping improve a patient’s outcome, while at the same time avoiding the need for low-risk individuals to have regular and invasive monitoring or even unnecessary treatment.”

The research was funded by the Medical Research Council and United European Gastroenterology, with support from the National Institute for Health Research Cambridge Biomedical Research Centre.

Paper reference: Killcoyne, S. et al. Genomic copy number predicts esophageal cancer years before transformation. Nat Med; 7 Sept 2020; DOI: 10.1038/s41591-020-1033-y

New research shows steroid improves survival of critically ill Covid-19 patients

New research published today (02 September) has been able to show that using the steroid hydrocortisone on patients with severe COVID-19 symptoms improves their recovery.

Patients, NHS trusts and local research teams at hospitals across the Eastern region including Cambridge University Hospitals, have contributed important data to new global research which shows that corticosteroids can significantly improve outcomes for severely ill patients with COVID-19.

The research papers published in the Journal of the American Medical Association (JAMA) reinforce evidence that these inexpensive and widely available drugs improve outcomes for the most critically ill patients with the disease. One paper suggests the risk of death can be reduced by up to 20%.

The papers include findings from the National Institute for Health Research (NIHR) supported REMAP-CAP study, which is being conducted across 15 countries around the world and led in the UK from the NIHR Imperial Biomedical Research Centre.

Working closely together to help deliver rapid recruitment, NHS trusts and the NIHR’s Clinical Research Network (NIHR CRN), and research institutes from the devolved nations helped recruit 71% of all global study participants from right across the UK.

The results from the REMAP-CAP trial show a high probability that among critically ill patients with COVID-19, treatment with a seven-day course of hydrocortisone improved outcomes such as survival and more rapid recovery, compared with no hydrocortisone treatment.

An additional paper, co-ordinated by the World Health Organisation (WHO) and led by researchers at the University of Bristol and the NIHR’s Bristol Biomedical Research Centre, provides a meta-analysis (evidence summary) of global steroid use across seven randomised controlled trials (RCTs) in 12 countries spanning five continents. It also included data drawn from REMAP-CAP and the NIHR-funded RECOVERY trial, which has already shown that the steroid dexamethasone can be successfully used in treatment of moderate to severe Covid-19. It concludes that corticosteroids can reduce the risk of death in the most ill patients by up to 20%.

Dr Charlotte Summers, Principal Investigator for the REMAP-CAP trial at Cambridge University Hospitals (one of the region’s sites delivering the trial) and Critical Care Lead for the NIHR Clinical Research Network Eastern, said:

“This result from REMAP-CAP provides further support for the finding from the RECOVERY trial, suggesting that steroids improve survival for critically ill people with COVID-19. The breakthroughs we have made so far are testament to NHS teams unwavering determination to improve the outcomes of our patients by offering them the opportunity to participate in research.

“There are still more questions to be answered in relation to COVID-19, but with our country’s unique NIHR community, along with those who participate in research, we’re in the best possible position to succeed.”

NHS chief executive, Sir Simon Stevens said: “One of the distinctive benefits of having our NHS is that we’ve been able to mobilise quickly and at scale to help researchers test and develop proven coronavirus treatments. Just as we did with dexamethasone, the NHS will now take immediate action to ensure that patients who could benefit from treatment with hydrocortisone do so, adding a further weapon in the armoury in the worldwide fight against Covid-19.”

Dr Charlotte Summers, Principal Investigator for the REMAP-CAP trial at Cambridge University Hospitals explains the importance of the study. 

Combining PCR and antibody tests at point of care dramatically increases COVID-19 detection in hospitalised patients

Point-of-care testing – in other words, testing patients as soon as they arrive at the hospital – is essential for enabling healthcare workers to rapidly diagnose patients and direct those who test positive for infection to dedicated wards. A recent study showed that SAMBA II, a new point-of-care PCR test for SARS-CoV-2 developed by Cambridge researchers, was able to dramatically reduce time spent on COVID-19 ‘holding’ wards – allowing patients to be treated or discharged far quicker than with current lab testing set-ups.

Gold medal for Professor Gordon Dougan

The Sabin Vaccine Institute (Sabin) have announced (13 August), that it has awarded its annual Albert B. Sabin Gold Medal to Gordon Dougan, FRS, professor in the Department of Medicine and the Cambridge Institute for Therapeutic Immunology and Infectious Disease at the University of Cambridge and antimicrobial theme lead for the NIHR Cambridge Biomedical Research Centre (pictured right).  

The Gold Medal, now in its 27th year, is Sabin’s highest scientific honour, given each year to a distinguished member of the global health community who has made extraordinary contributions to vaccinology or a complementary field.

Past award recipients, include leaders of vaccinology and vaccine advocacy such as Drs. D.A. Henderson, Maurice Hilleman, Anne Gershon, Myron Levine and Paul Offit.

“We are pleased to present the Gold Medal to Gordon,” said Amy Finan, Sabin’s chief executive officer. “His work demonstrates a life-long commitment to innovating the development and delivery of vaccines, translating scientific research into practical tools and encouraging the next generation of leaders in vaccinology. His dual commitment to science and advocacy exemplifies Dr. Albert B. Sabin’s legacy in harnessing innovation for good and the belief that everyone, everywhere should have access to lifesaving vaccines.”

Professor Dougan’s research in vaccine discovery and delivery has focused on two key areas; equitable access to vaccines and information, and the application of genomics to enable vaccine development.

“I’m honoured to receive this award named after Dr. Sabin, whose ground-breaking invention and successful global distribution of the trivalent oral polio vaccine relates to some of my proudest professional accomplishments,” said Professor Dougan. “Open access data and technology has empowered scientists and researchers, including in low- and middle-income countries, to accelerate progress on vaccines that may be of low commercial priority, but make a substantial difference to the quality of life and health of vulnerable populations around the world. I am proud to have supported this work.”

Professor Dougan has a wealth of experience. He spent 10 years at the Wellcome Foundation (now Wellcome), where his team utilised recombinant engineering to define the protective antigen, pertactin, now a component of whooping cough vaccines. He then moved to the Imperial College London, where he established the Centre for Molecular Microbiology and Infection.

He then assembled a world-class program for teaching and research at the Wellcome Sanger Institute in Cambridge. While there, he built a department that led research on pathogen genomics and disease tracking, highlighting antimicrobial resistance as a major public health concern and pioneered the construction of attenuated strains of salmonella to aid in the development of typhoid vaccines.

The open access data and technology generated under his leadership at the Institute directly impacted the creation of vaccines against many diseases including pertussis, typhoid fever and cholera, and his multi-faceted coalition-building work with the World Health Organization and Gavi, the Vaccine Alliance, led to the successful delivery of several affordable vaccines around the world. 

View the video highlighting the 2020 Albert B. Sabin Gold Medal and Sabin Rising Star Award, including remarks by Professor Dougan.

The 2020 Albert B. Sabin Gold Medal was made possible in part by a grant from the Bill & Melinda Gates Foundation, and sponsorship by GSK; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Pfizer; and Takeda. Sponsors have no role in Sabin’s program design, development or outputs, including findings and analysis.

Adapted from Sabin Vaccine Institute’s press release

Transgender and gender-diverse individuals are more likely to be autistic and report higher autistic traits

New NHS service enables people to sign up to be contacted for COVID-19 vaccine studies

A new NHS service has been launched, helping people across the UK sign up for information on the new COVID-19 vaccine trials.

The new NHS Covid-19 vaccine research registry will help large numbers of people be recruited into the trials over the coming months, potentially leading to an effective vaccine being identified and made available to the UK public against coronavirus earlier. It has been developed as part of the UK Government’s Vaccine Taskforce, in partnership with the National Institute for Health Research (NIHR), NHS Digital, and the Northern Ireland, Scottish and Welsh Governments. We are also collaborating with ZOE, the company behind the Covid-19 symptom study who have 3.5 million UK users of their app, to work together to enrol their volunteers onto vaccine trials.

John Nother, National Institute for Health Research (NIHR) Chief Digital Officer, said: “This new online service will be a vital tool in the fight against this disease as large scale vaccine studies get underway within the UK.

“The new system will enable researchers to quickly identify and match suitable and willing volunteers to appropriate vaccine trials. In doing so, it will bring enormous benefits, not only to the NHS and health researchers – but to everyone living in the UK.

“Signing up and giving your permission to be contacted means you may be amongst the first to find out about opportunities to take part in trials and the latest, cutting-edge COVID-19 vaccines. There is no obligation to join in any study, if you are contacted. But by taking part, you could help researchers find a vaccine to protect us all more quickly – which in turn could help the NHS and save lives.”

There are a number of vaccines being identified and safety-tested at the moment, but only large scale trials can give scientists the information needed about how effective they are. The NIHR working with the NHS aims to recruit over half a million people onto the registry, which will allow people to be put in touch with the vaccine trials in the coming months. Researchers are looking for people from all backgrounds, ages and parts of the UK, including both people with or without existing health conditions, to take part in vaccine studies, to make sure that any vaccines developed will work for everyone.

Jonathan Wolf, CEO of ZOE, of the COVID-19 Symptom Tracker app:
“The altruism of the UK public continues to amaze us. To have nearly four million people participating in citizen science against COVID, really does restore your faith in humanity. Joining forces with NIHR will enable the UK and our volunteers to be at the forefront of vaccine testing and ultimately look to end this pandemic sooner rather than later.”

The service is available to anyone aged 18 or over, living in the UK. To register, people fill in some personal and contact details, and answer a series of basic health screening questions on an NHS.UK website form. The service is highly secure, with personal data and permissions held in a NHS system managed by NHS Digital, the national organisation responsible for IT in the health and social care system.

People registering their details through the service are not signing up to take part in a specific trial or study. Instead, researchers working on vaccine studies supported by the NIHR will be able to search for volunteers who have signed up to the service.

When a suitable volunteer has been identified, the researchers will send an email or text to anyone who matches the criteria for their study. This will provide more information about the study – and offer the user the opportunity to contact the research team and find out more, or express an interest to take part.

There is no obligation to take part in any study and people who sign up can change their mind and remove their contact details from the registry at any time.

To find out more, visit: www.nhs.uk/researchcontact. More information about taking part in research and other opportunities to take part in COVID-19 research can be found at www.bepartofresearch.uk

Written by the NIHR

Sponge on a string test to transform oesophageal cancer diagnosis

A ‘sponge on a string’ pill test can identify ten times more people with Barrett’s oesophagus than the usual GP route, according to a new study funded by Cancer Research UK and published in  The Lancet today (31 July 2020). The test, which can be carried out by a nurse in the GP surgery, is also better at picking up abnormal cells and potentially early-stage cancer.

Barrett’s oesophagus is a condition that can lead to oesophageal cancer in a small number of people. It’s usually diagnosed in hospital by endoscopy (passing a camera down into the stomach) following a GP referral for longstanding heartburn symptoms.

The Cytosponge test (pictured top right), developed by researchers at the University of Cambridge and supported by the NIHR Cambridge BRC, is a small pill with a thread attached that the patient swallows, which expands into a small sponge when it reaches the stomach. This is quickly pulled back up the throat by a nurse, collecting cells from the oesophagus for analysis using a new laboratory marker called TFF3.

The pill is a quick, simple and well tolerated test that can be performed in a GP surgery and helps tell doctors who needs an endoscopy. This can spare many people from having potentially unnecessary endoscopies.

The researchers studied 13,222 participants who were randomly allocated to being offered the sponge test or being looked after by the GP in the usual way. Over the course of a year, the odds of detecting Barrett’s were ten times higher in those offered the Cytosponge with 140 cases diagnosed compared to 13 in usual care. In addition, the Cytosponge diagnosed five cases of early cancer (stage 1 and 2), whereas only one case of early cancer was detected in the usual care group.

Alongside better detection, the test means cancer patients can benefit from kinder treatment options if their cancer is caught at a much earlier stage.

Lead researcher Professor Rebecca Fitzgerald, based at the University of Cambridge and funded by Cancer Research UK, said: “It’s taken almost a decade of research and testing thousands of patients to show that we’ve developed a better route to diagnosing Barrett’s oesophagus. And the sponge could also be a game-changer in how we diagnose and ensure more people survive oesophageal cancer. Compared with endoscopies performed in hospital, the Cytosponge causes minimal discomfort and is a quick, simple test that can be done by a GP. Our test is already being piloted around the country, so we hope more people across the UK could benefit from it.”

Because COVID-19 has reduced the number of endoscopies that can be carried out by the NHS, one UK hospital has already fast-tracked the Cytosponge into use in order to help identify priority cases with suspected cancer who need further tests urgently.

The researchers are currently putting the Cytosponge test through an economic evaluation and hope that it will be rolled out within GP practices within three to five years. It’s expected that the Cytosponge will be offered by GPs to patients on medication for acid reflux symptoms.

Cancer Research UK-funded scientist Professor Peter Sasieni, whose King’s College London team have been leading the clinical evaluation of the Cytosponge over the last decade, said: “The results of this trial exceeded my most optimistic expectations. Use of Professor Fitzgerald’s simple invention will hopefully lead to a significant reduction in the number of people dying from oesophageal cancer over the next 20 years. This trial found that both patients and staff were happy with the Cytosponge test and it is practical to consider rolling it out within the NHS.”

Dr Julie Sharp, Cancer Research UK’s head of health and patient information, said: “It’s great news for patients that there’s proven benefit to taking the Cytosponge test, and they won’t have to undergo a potentially uncomfortable endoscopy unless it’s needed.

“We hope that people will be able to access the Cytosponge from their GP as soon as possible. It will also help doctors enormously, as it will allow them to more accurately predict if someone is at risk of oesophageal cancer.”

Around 9,200 people are diagnosed with oesophageal cancer in the UK each year and around 7,900 sadly die. Early diagnosis is crucial to patients’ survival and a shift in stage can have a large impact on outcomes. 85% of people diagnosed with the earliest stage of oesophageal cancer in England survive their cancer for 1 year or more. This figure drops to 21% if the cancer is diagnosed at the most advanced stage.

Liz Chipchase, a retired scientist from Cambridge, was one of the people who took part in the Cytosponge clinical trial. Liz felt in good health, but abnormalities were discovered and she was referred for further tests. Not only did Liz have Barrett’s oesophagus, she also had cancer.

“If I hadn’t been invited and gone on the trial, I would’ve had no idea that I needed treatment for an early stage cancer. And I’m also aware that the survival rate for oesophageal cancer isn’t good, so the fact I am clear of cancer is wonderful.

“I feel so lucky thinking about the chain of events that led to the cancer being caught when it was. To me, this trial saved my life.”

Written by Cancer Research UK

New funding boost to speed up diagnosis in oesophageal cancer

Cambridge will lead on improving early detection in oesophageal cancer as part of a Government backed project

Some people who have long-term symptoms of heartburn or acid reflux may go on to develop a condition called Barrett’s oesophagus. This is where abnormal cells develop which could turn into cancer.

This type of cancer can be hard to detect until the late stages and for some it becomes life-threatening. Therefore, early intervention is important in order to start treatment as soon as possible.

Today (Friday 3 July), the Government has backed funding of £16 million to six of the UK’s most innovative specialist health projects, to develop precise medical solutions and improve early detection in some life-threatening diseases such as cancer and Crohn’s disease. It will mean patients could receive earlier and a more accurate diagnosis.

As part of the Government’s announcement, Cambridge has been selected for one of these health projects in improving early diagnosis for oesophageal cancer.

Cambridge researchers will lead on the early detection programme with the aim to diagnose up to 50% of oesophageal cancer cases earlier, which means patients can start treatment sooner, ultimately saving more lives.

Science Minister Amanda Solloway said: “Our brilliant scientists and researchers in Cambridge are harnessing world-leading technologies, like AI, to tackle some of the most complex and chronic diseases that we face.”

“Tragically, we know that one in two people in the UK will be diagnosed with some form of cancer during their lifetime.

“The University of Cambridge project we are backing today will help ensure more lives are saved and improved, as it aims to diagnose up to 50% of oesophageal cancer cases earlier.”

Other projects receiving funding include:

• Actioned, led by Queens University Belfast which is using artificial intelligence to achieve more accurate and earlier diagnosis of early relapse in colon cancer, improving the outcomes for patients;
• A University of Glasgow-led project working to identify growths that are most likely to develop into bowel cancer, which is the second biggest killer among cancer related deaths in the UK.
• University of Manchester led research into when liver problems – which affect up to four in 10 people – can lead to liver scarring, and sometimes complete liver failure. Current tests pick up advanced scarring, but don’t pinpoint early disease, or those patients who are destined for much worse. The project will use new software to come up with much better, much earlier answers. identifying liver damage earlier and more accurately.
• University of Oxford is working to improve survival rates in people with lung cancer, the deadliest form of cancer in the UK. It will bring together existing work being led by the NHS, universities, cancer charities and digital health companies to integrate the best of digital imaging and diagnostic science to help identify cancerous tumours in the lung earlier.
• Motilent, is working on healthcare solutions to more effectively treat Crohn’s disease, a painful, lifelong inflammatory condition affecting 180,000 people in the UK. Through the use of artificial intelligence, it will seek to accurately predict when to start and stop drug use to control the disease, which currently has a 60% failure rate, and which can lead to further, irreversible damage to a patient’s bowel.

Of the £16 million awarded today, over £13 million will be delivered by the Government, while up to £3 million will be made available from Cancer Research UK, to specifically support the oncology focused projects.

The funding, delivered through the Industrial Strategy Challenge Fund, is part of a government programme in data to early diagnosis and precision medicine. The competition is run by Innovate UK on behalf of UK Research and Innovation (UKRI) and forms part of the government’s commitment to increase research and development investment to 2.4% of GDP by 2027.

National research platform launches new website

Over the last 10 years the NIHR BioResource has made vital contributions to research across the country. To maintain their success, a new website has been created to continue their growing work. The address is the same, but the next time you visit the NIHR BioResource website, you’ll see it has a brand new look, ready for researchers and the public.

The NIHR BioResource is a nationwide platform that supports research in a number of health conditions. They bring people who have consented to be approached to take part in research with researchers who need volunteers for their studies. The team have over 150,000 people, healthy volunteers as well as patients with common and rare diseases, all willing to participate in research and has supported more than 200 studies.

Today (01 July) the NIHR BioResource launches a new website to encourage more people to get involved, showcase their research studies and provide an information platform for researchers, academics, clinicians and industry partners alike.

The new site has a wealth of information about their research service, which has been streamlined into a simple layout with a modern and a user-friendly look and dedicated sections for the researchers and the public.

For researchers, there is information on how the NIHR BioResource can support their study, whether it involves the recall of participants by a specific genotype and/or phenotype, what services it can provide, including accessing data and/or samples, and how to access them.

For the public, there are details on their nearest centre, summaries of the studies they can be involved in and stories from participants who have taken part in research.

The website was designed with members of the public and researchers to make sure the content and layout were suitable to both audiences.

The team hope the new website will be a useful source of information for people wanting to taking part in research or help health researchers who need participants for their study.

Dr Nathalie Kingston, Director of the NIHR BioResource said: “The NIHR BioResource is a vital research platform which serves both the research community and the public. We needed to make sure we provided a website that suited the needs of both audiences.

“More and more people want to take part in research or run a clinical trial because they want to help the NHS, especially during these challenging times. Therefore, having a website which people can easily navigate through and find the correct information is essential.

“With that in mind, we worked with members of the public and researchers to create a bespoke website with a dedicate space for the public and researchers that would help signpost the information they need and what the NIHR BioResource can offer.

“Research has never been more important than it is now. We hope more people who come to our new site will be inspired and want to join the NIHR BioResource or use the service to support their own research.”

TACTIC-E trial to test whether a simple microbe could be an effective treatment for COVID-19

As part of a new trial led by Cambridge University Hospitals and supported by NIHR Cambridge Biomedical Research Centre, a microbe will be used to treat severe COVID-19 in an experimental drug known as EDP1815. Developed by Evelo Biosciences, EDP1815 is a naturally occurring microbe that has been isolated from the small intestine of a human donor.

EDP1815 works by communicating with immune cells in the small intestine, which in turn communicate with other immune cells around the rest of the body. Via the gut immune cells, EDP1815 can broadcast a message to the immune cells in other organs to reduce production of the chemical messengers, known as cytokines, that cause inflammation (and damage to organs), while encouraging anti-inflammatory messages instead. Most importantly, EDP1815 does not affect cytokines known as type-1 interferons, which are essential allowing people to recover from infection. In this manner, the drug may support an immune response that is ‘just right’ – reducing harmful immune responses while supporting the immune system to clear the virus.

One of the key reasons for selecting EDP1815 for this study is its safety profile, which means it will be safer to use in many of the vulnerable groups that are at greater risk of COVID-19 complications. It is not absorbed into the body, and only persists while the patient continues on the drug.

EDP1815 is being tested as part of a newly launched trial, known as TACTIC-E, which has been designed to test experimental drugs that may treat COVID-19, as well as investigating whether combinations of drugs that are already in use for other conditions can be effective. As with similar trials, such as TACTIC-R and RECOVERY, further treatments can be added as they are identified. Each of the treatments will target as yet unexplored aspects of COVID-19, offering the chance to quickly test new treatments as well as shedding new light on how SARS-CoV2 causes such severe disease in some people.

A second arm of TACTIC-E aims to reduce the damage seen in the lungs of patients with severe COVID-19, using a combination of ambrisentan and dapagliflozin (both manufactured by Astra Zeneca), which are licensed for pulmonary hypertension (elevated pressure in the lungs) and type 2 diabetes respectively. People with cardio-metabolic diseases (such as obesity, type 2 diabetes, heart failure or kidney disease) are known to be at higher risk of serious complications from COVID-19.

Ambrisentan helps to relax the arteries within the lungs, improving blood flow and oxygen pick up as well as having an anti-inflammatory effect. Dapagliflozin, when used together with ambrisentan could help counteract changes in fluid distribution that ambrisentan can cause. Researchers also believe that dapagliflozin may have further beneficial effects for COVID-19 treatment, due to its ability to support heart and lung function by balancing glucose and sodium in the blood.

The TACTIC-E trial will recruit patients admitted to hospital with COVID-19 who are at risk of entering the second stage of COVID-19 disease, which occurs around the second week following infection. It is during this phase that immune damage and severe respiratory symptoms begin to develop, and researchers believe that the treatments being tested in the trial will be most effective during this period.

It is anticipated that fewer than 500 patients per arm will be needed to assess the effectiveness of each treatment, but as the number of people with COVID-19 continues to decline across the United Kingdom, there are plans to open the TACTIC-E trial in nations where infections remain high. This will ensure that researchers can quickly understand whether or not these treatments are effective.

TACTIC-E Principal Investigator and Consultant Clinical Pharmacologist at Cambridge University Hospitals NHS Foundation Trust (CUH) Dr Joseph Cheriyan, said “COVID-19 is a complex disease that affects people in different ways and we are going to need a range of treatments in our armoury to be able to beat it.

“On the Cambridge Biomedical Campus, we are uniquely placed to work in the NHS alongside academia and industry to bring early phase drugs into circulation, potentially making a massive difference to the lives of many, many people.

“We have brought all this experience to bear with TACTIC-E. We will be trialling treatments that a panel of independent experts consider most likely to work, which are either already licensed, or known to have excellent safety, and observe them very closely to see what happens in order to identify successful drugs early on.”

Professor Ian Wilkinson, Director of the Cambridge Clinical Trials Unit, and Professor of Therapeutics at the University of Cambridge said “As we enter the next phase of the COVID-19 pandemic, Cambridge is proud to play a role in the rapid evaluation of potential treatments.

“The TACTIC-E trial has been carefully designed to swiftly detect effectiveness of potential treatments using small numbers of patients. It has a strong focus on collecting high quality data to confirm safety and effectiveness, enabling our manufacturing partners to gain the necessary approvals for widespread international use.”

The trial is led by the Cambridge University Hospitals NHS Trust and is supported by the NIHR Cambridge Biomedical Research Centre. Funding and drug supply for the trial has been provided by Astra Zeneca and Evelo Biosciences.