This means we could get away from needing neurologists and no longer have misdiagnoses. Both excellent outcomes if we could get stroke leadership to drive these results.
http://www.nihr.ac.uk/news/chipping-away-at-stroke/5509
Stroke is the fourth single leading cause of death in the UK, with
more than 100,000 strokes occurring each year. That is around one stroke
every five minutes, according to recently published statistics by the Stroke Association. Stroke can also leave people severely disabled.
Even though stroke has become a common condition worldwide - every
two seconds, someone in the world will have a stroke - it can still be
difficult to diagnose.
A biosensor, called SMARTchip, has been designed to detect whether a
person has had a stroke or not. The development of the SMARTchip has
been led by Professor Nicholas Dale from Warwick University. The
clinical trial aspect of the study has been led by Professor
Chris Imray at University Hospitals Coventry and Warwickshire NHS Trust.
Professor Christine Roffe, NIHR Clinical Research Network (CRN)
Stroke Specialty Lead for West Midlands, explains: “The biosensor is
trying to identify an increase in the level of purines in the blood, as
it is believed to be an indicator of a stroke.”
Professor Roffe, who has been part of the research team to assess its
effectiveness, said: “One third of all stroke patients are mimics. For
example, some patients present to hospital with stroke symptoms, but are
in fact suffering from migraine.
“The
SMARTchip has the potential to speed up diagnosis and reduce doubt, by
supporting our clinical diagnostic skills and other tests. It is vital
to act fast. Any indecision can increase the time it takes to assess the
best course of action.
“However, it can even be hard for a stroke physician to decide
whether a patient has had a stroke or mimic, especially in young people.
If there is ever indecision you treat them as if they have had a
stroke, as you don’t want to wait or treat them for mimic, which could
potentially ruin someone’s life.
“Although if people suffering from a mimic are treated as though they
have had a stroke that creates major capacity issues for hospitals.”
Professor Roffe, stroke medicine lead at University Hospitals of
North Midlands NHS Trust, added: “The stress of making these decisions
is all worth it when you see patients walk out the next day.”
In 2013, the project received a £471,000 grant from the NIHR Invention for Innovation Programme.
Professor Roffe first met Professor Dale at the CRN Stroke meeting.
She said: “Nick attended the meeting to present his research idea and
receive feedback from stroke research experts. It seemed to be a
worthwhile study and as I’m the lead in West Midlands, I agreed to
support Nick with the grant proposal, for which I became a co-applicant.
I also set up the clinical protocol for the study.”
The SMARTchip started out life as a SMARTcap, which was a vial with a
biosensor inside. This was further developed into the smaller
SMARTchip. Professor Roffe said: “It just requires a pinprick of blood
to be put on the biosensor, which is then put into a machine to measure
the levels of purines - this has been a much more reliable tool for
reading the blood sample. As it only requires a small blood sample it
reduces the chance of haemolysis, which is the rupturing of red blood
cells releasing their contents into surrounding fluid, which can
increase the level of purines.”
The support provided by the CRN was important to this study, as Dr
Roffe explains: “You can’t run a study like this without the
infrastructure and research nurses support the Network provides. This
enabled us to deliver the study over three different sites across
England.
“The research nurses were key, as they identified appropriate patients and recruited them straight away.”
Norman Phillips, who suffered a stroke in 2003, has been involved
with the study from the very beginning and even attended the NIHR
funding meeting.
Norman, 68 from Coventry, said: “I’ve helped with several studies
over the past few years. With the SMARTchip study I read through the
protocols from a public perspective to make sure it made sense and
thought about its impact on real people.
“Research documents often contain scientific language, which the
public don’t need to see, so I suggest language that people will
understand.
“Also from my experience I have questions and thoughts about the study that the researchers may not have thought of.”
Professor Roffe said: “Norman certainly keeps us on our toes and reminds us all why we are here, which gives us a real drive.”
The trial is in the last phase of recruitment, which will end in
March 2017. The data will then be analysed and a report produced for the
NIHR Invention for Innovation committee.
Professor Roffe added: “The next stage will be undertake further
research to see how and where it could be used clinically for stroke.
The hope is that they would be rolled out in ambulances to speed up
diagnosis. Also to find out what other conditions the biosensor could
identify.”
An article was recently published in The Observer about the SMARTchip study.
University Hospitals Coventry and Warwickshire NHS Trust is also the study sponsor.
Showing posts with label purines. Show all posts
Showing posts with label purines. Show all posts
Friday, March 10, 2017
Tuesday, January 24, 2017
In search of the stroke detector
This line is totally fucking appalling.
But paramedics’ guidelines, such as facial paralysis or slurred speech, do not offer a foolproof diagnostic tool: up to 50% of all pre‑hospital stroke diagnoses turn out to be inaccurate.
What are the statistics about that from your hospital? Do they even know? If not, that is pure incompetency.
https://www.theguardian.com/science/2017/jan/22/stroke-detector-biosensor-diagnosis-nicholas-dale--breakthrough
Stroke, or “brain attack”, is the third biggest killer in the western world, after cancer and heart failure. The life-changing effects associated with this simple, Anglo-Saxon word are readily explained: a stroke occurs when the blood supply to the brain is disrupted by a blood vessel either bursting or blocking, so that the part of the brain supplied by this blood vessel dies.
The brain is a much more complex organ than the heart. While strokes are a common feature of everyday life, precisely how and why they occur is far from straightforward.
Each year in the UK, there will be about 50,000 brain attacks. One-third of those affected will die; one-third will be left severely disabled; and about one-third will make some kind of recovery. In the time it takes to read this article, approximately nine people in Britain, from across all age groups, will have suffered a stroke.
Or did they? For the brain is not only super-sensitive territory – as the human animal’s command HQ – it is also top secret. Despite extraordinary progress in MRI scans, the brain remains essentially mysterious and the symptoms of its dysfunction can be hard to diagnose with certainty. An elderly man presenting himself at A&E with unsteady gait and a slurring of his words could be suffering a stroke – or he might just be intoxicated. Treat him for the former, and you’ll save his life; treat him as a drunk, and he might die.
This is not the only way in which stroke sufferers find themselves trapped in a medical lottery. From the beginning of a stroke, every minute, even every second, becomes a matter of life or death in which the patient’s response is crucial. The onset of a brain attack is bewildering and confusing. For patients in the midst of a medical emergency, the key to the best recovery is rapid recognition of the attack followed by the prompt implementation of brain-saving treatment. But rapid recognition is easier said than done.
All strokes are unique, with a multiplicity of symptoms ranging from a drooping facial muscle to total unconsciousness. But paramedics’ guidelines, such as facial paralysis or slurred speech, do not offer a foolproof diagnostic tool: up to 50% of all pre‑hospital stroke diagnoses turn out to be inaccurate.
The diagnostic predicament is also bedevilled by the phenomenon of “mimics”. For example, a patient might come to A&E with a very bad migraine, exhibiting all the symptoms of stroke. Devoting the resources of stroke treatment to such a mimic is costly in both time and resources, the last thing a cash-strapped NHS can afford.
In A&E, one of the biggest – and potentially most expensive – problems faced by doctors and nurses is how to weed out the mimics and decide if a patient has or has not suffered a stroke. This decision can be fateful. Send the patient for immediate treatment, and all kinds of good outcomes might follow. Delay an hour, and the patient might be on the road to severe disability, even death.
As long ago as 1998, the complex challenges of stroke diagnosis began to intrigue an inquisitive Scottish neuroscientist named Nicholas Dale. He takes up the story: “Some strokes are really obvious. The brain scan shows exactly what’s happened, and everyone is in agreement. But then there are those strokes where the brain scan doesn’t really show anything, even though the symptoms are there. Those are what you might call ‘possible strokes’. What is a clinician supposed to do?” To this last question, Dale would come eventually up with an answer about the size of a thumbnail: the SMARTChip.
Twenty years on, Dale’s tortuous journey into the dark maze of neurological emergency is reaching a climax. After a series of nationwide clinical trials, the Observer can report exclusively that Dale and his biosensor company, Sarissa, an offshoot of Warwick University, are on the threshold of a remarkable breakthrough in stroke diagnosis.
Dale’s pioneering contribution to stroke medicine is a classic tale of scientific innovation replete with accidental discoveries, chance meetings and frustrating setbacks. Add this to the sheer slog of a determined neuroscientist who seems professionally addicted to finding bees in his bonnet, and you begin to approach the story of the smart chip that saves lives.
Dale’s breakthroughs in stroke prevention had mundane beginnings. “My original work,” says Dale with a wry smile, recalling his graduate years in Bristol and St Andrews, was “on how tadpoles swim”.
We need not dwell on Dale’s career in the society of the tadpole. Suffice to say that by 1997, he needed to invent a biosensor to measure the substance adenosine. “I wanted to measure adenosine,” he says, “because I thought that its gradual accumulation in the tadpole’s spinal cord controlled how its swimming slowed over time and ultimately stopped.”
Dale duly published his tadpole findings. It was then, in 1998, articulating a vague thought in the back of his mind, that he uttered to himself the sentence – “This biosensor must be useful for other things” – that would not only change his life, but profoundly influence the fates of many UK stroke patients. At this stage, his aspirations were half-formed, and he had no plan. All he knew was: he was done with tadpoles.
Dale admits that he wanted to do work that did not – as tadpoles always did – provoke smiles of disbelief. “I wanted to find an application for these sensors that was real and important.”
He pauses to recall another turning point. “One of my colleagues in Scotland said: ‘The person you need to talk to is Bruno Frenguelli. He’s interested in models of stroke.’ So I met Bruno,” says Dale, with disarming simplicity, “and told him about my biosensor.”
Dale and Frenguelli were a perfect match. Dale was becoming a master of biosensor technology, whose microchips could measure anything. Frenguelli, a neuroscientist at the University of Dundee, had things he wanted to measure, but no way to make the measurement. Soon, Dale was ferrying his biosensor kit in his car across the Tay Bridge to Dundee, and setting up in Frenguelli’s lab. “We both vividly remember our first joint experiment,” says Dale, “because it was so exciting.”
But then what? The bees in Dale’s bonnet began buzzing again. His biosensor was too cumbersome and fragile for any serious medical applications. “I started to think: could we not make something smaller?”
In 1999, Dale was puzzling over how he might do this – “I realised I would need polymers” – when there was a knock at his door. “And in came this guy I’d never seen before.”
“Hello”, said the newcomer. “I’m Enrique Llaudet.”
Llaudet, a Spanish organic chemist, was a whiz with polymers. Just what Dale needed to create new ways of making tiny biosensors.
So began an eight-year relationship, partly sponsored by seed money from a small Scottish charity, and later by the Wellcome Trust. Now Dale and Llaudet, with Frenguelli in the background, began to develop a tiny biosensor, the ancestor of Sarissa’s smart chip.
There were, inevitably, setbacks. At times, the technology let them down; at times, the funding dried up. But Dale, a natural team player, continued to develop his group, which now included Chris Imray (a heart surgeon at University Hospitals Coventry and Warwickshire NHS Trust), Christine Roffe (a stroke specialist at University Hospitals of North Midlands), Gary Ford (Oxford Academic Health Science Network), Everard Mascarenhas (Sarissa’s CEO), and Faming Tian and Shabin Joshi (both also at the Coventry and Warwickshire).
By now Dale had moved to Warwick to take up a chair in neurosciences. In 2004, Sarissa filed its first biosensor patent, but then Dale found himself in a blind alley. “We had the means, and we had the ideas, but we were getting nowhere. We tried to raise funds for treating foetal hypoxia.” He laughs: “I soon realised that the middle-aged white males who controlled the purse-strings just aren’t interested in babies.”
Finally, Dale returned to stroke. He had puzzled over its mysteries for years, but had never really grappled with the practicalities. Now he began to advance a brilliant hypothesis, developed in collaboration with Chris Imray. This – the measurement of purines in the blood – had the elegance of simplicity. Imray and Dale had begun to prove that, at the onset of stroke, the brain releases a detectable quantity of purines into the blood. If Dale’s smart chip could measure this surge, it could provide positive proof of stroke. For Dale, “elevated purines” would be the criterion by which he would definitively determine the onset of a brain attack.
Today, in the stroke units where Dale’s hypothesis is being tested, nurses have come to recognise that a high purine reading immediately indicates that stroke is a probable diagnosis.
In 2004, that was all in the future. First, Dale had to persuade the medical profession to undertake a clinical trial. It was his contention that Sarissa’s biosensor could weed out the “mimics” that bedevil stroke treatment.
Sarissa made its first commercial sales in 2005. Its biosensors (aka Sarissaprobe) had potential in clinical diagnosis, but, says Dale “we still didn’t have a product that was close to being useful for clinicians and nurses”. In simple terms, Dale’s biosensor would not work in blood.
Blood is the one thing that medics the world over like to test. But blood, as Dale puts it, “is a complex environment. We had to make our sensors a whole lot more selective if we were to measure a surge in purine levels. This was Faming Tian’s brilliant contribution.”
At the same time, Dale was stepping up the presentation of his biosensor to funding bodies. In 2013, he made a pitch to Invention for Innovation, a committee of the National Institute for Health Research. He will probably never forget this moment:
“I made my presentation, and then this clinical biochemist launched into a statement – it was nowhere near an inquiry – which became so hostile that I felt as if I were a delinquent teenager. There was, he told me, no need for this kind of technology. I was stunned by the aggression and the hostility. When this man had finished, I could not think initially how to respond, so I just said, ‘Was there a question?’” The committee burst out laughing. Dale left the meeting with a sense of failure, but he was wrong.
The committee decided to take a punt on his smart chip, after all. Three years ago, Dale and his colleagues began clinical trials in three UK hospitals, Salford, Coventry and Stoke-on-Trent.
Royal Stoke University Hospital, on the west of the city, is just over 10 years old, and a showcase of New Labour’s commitment to a revitalised NHS. Once, in the bad old days, Stoke was served by two separate, Victorian hospitals, with patients ferried between A&E and the stroke unit, which were in different buildings. Now, with A&E just a lift ride away, everything is under one roof with acres of parking space for doctors, nurses, patients and their families.
Inside, long shiny corridors and blinking tiers of lifts take the visitor into the heart of an impressively modern teaching hospital that caters for a population of about 600,000 in Stoke and Stafford. Add Derby, Macclesfield, Wolverhampton, Walsall, and Telford and you are looking at a catchment of 1.5 million. This is Nick Dale’s designated stroke laboratory, and it’s here, for the past three years, that his biosensor has been tested, under Professor Christine Roffe, a dynamic, highly practical director who has placed her team at the forefront of stroke research in the UK, especially as a pioneer of mechanical thrombectomy. She has been here since 1996, heading a unit that consists of six consultants, two specialists and 10 research nurses.
But paramedics’ guidelines, such as facial paralysis or slurred speech, do not offer a foolproof diagnostic tool: up to 50% of all pre‑hospital stroke diagnoses turn out to be inaccurate.
What are the statistics about that from your hospital? Do they even know? If not, that is pure incompetency.
https://www.theguardian.com/science/2017/jan/22/stroke-detector-biosensor-diagnosis-nicholas-dale--breakthrough
Stroke, or “brain attack”, is the third biggest killer in the western world, after cancer and heart failure. The life-changing effects associated with this simple, Anglo-Saxon word are readily explained: a stroke occurs when the blood supply to the brain is disrupted by a blood vessel either bursting or blocking, so that the part of the brain supplied by this blood vessel dies.
The brain is a much more complex organ than the heart. While strokes are a common feature of everyday life, precisely how and why they occur is far from straightforward.
Each year in the UK, there will be about 50,000 brain attacks. One-third of those affected will die; one-third will be left severely disabled; and about one-third will make some kind of recovery. In the time it takes to read this article, approximately nine people in Britain, from across all age groups, will have suffered a stroke.
Or did they? For the brain is not only super-sensitive territory – as the human animal’s command HQ – it is also top secret. Despite extraordinary progress in MRI scans, the brain remains essentially mysterious and the symptoms of its dysfunction can be hard to diagnose with certainty. An elderly man presenting himself at A&E with unsteady gait and a slurring of his words could be suffering a stroke – or he might just be intoxicated. Treat him for the former, and you’ll save his life; treat him as a drunk, and he might die.
This is not the only way in which stroke sufferers find themselves trapped in a medical lottery. From the beginning of a stroke, every minute, even every second, becomes a matter of life or death in which the patient’s response is crucial. The onset of a brain attack is bewildering and confusing. For patients in the midst of a medical emergency, the key to the best recovery is rapid recognition of the attack followed by the prompt implementation of brain-saving treatment. But rapid recognition is easier said than done.
All strokes are unique, with a multiplicity of symptoms ranging from a drooping facial muscle to total unconsciousness. But paramedics’ guidelines, such as facial paralysis or slurred speech, do not offer a foolproof diagnostic tool: up to 50% of all pre‑hospital stroke diagnoses turn out to be inaccurate.
The diagnostic predicament is also bedevilled by the phenomenon of “mimics”. For example, a patient might come to A&E with a very bad migraine, exhibiting all the symptoms of stroke. Devoting the resources of stroke treatment to such a mimic is costly in both time and resources, the last thing a cash-strapped NHS can afford.
In A&E, one of the biggest – and potentially most expensive – problems faced by doctors and nurses is how to weed out the mimics and decide if a patient has or has not suffered a stroke. This decision can be fateful. Send the patient for immediate treatment, and all kinds of good outcomes might follow. Delay an hour, and the patient might be on the road to severe disability, even death.
As long ago as 1998, the complex challenges of stroke diagnosis began to intrigue an inquisitive Scottish neuroscientist named Nicholas Dale. He takes up the story: “Some strokes are really obvious. The brain scan shows exactly what’s happened, and everyone is in agreement. But then there are those strokes where the brain scan doesn’t really show anything, even though the symptoms are there. Those are what you might call ‘possible strokes’. What is a clinician supposed to do?” To this last question, Dale would come eventually up with an answer about the size of a thumbnail: the SMARTChip.
Twenty years on, Dale’s tortuous journey into the dark maze of neurological emergency is reaching a climax. After a series of nationwide clinical trials, the Observer can report exclusively that Dale and his biosensor company, Sarissa, an offshoot of Warwick University, are on the threshold of a remarkable breakthrough in stroke diagnosis.
Dale’s pioneering contribution to stroke medicine is a classic tale of scientific innovation replete with accidental discoveries, chance meetings and frustrating setbacks. Add this to the sheer slog of a determined neuroscientist who seems professionally addicted to finding bees in his bonnet, and you begin to approach the story of the smart chip that saves lives.
Dale’s breakthroughs in stroke prevention had mundane beginnings. “My original work,” says Dale with a wry smile, recalling his graduate years in Bristol and St Andrews, was “on how tadpoles swim”.
We need not dwell on Dale’s career in the society of the tadpole. Suffice to say that by 1997, he needed to invent a biosensor to measure the substance adenosine. “I wanted to measure adenosine,” he says, “because I thought that its gradual accumulation in the tadpole’s spinal cord controlled how its swimming slowed over time and ultimately stopped.”
Dale duly published his tadpole findings. It was then, in 1998, articulating a vague thought in the back of his mind, that he uttered to himself the sentence – “This biosensor must be useful for other things” – that would not only change his life, but profoundly influence the fates of many UK stroke patients. At this stage, his aspirations were half-formed, and he had no plan. All he knew was: he was done with tadpoles.
Dale admits that he wanted to do work that did not – as tadpoles always did – provoke smiles of disbelief. “I wanted to find an application for these sensors that was real and important.”
He pauses to recall another turning point. “One of my colleagues in Scotland said: ‘The person you need to talk to is Bruno Frenguelli. He’s interested in models of stroke.’ So I met Bruno,” says Dale, with disarming simplicity, “and told him about my biosensor.”
Dale and Frenguelli were a perfect match. Dale was becoming a master of biosensor technology, whose microchips could measure anything. Frenguelli, a neuroscientist at the University of Dundee, had things he wanted to measure, but no way to make the measurement. Soon, Dale was ferrying his biosensor kit in his car across the Tay Bridge to Dundee, and setting up in Frenguelli’s lab. “We both vividly remember our first joint experiment,” says Dale, “because it was so exciting.”
But then what? The bees in Dale’s bonnet began buzzing again. His biosensor was too cumbersome and fragile for any serious medical applications. “I started to think: could we not make something smaller?”
In 1999, Dale was puzzling over how he might do this – “I realised I would need polymers” – when there was a knock at his door. “And in came this guy I’d never seen before.”
“Hello”, said the newcomer. “I’m Enrique Llaudet.”
Llaudet, a Spanish organic chemist, was a whiz with polymers. Just what Dale needed to create new ways of making tiny biosensors.
So began an eight-year relationship, partly sponsored by seed money from a small Scottish charity, and later by the Wellcome Trust. Now Dale and Llaudet, with Frenguelli in the background, began to develop a tiny biosensor, the ancestor of Sarissa’s smart chip.
There were, inevitably, setbacks. At times, the technology let them down; at times, the funding dried up. But Dale, a natural team player, continued to develop his group, which now included Chris Imray (a heart surgeon at University Hospitals Coventry and Warwickshire NHS Trust), Christine Roffe (a stroke specialist at University Hospitals of North Midlands), Gary Ford (Oxford Academic Health Science Network), Everard Mascarenhas (Sarissa’s CEO), and Faming Tian and Shabin Joshi (both also at the Coventry and Warwickshire).
By now Dale had moved to Warwick to take up a chair in neurosciences. In 2004, Sarissa filed its first biosensor patent, but then Dale found himself in a blind alley. “We had the means, and we had the ideas, but we were getting nowhere. We tried to raise funds for treating foetal hypoxia.” He laughs: “I soon realised that the middle-aged white males who controlled the purse-strings just aren’t interested in babies.”
Finally, Dale returned to stroke. He had puzzled over its mysteries for years, but had never really grappled with the practicalities. Now he began to advance a brilliant hypothesis, developed in collaboration with Chris Imray. This – the measurement of purines in the blood – had the elegance of simplicity. Imray and Dale had begun to prove that, at the onset of stroke, the brain releases a detectable quantity of purines into the blood. If Dale’s smart chip could measure this surge, it could provide positive proof of stroke. For Dale, “elevated purines” would be the criterion by which he would definitively determine the onset of a brain attack.
Today, in the stroke units where Dale’s hypothesis is being tested, nurses have come to recognise that a high purine reading immediately indicates that stroke is a probable diagnosis.
In 2004, that was all in the future. First, Dale had to persuade the medical profession to undertake a clinical trial. It was his contention that Sarissa’s biosensor could weed out the “mimics” that bedevil stroke treatment.
Sarissa made its first commercial sales in 2005. Its biosensors (aka Sarissaprobe) had potential in clinical diagnosis, but, says Dale “we still didn’t have a product that was close to being useful for clinicians and nurses”. In simple terms, Dale’s biosensor would not work in blood.
Blood is the one thing that medics the world over like to test. But blood, as Dale puts it, “is a complex environment. We had to make our sensors a whole lot more selective if we were to measure a surge in purine levels. This was Faming Tian’s brilliant contribution.”
At the same time, Dale was stepping up the presentation of his biosensor to funding bodies. In 2013, he made a pitch to Invention for Innovation, a committee of the National Institute for Health Research. He will probably never forget this moment:
“I made my presentation, and then this clinical biochemist launched into a statement – it was nowhere near an inquiry – which became so hostile that I felt as if I were a delinquent teenager. There was, he told me, no need for this kind of technology. I was stunned by the aggression and the hostility. When this man had finished, I could not think initially how to respond, so I just said, ‘Was there a question?’” The committee burst out laughing. Dale left the meeting with a sense of failure, but he was wrong.
The committee decided to take a punt on his smart chip, after all. Three years ago, Dale and his colleagues began clinical trials in three UK hospitals, Salford, Coventry and Stoke-on-Trent.
Royal Stoke University Hospital, on the west of the city, is just over 10 years old, and a showcase of New Labour’s commitment to a revitalised NHS. Once, in the bad old days, Stoke was served by two separate, Victorian hospitals, with patients ferried between A&E and the stroke unit, which were in different buildings. Now, with A&E just a lift ride away, everything is under one roof with acres of parking space for doctors, nurses, patients and their families.
Inside, long shiny corridors and blinking tiers of lifts take the visitor into the heart of an impressively modern teaching hospital that caters for a population of about 600,000 in Stoke and Stafford. Add Derby, Macclesfield, Wolverhampton, Walsall, and Telford and you are looking at a catchment of 1.5 million. This is Nick Dale’s designated stroke laboratory, and it’s here, for the past three years, that his biosensor has been tested, under Professor Christine Roffe, a dynamic, highly practical director who has placed her team at the forefront of stroke research in the UK, especially as a pioneer of mechanical thrombectomy. She has been here since 1996, heading a unit that consists of six consultants, two specialists and 10 research nurses.
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