(0:09) James: I am talking to Virginia Newcomb, who is one of the Theme Leads for the HealthTech Research Centre in Brain and Spinal Injury. And Virginia, your theme is about acute care and monitoring. So let's pick one of those to start with. What's acute care? What do we mean by that?

(0:25) Virginia: So by acute care, I guess we mean everything in those initial first few hours to days after a patient's injury.

(0:31) James: At the roadside, before you get to hospital, that would count as acute care?

(0:35) Virginia: Yeah, so it could count as acute care. I guess it's also, it depends on how you want to cut acute care. So some people will believe that acute care starts as soon as someone comes to the hospital and anything in that phase is pre-hospital, or someone's in the GP surgery, is that acute care or not? But my personal view is that anything that happens in those first few hours to days, and even those initial weeks, could be regarded as acute care and as something that we should look at as the Brain HRC.

(1:12) James: Yeah, and I guess brain injury is this sort of weird thing, isn't it. In that you don't actually do anything about that first brain injury, certainly with traumatic brain injury, you can't make that better, right? So what do we mean by actually a care in that stage? What kinds of things are we doing to patients?

(1:30) Virginia: So you're right, so patients have this initial primary injury and that happens at the time of impact, whatever that might be. And so what we're really trying to do is to try and prevent any ongoing injury, so minimise the extent of that primary injury and then prevent secondary injury from occurring. So a lot of the things that we do in that initial phase is about making sure that everything else is as perfect as it can be. So for example, we know that if someone becomes hypotensive (so has a low blood pressure) or if someone becomes hypoxic (so they don't have enough oxygen in the blood) that that will give someone a much worse outcome than if all of those things were kept perfectly normal. And so we try as best we can to prevent any of these secondary injuries occurring. So that way we can get people the best outcome that we can after their brain injury.

(2:26) James: Yeah, and I guess that's a link to monitoring then, because it's measuring the pressure and it's measuring the oxygenation.

(2:32) Virginia: So the monitoring can range from being as simple as just looking at oxygen saturations, all the way through to doing non-invasive measurements of the brain. So you can do non-invasive measurements of the pressure inside the head, so ICP, intracranial pressure. All the way through to actually doing invasive monitoring, where we might put specific probes in someone who's got a very severe brain injury, so that we can manage the pressure inside their head. But also make sure that the metabolic profile of the brain is optimised for that patient, so we can also monitor the brain oxygen level, the brain glucose level, and some other metabolic parameters using something called microdialysis.

(3:17) James: Yeah, so I had one of these triple bolt things screwed in my head, which was measuring those things, right, the pressure and oxygenation, some of that sort of metabolic stuff that's happening inside there. So what are the big innovations? I mean, we don't know what they all are, right, that's the point of the centre, but what kind of areas do we think we're going to see real change over the next few years?

(3:37) Virginia: I think that there's a number of really exciting areas, I think, particularly in the acute space. So, if we think about head injury as being a spectrum, so we have those on the more mild end of the spectrum (and that's where I do a lot of my own work), innovations that we may see there are using modalities like blood biomarkers. When your brain is injured, it releases proteins, and inflammatory markers, and other markers into the blood. We are at a time when these are becoming easier and easier to measure, including point of care devices that we can actually use in our emergency departments and elsewhere. And so we may be able to use these markers to help us, firstly diagnose that someone's got a brain injury, but also help us understand if someone's going to have ongoing problems after their brain injury.

(4:27) James: Yeah, and I guess in both those cases, you're then directing people to the right services. And that might be hospital now, it might be GP in six months. But, you know, these are things to look out for down the line.

(4:40) Virginia: Yeah, absolutely. I think the problem we have with those on the more mild end of the spectrum is that (because often they'll have a CT that's normal, or near normal, or they may not even have a CT) is that they often find it difficult to get the help that they need. So we know that patients, even with normal scans, can have ongoing problems for months or years afterwards. But unfortunately, in our constrained system, they don't often get referred to services in that acute phase. If we can identify those who really have had a significant injury, using these markers, then maybe we can help people earlier and so get them better outcomes.

(5:16) James: Yeah, so they can plug into those kind of rehab services and support things, which are kind of there, but are also overwhelmed. So I guess we don't want to send people with CTs that don't need one. We don't want to push everyone into rehab because it won't benefit everybody. But we know lots of people miss out on it.

(5:32) Virginia: Yeah. We shouldn't be shy about actually establishing what the extent of the problem is, because, if we do understand the extent of the problem, then we can advocate for more resources and services. But if we at the moment do what we're currently doing, which is we just send people home and don't let them get the help that they need, then we're never going to improve what we do.

(5:53) James: Yeah. So this monitoring, you talked about sort of on the spot tests. How long would people normally monitor for? If you're a more severe injured patient, you're in hospital, are you going to be monitored for a week, two weeks?

(6:08) Virginia: So it's a little bit of a how long is a piece of string kind of a question. So the patients, particularly those with the invasive monitors (such as the intraparenchymal pressure monitoring, measuring that pressure inside the brain) we’ll monitor them for as long as they need. So some patients who we put the monitors in will only have to have treatment for this high pressure to lower it and to make sure that they've got enough blood flow to their brain for a day or so, whereas others might need it for two or three weeks. So it's really on a case by case basis, depending on what the patient themselves need in order to help them get the best care that they can get.

(6:44) James: Yeah, and is this a sort of constant real time monitoring? Are we taking samples and sending them to a lab? Or is it just on a monitor where you can see the bips and the graphs going?

(6:55) Virginia: Yeah, so it depends on what we're monitoring. So the measuring the pressure inside the head, that is constantly there, so that's from moment to moment. Whereas things like our microdialysis, it has to go into a machine and be measured. We also use (in these patients) very simple monitors in a very clever way. So we know that one of the main aims of reducing the pressure in the head, is actually to make sure that we maintain the cerebral perfusion pressure (so how much blood flow the brain is getting), to make sure that the brain is getting all of the oxygen and other nutrients that it needs. And so we can use the pressure in the head, and your own blood pressure elsewhere in the body, can tell us how sic you brain is, and help us optimise the perfusion pressure that were doing. So we do that using a piece of software (that's been developed here in Cambridge by Peter Smielewski and colleagues) called ICM Plus. That allows us to see whether or not the brain is auto-regulated or not, and again, that's a monitor that we have there constantly while the patients have these pressure probes in their heads. And so we see that from second to second or even higher resolution.

(8:12) James: Yeah, and then I guess you can act straight away. If things look like they're going in the wrong direction, it might just be some medication or something to set things back on track again, so we avoid those kind of secondary injuries. So what are the different technologies that are coming through at the moment that might help us control some of those conditions that we've talked about in the brain?

(8:33) Virginia: So one of the ones that I think is particularly exciting coming through, is something that can help control the temperature of our patients and cool them down. So we know that when someone's pressure goes up in their head, one of the things that actually can help potentially protect the neurons, but also bring that pressure down, is to have a cooler temperature. So we know that having a fever and having a hot brain is actually a very bad thing. We've got some clues and hints that maybe having a cooler brain might be a good thing to do. But if you cool someone and you cool the whole of their body, there's a whole lot of side effects to doing that. For example, your heart gets very slow, or the rest of your organs start working a bit slower as well.

So one of my colleagues, Andrea Lavinio (in conjunction with Seletherm) is actually developing what looks like a neck collar that goes around a patient's neck and is actually a cooling device. And the thought behind it is that if you cool the vessels going into the brain first, then the brain will get cooler and you won't need to have as much cooling of the rest of the body. And I think this will be a really interesting innovation to do, and will allow us to re-look at whether or not we should be cooling these patients in future clinical trials. So I think that's a potentially very exciting innovation that will come out of the HRC.

(9:58) James: And obviously we need to detect these things, hence the monitoring. You talked earlier on about non-invasive monitoring. How do those things work? Are we looking through the head?

(10:07) Virginia: Yes, it depends on the monitor that we're using. Probably the most common type of non-invasive monitor is an ultrasound probe. There are bits of your skull where the bone is a bit thinner (particularly on the side of your head, so over the temporal area), and you can use the ultrasound probe there to be able to see the blood flow of the vessels inside the head. From there, you can work out someone's pressure inside their head.

But you can also do an ultrasound if you shut someone's eye and you just gently put a probe on the eyeball, (so with the skin over it, so a shut eye) then you can actually measure the width of your optic nerve. And that, again, will tell you (because the optic nerve goes straight into the brain) whether or not someone's got high pressure or not. So that's probably the main non-invasive monitoring that we use. But there are, of course, other monitors that we could use that are non-invasive. For example, EEG is a non-invasive modality where we put probes around the head and look at the electrical activity of the brain as well.

(11:10) James: Yeah. And, of course, people out there listening to this with fantastic ideas for things we haven't even thought of, (Virginia: Absolutely), who are going to come forward to the HRC at once with their fantastic new innovations.

(11:22) Virginia: Send them in! And I often think that sometimes, you know, things from other industries or other diseases or so, we should all learn from each other. Because there are some fantastic ideas out there that we just aren't aware of. So absolutely bring them in.

(11:34) James: Are we seeing improvements in outcomes already with these technologies? Because we can act earlier, because we've got this information, are people doing much better six months, a year, two years down the line already? Is there much scope to improve those things moving forwards?

(11:52) Virginia: So we have a lot of evidence that if we have high intracranial pressure (so we have a swollen brain) and we let that swelling occur for a long period of time (so someone has a higher dose of that raised pressure) then it's associated with having a poor outcome. And we do have some studies showing an association between treating this and then having a better outcome. And same as we have an association of if someone's brain doesn't have enough oxygen to it (using our probes that go into the brain, our brain tissue oxygen monitors), then actually managing it, maybe something that is helpful.

But of course, in medicine, what we want to have is randomised control trials to prove that something works. And we don't have any good randomised control trials in this area. But it's a bit of a watch this space. So there's currently running a couple of brain tissue oxygen monitoring trials. One based in the US called Boost 3 and one based in Australia called Bonanza. And so it may be in the next two or three years, we really get the evidence that monitoring the brain tissue oxygen, in conjunction with the pressure probes, is something that's a good thing to do. I think there'll be a subset of patients in there that it's a really crucial thing to do, and maybe it's not so useful in other patients. But understanding that will be really important so that we can target these probes, and what we do with the probes (because a probe only gives us a number) it's about how we manage the patients so we can better target that in the future.

(13:22) James: Yeah, so I guess the next stage is the treatment. So you've discovered that there's lack of oxygen, what are you going to do about it? And what do you do? Do you just put people on ventilators and increase the oxygen that's going into their body? How do you treat patients like that?

(13:35) Virginia: So it depends on the cause of their low oxygen. So in the hyperacute phase (so if someone isn't already intubated, so they might be by the roadside and so on) then absolutely, if they're unconscious, then putting an intubating them (helping their breathing with a ventilator) and giving them higher oxygen is absolutely what you need to do. When we've got someone in the intensive care unit, and we've got one of these probes in their head that tells us that this is localised in the brain (not enough oxygen) sometimes the right thing to do is to increase the oxygen that we're giving the patient. But sometimes there are other things that we actually should do to improve it. So it might be that they're anaemic (and so they don't have enough haemoglobin in their blood) so giving a unit of PAX cells is what we need to do. Or it might be that we actually need to improve the cerebral perfusion pressure (so the blood flow going into their brain is what we need to do to improve the oxygenation). And so these trials that I mentioned have actually got algorithms where they work through the different ways that we can improve the oxygen to see what's the best thing to do.

(14:43) James: Yeah. And I guess all the things we've been talking about really are moving towards a more sort of personalised care. So we don't just treat everybody who comes in exactly the same way. We find out what's best for that individual and kind of gear things towards them.

(14:57) Virginia: Yeah, and I think we've got a particularly big issue after a traumatic brain injury because it's a very heterogeneous disease (so everyone's head injury is different) and then the brain itself is so complex. So Andrew Maas (who's a great leader in our field) has said that traumatic brain injury is the most complex disease and the most complex organ. And that's really true. And so I think personalised care is what we will need to move towards. But it needs to be protocolised, so that way we're really thinking about each step as to what's the right thing to do for each individual patient, rather than just doing it randomly for each patient.

(15:39) James: Yeah. And I guess a common thread that's coming through in my conversations is the use of AI and machine learning. And does that have a role once we can teach the systems enough, collect enough data? Do you think that's going to have a role in saying, OK, I recognise this pattern. And in this case, we need to do X. And in this case, we need to do Y.

(15:57) Virginia: Absolutely. I think AI has so much potential. So it may not only tell us what might be the right thing to do, and that could be particularly useful if you've got either more junior staff looking after a patient, or if a patient's in a unit that's not as specialised as ours (so a bit more of a general intensive care unit) so having those triggers of what you should do would be really useful. But it may also be that AI can help warn us that something's going to happen to the patient, so we could perhaps stop it before it actually occurs. So it might be able to tell us that the patient's pressure in the head is going to go up. And so we could look earlier and think, what can we change now to prevent that pressure rise? So I think AI is a really exciting area. And I'll certainly be watching with anticipation in that space over the next few years.

(16:49) James: Yeah, kind of be interested to see what changes these technologies have. Some people are a bit kind of cautious about letting the machines do it. But often they're better than us because they don't have... Well, they only have the bias that we teach them, right? So we need to be careful in how we teach them.

(17:02) Virginia: And I think it's going to be like everything, it'll be Goldilocks, won't it? That we have to have just enough AI that we can make use of it, but then we probably need to have oversight and really understand what it's telling us. And a lot of AI will give a probability of something happening, and so I think you really need to understand that. So there'll be certainly a lot of learning for all of the people who look after people with brain injuries as AI comes into the space, so we can use it ethically and properly, rather than just choosing it.

(17:36) James: So it's quite early for the HealthTech Research Centre at the moment. In five years' time, do you think that acute care and monitoring will be radically different from the way it is at the moment? Is it going to be a sort of gradual evolution of things already happening? Or is something just dramatic going to change in the next four or five years?

(17:54) Virginia: So I think everything we do is sort of an evolution, so everything builds on itself. But I think we are at the cusp of potentially changing key things that we do for patients. So one of the examples I gave at the beginning of brain biomarkers, and we're about to start a big study on biomarkers in patients with mild head injury who present to emergency departments. It's a study that will recruit 2,000 patients in 10 emergency departments around the UK. And at the end of that, in four years' time, we'll either have shown that yes, biomarkers are really useful in our clinical practice, or no, actually, we should forget about them and we shouldn't use them. So if we do show them that they're useful, then maybe in four or five years' time, we'll actually start using them in our clinical practice.

So I think there's definitely (if we come back and have this conversation in five years' time) we will be talking about different things. And hopefully we'll be talking about a lot of innovation within the HRC that has changed what we're doing for our patients and all the clinical pathways that are going on.

(18:58) James: Great. Well, I'm going to hold you to that, Virginia. But for now, I'll say thanks ever so much for joining me. It's been really interesting to have a conversation and we'll see what happens in the future. Thanks very much.

(19:08) Virginia: Thank you very much, James.