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Deprescribing long-term opioids, Diagnosing concussion

Opioids for long-term pain and evidence for helping people to come off the drugs. An objective pitch-side test that takes the guesswork out of diagnosing concussion.

Research suggests opioids don't work in long-term chronic pain but dispensing in the UK has risen four-fold since the nineties, and we consume more than any other country in Europe. There is a dearth of good evidence for how best to help people come off these drugs. Mark Porter meets the team trying to change that. And an objective pitch-side test that takes the guesswork out of diagnosing concussion.

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28 minutes

Programme Transcript - Inside Health

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INSIDE HEALTH – Programme 9.

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TX:Ìý 05.03.19Ìý 2100–2130

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PRESENTER:Ìý MARK PORTER

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PRODUCER:Ìý ERIKA WRIGHT

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Porter

Hello.Ìý Coming up today:Ìý Concussion – an all too common problem in sports like football and rugby, and one that can have disastrous consequences.

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Clip

So, I went down, kind of I was groggy and I decided it was big and brave to get up and carry up, which I can categorically state now is not big and brave at all.

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Porter

I meet the team working on a new pitch side test that will take the guesswork out of diagnosing concussion.

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But first, the worrying rise of opioid painkillers.Ìý A topic we’ve discussed before on Inside Health, but we haven’t covered how to turn the tide by helping people come off the drugs.

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The number of opioids, like codeine, tramadol and morphine, prescribed in the UK has risen fourfold since the nineties, and we consume more than any other country in Europe.Ìý The UK is still some way behind America where doctors talk of an opioid crisis that is claiming tens of thousands of lives each year.Ìý But where the USA leads, we often follow.

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Opioids work well when taken for short-lived pain following injury or surgery and for people with cancer but research suggests that they are not that helpful in people prescribed them for chronic longer-term pain caused by conditions like back trouble and arthritis.Ìý And yet, that’s exactly what well over a million people in the UK are currently taking them for.Ìý

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They may be getting little or no pain relief from the drugs, but they are likely to experience side effects.

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The UK’s Commission on Human Medicines has set up a new Opioid Expert Working Group, in light of growing concerns about overuse and misuse.Ìý Its chair is Professor Jamie Coleman.

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Coleman

We don’t believe that the problem in the UK is anywhere near the rates in the United States but the UK are trying to make sure that patients have access to these medicines but we help curb the over-prescription, for example, in non-cancer indications these drugs have become over-used to an extent.Ìý And that actually because they may be used in higher doses or for longer times than necessary, due to the nature of the drugs, that people do become dependent upon them.Ìý Another area that we’re looking at is the availability of some of the weaker opioids – drugs such as codeine – and whether they should be available from pharmacists in conjunction with paracetamol over-the-counter and it’s really whether that remains appropriate or whether actually that might increase the risk of over-prescription and potentially diversion and misuse of the medicines.

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Porter

Are you worried that if we don’t take action we follow America and the problem get much worse – is that a real danger?

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Coleman

I think, to be honest, it probably is.Ìý I think we’ve seen it in many developed nations, is where actually this is a problem.Ìý And whereas I was brought up and probably you were on how we prescribe medicines, with very little advice about taking away medicines or de-prescribing, as we now call it, I think there is a gathering evidence base and we certainly know that there are effective ways to do this and that there are ineffective ways to do it, which of course lead to potentially further harms.Ìý So, yes, that’s part of the evidence that we’ll be gathering to ensure that, from a regulation point of view, that we do not only point out the potential risks but we actually provide some sensible actions about what to do about those risks in the form of deprescribing.

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Porter

Professor Jamie Coleman.

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But deprescribing, that’s helping people come off long term opioids, isn’t easy. ÌýNot least because there’s a dearth of good evidence on the best way to do it – incredible given the scale of the challenge many countries now face.

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A team at the University of Warwick is working to change that.

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Tyson

My name’s Colin Tyson.Ìý I wore my back out working in heavy industry and that meant I got sciatica down both legs. ÌýSo, I couldn’t do anything without being in pain, whether I was standing, sitting, lying down.Ìý Had trouble sleeping.Ìý Couldn’t do my job.Ìý As far as I was concerned, my life was over and even tried taking an overdose to end it all.

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Porter

When things were at their worse in terms of pain how much medication were you taking and what were you taking?

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Tyson

I was on loads of different painkillers.Ìý I was taking coproxamol 12-14 a day.

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Porter

So, that’s nearly twice as much as you should be taking.Ìý That’s a paracetamol and opiate mix, yeah.Ìý

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Tyson

That’s it, that’s right.

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Porter

Were they actually helping with the pain?

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Tyson

To start with, yeah.Ìý But then you started to get breakthrough pain and so I just increased the dose and I was on a slow release tramadol, I was only supposed to take one a day and I’d got up to three a day.

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Porter

So, you were taking three times as many as you were supposed to…

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Tyson

You should do, by the end yeah.Ìý Now know that my body was becoming tolerant to it.Ìý

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Sandhu

My name is Dr Harbinder Sandhu, I’m an Associate Professor at the University of Warwick Clinical Trials Unit.Ìý

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So, these could be people with arthritis perhaps, muscular skeletal pain conditions, could be pain arising from injury.Ìý And the reason why they were prescribed, first of all, I guess, was because they are effective in the short term.Ìý And it’s only now evidence is emerging that long-term use of them does not help with pain and in fact people are at a high risk of becoming dependent on them.Ìý They can develop a tolerance, which means they are seeking higher doses and therefore their side effects are also increased as well.

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Porter

And what sort of side effects are we talking about?

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Sandhu

Severe constipation, nausea, memory loss, not being able to concentrate, higher risk of falls leading to fractures as well.Ìý It can lower immunity, so again leading to other complications, as well as affecting people’s mood, so people can feel quite low and become quite withdrawn as well.

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Porter

If we now know that they shouldn’t be used in the long term for chronic pain and that they have lots of potentially very serious side effects, I mean we should be getting people off these medicines but what are the challenges of doing that?

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Sandhu

So, we have the challenges of the prescriber, what else is available, what else can they actually offer their patients who are coming in seeking help with their pain.Ìý And for the patient, it’s well actually I need something now to help fix the problem.

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Tyson

I was suicidal with the pain for three years and then it took 10 years altogether to get off, my sleep pattern was completely ruined, made my brain fuzzy and I was paranoid and that because I just couldn’t do anything.

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Porter

I mean were you drowsy during the day?

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Tyson

Oh yeah, I was…

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Porter

Sedated.

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Tyson

… you know, yeah.Ìý And my son was at university in Loughborough so I was commuting to Loughborough and because I was paranoid then I used to either be driving too slow to keep away from the traffic or belting it to get ahead of the traffic, so I was a danger.

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Porter

How did you feel as you were coming off the medicine?

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Tyson

Everything started waking up, I thought I’d lost my memory at one time and I got my short-term memory back and I started being able to function.

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Porter

What do you take painkiller wise now?

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Tyson

I don’t.Ìý I keep off them.

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Porter

Had anyone ever suggested to you that you cut down on your painkillers, any of the doctors that you’d seen over all those years?

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Tyson

No.

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Porter

But it’s a decade of your life at least.

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Tyson

That I won’t get back, no.

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Sandhu

Unfortunately, there’s little guidance and support at the moment and evidence as to what actually helps people come off safely, taper off their opioids and be able to manage their pain using different techniques.Ìý And that’s what our study, our trial, at the University of Warwick is hoping to achieve.Ìý This is one of the first trials in the UK, we’re testing a package of care that will help people give them the confidence to be able to come off their opiates and be able to manage using non-drug techniques.

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Porter

Why hasn’t this research been done before?Ìý This is a problem that’s been growing and growing and growing, it’s hard to believe that we haven’t looked at the best way to help these people.

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Sandhu

Yes, and I think the epidemic internationally has definitely highlighted the problem in America, for example.

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Porter

So, what approaches are you using that might be adopted by people like me, at the coalface in clinical practice?

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Sandhu

So, we have developed a package of care which involves group work.Ìý So, there’s three days delivered by a trained nurse and really importantly somebody who’s actually come off opioids and you learn about what opioids are, how they work in terms of pain, the side effects because quite often people don’t really match up the side effects that they’re experiencing with the opioid medication that they’re taking.Ìý And then giving them other techniques to help manage the pain.Ìý So, stress management techniques, learning to use relaxation; cognitive behavioural approaches; challenging and helpful thinking patterns, trying to put into place set goals for themselves.Ìý And so, that’s the group element of the programme.Ìý And then they have a one-to-one session with a nurse who actually generates a tapering plan and will help them reduce.Ìý And that contact point is quite important.

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Porter

This is the difficult thing for me, on the one hand we have patients who are in agony, who say you can’t leave me, I need more medicine.Ìý On the other hand, I meet people who’ve come off their opioids who say they’ve got their life back.Ìý It seems that we’ve got two extremes.

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Sandhu

We do and I think for a lot of people the fear that they have of coming off is the withdrawal – is my pain going to increase and how will I manage without medication because these medications have become the safety net for a lot of people.

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Porter

These drugs may not be effective for long-term pain like backpain, for instance, but they do dull pain from other things – emotional pain, for instance – and people with chronic pain often have quite complex problems don’t they.

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Sandhu

You’ve hit the nail on the head there.Ìý It’s the complex nature of chronic pain.Ìý So, we can’t just deal with one aspect, which is why the programme we’ve developed does look at the medication aspect, as well as the emotional aspect, as well as giving them the confidence to take control back.

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Porter

Who should we be identifying as the group that should be coming off these medicines because there are some people out there who are taking opioids for their long-term pain and they’re well managed, they’re happened, they’re comfortable?

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Sandhu

Yes, absolutely.Ìý For some people low doses over a long period of time, it helps them, it lets them live the life that they want.Ìý But these are the people whose pain is not getting any better, who are constantly coming back, perhaps seeking higher doses, side effects are completely taking over their lives.Ìý And so, as part of the study, we’re doing a cost effectiveness analysis, which will mean that we will actually be able to see, in the long run, what is the benefit of running a programme like this against other costs of the NHS.Ìý Because, for example, in 2014 there was something like 23 million prescriptions costing over £300 million to the NHS for opioids specifically.Ìý A programme like this could help people come off and also then, in the long run, avoid a lot of further complications.

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Tyson

I still get pain but I use various methods to distract the mind from the pain.Ìý I was just a zombie and I’m not a zombie anymore.

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Porter

Colin Tyson who is part of Dr Harbinder Sandhu’s team at Warwick. ÌýAnd there is more information on that study on the Inside Health page of the Radio 4 website, where you can also sign up to our weekly podcast, and find out how to get in touch.

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Our item on haemochromatosis, which leads to iron overload and problems like liver disease, prompted this email from Chris.

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Chris (read)

My son was diagnosed two years ago when his ferritin levels were found to be extremely high. ÌýDespite having a grandparent with the condition, it took three further tests to confirm he definitely had an issue. ÌýThen there was a long wait to see a specialist, followed by a further three-month delay before starting treatment. ÌýAll in all, it has taken nearly two years for his iron levels to get down to normal. ÌýMy advice to anyone who has concerns is to be proactive.

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Porter

I think Chris is suggesting that it’s often the squeaky wheel that gets the grease.

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If you are a rugby fan then you will be aware that concussion is taken far more seriously than it used to be and it’s not the only the sport to introduce new guidelines to help spot and look after players that may be concussed. ÌýOthers, like hockey and football, have introduced stricter guidelines too, although they are not always applied as rigidly as they should be, particularly outside international and big league matches.

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And even if referees and touch-line staff are extra-vigilant, concussion is still surprisingly hard to spot, particularly when players, keen to stay on, minimise their symptoms. ÌýBut missing it can have catastrophic consequences.

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°¿â€™L±ð²¹°ù²â

My name’s Nic °¿â€™L±ð²¹°ù²â.Ìý I’m 26 years old.Ìý I was 15 when I suffered a brain injury playing rugby.Ìý I was training with Welsh Exiles a couple of weeks before our first game in front of selectors.Ìý I was in a maul drill and my head was against the pad.Ìý I took a first knock on the head, somebody came in and kind of hit me on one side of the temple while my head was kind of secured to somebody’s leg pretty much.Ìý So, I went down, kind of I was groggy and I decided it was big and brave to get up and carry on, which I can categorically state now is not big and brave at all.Ìý And I took a second knock to the head, just a basic two on one passing drill, I caught the ball, I was tackled and it was after the second knock that I didn’t get back up.Ìý I was rushed into hospital in a coma and I’ve been left with the effects of a traumatic brain injury ever since.

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Belli

My name is Tony Belli, I’m a Professor of Trauma Neurosurgery at the University of Birmingham and Queen Elizabeth Hospital.Ìý So, it’s a collision that causes an injury to the brain and may not necessarily even be a collision that kind of involves a blow to the head, it could be the torso, for example, the cervical spine.Ìý There isn’t really a single response that you get from a patient who’s been concussed and this causes quite a lot of confusion because you can get from somebody who’s acting perfectly normally for a short period of time, for example it causes some brief impairment of consciousness and they can go through somebody’s, for example, out cold on a pitch for several minutes.Ìý So, clearly there isn’t one response.

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Porter

So, how do we diagnose concussion in a player accurately?

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Belli

This is extremely tricky and this is probably where the problems lie in that diagnosing concussion is probably one of the most difficult things to do in medicine.

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Porter

So, the referee’s standing up saying how many fingers can you see, those sorts of basic tests that we hear about people being used, I mean they’re not much use are they?

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Belli

No, they’re not much use at all.Ìý In fact, they can give you complete sort of false reassurance.

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°¿â€™H²¹±ô±ô´Ç°ù²¹²Ô

My name is Patrick °¿â€™H²¹±ô±ô´Ç°ù²¹²Ô.Ìý I’m a Clinical Research Fellow and a Sport and Exercise Medicine Registrar at the Queen Elizabeth Hospital, work at a professional football club and so I sit pitch side looking after players.Ìý And certainly if you picture the scene that you’re in a noisy environment with lots of people watching and you’ve seen an incident that you’re concerned about and you go on to the player, it’s cold and it’s rainy, you’ve got your manager and the rest of your team wanting to keep going with the game and get things going and you have the referee telling you he wants to sort of hurry things along and then you’ve got your player that you’re concerned about, who maybe doesn’t speak any English, doesn’t really want to talk to you and says, not so politely – there, there dear chap, I’m absolutely fine, please let me get on with the game.

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°¿â€™L±ð²¹°ù²â

When you’re a big tough lad and you’re in a big game you’ll try and say – listen doc, I’m fine, I want to get back out there.Ìý And I don’t encourage it, by any means, but the usual like where are you, what’s my name and then how many fingers and then can you walk in a straight line, can you close your eyes and can you touch your nose etc., they’re quite easy to play down slightly.Ìý So, long as you can pass them a lot of the time the doc will – yeah, okay, no problem.

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°¿â€™H²¹±ô±ô´Ç°ù²¹²Ô

One of the most often used tests, something called the Maddox questions, so those are five questions which you might be familiar with.Ìý So, we are we playing today; what half is it; who scored last in this game; who did you play last week and did you win or loss that game.Ìý So, you ask your player those questions and in developing the head injury assessment process in Rugby Union they looked at how well do those questions perform and what they found was if you go on and ask your player the first question, then he runs off, and you manage to catch up with him and ask him the second question and he’s run off again, and then he’s involved with play and you’re sort of shouting the third question to him.Ìý And so, in those cases it doesn’t perform very well.Ìý Using it a quiet sort of clinic room it’s about 30% sensitivity, so you’ll miss 70% of your concussions if you just rely on using that in a quiet room away from the pitch.

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Porter

At best it’s not great, is what you’re saying.

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°¿â€™H²¹±ô±ô´Ç°ù²¹²Ô

Potentially.

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°¿â€™L±ð²¹°ù²â

Ten years ago, the injury was and concussion was almost an unknown.Ìý I was kind of brought around in hospital in London and I was only there for a couple of days, which kind of – you know that says it all about the whole understanding of brain injury at the time.Ìý But when I got home, obviously, for a little while I didn’t recognise people around me, that came back but I couldn’t walk, I had no follow-up care in that respect.Ìý I learnt how to walk by holding on to my mother’s back, trying to get my feet moving, one in front of the other.Ìý My speech was just very slow, very slurred.Ìý For about six months I just completely shut myself off from the world.Ìý Had I have not had the second bump it would have been likely I’d have had mild concussion but nothing more, as opposed to now living with debilitating effects of a brain injury.

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Belli

There is something called the second impact syndrome.Ìý So, if your brain has been injured more than once and it hasn’t quite recovered from the first concussion then the brain can swell up and it can swell up in a way that you would normally see from a road traffic accident.Ìý So, we’re talking about big swelling and big neurological problems.Ìý And in extreme cases it can result in death.Ìý Obviously, this is rare, it’s not something that, fortunately, we see every week but it certainly is well described.Ìý But even for the ones that don’t die can be left with serious neurological consequences.

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ÌýSo, we know that after the first concussion the brain becomes vulnerable, so physiologically if you have a second insult within that vulnerability the effects are more than cumulative.Ìý The basis of this vulnerability is still not entirely well understood but it’s possibly on a metabolic basis because mitochondria, the fuel cells, become impaired and if they get a second hit before they’ve actually fully repaired themselves they stop working altogether.Ìý There is inflammation in the brain, same as you would get for any joint, for example, if you damage your knee or you damage an ankle, you go running and you twist it again and obviously the second insult is going to make it more inflamed, more swollen.Ìý The same happens in the brain.Ìý So, the number of different mechanisms are being explored but what we know for certain, if the brain hasn’t fully recovered from one injury and it gets hit again that window of vulnerability you can end up with something that shouldn’t really be a severe injury just looking at the mechanics of it but actually translates into something that is quite profoundly damaging for the brain.

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Porter

How quickly does it take the brain to recover from a typical concussion?Ìý So, the person’s not knocked out but they were impaired for up to five minutes, let’s say, what happens to their brain hour by hour, day by day afterwards?

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Belli

So, the brain will repair itself, there’s actually no cell death in a typical concussion as such but there is sometimes structural damage inside the cells.Ìý So, for example, the little bundles – sort of the fibres inside the cell can actually get stretched and they can split, they can be torn apart and these will take a few days to repair themselves.Ìý So, the time for return to normal is quite variable.Ìý Some individuals, if the injury’s been mild enough can actually feel fine even sort of within a few hours but some players can actually have symptoms for weeks, some for months and some, for a very small minority, the symptoms never settle, even after a single event because our ability to repair our nerve cells is actually probably on a genetic basis is extremely variable.

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°¿â€™H²¹±ô±ô´Ç°ù²¹²Ô

Sometimes the things that are most important to emphasise are the fact that playing on in a match after you’ve sustained a concussion is associated with roughly double the recovery time.Ìý So, that’s much, much longer that you’re going to be without that player in your team.Ìý For coaches or the sort of staff in the dugout, emphasising things like the fact that after a concussion they may well forget what their assignment is on the pitch, so they forget what their role is and they don’t perform it as accurately, is important.Ìý And the fact that they’re at increased risk of other injuries.Ìý So, rolling an ankle or a serious knee injury after they’ve had a concussion because things like their balance are impaired.Ìý And an objective pitch side test that will tell you, black and white, this is a concussion, or this isn’t a concussion would be tremendously useful both to allow you to diagnose people more accurately.Ìý So, you don’t miss as many concussions or you don’t misdiagnose things as concussion as often.

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Belli

It’s so difficult to spot when someone is being concussed, we really need something objective and even when you have a highly trained professional concussion could be missed.Ìý So, you need something objective.Ìý We have it for virtually all other areas of medicine but not for concussion, so our research is trying to develop something objective, quick, easy to understand, potentially portable, potentially pitch side.

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Porter

And how are you going about that?

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Belli

So, one of the tests we’re working on is actually the saliva test.Ìý Saliva is ideal because it’s not invasive.Ìý You collect saliva and then what we’ve identified is a potential biomarker, so signatures of the injury that we can use to make that diagnosis crystal clear.

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Porter

So, what they’re picking up is that the brain is injured, something in the brain is leaking into the blood and that’s getting into the saliva and you’re testing that, you can pick it up – is that how it happens?

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Belli

Traditionally, most of the biomarkers that we use in medicine work like that.Ìý These work differently.Ìý These biomarkers are actually there all the time and this is why they’re so quick, they don’t need to be released from the damaged brain and then make their way into the bloodstream and then into saliva, they’re actually present in tissues all the time.Ìý And what happens following a trigger, following a sort of insult, for example, they move in and out of cells very rapidly because what they’re doing is just switch on genes very quickly.Ìý So, if you’ve been injured they tell cells what to make and what not to make at any given time in response to that particular injury.Ìý But because they’re already physically present in the tissues actually their detection is really quick, they just some of them flow out of the cell quickly, some of them sort of get taken up by other cells very quickly, so the concentrations change very rapidly in response to an injury.Ìý It literally is the way cells communicate with each other.

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Porter

And how quickly would you be able to see the signs of a concussion in the saliva?

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Belli

Within minutes.

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°¿â€™L±ð²¹°ù²â

Obviously bringing in these new tests now, not only is it going to be a lot quicker, you can’t really swap your saliva sample for anybody else, you can’t play that down and it takes it out of the hands of the rugby player really.Ìý And I think that is important because as much as I condemn the actions, having learned the hard way myself, we’re kind of built with a mentality when you play rugby that you get up and you crack on with it.Ìý And taking that choice away from the player I think would be a huge step in the right direction for the safety of everybody really.

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Belli

Last season we did a large-scale study with the Rugby Football Union in England, where most of the incidents that occurred in the top two tiers of the games, the Premiership and Championship, were collected and we had saliva samples from players that were removed to be assessed for concussion and we had a number of controls of, for example, players that played the match but were not concussed.Ìý So, all that is being done and we are in the process of sort of finishing the analysis.Ìý This year we’re extending the study to other sports, so we’re actually working with the Football Premier League in England, we’re working with the England Cricket Board, so other sports have actually joined the study because what we want to make sure that we can generalise the findings from this study to other sports.

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Porter

And will this test be able to categorically say that a player hasn’t been concussed because that must be an advantage to the team, if you can say actually we thought this player – we’d have to take him off or her off but we don’t have to?

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Belli

I think it works both ways and this is absolutely important because if somebody hasn’t been concussed do we really need to lose play time unnecessarily, it’s not just because they’re going to miss the next match but we’ve seen this a number of times that when players are excluded from play for a good reason, that’s fine, but when they can’t play sometimes for weeks then you get the emergence of, for example, psychological problems and they lose sleep, they get anxiety, they get depression, so they get disconnected from their team.Ìý The safe approach could be – well let’s stop them playing for safety but there could be other problems down the line if you do that repeatedly and it’s not strictly necessary.

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Porter

So, where are you now in terms of results, what do you know about your tests, I mean is it accurate?

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Belli

What we’ve seen is actually phenomenally accurate, I mean I’ve been researching brain biomarkers for the last 20 years of my career and I’ve never seen anything so exciting.

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Porter

And at the moment you’re collecting the saliva samples and these are lab-based tests that you’re doing, what about the technology to take that to the pitch side, is that developing well too?

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Belli

That’s one step behind.Ìý But now that we know that these biomarkers are good it’s just a matter of assembling the right technology to get it to make it point of care.

Ìý

°¿â€™L±ð²¹°ù²â

I described it as after that day I kind of lost myself in that tackle.Ìý The part of the brain that was damaged, which was the frontal lobe, which controls emotions for one, I felt like I was turning into a horrible person I didn’t recognise, a big change in my personality, explained things like my short-term memory, again part of the injury, the agitation and the lack of concentration.Ìý All those things that I lost with the injury kind of put me out of education.Ìý Rugby was – it’s hard to explain how big a part of my life it was.Ìý So, I think the whole depression and the mental health side, I was being diagnosed with a number of years after, probably had a lot to do with the fact that I kind of spent my whole life doing something and then lost it in the click of a finger really.Ìý Like, my first Christmas present I can remember unwrapping was my rugby ball.

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Porter

Nic °¿â€™L±ð²¹°ù²â. ÌýAnd there is more information on Professor Tony Belli’s research on our website.

Ìý

Just time to tell you about next week when I visit a clinic for people who are frightened by the mere thought of a trip to the dentist. ÌýAnd we have an update on that old chestnut, gout, it’s more common than it used to be, and we are treating it more aggressively too. ÌýJoin me to find out why.

Ìý

ENDS

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