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Cholesterol-lowering drug, Defibrillators, Post-traumatic stress disorder and heart disease, Lack of drugs in pregnancy

'Gamechanger' cholesterol-lowering drug, public access defibrillators and when to use them, post-traumatic stress disorder and heart disease, lack of licensed drugs in pregnancy.

Statins have dominated the cholesterol-lowering field for some years but last week the results of an international trial of Evolocumab, one a new breed of medicines for reducing cholesterol, was hailed as a breakthrough. Professor Peter Sever, one of the leaders of the trial, explains how Evolocumab differs from statins and Dr Margaret McCartney takes a look at the trial.

You may have noticed them in work places, gyms, and other public spaces but do you know how and when to use a defibrillator? Every time someone has a cardiac arrest and CPR is performed we should also be running for the nearest defibrillator. But currently this only happens in 2-3% of cardiac arrests, putting thousands of lives at risk every year. Mark speaks to teacher Erica Melsom and the pupil, Alex Cowes, whose life she saved by using the school defibrillator. Professor Gavin Perkins explains why and when we should run and get one. And Mark demonstrates just how simple they are to use, even if you've never touched one before.

Posttraumatic Stress Disorder, a psychological condition which can begin after a traumatic event and last for many years, is the equivalent for your cardiovascular system of smoking 10 cigarettes a day. Dr Donald Edmondson explains how extreme stress takes a toll on our arteries.

More than 80% of pregnant women take at least one prescribed medication and yet very few of these drugs are actually licensed for use in pregnancy. Mark talks to Professor Anna David about why there has been a reluctance to license medications for use in pregnancy, what impact that has for pregnant women, and what needs to change.

Producer: Lorna Stewart.

Available now

28 minutes

Programme Transcript - Inside Health

Downloaded from www.bbc.co.uk/radio4

 

THE ATTACHED TRANSCRIPT WAS TYPED FROM A RECORDING AND NOT COPIED FROM AN ORIGINAL SCRIPT.  BECAUSE OF THE RISK OF MISHEARING AND THE DIFFICULTY IN SOME CASES OF IDENTIFYING INDIVIDUAL SPEAKERS, THE BBC CANNOT VOUCH FOR ITS COMPLETE ACCURACY.

 

 

INSIDE HEALTH

 

Programme 12.

 

TX:  21.03.17  1530-1600

 

PRESENTER:  MARK PORTER

 

PRODUCER:  LORNA STEWART

 

 

Porter

Coming up today:  Prescribing in pregnancy – why are so few of the medicines given to pregnant women licensed for the purpose?  And are women and their unborn babies missing out on R&D that the rest of us take for granted?

 

Post-traumatic stress disorder – could the anxiety associated with vivid flashback of past traumas be as bad for your heart as smoking 10 a day?  I will be talking to a researcher who is convinced it is.

 

And, continuing the heart theme, we take a closer look at defibrillators in the community. There are at least 20,000 defibs in public places across the UK but do you know where your nearest one is or what to do with it?

 

But first a new drug that has hit the headlines.  The PCSK9 inhibitor evolocumab may not trip off the tongue, but it’s one of new breed of cholesterol lowering medicines hailed as a breakthrough in a field that, until now, has been dominated by the statin family.  An international trial of over 27,000 patients attracted widespread coverage in the media after showing that adding evolocumab to statin therapy further reduced the risk of stroke and heart attack.  But at considerable cost, with a retail price of around £10 a day, that’s 200 times the price of the most commonly prescribed statins.

 

Peter Sever is Professor of Clinical Pharmacology at Imperial College, London and one of the organisers of the study.  Peter, how do these new drugs work?

 

 

Sever

A few years ago a new chemical substance, a protein, was discovered which was released from liver cells called PCSK9.  And what this protein does, it interferes with the way in which the liver clears cholesterol from the bloodstream.  And the more of this protein that’s produced the more the interference and thence the level of cholesterol in the blood goes up.  So what this drug does it’s an antibody, it blocks the PCSK9 protein and it allows the liver to be more efficient, to take up cholesterol and lowers the level of bad cholesterol in the blood.

 

Porter

And that compares to what with statins, what are they doing?

 

Sever

Well statins act in a totally different way.  They actually inhibit the synthesis of cholesterol by attacking one of the enzymes that are in the – what we call – the biosynthetic pathway.

 

Porter

Looking at your trial the standout figure for me was what the numbers needed to treat and that’s that you had to give this drug in conjunction with a statin to 74 people to prevent one heart attack or stroke over a two year period.  Now that’s great news for that one person but given that this is a very expensive drug and quite a new and exciting breakthrough that’s been put forward were you not expecting a better result than that?

 

Sever

That’s not that different from the numbers needed to treat with statins, for example, when they’re given to people who’ve not had a myocardial infarct.  So we’re in the same sort of ballgame as for many other treatments.  Now the second issue you raise is of course the cost and really the important factor there is what we call cost effectiveness and these analyses have yet to be done based on the trial data.  But I very much suspect that when we’re dealing with high risk people – people who’ve had a stroke, who’ve had a heart attack – that this drug when added to statins will turn out to be cost effective.

 

Porter

Well listening in our Glasgow studio is Margaret McCartney.  Margaret, this trial’s had a lot of publicity, what’s your take on it?

 

McCartney

Well my take on it is that it’s a very expensive drug and as you’ve just said the number needed to treat is really quite high, so the vast majority of people who are taking it wouldn’t get a benefit from it.  And it’s important as well to consider what this trial actually looked at.  So the primary end points were major cardiovascular events, things like heart attacks and strokes, and that’s where the number needed to treat is.  But the overall death rate wasn’t altered.  So it didn’t actually save lives.  Now you could argue that two years is not long enough but I would argue that for such an expensive drug you really need to prove that it is worth the cost and that means really getting I think longer term data that would show that it is lifesaving because at the moment we cannot say that it is.

 

Sever

This was a trial carried out in very, very high risk patients who’d already had a heart attack or a stroke, they were already on the optimal doses of lipid-lowering treatment with a statin.  And after two years the trial was stopped largely on the recommendation of the Data Safety Monitoring Committee because of the major benefits afforded to those who were taking the drug.  Now as with many, many other trials that have been conducted in people who’ve already had a heart attack, who are already on statins, the first thing you see is that there is a reduction in the risk of another coronary, another myocardial infarct, or in this case another stroke, you do not see early on in trials a reduction in mortality.  If we’d carried on the trial for three, four or five years it is highly likely that that absence of mortality effect would have been reversed.  And I’m very, very confident that when we follow some of these patients up we will see a reduction in both cardiovascular and all-cause mortality.

 

McCartney

We have to get this into perspective.  Yes you’ve got a drug that makes a bit of a difference but it is only a bit of a difference, this is not night and day.  So looking at that trial, as published in the New England Journal of Medicine, 9.8% of the people who were on this new drug had a major cardiovascular event compared with 11.3% who used the placebo.  So the vast majority of people if you were going to have a heart attack or stroke you were going to have it anyway whether you were on a placebo or not.  So it does make a bit of a difference, a difference of 1.5%, but it does not eliminate the risk of heart attacks or strokes.  But the other thing is is that the best way to spend the money?  So we know, for example, stopping smoking – that makes a huge difference – but we know that smoking services or stop smoking services in the UK in the NHS have been cut.  A Mediterranean diet – there is good evidence that that cuts down the risk of heart attack or stroke in primary prevention – people who haven’t had it for the first time, it was likely has an effect for repeated events.  Again where is the support for that – dietician services are really hard to obtain in many areas.  So I just really worry that we’re putting big headlines out about a new drug and failing to take account of the holistic nature of people who are trying to prevent another heart attack or stroke.

 

Sever

I do absolutely agree with Margaret about the other approaches.  We should be doing more to stop our patients smoking, we should be doing more to change their diets but despite all the endeavours that we have made over the last 10 years we’ve been singularly ineffective.  And the one thing we know about this drug is it works.

 

Porter

One thing our listeners will want to know, should any of them ever end up on this drug, is how well tolerated it was and what sort of side effects did you see – is this a safe drug?

 

Sever

This is an extremely safe drug.  I mean the evidence that we’ve got now is based on twenty seven and a half thousand patients in this trial and many thousands of patients in other trials with similar drugs who have experienced no difference between those on drugs and those on placebo.

 

Porter

Professor Peter Sever.  And 10,000 of the participants in that trial are being followed for 5-10 years to monitor longer term safety and impact on death rates. Details of the original study are on the Inside Health page of the Radio 4 website.

 

Now from preventing heart attacks to treating cardiac arrests when the heart stops, or goes into an abnormal rhythm.  Most out-of-hospital cardiac arrests occur at home, but around a fifth happen in public places like airports, supermarkets and train stations where there is likely to be someone trained in resuscitation and, if you are lucky, a defibrillator.  A combination that can mean the difference between life and death.  As Fulford School in York discovered when pupil Alex Cowes had a cardiac arrest during a PE class and teacher Erica Melsom resuscitated him with the help of the school’s defibrillator.

 

Melsom

It was a day like any normal day.  We’d got a call to the main office, which is where I was at the time, to say that somebody had passed out in PE.  And at first I just thought oh it’s somebody who’s not had any breakfast and just gone and done PE and passed out.  Then when I actually reached the gym it was obvious that it was a very different situation altogether.

 

Porter

And everything went smoothly from your point of view in putting the pads on and the device working and everything?

 

Melsom

We actually worked as a team.  There was the PE teacher there who’d taken the lesson, there was myself and we called on the help of one of the other first aiders to actually run and get the defib while I was continuing CPR on Alex.

 

Porter

Alex, I presume you don’t remember much about what happened in the lead up to those events?

 

Cowes

No not at all.  I remember faintly waking up in the ambulance, obviously I’d no idea what had happened or what I was in this ambulance.  The paramedic just said to me – you’ve collapsed and they’ve had to perform CPR on you to resuscitate you.  I owe everything really, I mean they were unbelievable.  From what I’ve heard they were straight on it, performed the CPR, all worked as a team and it paid off and it was fantastic.

 

Porter

It certainly did pay off.  A grateful Alex Cowes.  But public access defibrillators are not being used as often as they should be.  Gavin Perkins is Professor of Critical Care Medicine at Warwick University.

 

Perkins

So about 30,000 people in the UK have an out-of-hospital cardiac arrest where resuscitation’s attempted by emergency services.

 

Porter

And what proportion of those would be the type of arrest that might be suitable for early defibrillation?

 

Perkins

So I think this is where timing becomes a critical part of it.  If you’re able to get a defibrillator to a patient very promptly then as much as 80% or eight out of 10 people would have sustained a cardiac arrest from a rhythm known as ventricular fibrillation, which is where the heart has an electrical storm, and it would potentially respond to defibrillation.  The longer that you leave it from the moment of collapse to attaching a defibrillator the lesser chance that they would potentially respond and the survival rate drops by about 10% for every minute that defibrillation is delayed.

 

Porter

And that’s important because unless the ambulance is right next to you an average response time is approaching 10 minutes if you’re lucky, I mean in my part of the country – I live in a rural area – it can be a lot longer than that.  So we are dependent on these community defibrillators in some situations.

 

Perkins

Where seconds count you can’t rely on an ambulance being outside every house or outside every shopping centre from the moment that someone will have a cardiac arrest.  Whereas public access defibrillators put that technology into the community and make it readily accessible and available to people.

 

Porter

Do we know what proportion of cardiac arrests that might benefit from defibrillation actually get it before the ambulance arrives?

 

Perkins

That figure’s actually disappointingly very small, it’s around about 2% of cardiac arrests where a public access defibrillator is applied to the patient prior to the arrival of the emergency services.

 

Porter

And why is that?

 

Perkins

So I think it’s probably for a combination of reasons.  I think firstly there is a lack of knowledge generally about what public access defibrillators are for as well as being uncertain that the technology’s there and potentially lifesaving.  There’s also the fact that people won’t necessarily know where the nearest public access defibrillator is.

 

Porter

One of the important things with using these machines is that you start CPR and hopefully somebody else goes to go and find the defibrillator, it’s not a matter of oh someone’s arrested we need to go and find the defibrillator is it?

 

Perkins

Yes you’re absolutely right.  When someone sustains a cardiac arrest the key thing to do is to alert the emergency services.  The telephone operator can assist you by providing you instructions on how to perform CPR and they can either send someone to go and fetch a defibrillator or they can advise you where to send someone.  But certainly the first thing you should do if you’re presented with someone having a cardiac arrest is to start CPR.

 

Porter

How would a member of the public know where their nearest defibrillator is?  If I dialled 999 because someone has had what I think is a cardiac arrest will the ambulance service tell me if there’s one locally?

 

Perkins

So I think if the system works well then an ambulance service would be able to identify if there’s a defibrillator close by to where you’re phoning from but I think that’s also one of the challenges, both in terms of registering where public access defibrillators are but also having that information immediately available to the ambulance service.

 

Porter

So let’s be clear about these devices.  If I get the device and I apply it to the chest of somebody, follow the instructions, can I do any harm – let’s assume that the patient’s just fainted and hasn’t had a heart attack and I’ve got it wrong?

 

Perkins

No, so you can do absolutely no harm with this equipment, it’s simple and safe to use and it will only deliver an electric shock to somebody that needs it.

 

Porter

What about cost effectiveness – these are not cheap machines and there could be an argument that we might be better spending the money elsewhere?

 

Perkins

The key is to put them places where there are large volumes of people passing through them but also to make sure that they’re there, that they’re visible and that we’ve got technology that can assist in making sure that the defibrillators are appropriately deployed.

 

Porter

But this is always going to be a problem, isn’t it, the cost effectiveness.  I’m thinking of my local one is actually on the public conveniences in the middle of the village.  I mean we live in quite a rural area and the fact that it’s there could be very important to the few people that might need it over a decade but it’s not going to get a lot of use, it’s never going to be deemed to be particularly cost effective but it could make a massive difference for the individual.

 

Perkins

So I think you’re right and in remote rural areas having access to a defibrillator really can be lifesaving.  What’s certainly clear is that having a public access defibrillator in a remote area’s a lot cheaper than posting an ambulance or a first responder to sit there waiting for that anticipatable cardiac arrest.

 

Porter

These devices are incredibly simple, there’s just two buttons on it that you need to know about.  The first one is the green one which says on and off and that’s the first step, stage one – turn it on. 

 

Defibrillator instructions

Call emergency medical services now.

 

Porter

It tells you exactly what to do.

 

Defibrillator instructions

Remove all clothing from chest and stomach.  Peel off the pad labelled one…

 

Porter

Now we’ve got the pads on the patient’s chest.  The next thing is the device will analyse the rhythm and recommend a shock if appropriate.

 

Defibrillator instructions

…touch the patient.  Shock advised.  Stand clear…

 

Porter

Now it’s asking me to press the button to give the shock.

 

Defibrillator instructions

Shock delivered.

 

Porter

So that’s the shock delivered.  Now what’ll happen is that you’ll carry on doing CPR if appropriate and the machine will go into a cycle then when it re-analyses and gives further shocks if need be.  But all you need to do is just listen to what it’s telling you.

 

Defibrillator instructions

Begin CPR now.

 

Porter

And this one’s even got a little button that if you press it it’ll give a sound prompt so you can get your CPR at exactly the right rate.

 

Trust me, if I can work one, so can you.  My surgery defib saved a life last year and not one of our patients, but a very fortunate passer-by who happened to arrest right outside our door. It doesn’t always end so happily, but if you don’t try……

 

There are more details on first aid courses and community defibs on our website.

 

Now to another hearty subject, and research suggesting that post-traumatic stress disorder (PTSD) is an important risk factor for cardiovascular disease.  We’ve known for a while that stress increases the risk of an early stroke or heart attack, but the relationship with PTSD seems particularly strong.

 

People with PTSD tend to relive frightening traumatic events through nightmares and vivid flashbacks.  Events like serious accidents, sexual assaults, terrorist attacks and military combat.  And new research suggests that their circulation is affected too.

 

Donald Edmondson is Director of the Center for Behavioral Cardiovascular Health at Columbia University and part of the team behind the meta-analysis that has highlighted a strong link between PTSD and stroke and heart attack.

Edmondson

PTSD is associated with about a 53% increased risk for incident cardiovascular events over the course of eight to 10 years.  And that’s on the order of about half a pack of cigarettes a day.

 

Porter

So to put that simply – people who’ve had PTSD are as likely to have a cardiovascular disease – a heart attack for instance – as someone who smokes 10 cigarettes a day and that’s a big increase in risk is it not?

 

Edmondson

It is a big increase in risk and there’s much less awareness in the public of PTSD as a risk factor for cardiovascular events because there’s been much less history of research in the area. 

 

Porter

How can we unpick the possible mechanisms here because there’s a number of things that could be at play, it could be something to do with the people who get PTSD, it could be something to do with the way that PTSD affects their lifestyle or it could be something to do with the PTSD itself?

 

Edmondson

PTSD is basically a chronic dysregulation that is rooted in adaptive evolutionary benefit that came from our early time on the savannah.  So if we see a sabre-toothed tiger coming after us we need more blood going out to the big muscles so that we can run fast to get away from it.  We also need our bodies to be able to fight off infection and clot up any tear to the skin that that sabre-toothed tiger happens to rip from us. 

 

Porter

But you would hope that you’re not meeting a sabre-toothed tiger 10 or 20 times a day but presumably somebody with PTSD is reliving that experience, is that what happens?

 

Edmondson

That’s exactly what happens.  So what we think of in PTSD is that our bodies can’t discriminate, our cardiovascular systems can’t discriminate between our actual experience of a sabre-toothed tiger and our mind’s reconstruction and reliving of that encounter.

 

Porter

And is that different from other stresses – things like day to day financial problems or relationship difficulties?

 

Edmondson

It’s different in terms of both frequency and intensity.

 

Porter

And the implications of reliving that experience or being in a heightened state on the vasculature are what?

 

Edmondson

They’re substantial.  So our blood vessels are exquisitely designed to be able to handle a variety of different levels of cardiac output.  We have endothelial cells that open up our arteries and close them in response to how much blood’s coming through.  Unfortunately the capacity of those cells to open and close the arteries degrades over time if you keep hitting it with excess blood flow through those arteries because as the sheer stress of that blood coming through so fast hits those endothelial cells occasionally will cause little microbe tears.  And when that happens all the immune response and coagulation ability that comes along with that fight or flight response now has something to do, it can go in and paper over and create basically a clot over those little microbe tears.  We call them plaques when they’re inside your arteries.  And what it does is it both hardens those arteries and it begins to stick out into the artery itself, so it restricts the blood flow through the artery.

 

Porter

So Donald, effectively, what’s happening is that by reliving these traumatic experiences the resulting physical adaptive responses are actually harming and prematurely ageing our arterial system and that’s how it’s linked to increased risk of stroke and heart attack.  But is that a recent understanding, have we known this for a long time?

 

Edmondson

We’ve known that our bodies respond to lower level stressers in this way but now we’re really starting to target some of the things that are uniquely dysregulating in PTSD, in particular in PTSD we have a sort of baseline autonomic dysregulation, such that all of the time the sympathetic nervous system, what causes that sort of fight or flight response, is just tuned higher generally.  Further our discrimination between things that are threatening in the environment and should trigger the fight or flight response and things that are safe in the environment is degraded and so people with PTSD end up seeing more things as threatening and therefore engaging that fight or flight response more frequently and inappropriately.

 

Porter

How would this change the management of PTSD going forward?

 

Edmondson

So a number of people have begun to wing in on this question.  There’s a fascinating new article that just came out from Yale University.  They’re arguing that we should begin more closely monitoring and managing cardiovascular risk factors in people who’ve developed PTSD or even people at high risk for PTSD.  If we can identify PTSD early and intervene early we may be able to disrupt or mitigate the cardiovascular consequences downstream.

 

Porter

Donald Edmondson talking to me from New York.  And there is a link to his research on our website.

 

Most pregnant women take some form of medication during their pregnancy, ranging from occasional over-the-counter antacids for indigestion, to prescription only medicines for problems ranging from sickness to epilepsy.  But how much do we know about the impact of these drugs?  Few are licensed for use in pregnancy, and most are never tested on pregnant women.  A situation that needs to change, according to Anna David, Professor of Obstetrics and Fetal Medicine at the Institute for Women’s Health at University College London.

 

 

David

For the major conditions that affect pregnant women, that cause diseases in pregnant women, we have no proper drugs that work.  So we’re talking about common conditions, so things like preeclampsia, where people get high blood pressure in pregnancy, protein in the urine and that affects probably up to about 3-5% of all pregnant women and it’s a major cause of death in women worldwide.  I mean obviously in the UK and developed countries it doesn’t cause death but it does cause a lot of problems for pregnant women.

 

Porter

And taking preeclampsia as a common example, we have no drugs because?

 

David

Well I think it’s because there is a general reluctance to develop drugs in pregnancy and this, I think, really goes back to the 1950s, ‘60s when there was all the problems with thalidomide, which was a great tragedy but it has left a legacy that pregnant women are not tested with new drugs, it’s really a very difficult field to get into because of the concerns that you will affect the mum and of course the baby.  But we know that about 15-20% of all pregnant women are taking drugs and this is increasing because women are becoming pregnant when they’re older, so they may have diseases like diabetes or high blood pressure and so they’re more likely to be taking drugs for their own medical problems when they become pregnant.  And many of these drugs have not been tested specifically to look for the effect on the foetus.

 

Porter

Do we think that women are being harmed as a result of that?

 

David

I don’t know whether we can say they’re being harmed but I think it is a real gap in our knowledge base.  What happens in pregnancy is women’s metabolism changes, your blood volume doubles and you alter how much oxygen you take from the environment.  And so that totally alters how you handle drugs and we really need a push to help the drug companies test out drugs in a specific way in pregnancy.

 

Porter

So it might not just be a matter of safety, it might be efficacy as well – do these drugs actually work, do they do the same thing in pregnancy as they do in people who aren’t pregnant?

 

David

Absolutely and we don’t know whether they do.

 

Porter

Are there many drugs that are specifically designed – licensed for use in women?  I’m thinking of one and it’s a drug that we use to facilitate abortion, which sort of sums it up really.

 

David

There are a few drugs that have been licensed.  The most recent I can think of is a drug called Atosiban which basically reduces contractions in women who have pre-term labour pains.  And that drug was licensed probably about the early 1990s.  And since then there have, as far as I’m aware, no other drugs that have specifically been licensed for use in pregnancy.  And it just shows you the amount of investment that we have in drug development in pregnancy is equivalent to some incredibly rare diseases and yet everybody comes from a pregnancy and it’s important that pregnant women have drugs.

 

Porter

Of course the biggest concern here for the mothers and for the doctors is that a developing growing baby is vulnerable to outside influences.

 

David

Well babies are very vulnerable but it does depend on when you actually expose the baby to or the mum to a potential drug.  So in the first 12 weeks of pregnancy the baby’s actually developing structurally, so if you expose a baby, a mum, to a drug that might have an effect on the structures of the baby then it will have an effect probably in the first 12 weeks.  But subsequently babies develop their brain, their heart and they grow hugely, so of course in the second two-thirds of pregnancy a drug might have an effect on the baby’s growth and development far more than actually on its own structures.

 

Porter

What about the future, what’s going to change, what needs to change?

 

David

I think what needs to change is we need to really invest and thing very clearly about how to get drugs for pregnant women.  One of the things that we’ve been working on is the whole language of doing clinical trials in pregnancy.  So, for instance, when you run a trial of a drug you have specific definitions of events called adverse events which define the harm that women – that adults are exposed to.  Now for the foetus we don’t have any language to describe these adverse events, so we’ve been developing with the medicines dictionary regulatory affairs a specific group of adverse event criteria which can describe what harms might happen to a foetus.

 

Porter

Things like?

 

David

Thinks like whether a foetus develops fluid in body cavities or whether they have any bleeding.  There is no actual way to describe that in the medical dictionary although there are 70,000 descriptions of other terms for little things like whether you have a sort of viral type flu like illness or whether you have a rash but there’s no way of describing that in the foetus, well not until recently and our work has actually developed the first set of criteria for clinical trials in the foetus.

 

Porter

It is odd, we’re sort of suffering from a legacy really of this thing – a woman’s pregnant don’t prescribe…

 

David

Absolutely.

 

Porter

And that’s sort of engendered into doctors isn’t it that it’s dangerous to give anybody anything unless you really think about it.

 

David

It is, it is a worry but clearly pregnant women present with diseases, I mean a mild condition something like morning sickness or nausea and vomiting in pregnancy is a huge problem, people take lots of days off work.  There’s 32,000 hospitalisations per year, think of all those hospital bed days, which are because there isn’t a licensed drug available.

 

Porter

And they also get inflammatory bowel disease, they get epilepsy, they get asthma, they get diabetes, they get a whole range of problems, they get the same problems that you and I get.

 

David

They do and they deserve some drugs which will help their treatment.

 

Porter

Professor Anna David.

 

And that is it for this series of Inside Health. We will be back in July.  Until then goodbye.

 

ENDS

 

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