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Statins in the media, Unusual neurological itch, The hunger hormone, Viagra

Has unbalanced media coverage of statins caused people to come off the drugs? An unusual neurological itch that is often missed. Plus the hormone that makes your tummy rumble.

Has media coverage of statins caused people to come off the drugs? An unusual neurological itch on the arms or back that is often misdiagnosed. Plus Ghrelin, the hormone that makes your tummy rumble and an unexpected surgical side effect that may help in the quest for people to lose weight. And the story of how Viagra was discovered.

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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 – Statins in the media, Unusual neurological itch, The hunger hormone, Viagra

 

Programme 5.

 

TX:  02.08.16  2100-2130

 

PRESENTER:  MARK PORTER

 

PRODUCER:  ERIKA WRIGHT

 

 

Porter

Hello.  Coming up today, an unusual cause of itching that’s foxed many a doctor.  A new approach to weight loss – how a team treating life threatening bleeds may have stumbled on a novel way of blunting hunger pangs.  And talking of stumbling onto a discovery – Carl Heneghan and Margaret McCartney continue their series on how serendipity has influenced modern medicine, with the story behind the discovery of Viagra.

 

But first, statins and new research showing that adverse media coverage has put some people off taking the drugs which offer protection against heart disease and stroke.

 

The story starts three years ago when the publication of a study claiming that statins were both effective and well tolerated attracted some criticism, including concerns about conflict of interest. The British Medical Journal then published two articles on statins, suggesting that side-effects may outweigh the benefits in people at low risk. And then, with unfortunate timing, NICE advised that the threshold for prescribing statins be lowered - a move that meant at least five million or so extra people might now be offered the drugs.

 

Little surprise then that the media feasted on the subject. Here is a clip from an interview we did two years ago with Professor Sir Rory Collins from Oxford University – the lead author of the statin study that kicked off the whole debate. He had concerns from the outset:

 

Collins

What makes me cross is the effect on patients and the public and their doctors about being misinformed.  Your patients are coming into your practice and stopping their statin as a result of this controversy.  If that’s occurring all over the UK, for higher risk patients, for example people who’ve already had a heart attack or stroke, that could be life threatening.

 

Porter

Two years later Prof Collins’ comment seems prescient. New research studying the impact of the media coverage on statin use during that period suggests that it did put a lot of people off.  The study was part funded by the British Heart Foundation. Professor Peter Weissberg is the charity’s Medical Director. What does he think of the way it was all reported?

 

Weissberg

I think where it’s gone a little bit wrong is that it’s being perceived to be a balanced argument, in other words that there really is uncertainty out there amongst the majority of medical professionals about the benefits and risks of statins.  It’s not surprising, very often, that the minority voice shouts loudest because they know they’re a minority voice and that tends to get reported as if it’s a balanced argument.  Whereas most of the medical experts, the epidemiologists, cardiovascular, prevention doctors, do not consider this to be a controversy.

 

Porter

This was slightly unusual in that it was both in the professional media and the lay media there was debates going on, so I can imagine in the consulting room the decision not to start or to stop a statin could have come from either the patient or the doctor.

 

Weissberg

No, you’re absolutely right, and one of the interesting outcomes was that doctors did fewer risk assessments during this period, which rather suggests that they don’t want to get into the discussion with the patient, largely because they were uncomfortable I think with giving clear guidance.

 

Porter

And of course the easiest way to do that is not to calculate whether they’re at 10% or at 20% or whatever.

 

Weissberg

Absolutely, there will always be a debate as to at what level of risk should you start suggesting somebody should take a drug, rather than just trying to tackle their risk factors by other mechanisms – we’ll always have that sort of controversy.  But just as I think even those people who are sceptical would accept that for people at very highest risk statins absolutely do have a benefit.  What we’ll be left debating is just where do you draw that line.

 

Porter

Peter Weissberg from the British Heart Foundation.

 

Liam Smeeth is Professor of Clinical Epidemiology at the London School of Hygiene and Tropical Medicine and one of the authors of the study.

 

Smeeth

There was a period of intense media coverage and public concern about statin side effects following the publication of two really opinion pieces in the British Medical Journal in 2013, that highlighted that statins have side effects and claimed very, very high levels of side effects.  A lot of the lay media covered this in great detail with a lot of coverage and there was a lot of Google searching going on by people we know for looking at statin side effects.  And we became interested in whether this had translated into less people starting statins or people stopping statins.  And what we found was while there didn’t seem to be much impact I who was starting statins following the media coverage there was quite a sharp increase in the number of people stopping.  And clearly the idea of you take a statin to prevent heart attacks and stroke is you take them for the rest of your life and once people stop we know they’re unlikely to restart.  And there was quite a big increase in the number of people stopping, a sort of 10% increase, which translates into hundreds of thousands of people in the UK.

 

Porter

Margaret McCartney’s listening in our Glasgow studio.  Margaret, you’re obviously working at the coalface, did Liam’s research translate into an effect that you noticed in the consulting room?

 

McCartney

I have to say not particularly but that would be in keeping with what Liam found, which was it wasn’t really a change in people who were starting on statins who would normally be having a conversation with their doctor, this was more people who’d been on the statin treatment longer term, who seemed to be not collecting or ordering their prescriptions as often.

 

Porter

Liam, did you look at the quality of the coverage that was out there and how accurate it was?

 

Smeeth

I was concerned about some of the initial coverage.  There were some misleading claims about the very high levels of side effects, where I think really we’re actually quite uncertain about that level.

 

Porter

It does seem a very polarised debate, you’re either pro or you’re anti, in most cases, the stuff you read in the media.

 

Smeeth

Certainly I did a media briefing related to this work and was portrayed in one media outlet as a supporter of statins, as if they were a kind of football team.  I don’t know where the idea comes from.  There’s also this confusion about that people are promoting statins because the drug companies make so much money from them, whereas in actual fact now they’re incredibly cheap and drug companies are trying to find more expensive alternatives.  So I think there is this polarisation, which is unhelpful, it’s unhelpful for patients.  I think the debate is really welcome, I think it’s great that health issues get in the media, obviously people are very interested, these are incredibly commonly taken drugs – a big decision whether to take a statin or not.  So I very much welcome the coverage and the debate, the problem for me is this balance.  And I think there are two issues.  One is that I think someone standing up and making a claim that perhaps is counterintuitive or counter the consensus, if I stood up and said – hey smoking’s really not that bad – I’d probably get on the news.  And if I stand up and say – smoking’s really bad for you – I wouldn’t get on the news.

 

McCartney

I think there’s a really interesting point about false balance.  I think that’s something that plagues the scientific community just in general, you know climate change being one big example, there seems to be often undue provenance given to this idea that you should have an equal debate where the scientific evidence is really, really clear about it.  But I do think that we should challenge debates with evidence and that’s a big problem – if you’ve got really high quality evidence, if you’re prepared to do randomised control trials, if you’re prepared to put all your data out there, I think we should do that and I think we should have a high quality debate based on really good evidence but also call people out when their evidence isn’t good enough.  And I feel I have a conflict of interest, I write for the BMJ, although I haven’t written about statins for ages, and I often do write about stuff that might be considered to be controversial but I try and reference stuff well, I try and make sure that I’m giving the best possible evidence based arguments and to be clear where the uncertainties lie and I think that’s where we get into difficulty. 

 

Smeeth

And the problem we’ve got is that these minority opinions, really sometimes without any evidence base, are really just viewpoints that are quite unusual, get this prominence and get an equal balance to the massive scientific consensus.

 

Porter

And to be clear, you’re talking about the one extreme of the statin debate who tend to be in the minority, tend to be quite vocal, who feel that really cholesterol’s nothing to do with heart disease, that statins are very bad for you etc., you think they’re being given undue prominence?

 

Smeeth

Yeah I think they are being given undue prominence, I think some of the media, you know, have latched on to it because it’s a news story, because people want to read about these new things.

 

Porter

Margaret, are you under editorial pressure to be controversial, to take a slightly left field stance on anything?

 

McCartney

No, no, no I genuinely don’t think I am.  I think – quite often I think I shy away from things, to be absolutely honest with you, for want of an easiest life but I hope I don’t do that too often.

 

Porter

Liam, what can we learn from this, I mean you’ve obviously identified what happened, do you think there’s a take home message for us in the media for starters or for the profession?

 

Smeeth

I think this issue of balance is a really good one, a really important one and I think the climate change example, Margaret gave, is very good.  And I think the danger is when that happens in healthy it can really influence people’s decisions, clinical decisions.  And how we maintain balance I think, as Margaret says, I think focusing on the actual evidence.  And there’s certainly nothing wrong at all pointing out that we’re really short of data and short of evidence on how commonly muscle side effects happen with statins, that’s the great thing to point out – we’re short of evidence.  But to claim that – don’t take statins they’ll cripple you – which is patently not true, is I think quite irresponsible.

 

McCartney

And from my own personal perspective I think there’s a lot of people would like to have high quality discussions in the consulting room about pros and cons.  And my own feeling is that people are actually well up for having intelligent debate about what the right thing to do is and to consider a variety of options, it’s no longer about doctor knows best, and part of that is being clear about uncertainty.  So I think it’s okay to say look we’re not sure about this, we don’t have all this data, however, we’ve got lots of experience, we’ve got lots of other data from elsewhere about statins.  I think it’s okay to do that.  What this study hasn’t been able to tell us, because it wasn’t designed to do that, is whether people made good choices or bad choices about taking statins, did people make high quality decisions based on really good quality evidence or were these poor judgements because they’d been supplied with bad information from non-evidence based headlines.

 

Porter

Margaret McCartney and Liam Smeeth. And there is a link to Liam’s study on the Inside Health page of the Radio 4 website. Where you will also find details of how to get in touch.

 

Two listeners who did just that emailed us within a few weeks of each other to ask about the same little known cause of itching – brachioradial pruritis. In both cases it affected their arms and had been present for many years and proved resistant to all attempts by their doctors to alleviate it. Until the penny finally dropped – for one of our listeners at least - when an MRI suggested a problem with his neck. Because, rather oddly, it is underlying nerve damage, rather than an issue with the skin, that is thought to be responsible for the troublesome itch.

 

Dr Nisith Seth is a dermatologist with a special interest in the condition.

 

Seth

Yeah it’s a completely counterintuitive and odd condition that we see because you have this itching sensation on the middle of the arm, which is somehow connected to the nerves in your spine.  And that’s what makes it difficult to diagnose, largely because most people, even many doctors, don’t really even know about it.

 

Porter

When was it first recognised?

 

Seth

It’s probably been kicking around for years and years actually.  But it’s become a little bit more known about in the last five or six years.  So what you might notice with this condition is an itching sensation on the middle of the arm, sometimes on the forearm or the upper arm, you can also get a burning sensation and in a few patients it’s made worse in sunlight.

 

Porter

What other possible diagnosis might it be confused with then?

 

Seth

A type of eczema because eczema’s often made worse around the arms, particularly on the bends of the elbows; psoriasis; other skin conditions like urticaria, which gives hives and which can come up in the sun.

 

Porter

And of course if the person’s had it for a long time and they’ve been scratching there they can actually get some changes in the skin that could look like eczema.

 

Seth

Absolutely, they can get thickening of the skin, the skin can be dry, discoloured and can have some of the changes which are sort of very typical of eczema and that’s one of the reasons why it’s confused for that.

 

Porter

You mentioned that it was worsened by sunlight in some cases, I mean one of our listeners noticed that and was told actually that he had a photosensitive rash and just to use sunscreen in the summer but that didn’t actually help him.  What’s actually going on in this condition?

 

Seth

What we think is going on is that the nerves that supply the skin are altered.  So there are various different nerve fibres and they emanate from the spine in the neck and those nerve fibres can be damaged in many different ways, in this case it may be from chronic sun exposure at the site of the skin but they can be damaged at any point in their path from their origin to the skin. So, for example, when they emerge from the spine they might be being compressed by the vertebrae, the bones, in the neck.

 

Porter

And that’s the case in our other listener who has had an MRI of the neck, they found a disc that was causing the trouble and that’s what clinched the diagnosis.  Now he’d initially been told that it was eczema, it was something to do with the sun, which he could understand but the fact that a nerve was pinched in his neck and was causing an itch in his forearm, he just can’t get his head round.

 

Seth

Yes.  But it sort of makes sense when you think about it as an electrical circuit, which is wiring up your skin, so when you touch something or when you feel something itchy, all that sensation is relayed back to your brain through this electrical system, so if there’s a faulty wire anywhere along it you’ll get an altered response to it.

 

Porter

But it is slightly odd, isn’t it, I mean medically if you look at damaged nerves anywhere else you tend to get other symptoms like perhaps pins and needles or a bit of weakness or numbness, I mean here you’re getting this intense itch, is there something funny about this particular circuit?

 

Seth

The upper body is much more sensitive to touch and to itch probably than other parts, just because that’s the way we’ve evolved – we need more sensitivity in our hands and upper body because that’s what we need to function.  And it can happen that other areas, in particular the upper back, and if anything that might be an even more common place, people often complain of a similar sensation on the upper back, an itchy back, and it’s often put down to old age or eczema but it’s a similar kind of problem – the wiring or the nerves from the spine are being altered.

 

Porter

Do you see many people with this condition?

 

Seth

I don’t see many people with the condition where it’s isolated on the arms but I do see quite a fair number of people who come to me with an itch on the back or a burning sensation and it’s often underdiagnosed.

 

Porter

Well if the patient’s lucky enough to come to see a doctor like you who recognises what it is, what happens next, how can you help them?

 

Seth

There are certain creams that can help, some very basic creams, things like menthol or creams that can affect the nerve endings – doxepin cream – and these can alter the way the nerves respond to itch and touch on the skin.  In a lot of cases this isn’t enough and people need to go on to tablets but they can have side effects and that’s often what limits their use because they can make you drowsy but it’s often worth trying to investigate and correct the underlying cause.  Scans can sometimes be helpful, such as an MRI scan, and then interventions, sometimes which might involve simple physiotherapy.  In extreme cases surgery might be needed but I’ve never seen that myself.

 

Porter

And if that rings bells you will find more information on brachioradial pruritis - and the related condition he mentioned there that causes an itchy back, that’s notalgia paresthetica – on our website.

 

Now to happy accidents and the last in our series where Margaret McCartney and Professor Carl Heneghan look at how serendipity has helped shaped modern medicine. Including one of the most famous drugs ever.

 

McCartney

So Viagra, it’s a story of a useless drug that had fantastic side effects, quite the opposite from what we usually get – we usually have a drug that’s got annoying side effects.  But in this case the Viagra’s side effect was actually the thing that we use it all for now and we know what that is, it creates erections and that’s why it’s such a valuable drug.  So research started into it in 1985, people were looking at a treatment for angina, what could they get that could open up the blood vessels to the heart and make the heart better supplied with blood and that’s in general what your treatment for angina are trying to do.  And they were testing a drug called Sildenafil, which was trying to block an enzyme that worked in the arteries of the heart, and it basically – it hardly worked at all, it was being tested in Pfizer’s lab in Sandwich in Southern England – and the trails showed that it didn’t make much difference to angina at all but the volunteers did come back and told the researchers something interesting.  In fact what was happening was it’s not making any difference to any other symptoms but what is happening is I’m getting more erections.  And then they went on and they did more experiments – they took penile tissue, they put it in test tubes and they found that adding some Viagra into that created relaxation of the blood vessels and an increased blood flow with the Viagra.  And we now know it’s the number one treatment I think that’s being used globally in its millions, it was the first oral treatment for male erectile dysfunction.

 

Heneghan

I think the Viagra is a really interesting example of why you do clinical trials and you collect all of the side effects.  And I think the one thing I remember about this is there is no such thing as a safe drug, so you have to collect the side effects.  In this case actually what was fortuitous is that the side effect led to, in people with erectile dysfunction, a marked change for them.  But interestingly common side effects of this drug have continued to be collected over time, include headache, visual disturbances that were found in 2005 and in 2007 the fact that it had serious hearing losses.  So no drug is without side effects.  And I think this is important because if you look at how people have gone on to use  Sildenafil, younger people use it because of a belief that it increases libido, improves your sexual performance, even increases penis size and all of these claims are not backed up by any evidence.

 

McCartney

The other interesting thing about this drug is it’s also being used in completely different applications.  So, for example, pulmonary hypertension, when there’s a high pressure within the blood vessels in the lungs, it can be useful for that and it’s widely prescribed for that, although it is quite a rare condition.  So it’s a drug that has different applications, it doesn’t work in just one place in the body but that also means that it has side effects that affect numerous places in the body as well.

 

Heneghan

That’s a really interesting point.  It started out as a prescription only medication but it’s actually become available now over the internet, on websites, and actually if you type into Google you’ll get something like 89 million hits for this drug alone.  There are lots of counterfeits, lots of claims out there.

 

McCartney

I agree and it uses so much marketing, I think going on to think that – particularly that young men or people who are maybe looking sort of these adverts online, it’s somehow – there’s a belief online that somehow this will make good better, in actual fact that’s not the case.  This is really for men who are experiencing erectile dysfunction – they don’t have an erection that lasts for long enough to have satisfactory sexual intercourse of whatever type.  That’s the reason it works, it’s not a kind of general sexual gift from the gods that’s going to make everything better already.

 

Porter

Margaret McCartney discussing Viagra with Professor Carl Heneghan.

 

And from one happy accident to another – this time in the quest to help people lose weight.

The story starts in a specialist unit for treating life threatening stomach bleeds at Southampton General Hospital where the team noticed an unexpected side effect once their patients recovered. As Consultant Interventional Radiologist Dr Rob Allison explains:

 

Allison

People sometimes present to hospital with profound bleeding from the stomach and one of the ways of treating that is to put a small catheter through a groin artery, up round into the stomach artery, they all connect inside, and block off that bleeding.  We get involved in this as a sort of day in, day out, job.  Of those patients that were treated one thing people noticed is that quite a lot of them lost a fair amount of weight after the treatment.  Now obviously we weren’t blocking off the stomach’s blood supply to make them lose weight, we were doing it to stop them from bleeding to death.

 

Porter

So this was a treatment that you were using for a very serious condition and it was essentially a side effect, a curious side effect.

 

Allison

Absolutely.  And studies then looked back at the weight of these patients when they’d had this procedure and they showed that if you blocked off one particular artery in the stomach the patients lost much more weight than if you blocked off other arteries to the stomach.  From that we looked at it a bit further and showed that the left gastric artery supplies the fundus to the stomach, which is the top of the stomach, sits just under the diaphragm, and that’s where the vast majority of the body’s ghrelin is produced.  Ghrelin is a hormone that’s involved intimately with people’s hunger, probably about 95% of the ghrelin in the body comes from the fundus of the stomach.  So you tend to find that people who are underweight have high ghrelin levels to try and make them eat.  So if you can reduce that hormone you could therefore suppress someone’s appetite.

 

Porter

And that was what you were inadvertently doing when you were treating people with stomach bleeds.

 

Allison

Absolutely, this was a side effect which people hadn’t really anticipated.  And the studies themselves showed that if you blocked off this left gastric artery in these patients that were bleeding they lost just under 8% of their bodyweight over their period in hospital, whereas when the study compared that to the other arteries – there are four main stomach arteries – if it was the other arteries treated that was only just over 1%.  So that’s a massive difference.

 

Porter

So there was already evidence out there to back up this thing that you’d noticed.

 

Allison

Absolutely and people are sick when they come into hospital with bleeds, life threatening conditions, so people will lose weight but I think it’s hard to argue that that isn’t a statistical difference.

 

Porter

An eight fold increase potentially.

 

Allison

Absolutely, it’s one of those side effects that you don’t really notice until you specifically take a step back and look at this and find out these other happy accidents to look at it and then use that to your advantage.

Bloom

Interestingly ghrelin stimulates the gut to contract and you know those nasty hunger pains that you get, that’s probably ghrelin.

 

Porter

So to put it very simply, the message it’s sending is your stomach’s empty?

 

Bloom

Yes that’s right.

 

Porter

Professor Steve Bloom from Imperial College London is a world authority on hormones and metabolism. So is ghrelin the hunger hormone, as so often portrayed in the media?

 

Bloom

It is the only one we’ve found which stimulates appetite and does so absolutely convincingly and regularly.  So I think actually its name is perfectly appropriate.  What’s much more tricky is to know whether it does it in you and me every day, for example if you feel hungry for a meal.  It is high when you’re starving and it is low when you’re not and whenever you get hunger pains if you measure the blood levels of ghrelin they go up, that’s when they peak.  So it seems to be having an effect causing contractions of the gut.  We know that when we give it as an infusion to human volunteers they all eat more and in fact some people in rather unfortunate circumstances it can be lifesaving – if they’ve got renal failure and have lost their appetite completely or if they’ve got cancer and have lost their appetite completely – in both cases it helps them get better.  So it’s a very useful thing for stimulating appetite but whether it does that normally every day in you and me, not sure about that.

 

Porter

If ghrelin levels are high how does that make somebody feel hungry, what’s it actually doing to the body?

 

Bloom

That’s interesting because it’s told us something about the mechanisms controlling appetite in the brain. So when you infuse ghrelin and increase the appetite you can see that part of the brain lights up, the bit called the hypothalamus, which is an old part of the brain controlling temperature and sexual interest and various fundamental things, including appetite and including energy expenditure.  And ghrelin lights up cells there, you can show that that’s where the cells are activated by ghrelin.  So it does appear to be acting in the right place to have an effect on hunger, which indeed it does.  The question really is – how important is it as an everyday regulator of our appetite?  And there I’d say, best guess, probably not very important.

 

Porter

If this is the only hormone that’s directly associated with hunger one can imagine it must have been targeted by other people previously.

 

Bloom

Yes you’re absolutely right.  Quite a lot of effort has gone in to finding things to block its release or block its action.  And while they’ve been successful in that clinical trials have not shown it reduces weight very much or indeed the amount of food you eat.  So it may well be that it’s not the most important thing controlling our appetite.  And rather inversely hormones that switch off appetite seem to be very much more important and the satiety hormones, as we call them, they all suppress ghrelin and so the way ghrelin’s controlled is probably via the satiety hormones, so they’re king of the castle and ghrelin is very much a second player.

 

Porter

So looking at this Southampton study, I mean ghrelin is one of the things that might explain their effect, I mean are you convinced by that?

 

Bloom

Well I’m pretty convinced by the Southampton study, I think that’s a very interesting new finding and important, whether the mechanism causing the loss of appetite is just ghrelin I’d say was fairly unlikely but it is a possibility.

 

Porter

Whatever the exact mechanism for the weight loss noticed after embolization of part of the stomach’s blood supply, the research continues. And not just in Southampton.

 

Allison

So the Americans are quick at picking these things up as well and they have performed the first in-man study to show yes it can be done and yes it’s safe to do it and to measure weight loss as its primary end point. 

 

Porter

So were these patients who have perfectly healthy stomachs and they’re actually using this technique to purely induce weight loss rather than treat a bleed?

 

Allison

These are people who are overweight, so they’re obese patients, to specifically see if blocking off this blood vessel could help them lose weight.  It’s a relatively straightforward procedure and if you compare this to bariatric surgery it’s a breeze in the park to be honest.

 

Porter

Gastric banding etc.,..

 

Allison

Yeah.  So that did show, over the first few months, that these people – their calorie intake was reduced and their weight also reduced.  And at the moment they have published data up to six months which shows that’s a continued reduction.  The issue at the moment is whether this is going to be a long term solution.  Obviously people can put the weight back on, however, embolization is also a technique that can be repeated.

 

Bloom

I think further work’s required, Ghrelin certainly is a hunger hormone, it certainly comes from that part of the body and removing it potentially could be important.  It’s just that all the rest of my experience suggests it’s a bit player, it’s not the most important hormone controlling hunger.

 

Porter

In a typical person who let’s face it in our modern society is rarely starving do ghrelin levels change that much during the day?

 

Bloom

No they don’t.  When the stomach’s empty or when the stomach’s full doesn’t make any difference to it, it goes on being produced.  So our first theory that food in the stomach would suppress it and absence of food would give you more hunger hormone seems not to be true.  So it shows that science is always discovering things aren’t as simple as they first seem.

 

Porter

So very true.  Professor Steve Bloom ending that report on the hunger hormone and the work of Rob Allison and colleagues at Southampton General Hospital.

 

Just time to tell you about next week, the last in the current series, when I visit a team pioneering a novel approach to treating painful hips using minimally invasive keyhole surgery.

 

 

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