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INSIDE HEALTH

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TX:听 23.04.13听 2100-2130

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PRESENTER:听 MARK PORTER

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PRODUCER:听 ERIKA WRIGHT

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Porter

Hello - coming up in today's programme:听 Getting the most out of your workouts - we examine the science behind pulse rate monitors.听 Side effects - and how to be sure a particular medicine is causing them; Margaret McCartney explains the rationale behind taking a drug holiday.听 And medicines for children - why there is growing concern about how little is being spent on research and development into treating childhood illnesses?

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Clip

At the moment in the UK we spend less than 拢10 per child on research which isn't very much really compared to the amount of money which is spent on research in adults which is then trying to deal with the diseases which probably had their origins in childhood to start off with.

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Porter

But first breast cancer and new guidance from America suggesting that women at increased risk of developing the disease should be offered oestrogen blocking drugs like tamoxifen to protect them. A move that is being mirrored here in the UK by the National Institute for Health and Care Excellence - NICE - which is currently putting the finishing touches to a very similar initiative.

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But what constitutes high risk? Well in the States doctors use an online questionnaire based calculator, with women deemed as having a 3% or more听 risk of developing breast cancer over the next five years being those most likely to benefit from the drugs.听 As an example any woman over 45 with two close relatives with the disease is likely to have at least a 3% risk.

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To explain more about the American proposals I am joined on Skype from Athens, Georgia by Dr Mark Abel, an epidemiologist at the US Preventive Service Task Force.

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Abel

Well women can consult an online breast cancer risk tool and use that to better quantify their risk and see just what their risk level is.

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Porter

And what can we do for these women at the moment?

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Abel

Well of course we recommend mammography for women of the appropriate age.听 Studies have shown that currently only about, in the United States, only about 3-5% of women who could potentially benefit from taking these medications are actually taking them.

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Porter

So at the moment we're effectively - we're screening these women but we're not doing anything actively to reduce their risk.听 How do we know that these medicines work, what's the evidence behind them?

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Abel

Well there are two medications that have been approved - tamoxifen and reloxifene - and in a group of a thousand women who are at increased risk for breast cancer, using these medicines will prevent between seven and nine breast cancers over a five year period.

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Porter

And how long will these women be given the medication for?

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Abel

Well normally they take them for five years.听 Generally women of 40 to 70 years of age are who we've recommended consider these medications.

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Porter

And what happens after that five year risk - does their risk - their lifetime risk always stay lower having taken the drugs for five years?

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Abel

Well there does appear to be a persistent benefit, even after they stop taking the medications.听

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Porter

And are all women suitable for these drugs?

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Abel

No I think two very reasonable women looking at the evidence might make very different decisions that it really - in general women who are somewhat younger, those who are at increased risk or even higher risk for breast cancer and who don't have a uterus tend to have the best benefit, these drugs do have some pretty serious side effects and women have to take that into account.

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Porter

Dr Mark Abel talking to me from Georgia via Skype. And we have a link to that online risk calculator for breast cancer on the Inside Health website at bbc.co.uk/radio4.

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The idea of using oestrogen blockers like tamoxifen to prevent breast cancer may be new, but doctors have plenty of experience of using it as an add-on treatment for women who have developed the condition.听 And we have had a number of e-mails asking about side-effects, including one from Erin specifically querying whether tamoxifen can cause fatigue, as she has felt wiped out since starting the drug after she was diagnosed with cancer. Well to find out more I went to see Mr Charlie Chan, Consultant Breast Surgeon at Cheltenham General Hospital.

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Chan

The problems that most people complain about are the sort of menopausal symptoms like hot flushes and night sweats and weight gain and I think probably a significant minority, anywhere between 30 and 50% of people, who have breast cancer who take tamoxifen or one of these newer tablets, will experience some of this.听 But...

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Porter

It's effectively blocking the effect of any oestrogen that you've got, so it's bringing on a menopause...

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Chan

Exactly, exactly...

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Porter

... that's how it works.

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Chan

The way it works is that many normal breast cells respond to oestrogen, it's the normal way that your breast detect the changes in your body, particularly during your cycle or when you're pregnant.听 And then when the cancer cell - when these cells mutate to become cancers - about two thirds of the breast cancers that result retain this oestrogen sensitivity and this is manifest by little sensors of the surface of the cells and these are called oestrogen receptors.听 And tamoxifen was then trialled in the late '70s in the laboratory and we found that tamoxifen basically covered up these sensors with a non-stick lining, so therefore these cancer cells that relied on oestrogen - needed oestrogen to grow - and that if you covered up these sensors with tamoxifen you starve the cancer cells of oestrogen and therefore the cancer cells would shrivel up and die.听 And so that's how tamoxifen works.听

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But in terms of if you might call serious side effects, in the sense the ones that might perhaps influence your long term health, tamoxifen can increase very, very slightly one's risk of having a thrombosis or a stroke or something like that.听 Now of course as soon as I say this of course everyone's going to get very worried but actually you have to remember that the degree of extra risk you get with tamoxifen is very similar to the degree of extra risk you get for women on HRT, young women on the pill or women who are pregnant and I don't think we would stop any of those three groups of women from carrying on as they were, it's just a function of the fact that tamoxifen is an unusual beast in that in a sense it's an anti-oestrogen in the breast but it's a positive oestrogen elsewhere.听

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And we know that tamoxifen also has positive oestrogen effects on the womb, on the lining of the womb.听 Tamoxifen can increase very, very slightly the risk of having abnormal changes with bleeding and also rather worryingly you might say increase the risk of cancer of the lining of the womb - this is called endometrial cancer.听 But in fact if you look at that risk actually the risk is very small.听 So if you take 10,000 women who take tamoxifen for breast cancer, alright, then you will increase the risk of getting endometrial cancer from three in 10,000 for women who don't take tamoxifen to six in 10,000 if you take tamoxifen for breast cancer.听 But if you offset that against the women who actually would be saved you've actually saved for those 10,000 women almost a thousand lives.听 And so it is a massive benefit in favour of taking the tablets but one just has to be aware of this so women know to go to their doctor if they get some funny discharge.

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Porter

Erin talks here about this feeling washed out, generally lacking in energy, and it's actually a story I've heard as well, is this tamoxifen or is the result of being treated for breast cancer or what - is it a common problem?

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Chan

Yeah I think it is a pretty common problem in people who've had breast cancer.听 I don't think you can attribute this only to the tamoxifen.听 Many ladies who get breast cancer are in the prime of their life, they're either approaching their menopause or they're just afterwards and of course will often feel a bit more listless and a bit more tired.听 And so you have to try and see whether you can separate that from the effects of their treatment, the effects of surgery, radiotherapy if you have it, chemotherapy and of course the psychological anxiety - all those things add up into this fatigue.听 But nevertheless I think you might say that for some women, alright, tamoxifen may be one of the reasons why they feel listless and tired but by no means would you say that's true for everyone who's on tamoxifen.

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Porter

And how long are these women going to be on it for - where are we now in terms of optimal duration of therapy?

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Chan

Well the original studies on tamoxifen, that were done in the late '70s and early '80s, we actually didn't know how long to give it for and so the studies that were done then were done for two years, three years and five years and we found that two years was much better than being on no tamoxifen, three years was slightly better and five years was slightly better than three.听 And so the sort of norm that we've had for the last generation of giving tablets for five years has held sway for some time.听 But of course there was the question about well is five years long enough, is it better if you give it for longer?听 And there have been a number of studies which have been looking at giving tamoxifen or similar drugs for 10 years instead of five.听 And these have taken a long time to come to fruition, purely because of the length of time it takes to get those results.听 But it's starting to appear now that perhaps actually for patients it may be better to give the tablets for longer rather than shorter.

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Porter

So looking at Erin's case here, I mean she was diagnosed with breast cancer last year so one assumes she's been on tamoxifen since then, I mean she's got at least four more years to go likely and possibly even longer, if these study results come in, what would you do if there was some question about it being related to tamoxifen, is there an alternative that you can try to see?

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Chan

I think there's lots of different things and I think the important thing actually for Erin and any lady who has this problem is actually get back in contact with the people who've been looking after them and that might be going back to speak to a breast care nurse, it might be going back to speak to your consultant because if you have problems you can do other things, you can perhaps take the tablet at a different time or you can cut the tablet in two and take a bit in the morning or a bit in the evening.听 But certainly if someone's having real problems often I will say to people look actually have a drug holiday, maybe stop it for two or three weeks, see if you feel better and then maybe re-start it and see if that brings back the same problems.

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Some people feel concerned that maybe stopping their tablets might harm them and reduce their chances of being okay but actually stopping it for two or three weeks won't make any difference at all and if your life is being ruined from the quality of life point of view then I think it's really important that we get on top of that.

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Porter

And of course if you don't get better during that drug holiday then it suggests that it's not the drug that's causing it and you can then start looking elsewhere because there are lots of different causes.

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Chan

So lots of different ways in which you can approach this issue.

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Porter

Breast surgeon Charlie Chan.听听 And you will find more information on tamoxifen, and听 NICE's proposals to offer it to some women with a family history of breast cancer on our website - go to bbc.co.uk/radio4 and head for our page.听 And we'll revisit the subject in more detail when NICE does release its proposals, hopefully in June.

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Inside Health's Margaret McCartney has been listening in our Glasgow studio.听 Margaret, Mr Chan mentioned there drug holidays as a relatively simple way of matching side effects to a particular medication - is that a technique you use?

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McCartney

Yes and I think it's a very interesting idea.听 So this is not a break just because you've run out of your medication or you forget to take it, it's more of a planned decision between the patient and the doctor to stop a particular medication for a period of time to find out whether that's a useful thing to do or not.

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Porter

So let's assume that a patient is questioning whether they're getting a side effect from the medicine, of course they might be on more than one medicine, that's what makes it so difficult, how do you practically use a drug holiday?

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McCartney

Well I think it's all down to individual decision making, so it's the kind of thing that a doctor and a patient could sit down together, work out what medication the patient was on, what side effects we think are most likely to be caused by what, if it's something that a medication can be stopped altogether for or whether it's worthwhile doing almost an experiment of trying taking the patient off that drug for a period of time to find out if side effects that we think are attributable to that drug go away or stay.

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Porter

So for how long do you take the people off the medicine?

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McCartney

I think the commonest drug that we're often interested in finding out whether the side effects are truly down to that drug or not are in the statin group of medications, which I have to say most people over the age of 45 seem to be on one or about to be going on one now, so we've got millions of people really in the country that take them to lower their risk of having a heart attack or a stroke in the future.听 But the problem with the statin drugs is that when you look at the list of side effects on the packet there's lots and lots and lots of them and it could be quite hard to work out whether the side effects are down to the medication or not, particularly because some of the side effects are quite vague - like muscle aches, muscle pain, early fatigue on walking, tiredness, memory loss - so it can be quite hard to work out whether these side effects are down to the medication or not.听 So sometimes coming off the drugs for a matter of weeks - and that's always done in combination with a consultation with the doctor where you decide what's useful to stop and what's not - and then reviewing the patient a few weeks on to find out what's happened and whether or not the side effects have improved or not.

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Porter

I use drug holidays in statins a lot too and one of the problems you have is that when you say well maybe we should take you off your statin for six weeks or so the patient looks at you aghast sometimes and say well I was put on this after my heart attack or because my consultant cardiologist said I need to take it, they think they're going to run into trouble immediately if they come off it.

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McCartney

Yeah I mean obviously you want to make a decision on an individual basis but generally statins are drugs that are given for years and years in order to see an effect over years, not over days or weeks.

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Porter

And it's particularly important we know if they're causing a problem because if you're writing off a class of drugs they might not be able to take them again so we need to be sure that it is that drug that's causing the problem.

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McCartney

Yeah, now there was a really interesting study that was published in the annals of Internal Medicine which was an American study earlier this month and they looked at people who had stopped statin medication and what they found was that many patients who had stopped statins later restarted them and it was just a computer based study, they didn't actually go and ask individual patients, but what they were inferring was some people will stop statins in the past because of side effects but maybe will start them again in the future, without side effects.

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Porter

That's the other thing, once you've withdrawn the drug and you've shown the side effect disappears that you think was attributed it, do you reintroduce the drug to be sure?

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McCartney

Yeah, now some people would say that you should.听 Now we all know about the placebo effect when taking a medication that doesn't actually do us any good feels as though it does us some good but there's the opposite effect, the nocebo effect, when we take something that doesn't any effect on us but we feel as though we get side effects from it.听 So it can be quite useful to reintroduce a drug see if you get the same side effects and that pretty much proves that for that person they're getting side effects caused by that medication.

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Porter

And in some cases Margaret we find that the people don't need to go back on the medicine.

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McCartney

That's right and there's certainly - I've had many patients who have managed to do things like lose weight or reduce salt in their diet, increase their exercise and they don't need blood pressure tablets anymore when they've made all the different changes to their lifestyle.听 I suppose the other big area is in chronic medication headache, now for a long time it was thought that people had chronic headaches they needed more pain medication rather than less and of course it seems quite logical if you're in pain to take some pain medication.听 But of course we now know that one of the causes of chronic headache, even migraine headache, can be actual overuse of pain medication and NICE now recognise, really quite strongly, that all pain medications can be implicated in chronic headaches and actually withdrawing them can actually make a much bigger difference than keeping going with them, which can actually make the symptoms even worse.听 And what they recommend thinking about is different types of medication, prophylactic medication for a chronic migraine rather than taking pain medicine all the time when that can sometimes exacerbate it.

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Porter

Sometimes less is better than more. Margaret McCartney - thank you very much. And don't forget if there is a health issue that you would like Margaret or me to look into, then please do get in touch - send an e-mail to insidehealth@bbc.co.uk

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All of the treatments we have discussed so far in the programme are designed specifically for adults - and thoroughly tested to ensure that they do what they are supposed to, and that they are safe. But the same can't be said for prescribing for children because many of the drugs we use have never been formally tested in younger people. And it's not only our children who could be missing out.

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Professor Neena Modi heads the Royal College of Paediatrics and Child Health Commission on Child Health Research.

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Modi

We've shown that less than 拢10 per child per year is spent on research for children.听 Conversely around 拢50 per adult per year is spent again in research, that's a huge discrepancy.听 If you look at the major burden of disease areas then 60% is suffered by children and yet only 12% of the research endeavour is focused upon children, so there's a huge mismatch between the burden of disease suffered by children, the amount of life years that can be gained from research involving children and yet the resources, which are all focused towards the older adult end of the spectrum.听 This just is bananas, it doesn't make sense, surely we should be focusing our research effort where it's going to make the most good, which means helping the whole population lead a long and healthy life.

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Porter

As a result many of the medicines prescribed by paediatricians are not licensed for use in children because the research simply hasn't been done. Jacqui Clinch is a paediatric rheumatologist at Bristol Children's Hospital:

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Clinch

Yes in paediatrics, until very recently, the vast majority of medications we used in all aspects of child health, including my own speciality with arthritis, were off licence.

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Porter

So you're assuming, effectively, that your patients are mini-adults and will respond in the same way?

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Clinch

The assumption has been for many years, until the last couple of decades, that they are indeed mini-adults and we just reduce the dose according to their weight but we assume that they metabolise the drugs in the same way as adults and the side effect profile also matches that of adults.

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Porter

But is that right?

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Clinch

No, we've recently become extremely concerned about this and very determined to evaluate drugs for children in their own right.

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Porter

And is that because these drugs are likely to have different effects in children, are they likely to have different side effects in children, what's the main driver for that?

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Clinch

The main drive is getting a medication that is right for the child, that includes side effects, it also includes efficacy - so how good a drug is at treating a disease in a child?听 Is the drug acting in the same way in a child?

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Modi

How do we know what medicines are going to work best?听 We can't simply do a research study in adults and say okay this medicine works great in adults, therefore, it's going to work well in children.听 Let's take medicines for babies - my field.听 Over 90% of the medicines that we use in newborn practice have not been developed primarily for use in babies, nor have they been properly tested in babies, the studies have just not been done.听 You cannot extrapolate treating a disease in adults to treating that same - apparently same disease in children, not only might the disease itself be different in childhood but the child himself or herself may well respond differently to the treatment.听 So children need to be involved directly in any research that is designed to improve the treatments that they receive and the ways in which their health can be preserved and extrapolating from other age groups is not serving them well.

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Porter

But investing in more research and development into childhood illnesses doesn't just benefit children. Howard Clark is Professor of Child Health at the University of Southampton.

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Clark

My own personal practice is looking after babies in the neonatal unit and I'm very aware then that everything that we do to those babies when we're looking after them in intensive care is going to have lifelong implications for them.听 We set up patterns of behaviour which are going to govern whether they lead long and healthy lives or whether they succumb to one of the rising tide of non-infectious diseases like chronic obstructive pulmonary disease, emphysema, cardiovascular disease, which most of us in the Western world are actually dying from now.

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Porter

And of course the way the service is set up at the moment is when you get to adulthood we throw a lot of resources at treating the end result of problems that started under your watch I suppose.

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Clark

That's right, so when babies are born prematurely they need to be ventilated because their lungs aren't mature enough and therefore their lungs are susceptible to damage which sets them up then for having chronic inflammation in the lungs and some of them will have a chronic lung disease picture which is a little bit like the emphysema which we see in much older people, who may have developed that, so we're researching into how we can minimise that injury to the lungs.听 And in the same way that we are then looking at the mechanisms of causing that damage we're beginning to understand how some of the things that we're learning in children are actually applicable to the development of the disease which is present in adults.听 A very good example of that is our work on lung surfactant, which is the substance which lines the lungs and enables - stabilises the lungs, stops them collapsing.听 Now small babies don't have enough of this surfactant because their lungs aren't mature enough and that's why they need to be ventilated.听 We've learnt that there are some components of that which has turned out to be quite relevant as a marker of injury in the blood of adults who have developed this emphysema type of picture.听 So things that we've initially started to look at in small babies have implications for understanding disease mechanisms later on as well.

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Porter

And would it be fair to say that historically paediatricians like you wouldn't have spoken to the respiratory physicians looking after people with emphysema and probably still don't in many hospitals?

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Clark

Yes, you're absolutely right because care of these individual patients is going on in different parts of the hospital, these people don't frequently meet.

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Porter

Is it difficult to get funding for this sort of long term preventative research because it's quite difficult to see where the vested commercial interest - which of course drives a lot of what we do, there isn't a quick fix drug to fix this, this is more about attitude?

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Clark

You have put your finger on it.听 Commercial interest in sponsoring research are far fewer in childhood because the hospitals are full of old people, older people, adults with these diseases and so the research tends to be focused on essentially what are symptomatic treatments and don't address the origins of the disease.听 So our hope is that by looking and researching more into the early origins in early infancy and childhood we will be able to prevent the development of those diseases.

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Modi

Pharmaceutical companies are of course - they are companies, they have a responsibility I guess to their shareholders, they're interested in the bottom line, the financial bottom line and clearly there's a lot of money to be made from treating illness in a large adult population.听 But wouldn't it be magnificent if pharmaceutical companies suddenly said to themselves gosh if we could understand how to preserve health and we can create treatments which could be applied early on in life so that an infant has the best chance of living a long and healthy life, just think how much money we would make, wouldn't it be marvellous if pharmaceutical companies suddenly woke up to that fact?听 I hope that any captain of industry listening to this doesn't think about this as something that rests in cloud cuckoo land.

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Clinch

Unfortunately still big pharma doesn't have an enormous interest in looking at childhood research.

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Porter

But there are presumably ethical hurdles as well, it's difficult, isn't it, to - when you're looking at recruiting four or five - five year old children into a trail perhaps, people would be more wary of that?

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Clinch

Historically ethically people have struggled with that.听 I think we have to turn that question around and say actually if my child has a very difficult disease I would like research to be going on in that condition so that my child can get the best treatment possible.听 And regulations and research around childhood are very stringent and no one goes into a research project lightly.

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Porter

And what sort of response do you get from parents?

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Clinch

Extremely positive.听 There's a fear around asking parents about research but the vast majority of parents are only too happy to look at research projects and help as much as possible.听 We have a very active parents' forum in childhood arthritis and they inform the research that they want us to do and it's not always the research that we want to do but a lot of that research is about new medications, making sure that they're efficacious so that they work well and that they remain safe, so really we're responding to the parents' requests.

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Porter

Dr Jacqui Clinch. And you will find more information on the dearth of research into childhood illnesses and what can be done about it on our website - bbc.co.uk/radio4 and click on I for Inside Health.听 And do get in touch if you would like more information on anything from arthritis in children to zinc deficiency.

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Last week's item on high intensity exercise prompted a number of you to get in touch after I suggested that you should never let your heart rate go above 220 minus your age. Some of you thought that was overly conservative, while others suggested a lower threshold to be extra safe. Professor John Brewer is Director of Sport at the University of Bedfordshire.

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John, the 220 minus your age is a widely used formula for working out your maximum permissible heart rate during training, but where does it come from?

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Brewer

Well the heart is like any muscle Mark and as you get older the performance of our muscles declines and in the same way, to a certain extent, the performance of the heart declines, so the maximum rate at which the heart can beat or contract every minute will gradually get a little bit less as people get older.听 And research has shown that if you apply the formula of 220 minus the age of an individual that will give you a general guide as to the maximum heart rate or beats per minute that the heart muscle can achieve.

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Porter

And that maximum heart rate is not necessarily the same as an ideal one for training because there's actually a training range that comes in below that as well isn't there?

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Brewer

Oh very much so and most people would suggest - physiologists, sports scientists like myself - that you should train towards maximum but certainly not at too high an intensity and we know from lots of training studies that you can exercise at 50, 60, 70% of your maximum heart rate in a nice safe zone and still get some really positive benefits to health and fitness.听 Now clearly if you're an elite athlete - somebody like Mo Farah or a premier league footballer - you will do much more high intensity, you'll perhaps push yourself to close to your maximum.听 But for the average lay person who perhaps wants to take part in a 10K or swim regularly in a swimming pool exercising at around 60 - 70% of maximum is a great training guide.

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Porter

So it's 220 minus your age and 60-70% of that is a very gentle way of doing it.听 Now we get lots of criticisms from fitter older people and I know you're - what you're in your early 50s now and you've just London -听 run the Marathon - so this would apply to you, they're saying that that's a load of rubbish I need to push myself much harder than that.

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Brewer

Look the 220 minus age is a guideline and there will be people who have a maximum heart rate that is according to the prediction higher than the predictive value or there will be some who have a lower value.听 What we do know is, again just like any muscle, if you exercise it regularly, you give it a moderate amount of stress, then you'll retain its performance.听 And so people who are older but fitter will very often be found to have a higher actual maximum heart rate than the predicted value.

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Porter

So this is just a guide but it's a useful one for anyone embarking on exercise for the first time.

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Brewer

It's a useful guide but like with any guide it is just a general value and there will be many people who have maximum heart rates that are above that guide for their age and there will be some who have lower values.听 If you do have a lower value it's not necessarily a problem, it just shows that your heart doesn't beat quite as quickly as somebody of the same age who has a predictive value that's a little bit higher.

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Porter

Professor John Brewer thank you very much.

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Brewer

Thank you.

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Porter

And that's it for this series - Inside Health will be back at the end of June so please do get in touch with any queries you would like us to look into.听 Until then, goodbye.

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ENDS