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INSIDE HEALTH

Programme 4. - Emergency abdominal surgery, Thermometers, Vitamins and Dementia, Risk

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TX:Ìý 30.06.15Ìý 2100-2130

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PRESENTER:Ìý MARK PORTER

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PRODUCER:Ìý ERIKA WRIGHT

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Porter

Coming up in today’s programme:Ìý

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Thermometers – which type your family should be using, and which they shouldn’t.

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Vitamins and dementia – could supplements that lower the levels of the amino acid homocysteine slow the onset of Alzheimer’s disease?

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Smith

High homocysteine in the population is associated with a doubling of the risk of developing Alzheimer’s.

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Porter

And what sort of proportion of the UK population would have higher than normal levels?

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Smith

The over-60s - about half of the over-60s in this country will have raised levels of homocysteine.Ìý That’s about seven million people.

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Porter

More on the homocysteine controversy later.Ìý But first new data suggesting that too many people in the UK are dying following emergency bowel surgery because best practice isn’t being followed.

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Laparotomy involves opening up the abdomen to treat life threatening problems like a perforated bowel, blockages and bleeds. Close to 40,000 are performed every year in the UK but figures published this week suggests that more than 1 in 10 people undergoing emergency laparotomy die within 30 days of their operation – up to five times more than would be expected after planned procedures such as heart and cancer surgery.

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The audit by the Royal College of Anaesthetists found, for instance, that 1 in 6 patients needing emergency laparotomy did not get to the operating theatre within the recommended timeframe, and many who were at high risk of infection did not receive timely antibiotics. Factors that could contribute to a higher than expected death rate, fuelling concerns that this is a Cinderella procedure that is not getting the attention it deserves.

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Dr Dave Murray is a Consultant Anaesthetist at the James Cook University Hospital in Middlesbrough and National Lead for the audit.

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Murray

The sort of standards of care we are looking at, one of the key things is about whether or not consultant surgeons are available and able to review patients within 12 hours of being admitted.Ìý So you get senior decision makers to see the patients relatively early.Ìý Things like once you have decided they may need surgery, whether you get access to a CT scan to help diagnose the problem.

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Porter

I mean you work in a hospital, why is it do you think that bowel procedures may not be given the priority that they should be?

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Murray

I know in talking to people around the country the difficult decisions they have to deal with every day.Ìý There’ll be times when on any morning you can discover that you’re short of nursing staff, for instance, which means you don’t have enough staff to run all your operating theatres.Ìý Someone has to make a decision do we cancel an elective list or do I cancel an emergency list.

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Porter

The emphasis for other hospitals is in maintaining and running their elective and planned surgery, it’s got to go smoothly – the nine to five stuff.Ìý And do you think that’s having a knock on effect then on emergency provision?

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Murray

We don’t know from the audit but I think it has to be something we start to look at.Ìý And I know other targets have been implicated in distorting the delivery of care.Ìý And so there might be these laws of unintended consequences which by publishing this audit we’re now actually starting to see the consequences.Ìý We haven’t found that specifically in this audit but I think it does have to be part of the debate as we go forward in improving care for emergency patients.

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Porter

This is a common emergency procedure and people listening to this might be a bit alarmed if they were to end up under the surgeons with an acute abdomen, with a painful tummy, what would you say to them?

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Murray

I would say to the patients that ask what is my risks associated with this, how are you going to mitigate them, am I going to go to an intensive bed afterwards, do I need to go to an intensive care bed afterwards and ask questions to get the answers that impact on the delivery of your care.

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Porter

Dr Dave Murray. And there is a link to the laparotomy audit, which lists results hospital by hospital across England and Wales, on the Inside Health page of the Radio 4 website.

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Now on one of the hottest days of the year so far, it seems only fitting to move on to thermometers, albeit the type used to look for fevers in children rather than meteorological.

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Researchers from the Universities of Oxford and Washington have looked at different thermometers on sale in the UK. They found that nearly 1 in 10 were forehead strip thermometers, the very type the National Institute for Health and Care Excellence specifically advises parents NOT to use.

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Dr Matthew Thompson is one of the authors of the study and he spoke to me from Seattle.

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Thompson

Here’s the problem – these are all thermometers which are CE approved, so they’re legal legitimate thermometers and these are ones we purchased in the UK.Ìý And I think it’s difficult for parents, they can see things online or at the chemist that they simply should not be buying.Ìý So it does tell you something about the difference between getting a device or thermometer approved in the UK and Europe and what clinicians, GPs and parents should actually be using.

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Porter

What does NICE say about what constitutes a high temperature and how to act on it and how does that compare to the information that’s coming in the leaflets with these devices?

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Thompson

Well NICE is very specific, they say a fever is 38 degrees Centigrade or more.Ìý But curiously enough very, very few of these thermometers actually said the same as NICE.Ìý So only 17 of these 123 thermometers gave the same fever threshold as NICE.Ìý And many of them didn’t even define what they consider a normal temperature.Ìý So a parent using these – one of these thermometers is really in the dark about what this number that they get means.Ìý And I think for thermometer manufacturers what we’re not saying is that they have to reinvent the wheel here, there’s a really fantastic resources that NICE produces, which are these patient information leaflets, or parent information leaflets, that they can simply incorporate in their devices and in their packaging.Ìý And what that does for the thermometer manufacturer is let them use a really good evidence based information source and what it does for NICE is lets them disseminate their best practices right there into the parent’s home, into their bathroom medicine cabinet, which is a kind of a unique way for NICE to spread their information.

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Porter

It does seem that both parties might be missing a trick there.Ìý Did you find any of that sort of information in any of the packs?

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Thompson

Almost none, almost none.Ìý I mean I would say very few of these thermometers gave bad or wrong advice but curiously enough nearly 90% didn’t say how they should manage a fever and almost as many didn’t give any advice about how the parents should interpret fever in their child.Ìý And the NICE guidelines are really quite helpful in this respect, they give some very specific advice about how parents should assess their child when they’re at home, when they should seek advice from a healthcare professional but almost all of that information was missing from these thermometers.

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Porter

Matthew Thompson. Doctors today are far less aggressive when it comes to lowering high temperatures than they used to be during the early part of my career. Though the change in attitude doesn’t seem to have percolated down to most families. Dr Margaret McCartney has been listening in our Glasgow studio.

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McCartney

Well I remember being a very junior GP and being taught that the most important thing to do was get the temperature of the child down.Ìý So you’re to stand at the window to try and cool the child down, you’re to sponge them down with water to try and make them cooler.Ìý And we now know that this was absolutely a waste of time.Ìý The purpose of all this temperature cooling was to try and prevent febrile seizures which can sometimes happen if the temperature is very high.Ìý But it’s now known that the febrile seizure, the febrile convulsion, is not related to temperature but to underlying illness and bringing the temperature down will not help to prevent that.Ìý So certainly if a child is uncomfortable and hot certainly help them, look after them, do what you think you should do but you don’t need to get the temperature down because that’s not going to prevent a febrile convulsion.

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Porter

So temperature is still – fever is still an important clinical sign, we still rate it when we’re looking at children, it’s a very important clinical sign but we don’t treat the temperature itself, we treat the child.

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McCartney

Totally, totally, now under the age of six months temperature is still a really important thing if you’re assessing an unwell child because the temperature might indicate serious underlying illness in a child who’s unwell.Ìý But bigger than that temperature is one factor in a whole lot of other factors and how the child is is probably the most important thing of all, you can be a well child with a high fever or a very sickly child with not a very big fever.Ìý So the NICE guidelines is quite clear – you want to make sure that you’ve got a child who’s well enough to be looked after at home even though they’re unwell, do they need to be assessed by a doctor or not – that’s a parent’s call to make.Ìý But in terms of getting the temperature down what you’re really treating is the child’s distress, so a child could be distressed and have a normal temperature, a child could be under stress and have a high temperature.Ìý What’s really important is treating the child and the child’s symptoms and how the child is, not just what the thermometer reading is.

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Porter

And by treating we’re talking about the routine use of things like paracetamol, we would no longer recommend that for a child who’s not distressed just because they’ve got a temperature.

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McCartney

That’s exactly right.Ìý So if you’ve got a child who’s poorly, a child who’s unwell, a child who’s fevered, hot, generally miserable yes I would certainly use paracetamol then.Ìý But if the child just had a temperature and was otherwise running around and feeling completely well – nope, I wouldn’t be giving any paracetamol.

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Porter

And to be clear again and that’s because using paracetamol and other methods to bring a child’s temperature down doesn’t affect their chances of getting a febrile seizure or convulsion.

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McCartney

That’s exactly what the NICE guidelines say.

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Porter

Margaret McCartney. And you can download a copy of that guidance from the NICE website – just type NICE and feverish illness in children into your search engine and it should take you straight there.

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Now to a controversy that has been raging since I was a child…

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Music – 1969 music clips

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Sounds of 1969, and the year a link was first identified between blood levels of the amino acid homocysteine and heart attack. The man responsible was an American doctor - Kilmer McCully - and his theory divided opinion then, and is still doing so now. The latest controversy surrounds another link - between homocysteine and dementia – and whether or not vitamins that lower levels of the amino acid can protect against conditions like Alzheimer’s disease.

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Researchers from the University of Oxford have published a paper showing that vitamin supplements can help slow the disease in some people but others, also from Oxford, have since published another study suggesting they don’t.Ìý

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All very confusing. And to unpick what it all means, we have to go back to the beginning.

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Music

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David Smith is Professor Emeritus of Pharmacology at the University of Oxford, and the man behind the first study that suggested B vitamins are beneficial in people with dementia.

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Smith

The story starts with young children who develop stroke and heart attacks and it was found that this was due to the presence in the urine of large amounts of homocysteine.

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Porter

Now these children had a genetic glitch that meant they produced far more of this than you and I would but it made people think that it was somehow harmful to the lining of our pipes and our brains possibly.

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Smith

It started the McCully hypothesis that raised homocysteine could be bad for the vascular system.

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Porter

And is that the link with dementia, is it the effect that it has on the vascular system?

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Smith

It’s a debatable question.Ìý Some people think it is, some people think it’s probably not.Ìý I’m sitting on the fence – I think it’s both, I think it’s directly linked to dementia because it’s directly related to the pathological signs of Alzheimer’s in the brain.

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Porter

So it’s having an effect on the blood supply to the brain but also on the structure and function of the brain?

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Smith

Yes correct.Ìý Raised homocysteine is strongly related to the rate at which the brain is shrinking.

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Porter

And you’re measuring that shrinkage by doing scans?

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Smith

By doing MRI scans.Ìý And high homocysteine in the population is associated with a doubling of the risk of developing Alzheimer’s.

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Porter

And what sort of proportion of the UK population would have higher than normal levels?

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Smith

The over-60s - about half of the over-60s in this country will have raised levels of homocysteine.Ìý That’s about seven million people.

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Wald

My name’s David Wald, I’m Professor of Cardiology at Barts and the London School of Medicine.Ìý Homocysteine is a waste product, so it’s actually an amino acid and it’s broken down from the sort of proteins that we eat when we eat fish and meat.Ìý It serves no useful function and the body likes to get rid of it and it does that mainly by recycling it back to another amino acid called methionine, which does have use.

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Porter

What’s the relationship between homocysteine and vitamin status?

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Wald

The lower your B vitamin status the higher your homocysteine will be.Ìý And the B vitamins that are particularly important are folic acid, vitamin B12 and vitamin B6.Ìý These B vitamins act as ingredients in the recycling pathway, without those the body can’t really cope with the homocysteine which builds up.Ìý If you have a diet which doesn’t have much vegetable content then you’re natural folate levels will be low and homocysteine levels will tend to rise.Ìý Equally if you have a diet which is very rich in meat it will tend to rise.

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Porter

So is the homocysteine doing something to our vasculature and to our brains?

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Wald

Well that’s a golden question and it excites scientists all over the world as to trying to understand the mechanisms behind this possible association.Ìý And the reality is we simply don’t know.Ìý That may sound surprising but actually we don’t know the mechanisms behind many things that cause disease, for example cholesterol causes heart diseases but the exact mechanisms behind that are still unclear.Ìý For homocysteine there are three theories, one is that the homocysteine is actually damaging the lining of blood vessel walls and it’s the lining of blood vessels which tends to become diseased in conditions like heart disease and stroke.Ìý The other is that it may actually make the blood more sticky and therefore more likely to cause a heart attack or stroke.Ìý In terms of dementia there is also some suggestion that high homocysteine levels may have a direct toxic effect on nerve cells.

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Porter

So looking at the brain it’s possible that the homocysteine would be affecting the vasculature, the blood supply to the brain, and may be having a direct effect on the nerve tissue itself?

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Wald

It’s possible but one has to be clear that there’s still uncertainty over that.Ìý I think the position we’re at with the dementia story is that there is a clear association in prospective studies, there’s about a 50% increased risk of dementia for a five unit increase in homocysteine.Ìý But that does not prove cause and effect and the trials that have been done are inconclusive, they do not prove it, they do not disprove it.

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Benelam

My name’s Bridget Benelam and I’m a senior nutrition scientist at the British Nutrition Foundation.Ìý For folic acid or natural folates you’d typically find them in green leafy vegetables, so like kale, spinach…

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Porter

I’ve got a big bag of kale here, it’s a huge bag…

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Benelam

B6 more in sort of cereal foods and B12 is only found in animal products, so you find it in milk, dairy, in meat and in eggs.

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Porter

But how much would people need to eat to get the sort of doses used in the studies because they were using very high dose supplements, I mean looking at one study it used folic acid folate .8 of a milligram, how many bags of kale would I need to eat to get to .8 of a milligram of folic acid?

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Benelam

It’s quite a big bag there, you’d have to eat four bags in a day to get that dose.

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Porter

And looking at the B12 dose, a dose of half a milligram a day?

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Benelam

So cheddar’s quite a good source for example of B12, you’d have to eat about two kilos of cheddar to get that dose in a day.

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Porter

Two kilos of cheddar?

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Benelam

Yes.

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Porter

What about B6, one of the studies used 20 milligrams a day – how many eggs, for instance, would I have to eat to get that?

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Benelam

So you’ll find B6 in the yolk of eggs and you’d probably have to eat around 300 eggs in a day to get that dose.

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Porter

That’s tricky.

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Benelam

Yeah.

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[Cracking eggs, whisking]

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Smith

What we’ve done in Oxford is a trail called VITACOG where we recruited people with mild cognitive impairment, people living in the community, mild memory problems, they were worried about their memory, you test them and they do actually have poorer memory performance than normal people for their age but otherwise they’re not – don’t have a disease, they’re not patients and we recruited 270 and they volunteered for a trial.Ìý So we gave half of them high dose B vitamins and half of them placebo.Ìý And we followed them for two years and we found a dramatic effect of the B vitamins on the rate of shrinkage of the brain.

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Porter

What effect did it have on their – on their cognitive ability, their testing and their memory, if you like?

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Smith

Well the effect on various cognitive tests was also quite strong, it slowed down the decline of memory almost completely.

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Porter

Why then did a large meta-analysis study from Oxford as well looking at evidence from around the world come to the opposite conclusion and say look we don’t think that using these vitamins has any significant impact on decline?

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Smith

Well this was carried out on normal elderly, not people with mild cognitive impairment, they carefully excluded people with cognitive impairment.Ìý So they were looking at changes in the normal elderly and one wouldn’t actually necessarily expect any effect.

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Porter

You’re convinced that there’s good evidence then to show that we should be using vitamins in people who are showing signs of trouble, in terms of memory, and who have higher than normal levels of homocysteine, probably because they’re deficient or have sub-optimal levels of the B vitamins?

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Smith

Yes.

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Porter

You’re convinced of that?

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Smith

I’m convinced about that.Ìý And I think we should do something about it.

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Porter

As a GP and a pragmatist at the moment everybody I refer to a memory clinic, our local memory clinic insists on this, we routinely do a vitamin B12 and folic acid level.Ìý So if they’ve got normal levels is there any point in testing their homocysteine?

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Smith

Well that’s a very good question, it wouldn’t be if the tests were accurate.Ìý The folate’s okay, the folate’s accurate, but the B12 test as currently used round the world is hopelessly inaccurate and gives a lot of false positive, that’s one thing.Ìý The second problem with this test is that the cut off levels, which are widely used in UK health service, are far too low.Ìý Homocysteine testing is much more sensitive.

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Porter

What’s happening in memory clinics, dementia services, abroad?

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Smith

Well Sweden is a very good example.Ìý In Sweden they screen people in their memory clinics for homocysteine and if the homocysteine is above a certain cut off value they offer them B vitamins.

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Porter

David Smith. We did ask one of the authors of the other Oxford University research that contradicted Professor Smith’s conclusion for an interview but he was unavailable.

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Walton

Vitamin B and whether people should take vitamin B to ward off dementia is definitely a divisive topic at the moment.

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Porter

Dr Clare Walton is Research Manager at the Alzheimer’s Society.

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Walter

The studies that have actually shown some benefits in some people with vitamin B have used very high doses, doses that we probably wouldn’t want to fortify your foods with.Ìý If that’s the only evidence that’s positive there’s not much to suggest we should be fortifying foods.Ìý There’s actually much more controversy around whether taking vitamin B to reduce your homocysteine levels can help prevent dementia.Ìý Based on current evidence it would look like the majority of people probably would not benefit from taking vitamin B in order to prevent dementia.Ìý But the evidence suggests that some people, people perhaps that already have memory problems and have high homocysteine might benefit.

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Wald

Certainly to the extent that trials have been done that have given people B vitamins or placebo they have not demonstrated an improvement in cognitive function over a relatively short timeframe – two to three years.Ìý Now some people have argued that that is clear cut evidence that B vitamins don’t or won’t work in preventing dementia.Ìý Other people have argued that that is not actually the right type of evidence, what we need is a long term randomised trial which specifically looks at dementia as the outcome.Ìý And that trial has not happened.

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Porter

And one of the other problems of course is that dementia itself is quite a vague term, there’s a number of different pathologies that can be going on within the brain to cause a similar set of symptoms, so we might be treating more than one condition.

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Wald

That’s absolutely right, it’s one of the other complexities in the dementia story which contrasts with the cardiovascular story.Ìý Dementia is not just one disorder.

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Porter

But where are we in the world of cardiovascular medicine because this has been a debate that’s been raging for longer in that field, do we have conclusive proof now in your mind that homocysteine is an important factor in heart disease and stroke?

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Wald

I think we do and I think that proof came relatively recently.Ìý More than 20 years ago there were studies which showed the association that we’ve discussed and then there came about a decade in which trials were done to see whether if you gave B vitamins, in particular folic acid, you could reduce the risk of heart disease and stroke.Ìý And rather surprisingly those trials turned out to be negative…

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Porter

They didn’t work.

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Wald

It didn’t appear to work.Ìý And that was surprising, particularly as there was a whole other chunk of evidence out there and this evidence was very compelling, based on the fact that in the population about 10% of us, 1 in 10 us, have genetic variations which pushes up our homocysteine levels.Ìý That provides an opportunity for what you might think of as a natural randomised trial, nature has effectively randomly allocated this mutation to some people and not to others and those people would not be expected to differ in any other ways.Ìý And it was very clear that people who had this mutation had a higher risk of heart disease and stroke.Ìý

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Now it’s hard to argue that away and when you get a set of randomised trials, as we did, that were negative the sensible thing to do is to try and reconcile these two types of evidence.Ìý But what actually happened is these trials divided the scientific community – there was a group of scientists who said B vitamins are useless, no point giving them, and there was another group of scientists were saying hang on a minute these trials are certainly negative but you simply can’t ignore this rather inconvenient evidence from the genetic studies.Ìý

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Now just a few months ago a very large Chinese trial was published and this was a 20,000 person trial and actually it showed a 20% reduction in the risk of stroke among people who were randomised to B vitamins and importantly to folic acid.Ìý And the key difference between that trial and all of the others is that none of them were taking aspirin.Ìý Why is aspirin involved?Ìý Well it’s quite possible that aspirin, which stops the blood sticking when you’re at risk of having a heart attack, it’s quite possible that that actually masked the effect of folic acid because as I mentioned earlier homocysteine might operate by making the blood stickier and if you’re already on aspirin there’s nothing more for folic acid to do.

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Porter

So there was an effect but it was being masked in the previous trials by aspirin?

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Wald

That was the theory and it looks like that that is the case.

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Porter

Professor David Wald. And if you’d like to know more about the various studies we’ve discussed you will find some useful links on our webpage. Just type inside health and homocysteine into your search engine.

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Now time for another in our series that sets out to demystify the terminology we use when discussing research. This week Carl Heneghan, Professor of Evidence Based Medicine at the University of Oxford, and our very own Dr Margaret McCartney are discussing risk. Specifically the difference between absolute and relative risk. So for example, let’s imagine a newspaper article that reports on new research showing that drinking wine can double a woman’s chances of developing breast cancer. How should a reader interpret that?

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McCartney

Okay so it would be my silent scream moment, it drives me absolutely up the twist because to make sense of any number like that you have to know what was my chance to start off with and what is my chance going to increase to.Ìý So I’m always most interested in absolute risk, that’s the one that’s key and I think people should always be looking out for.Ìý So say for example you say that a glass of wine could double my risk, well that would put it up to 10 in a hundred, which means it goes from 5% to 10%, now that is a doubling of risk but it’s also quite a small overall increase in risk.Ìý So the problem is that for relative risk you can tell someone it’s doubled or tripled or quadrupled but that still can be quite a small number, so you have to know what the absolute risk is, what’s the percentage risk, what’s the number in terms of out of a hundred or out of a thousand, what’s that number, that will give you absolute risk and from there you can work out where the relative risk came from.

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Heneghan

A very good example of this was there was about 20 years ago there was a scare around the contraceptive pill and deep vein thrombosis and the headline was:Ìý Contraceptive Pill Doubles Your Risk.Ìý Now what happened is people just suddenly said well I’m going to stop taking that pill but the key question you’ve got to ask is what is my baseline risk.Ìý And it turns out that if you take a female of child bearing age their baseline risk is about 15 per 100,000 risk of having a deep vein thrombosis, if you double that it goes to 30 per 100,000.Ìý So the absolute increase is very small.Ìý It turns out that you stop taking the pill as a female and get pregnant your risks goes up four fold, so it goes up to about 80 per 100,000.Ìý So actually the key question is always, always, when somebody says something that is a relative measure you go what is your absolute risk.

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Porter

Margaret this is the old adage, isn’t it, that twice not very much is still not very much.

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McCartney

Is still not very much, yeah, and this kind of thing just drives me mad, you see it in the press all the time, something or other has doubled its risk.Ìý And I’m sick to death of going back to the research paper that doesn’t actually say what the risk was to start with, it just says what the risk doubled to.Ìý And very often that’s all that comes out in a press release, very often that’s all that comes out in the media reports, so it’s really hard for a reader to work out actually what does this mean for me as an individual.

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Heneghan

So Margaret’s really right, there are only two calculations that you need to know in healthcare.Ìý One is a divide and one is a take away.Ìý And the divide is a relative measure, a relative risk, and the take away is an absolute measure – absolute risk.

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Porter

Practically may I ask you both to give me one tip for somebody who’s reading their next article tomorrow in a newspaper that says that they’re going to be at increased risk of doing something, what question should they ask?Ìý One question from you Margaret.

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McCartney

What was my risk to start off with and how much will this risk put it up by.

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Porter

Carl?

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Heneghan

Yeah well I would have said that what Margaret does, I would also say – and we have a lot of fun about this – is go and find out where did that risk come from, what was it based on and it could be something completely arbitrary like an animal study, so ask what type of study this is.

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McCartney

And I would say to people pretend you’re going to the bookies, what are my chances of my horse winning if I do this particular thing or don’t do this particular thing…

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Porter

None in my experience.

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McCartney

What’s the number, what’s the chances – is it one in seven, is it one in eight, is it in one in 500, is it one in four million?Ìý Get the numbers that you need to make sense of the statistics that are being presented to you.

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Porter

Margaret McCartney and Carl Heneghan who will back with more pearls of wisdom later in the series.

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Just time to tell you about next week when we will be examining the weight loss properties of low carb diets and how to make childhood jabs a less painful experience – for all concerned.Ìý