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INSIDE HEALTH

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Programme 8. - Off-patent Drugs Bill, Pre-diabetes, Sepsis, All-cause mortality

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TX:听 28.07.15听 2100-2130

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PRESENTER:听 MARK PORTER

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PRODUCER:听 ERIKA WRIGHT

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Porter

Coming up today:听 Pre-diabetes 鈥� a new label that could be applied to as many as one in three British adults. But how valid is it?

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Clip

One of the problems with pre-diabetes is that there are three doors in, there aren鈥檛 actually any doors out, there is no official way I鈥檝e discovered of being undiagnosed with pre-diabetes.听 Now if all three measures correlated 100% there would be no problem but in fact they overlap very weakly.

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Porter

And sepsis 鈥� one campaigning charity believes over 12,000 lives could be saved every year in the UK through earlier diagnosis and better management of a condition which can rapidly lead to shock, multiple organ failure and death.

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Clip

It was the junior anaesthetist that was walking past to start his shift 鈥� everything鈥檚 a bit hazy for me at this point but my mum said he even still had his rucksack on 鈥� and was asked for his opinion.听 It was that man that turned out later to save my life.

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Porter

More on Anna鈥檚 story later. But first a new bill 鈥� The Off-Patent Drugs Bill 鈥� recently re-introduced to Parliament amid concerns that people are missing out on life saving treatments because the NHS is not using some drugs outside their licensed indications. Doctors can prescribe off licence, but are often wary of the repercussions.

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Dr Margaret McCartney is in our Glasgow studio. Margaret, what sort of treatments are we talking about?

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McCartney

Well one that listeners may well have heard about relates to a study published a few days ago, it was a very interesting study, a big analysis looking at a very cheap commonly used, an old class of drugs which up till now have been used in women who have got thin bones or osteoporosis to try and strengthen them and this study said here鈥檚 a new use, if we use this in women with certain types of early breast cancer it can help to prevent spread later on into the bones.

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Porter

So effectively this is calling upon doctors to use a treatment that鈥檚 got one licence indication for another indication, what鈥檚 the problem there?

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McCartney

That鈥檚 right, the bottom line is that this is a different use of a commonly used and cheap generic drug, so the medicines and healthcare regulatory authority have not put a rubber stamp on this drug to say this has a licence for use in this particular situation in women who鈥檝e had breast cancer.

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Porter

And does that rubber stamp matter, I mean if this paper鈥檚 been published in The Lancet, in this case, why can鈥檛 I start using this drug in patients of mine with breast cancer?

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McCartney

Well that鈥檚 a really good question and I don鈥檛 think there is a reason for you not to start on it if you felt it was appropriate for your patient in her circumstances.听 So the issue is now whether NICE will endorse this and tell doctors widely to start using it but if they do this will be a drug which is not licensed for that specific use.

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Porter

But if NICE doesn鈥檛 recommend unlicensed drugs do they get used?

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McCartney

Well should they get used, I suppose is the bigger issue, so licensing is a kind of safety net, it鈥檚 to try and stop doctors prescribing drugs wildly where they shouldn鈥檛 be used, where there鈥檚 no evidence of use and where it actually may do net harm to patients.听 But the problem is that getting a licence for a drug company costs a lot of money, they have to submit trials which are usually big and expensive to do to the medicines and healthcare regulatory authority to then get a licence.听 So in general pharmaceutical companies will want to be making a return on that, they don鈥檛 want to lose all the money on it and when you鈥檝e got these very cheap off-patent old drugs there鈥檚 no incentive for any pharmaceutical company to go and do lots of big trials because they鈥檝e already been done in order to try and make money out of this because it鈥檚 a generic drug, these drugs cost pennies.

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Porter

Well let鈥檚 go back to your example of this bone drug being used in women with breast cancer.听 One of the charities estimate that something like 34-35,000 women every year are missing out on this treatment because it鈥檚 not licensed and therefore doctors are reticent to use it.听 How is the Off-Patent Drugs Bill going to help, assuming NICE does not issue guidance, how is this new bill going to help them?

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McCartney

Well in essence it has many good points to it and the bottom line is that it intends to put into UK law a duty on the government to step in where there鈥檚 no incentive for a pharmaceutical company to obtain a licence for an old product.听 So it鈥檚 asking the government to act in the public interest and obtain a licence so that an off-patent treatment could become licensed for a new use.听 And this would be done via NICE driving NICE to do a technology appraisal, which you would them to assess the evidence and make a judgement as to whether or not a drug could have a particular licence.

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Porter

Playing devil鈥檚 advocate here, could the drug company themselves not look at this new indication and think ooh if we apply for a licence we can patent that and make more money?

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McCartney

Well again this is something that I think I would be a bit concerned about, always unintended consequences do happen.听 I think it鈥檚 fair to say that the law around intellectual property rights is complex and I鈥檓 clearly not an expert in it.听 But I am told that this has been looked at fairly thoroughly and that there are revisions to the bill which is going to be presented to parliament later this year.听 We haven鈥檛 seen the full text of it yet and I鈥檓 sure that the lawyers will be all over it trying to work out any pros and cons that may result, particularly unintended consequences.

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Porter

Thank-you Margaret and, as usual, you will find some useful links on Margaret鈥檚 blog 鈥� details are on the Inside Health website.

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Now a new variant of diabetes 鈥� well, sort of. Pre-diabetes is already well established in America and now the label has arrived here and could be applied to as many as 11 million adults across the UK.

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Using one of three measures 鈥� a person鈥檚 fasting blood glucose level; how they react to drinking a sugary drink; or an HBA1c test that gives an idea of glucose levels over weeks 鈥� it is possible to identify people with borderline normal readings. And it鈥檚 this grey area between diabetes and normal that is being called pre-diabetes, with research suggesting that as many as 1 in 10 people so labelled will go on to develop full blown Type 2 within a year.

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But the new label remains controversial, not least because opinion differs as to what is normal and what鈥檚 not, and how you test for it. Edwin Gale is Emeritus Professor of Diabetic Medicine at the University of Bristol.

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Gale

To explain the story of pre-diabetes I should first of all say that everyone鈥檚 blood glucose tends to rise as you get older.听 Now there are three ways of defining a blood glucose.听 So one of the problems with pre-diabetes is that there are three doors in, there aren鈥檛 actually any doors out, there is no official way I鈥檝e discovered of being undiagnosed with pre-diabetes.听 Now if all three measures correlated 100% there would be no problem but in fact they overlap very weakly.听 For example, fasting blood glucose overlaps by only about 30% with the definition of diabetes in terms of a glucose tolerance test.听 So the result of having this very wide net is that you鈥檙e catching an awful lot of fish and you鈥檙e not necessarily catching the people you want to catch.

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Porter

So it鈥檚 quite possible to get two different results, you could be told you have pre-diabetes on one and be told you鈥檙e perfectly alright on another?

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Gale

Absolutely, in fact quite a few people who terms in HPA1c have pre-diabetes don鈥檛 on strict glucose criteria, so you鈥檙e going into a semantic circle as to what exactly you鈥檝e got.

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Porter

We鈥檙e picking a lot of people up with pre- so-called pre-diabetes.

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Gale

Well of course you are, I can speak to that personally because I鈥檓 70 so I guess I class as elderly and I also have pre-diabetes in terms of a mildly elevated blood glucose.听 But so do most people over the age of 80, in fact over the age of 80 74% of women and 55% of men have diabetes or pre-diabetes, so it鈥檚 a normal ageing phenomenon.听 And we鈥檙e left with a question of what鈥檚 disease, what is normal ageing process.听 If you put that label upon someone what evidence have you got that you can actually help them?

Porter

Well that鈥檚 my next question.听 So if somebody鈥檚 coming in who is 78 and otherwise fit and well and is found to have sugar levels in this borderline range and have pre-diabetes I can see the diagnosis might not be 鈥� putting a label on might not be that useful.听 But if they鈥檙e 40 and they鈥檙e six stone overweight, they鈥檙e a smoker and they鈥檝e got lots of other risk factors it might just be useful in terms of galvanising some action, both on behalf of the doctor and the patient.

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Gale

Well here you come absolutely to the nub of the issue.听 Telling someone they鈥檝e got a blood glucose that鈥檚 high at the age of 30 is actually something that makes a huge difference to their life and which they can do a lot about.听 But there鈥檚 in fact no evidence at all that in the elderly person, as against the young person, that that intervention will be helpful.

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Porter

So pre-diabetes may not be useful at the age of 90, at one end of the spectrum, it probably is very useful in your mid-20s, it鈥檚 the grey area in between which is actually where a lot of these people are being picked up, so it鈥檚 middle age and older.

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Gale

I think my grouse there is that we have a diagnosis and a guideline based on a one size fits all number, it鈥檚 ludicrous to give a single number to every member of the population.听 And I think that鈥檚 the entire problem.

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Porter

Well listening to that in the studio with me is Simon 翱鈥橬别颈濒濒 who鈥檚 director of health intelligence at Diabetes UK and Dr Margaret McCartney is in our Glasgow studio.听

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First of all Simon, what do you think of the term pre-diabetes?

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翱鈥橬别颈濒濒

Diabetes UK doesn鈥檛 really like it and when we鈥檝e spoken to people who are at risk of diabetes the problem is they seem to think that means they鈥檙e diagnosed with diabetes, they鈥檙e just diagnosed a bit earlier and it鈥檚 sort of inevitable that they鈥檒l go on to develop diabetes.听 And of course that鈥檚 not the case, only 5-10% of people who would fall into a pre-diabetic range will actually develop Type 2 diabetes in the following year.听 We wonder that therefore that actually makes them think because it鈥檚 inevitable I might as well just not do anything and let it happen.听 However, I think there is a really important thing that people in this early stage where their blood glucoses aren鈥檛 quite working properly 鈥� if they鈥檙e overweight, if they鈥檙e not very active 鈥� they can do something to actually reduce that risk.听 Therefore we prefer the term to be at high risk of Type 2 diabetes.

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Porter

Margaret, do you use the term pre-diabetes in your consulting room?

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McCartney

No I don鈥檛 and I have to say I鈥檓 very suspicious of the medical industry鈥檚 desire to start categorising more people with having pre- something.听 We鈥檝e seen it with pre-dementia, we鈥檝e seen it with pre-hypertension and this, I think, is yet another instance of criteria being brought down, more people being caught in the net and the question is how many of those people will benefit from an earlier diagnosis of something that may never happen to them.

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Porter

Simon, let鈥檚 pick up on Prof Gale鈥檚 concerns.听 Firstly the cut offs 鈥� are you confident that we鈥檝e got the cut offs in the right place?听 Looking on the Diabetes UK website I mean they talk about a fasting plasma glucose 5.5 -7 means that you鈥檝e got pre-diabetes.

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翱鈥橬别颈濒濒

Yeah I mean I think this is a really good question Mark.听 There are lots of different people saying different things and that鈥檚 where the confusion lies.听 So we talk in the UK about an HPA1c, that long term blood glucose, being over 6, in the States they talk about being over 5.7.听 If you look at the population of the UK at 5.7 that鈥檚 puts eleven and a half million people at high risk.

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Porter

As do those criteria that I mentioned for the fasting.听 So one in three adults鈥�

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翱鈥橬别颈濒濒

Whereas if you move it to 6, which doesn鈥檛 seem a big move, that drops it down to four and a half million people.听 And I think it鈥檚 really 鈥� actually working out who is going to best benefit from being told they鈥檙e at high risk of diabetes and who is actually going to best be able to do something to prevent that happening and prevent the long term complications.

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Porter

So what鈥檚 being done about that because I know that you鈥檙e involved in the Type 2 prevention programme, a national programme?

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翱鈥橬别颈濒濒

We will be defining at criteria that works in terms of meeting the highest risk patients who are most likely to benefit.听 So it will be a slightly different cut off point I鈥檓 sure than ones we鈥檝e had before but hopefully it will refine that into the most high risk.听 That doesn鈥檛 mean that those who are the sort of lower level, especially if they鈥檙e overweight, shouldn鈥檛 be being encouraged to become more active and lose weight.

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Porter

Margaret, let鈥檚 pick up on Prof Gale鈥檚 other concern and that was that there鈥檚 no age adjustment.听 Given that this to some extent is a natural process, as we get older all of our sugar levels creep up a little bit, it鈥檚 surprising that the diagnostic criteria don鈥檛 reflect age as one of the criteria for interpreting it?

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McCartney

Well I think that GPs will often use discretion but the problem is that we鈥檙e judged by guidelines, we鈥檙e judged by QOF points in terms of what we鈥檙e meant to do, it鈥檚 meant to be a one size fits all to a certain extent.听 And I think we need much more leeway in order to have a bit of flexibility about how we interpret the data really when it comes to asymptomatic older people especially if those older people are frail.听 I think the medical industrial complex is really all for diagnosing things earlier, faster but we very rarely I think consider the harms that we do when we do that at the same time.听 And for older people I don鈥檛 think we accept what normal is enough.

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翱鈥橬别颈濒濒

I think we have to be very careful about how we interpret this and not over-medicalise, exactly as Margaret says.听

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Porter

It may be normal for them.

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翱鈥橬别颈濒濒

Exactly.

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McCartney

Absolutely.听 I mean you鈥檙e trying to pick up people who don鈥檛 have any symptoms from diabetes, so people who are otherwise well.听 What you鈥檙e really trying to do is prevent complications that will happen over decades if a diabetic state is left untreated.听 And if you鈥檙e already 75 or 80 it might take a couple of decades to start developing complications so the benefits that you might get from treatment are pretty low.

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Porter

Okay, so the last of Professor Gale鈥檚 concerns and that鈥檚 the three different tests that we鈥檙e using, I mean I have to write them down every time because I forget the figures, I鈥檓 sure you鈥檝e committed them to memory, but it is confusing, are we going to go with the one test?

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翱鈥橬别颈濒濒

Personally I think the HBA1c test is probably where most people are going but it is confusing and I鈥檇 hate to be a GP out there trying to decide what鈥檚 the best thing to do.

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Porter

Simon 翱鈥橬别颈濒濒 from Diabetes UK.听 And, if you are one of those GPs or nurses, then the type of test - and the thresholds that are going to be used for the national Type 2 diabetes prevention programme, that Simon mentioned there - should be announced over the next month or so.

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Now what do you think might be wrong with Anna because her doctors didn鈥檛 know?

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Anna

It started on the Monday morning, I just had general sore throat, coldy type symptoms and that evening sort of loss of appetite.听 The Tuesday I had extremely high temperature.听 On the Wednesday I spoke to an out-of-hours doctor who prescribed me anti-sickness tablets over the phone because I had quite bad sickness and diarrhoea. I found myself wandering round the house aimlessly at night.听 By the Friday, so this is five days later now of having these symptoms, I鈥檇 spoken to two triage nurses and a GP, came out in a rash all over my body, more of a mottled skin rash and at this point I started to struggle to breathe.

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Porter

Anna had developed sepsis 鈥� a condition that claims as many as 40,000 lives every year in the UK. It鈥檚 typically triggered by infections like pneumonia but in many cases the underlying cause is never identified. But whatever the trigger, time is of the essence 鈥� people with sepsis can rapidly progress from feeling unwell to developing shock and multiple organ failure within hours. Dr Ron Daniels is a Consultant in Critical Care and Anaesthesia and Chief Executive of the UK Sepsis Trust.

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Daniels

In sepsis it鈥檚 the response of the body to an infection.听 Most commonly chest infections, water infections and problems in the abdomen like a burst ulcer or a gallbladder infection.听 But a cut or a scratch or a bite can also quite easily lead to sepsis.

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Porter

Now those sorts of infections, I鈥檓 thinking of chest infections particularly, are very common and most people who get a chest infection will not get sepsis.

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Daniels

So it鈥檚 not the infection that causes the damage and ultimately the organ failure, it鈥檚 the way the body responds.听 So it鈥檚 the immune system kicking in.听 Now we鈥檒l all be familiar with some of the common signs of infection like having a fever but when that becomes more marked we start to see some unusual symptoms creeping in.听 So people might have what we call rigors, where they鈥檙e shivering uncontrollably and if these go on for a very long time that can be a hallmark of something more significant.听 They might notice that their breathing becomes laboured and fast and of course with a chest infection we might notice that but if it becomes more marked then it might be a hallmark that something else is going on.听 People can develop changes in their skin colour, they can develop a mottled skin or a marbled skin or they might start to feel very faint or indeed collapse.听 And these are all signs that the circulation is beginning to fail and that the situation鈥檚 becoming very much more critical.听 But a far more common sign that鈥檚 reported to us is something that鈥檚 really quite soft, that either patient reports I have never felt this unwell or their relative says to us, that I鈥檝e never seen this person behave like this.听

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Porter

But the immune response is generally regarded as a good thing, it鈥檚 what protects us, it鈥檚 what keeps us alive, it鈥檚 what stops the bacterium getting a foothold in us.听 So what鈥檚 going wrong in sepsis if the immune response is part of the problem?

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Daniels

Thinking about the immune response, if we can consider what happens when we cut ourselves 鈥� it becomes swollen and red and inflamed, the area around 鈥� and that鈥檚 because the body鈥檚 trying to deliver more blood to the area and it does that by opening the blood vessels up, hence the redness.听 But the good stuff that鈥檚 going to fight the infection and help to cause a blood clot to stop any bleeding is then going to be stuck inside the blood vessels, so the blood vessels become leaky in order to allow the good stuff to leak out into the fatty tissues and into the skin to fight the bugs and to help to cause the clot.听

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Porter

Which is a great thing if it鈥檚 happening locally in your finger.

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Daniels

Absolutely and that鈥檚 an adaptive response.听 But of course in sepsis this becomes overwhelming, this becomes uncontrolled, and it happens throughout the body.听 So all of the blood vessels open up and all of the blood vessels leak which starts to cause a drop in blood pressure which then starts to cause a compromise in the blood supply to organs and that鈥檚 why we see organs starting to fail in sepsis.

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Anna

I was then put in an ambulance and they said don鈥檛 worry you鈥檒l be fine, when you get to hospital they鈥檒l sort it out because they were so stumped by my symptoms, they had no idea what was wrong with me.听 It was then a junior anaesthetist that was walking past to start his shift and was asked for his opinion and it was that man that turned out later to save my life, who had treated someone the week before and knew all of the symptoms and said this young girl is extremely poorly she needs to be transferred to intensive care.听 And then he went on for the next 12 hours to look after me in that unit.

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Singer

I鈥檓 Mervyn Singer, I鈥檓 Professor of Intensive Care Medicine at University College, London.

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Porter

How good are we at managing serious cases of sepsis now?

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Singer

Well at the moment it鈥檚 very much literally as the name on the door says 鈥渋ntensive care鈥�, so we鈥檙e propping up the patient in the hope that they can get through this acute illness and recover thereafter.听 So it鈥檚 very much supportive care.听 The strategy is two-fold.听 One is obviously to recognise and jump on them quickly because clearly the earlier you can identify them the quicker you can institute what you hope will be the right therapy 鈥� antibiotics, surgery, whatever鈥檚 needed to correct the problem.听 But very much it鈥檚 propping up the organs, we don鈥檛 at the moment have the wonder drugs, the therapies, that can actually reverse the process or speed up recovery.

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Porter

If you had a hundred patients with sepsis come in what proportion would you expect to survive?

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Singer

For every hundred patients about 20-30 will die in the intensive care unit, a further 10 or so will not actually leave hospital and another 10-20 even may die in the next year.听 We鈥檝e had one patient who was with us a year and a half, he got married on the unit, he was so debilitated by the organ failure that followed on from the sepsis that it took a year and a half before he could get home and he was man in his forties.

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Anna

They still don鈥檛 know what I caught sepsis from, there鈥檚 still a big question mark over how I got it.听 I left the hospital with one word and that was sepsis.

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Sweeney

So sepsis is the presence of whole body inflammation in response to an infection and infections are not the only things that can do that.

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Porter

Tim Sweeney is a postdoctoral research fellow in immunity, transplant and infection at the Stanford School of Medicine in America and working on a new genetic test to differentiate sepsis triggered by infection from similar reactions that mimic it.

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Sweeney

What we see all the time is people after a major injury like a car crash or gunshot wound or after major surgery or a burn can also have this massive inflammatory response.听 And the two look the same, there鈥檚 no easy way to tell inflammation due to an infection from inflammation not due to an infection.听 And so it鈥檚 often thought that the safest thing in some cases is just to give antibiotics, which is to say to just treat as though there were an infection present.听 The problem with this is that if you give antibiotics to somebody who doesn鈥檛 need them that person can experience complications from the antibiotics themselves, it opens the door to opportunistic infections such as CDiff, it also increases the rates of antibiotic resistance.听 We don鈥檛 want to just go around treating everybody with antibiotics, we want to be judicious.

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Porter

But equally it鈥檚 vital that you give those who need the antibiotics prompt treatment, so you鈥檝e got to differentiate them quickly.

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Sweeney

Absolutely, so that鈥檚 the other thing, right, is that a lot of studies now have shown that a delay of even one hour of administering antibiotics to somebody who does in fact have sepsis can increase the mortality rate.

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Porter

In a hospital like yours what sort of proportion of people who appear to have sepsis might actually have this sterile response, where there鈥檚 no bacteria, they don鈥檛 need antibiotics?

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Sweeney

Well the hard thing is that we don鈥檛 have a good way to tell because typically the way we diagnose an infection is we draw some blood and we send that off to the lab to be cultured to see if any bacteria or fungi grew out of it.听 And we can do things like take a chest x-ray to look for pneumonia or take some urine culture to look for a urine infection.听 But there is no definitive test that says early on this patient does or does not have an infection.听 And so those sorts of numbers are sort of hard to come by because there鈥檚 always an argument about well how do we know for sure.

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Singer

Currently for example to grow a bug you have to take the blood, put it in a culture medium bottle, send it to the microbiology lab and if you鈥檙e lucky you may get a result 30% of the time after 24 hours, if not longer.听 Only about 30% of very sick patients can we actually find the bug in the blood.听 How many bugs do you think per mil of blood?

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Porter

A lot.

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Singer

Have a guess, how many?

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Porter

I have no idea.

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Singer

You鈥檝e got anything up to one to 10 per mil of blood.

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Porter

Which is a tiny number.

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Singer

The actual bacteremia per se isn鈥檛 the major problem.

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Porter

So terms that I would have been brought up with at medical school, I mean I鈥檓 going back to the eighties, so septicaemia, blood poisoning鈥�

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Singer

They鈥檙e a bit pass茅 I鈥檓 afraid, sorry.听 I think鈥�

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Porter

I鈥檓 getting to that age now.

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Singer

Yeah I know.听 Because of these newer insights we鈥檙e recognising that many of our long held precepts are actually wrong.

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Sweeney

Well one of the things that I set out to answer was can we establish a blood test that we can draw that can right away tell us does this person have an infection or not.听

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Porter

And what did you find?

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Sweeney

So we found that there are in fact a large number of genes whose expression levels are significantly different between patients who have sepsis and patients who have inflammation that is not due to an infection.听 And we used a way to select a sub-set of just 11 genes.

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Porter

You make it sound simple but it sounds like a very complicated test, is it something that would translate easily into, what I imagine, is going to have to be a bedside test used by doctors and nurses and read pretty quickly to be useful?

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Sweeney

The translation won鈥檛 be easy, although we can distinguish between persons with infection in large data sets, it took us several months to do it and physicians are going to need results in absolutely under an hour.听 And so one of the things that we鈥檙e working with some partners on is developing some technologies that can assay gene expression in the blood in a very fast manner.听 Somebody else may come along with a better set, what we鈥檝e shown is that there is diagnostic power in the gene expression space.听 I think it鈥檚 likely that a decade from now the way that we diagnose infections will be different than the way that we do it today.

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Porter

Tim Sweeney.听 In the meantime awareness and vigilance remain our best defence against sepsis - whatever the trigger.听 And there are some useful links on our website for healthcare professionals and the general public, just type sepsis and Inside Health into your search engine and it should take you there.

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Now to our final instalment in our series on statistical terms with Carl Heneghan -听 Professor of Evidence Based Medicine at the University of Oxford - and Inside Health鈥檚 own Dr Margaret McCartney. This week it鈥檚 mortality and while death may be the great leveller, not all deaths are equal.

听

McCartney

Ah so this is the difference between all-cause mortality, which means death no matter what the cause of it was, and disease specific mortality.听 And we get this a lot in press reports and in the media.听 And it鈥檚 the difference between dying at all 鈥� that鈥檚 your all-cause mortality 鈥� and dying of a particularly type of disease 鈥� like heart disease or cancer.听 And for me this is all about the frying pan and the fire, you can avoid dying from one thing but you鈥檒l die from something else anyway.听 And that鈥檚 why it鈥檚 really important, especially in screening programmes, we鈥檝e talked about this before, how important it is to make sure you鈥檙e looking at all-cause mortality, death no matter what.听 And that鈥檚 because some treatments are harmful.

听

Porter

So what we鈥檙e saying, let鈥檚 use breast cancer screening as an example, that breast cancer screening may reduce your chances of dying from breast cancer but it鈥檚 possible it could increase your chances of dying from something else.

听

McCartney

Yeah, so to use an analogy.听 Imagine for example you鈥檝e got an intervention that can stop people dying from shark bites, so that鈥檚 great, it鈥檚 a special big boat that you send out into the ocean.听 But the problem is that boat will sink within 30 minutes of getting on to it.听 So you can reduce your shark or your disease specific mortality with one intervention but the problem is that the intervention you use to try and treat that it will cause you to drown anyway.听 So you have to be really careful when you鈥檙e doing any screening programme that involves an intervention that your intervention isn鈥檛 worse than the disease that you鈥檙e trying to prevent in the first place.

听

Porter

So Carl when I鈥檓 looking at the results of a study published 鈥� in the lay media, I鈥檓 talking about now, is all-cause mortality something I should be asking for?

听

Heneghan

Yeah certainly and I think you should just ignore the disease specific mortality.听 It鈥檚 a sort of ruse to try and capture your attention.

听

Porter

So stats introduced by chance of dying of a heart attack or stroke and do they stop my chances of dying or delay my chances of dying?

听

Heneghan

Correct and that鈥檚 really important, particularly in cancer treatments because some of the cancer treatments can be toxic in a word.听 They work by making toxic cells and killing cells, the key is they may kill you at the same time.听 So you may have a certain treatment that improves the cancer specific mortality but has no effect on all-cause mortality.听 And at the end of the day all deaths are the same, it鈥檚 an objective measure, but what you want to do is improve the all-cause mortality.

听

Porter

So look for all-cause mortality.听 It鈥檚 not always mentioned though is it?

听

McCartney

It鈥檚 not always mentioned and not all studies鈥�

听

Porter

鈥� and there鈥檚 a reason for that.

听

McCartney

And there is a reason for that.听 I mean I think of people 鈥� the classic one is bowel cancer screening, so there鈥檚 lots of studies that have been done that says that bowel cancer screening reduces your risk of dying from bowel cancer but there are also really good studies that say it also does not reduce your all-cause mortality.听 So people will die at the same rate at the end of the day鈥�

听

Porter

But of something else.

听

McCartney

鈥�just not as often from bowel cancer.听 So you have to be really careful 鈥� is your screening programme overall giving you a benefit or is it not giving you a benefit.

听

Porter

And that鈥檚 the key, the difference between mortality and all-cause mortality is all-cause mortality 鈥� if that鈥檚 reduced you鈥檙e getting overall benefit.

听

McCartney

That鈥檚 right.

听

Porter

And that鈥檚 what we鈥檙e after.

听

McCartney

That鈥檚 right, that鈥檚 the key.

听

Porter

Margaret McCartney and Carl Heneghan.

听

This is the last in the current series of Inside Health but we are already working on the next run. So if there is an issue you think we should be investigating please do get in touch.听 You can e-mail insidehealth@bbc.co.uk or tweet me @drmarkporter.

听

We are not off air for long and will be back at the beginning of September. So, until then, goodbye.

听

ENDS