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INSIDE HEALTH 鈥� Obesity and smoking, Blood pressure, ADHD

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Programme 1.

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TX:听 13.09.16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 Blood pressure - lower is better according to a landmark trial we reported earlier this year. But controversy still rages over the findings of the SPRINT study which advocates a lower target when treating high blood pressure. So we have invited the lead author back.

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And ADHD - if you believe the hype doctors, teachers and even parents are being too quick to label difficult children as having ADHD. But if that鈥檚 the case why has the meteoric rise in prescriptions for drugs like Ritalin plateaued in recent years?

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But first, public enemy number one. But is that obesity or is it smoking? A clinical commissioning group in the North of England put the cat among the pigeons recently when it proposed delaying non-essential procedures for smokers and obese patients unless they gave up or lost weight. And it鈥檚 not the first time that obesity and smoking have been lumped together. Indeed it is now more than two years since the Chief Executive of the NHS, Simon Stevens, coined the phrase 鈥渙besity is the new smoking鈥�. But is the comparison helpful - for the individual or the nation鈥檚 health?

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I am joined by Dr Margaret McCartney in our Glasgow studio and in Merseyside by Simon Capewell, who鈥檚 Professor at Clinical Epidemiology at the University of Liverpool.

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So, is obesity the new smoking?

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Capewell

Yes, in many ways.听 In the 1980s we understood where damage was coming from in terms of smoking but tobacco control was just a theory.听 Since then we鈥檝e got on top of smoking, tobacco control is well established with work on pricing and marketing and so on.听 It鈥檚 the same with obesity right now 鈥� we know most of the calories are coming from junk food and sugary drinks, we know it鈥檚 loading up the children and adults.听 A third of children in this country are overweight or obese, two-thirds of adults overweight or obese.听 Physical activity is a bit of a minor distraction really.听 So we understand where the calories are coming from, we understand that they鈥檙e being produced by the multinational corporations.听 We have these big levers that worked for tobacco control 鈥� the affordability, the acceptability, the availability 鈥� the three As 鈥� and we鈥檙e just beginning to talk about using them.

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Porter

Margaret, what do you think the similarities are?

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McCartney

To me the biggest thing that they have in common is depravation.听 So if you are living in an area of social depravation, if you are someone who鈥檚 living in a more deprived environment, you鈥檙e much more likely to be obese and you鈥檙e also much more likely to have smoked in the past and now.听 And the other thing that I think is the more worrying parallel is that of social unacceptability, so I think smoking now is pretty much socially unacceptable in company, certainly if you鈥檙e eating it鈥檚 illegal in pubs, bars, public spaces but also in play parks and in cars, as well, it鈥檚 socially unacceptable I think in cars.听 But in terms of obesity I think there鈥檚 a really big issue there.听 I think it鈥檚 become socially unacceptable to be obese or to be overweight, I think that fat shaming 鈥� shaming people, making people feel embarrassed because of their weight 鈥� has become kind of socially acceptable in some areas and I think that鈥檚 a really big problem that does not help individuals.

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Capewell

Just to reinforce Margaret鈥檚 point.听 Yes there鈥檚 a lot of issues here about depravation and yes there is confusion about the victim and the activity.听 So rather than say obesity is the new smoking, it might be more intelligent to say calories are the new tobacco.听 We鈥檝e got on top of tobacco, can we get on top of calories?听 The plentiful supply of cheap ubiquitous junk food and sugary drinks.听 And the short answer is yes.听 So tobacco in the Second World War, four out of five men were smoking, and now it鈥檚 less than one in five.听 And that鈥檚 not personal choice, that鈥檚 not education, that鈥檚 a whole bundle of interventions pulled together into a strategy 鈥� hitting the price, the affordability, hitting where it鈥檚 provided the availability and as Margaret says, hitting the acceptability very hard, particularly around marketing, it鈥檚 no longer legal to market tobacco in this country and that鈥檚 the way it should be, we鈥檙e protecting our kids from tobacco, it鈥檚 about time we protected our kids from junk food and sugary drinks.听 So I agree absolutely with Margaret, we鈥檝e got to avoid the stigmatisation, it simply isn鈥檛 fair to point at a smoker and say 鈥� it鈥檚 your fault you鈥檙e addicted, you鈥檝e chosen this.听 Or point at an overweight person and say 鈥� you鈥檙e a gluten 鈥� it鈥檚 not fair.听 It - really in today鈥檚 society the miracle is that anyone is thin.听 Our children, from the moment they wake up, are swimming through a sea of calories.听 Turn on their smartphones or their iPads, turn on the TV, walk down the street with the billboards, go into any shop 鈥� even a chemist is selling chocolate 鈥� now what is that all about?

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Porter

Margaret, what about the balance here between personal responsibility and public health, how do you see that sitting in something like smoking and obesity?

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McCartney

Yeah, I mean I think personal choice is very important but the problem is we don鈥檛 all have free choice, that鈥檚 the issue, and if we did all have free choice you would expect the distribution of smoking and obesity to be the same right through the social gradients.听 You would expect people who were well off to be smoking or obese at the same rate as people who weren鈥檛 and that absolutely isn鈥檛 what you see, there鈥檚 a very clear social gradient.听 And that鈥檚 what worries me most.

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Porter

But I understand that but equally it鈥檚 not right to assume that obesity or smoking is something that鈥檚 done to you or happens to you.听 I mean lots of people from very advantageous backgrounds smoke and are obese too.

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McCartney

Absolutely and I think that鈥檚 why you have to look at the environment as well.听 So if you are someone who鈥檚 subjected to lots and lots of advertising you鈥檙e more likely to make particular choices compared with someone who鈥檚 not.听 And that鈥檚 when it comes to looking at the environment.

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Capewell

Sadly all the multinational corporations have one shared objective and that is to maximise profit for shareholders, everything else is just froth and image.听 And sadly we鈥檝e seen sugary drinks companies and junk food companies use exactly the same tactics as tobacco companies 鈥� deny using tactics to duck and weave, avoid effective interventions like regulation and taxation.听 So the first thing is to get smart and recognise the problem.听 Fortunately our UK government has, so the recent child obesity plan for instance, the government recognises there鈥檚 an obesity epidemic, particularly affecting children, the government acknowledges that they have a duty of care and the government places the responsibility fair and square at the door of industry.听 Government has been talking about a childhood obesity prevention strategy for almost two years, what came out was a rather sad diluted version, marketing to children was completely deleted and all the other things 鈥� price, promotions and effective reformulation, mandatory, level playing field 鈥� they had been deleted as well.听听 So we fear that the industry had lobbied very hard.

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Porter

Margaret, what do you say to those who might claim that the nanny state is being over interventionist?

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McCartney

On one level we would like government to help us to live full lives and to protect our health and wellbeing.听 We want to be sure that we have healthcare when we need it, we want to be sure that we have social care if we come across it.听 So you have to use your resources wisely 鈥� the NHS is in absolute crisis just now in terms of workload that it has to do versus austerity cuts that鈥檚 had to be made on it.听 But in amongst all of this I think it鈥檚 really important that public health messages bear in mind that at the end of the day we鈥檙e all individuals and many people that are overweight do feel very vulnerable and often find it difficult to ask for help.

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Capewell

The nanny state provides safe drinking water out of the taps, clean air for our children to breathe at home and in cafes and cinemas, safe roads, vaccinations 鈥� we enjoy the nanny state on a daily basis, this is why we鈥檙e all living to age 70 or 80 or 90.听 So that I think it鈥檚 a logical next step for the government to acknowledge the duty of care to children and take the next steps to make junk food and sugary drinks less acceptable and less available.

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Porter

Can I get your opinion on this proposal by the CCG in question that they might delay the treatment of smokers and obese in the same way 鈥� that if you smoke or you鈥檙e overweight your operation will be put back a year if it鈥檚 not essential?听 Do you think that鈥檚 helpful?

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McCartney

I mean I think that there definitely is a case sometimes to be made clinically to say that someone is likely to recover better from an operation, have better wound healing, for example, may have a less risky anaesthetic administration if, for example, some weight was lost or smoking was cut or whatever.听 So I can see that there may be clinical reasons to delay surgery if that鈥檚 agreed with the patient and that鈥檚 something that鈥檚 feasible and can be done.听 But I think this has been used simply so that CCGs don鈥檛 have to spend money in certain areas and that鈥檚 just not fair.

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Capewell

It鈥檚 grossly unfair because it鈥檚 stigmatising the individual, it鈥檚 pointing the finger at somebody who鈥檚 addicted to smoking or has already been traumatised by the environment and is now seriously overweight.听 This is disproportionate, it鈥檚 more of an issue in deprived households, so it鈥檚 widening the gap between rich and poor.听 And also it鈥檚 a cop out.听 There is a limit to the amount of money available for the National Health Service, it needs to be spent in the most effective and efficient way and just picking on two visible vulnerable groups and blaming the victims is just unfair and also it鈥檚 stupid because these folk are going to get more sick and going to come back to the NHS the year after or the year after that with a greater burden of disease causing additional costs.

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Porter

Professor Simon Capewell and the line 鈥渋t鈥檚 about tobacco and calories, rather than smoking and obesity鈥� will certainly stick in my mind. And Prof Capewell can be seen in person in York at this week鈥檚 Annual Meeting of the Society for Social Medicine speaking in favour of the motion: 鈥淭his house supports the nanny state鈥�.

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Earlier this year we reported on research that looked set to change the future of blood pressure management by advocating more aggressive treatment to achieve lower pressures than current targets. It was called the SPRINT study and suggested that aiming for an upper reading of 120, instead of the current 140, could dramatically reduce the odds of dying early. Even the team behind the study were surprised. As Paul Whelton, Professor of Global Public Health from Tulane University in New Orleans, told me back in February.

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Whelton

Out of the blue one day as I鈥檓 getting ready to get on a plane I get a call and they say 鈥� Good news, trial鈥檚 been stopped.听 And I was floored.

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Porter

You say good news, the trial is stopped 鈥� I mean to many of our listeners that might appear to be bad news.听 Can you explain why it was so exciting?

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Whelton

Yeah it was stopped for benefit and it was stopped very early, about three years in, because there was dramatic benefit for the group that had been assigned to the lower blood pressure.

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Porter

And Professor Whelton wasn鈥檛 the only one taken aback by the findings appearing to confirm that lower is better, and that we should be aiming for 120 as the new target blood pressure. SPRINT was hailed by many as a landmark study.

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But it has not been universally accepted. There have been concerns about increased side effects due to the more aggressive medication needed to hit the lower target. An issue that Margaret McCartney raised here on Inside Health in February.

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And over the summer the study got the thumbs down from heart specialists concerned about the way SPRINT researchers had measured participants鈥� blood pressure.

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Margaret McCartney is here to explain more.

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McCartney

Well all of this has come out from discussions at the European Society of Cardiology Meeting which took place recently in Rome.听 So the bottom line is that in most big high blood pressure trials of treatment blood pressure鈥檚 normally measured three times with an automatic monitor where the healthcare professional is in the room alongside the patient.听 But in the SPRINT trial healthcare professionals were trained to leave the room before the measurements had actually taken place.听 And the concern is that this would mean that you would get a lower blood pressure per se than you would have expected to had the healthcare professional stayed in 鈥� you don鈥檛 have that white coat high blood pressure thing anymore, you get an almost artificially low blood pressure in terms of what you鈥檙e measuring for the clinical trial.

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Porter

And that鈥檚 because having a doctor or nurse look at you actually raises your blood pressure slightly.听 So SPRINT advocated going for a lower target 鈥� 120 versus the sort of current standard of around 140 鈥� but what we鈥檙e saying is because of the way they measured the blood pressure they would have got a lower reading anyway, so there might not be that much difference between the two findings.

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McCartney

That鈥檚 the concern, that鈥檚 the concern and certainly we discussed it in the programme and we discussed the fact that it is a bit out of kilter with all the other studies that have been going on.听 The other thing to bear in mind that this was a really big study, it was done across 102 different centres, so you have to have some kind of standard way of working.听 And what I think researchers are now saying is we鈥檒l need to go back and ask all the different centres 鈥� how did you actually measure your blood pressure 鈥� and make sure we鈥檝e got our facts right because I think it鈥檚 still to be fair a bit unclear.

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Porter

But the striking thing for me is there were 9,000, just over 9,000 people in this study, I mean they were broadly divided into two arms.听 And let鈥檚 assume that everybody followed the instructions and they all measured the blood pressure in the same way, it might have been different from every other trial but they measured the blood pressure in the same way, one arm was treated to 140, the other arm was treated to the lower of 120 and the lower arm did better, so it doesn鈥檛 really matter how they measured the blood pressure does it, as long as they did it the same way?

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McCartney

I do think it does raise still questions about how relevant these are for the general population.

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Porter

Another issue for me Margaret, and this applies to all research in this area, is that blood pressure鈥檚 often measured very differently in the real world, rightly or wrongly it is, so how do we apply the findings to our own consulting rooms?听 A question I put to SPRINT author, Paul Whelton, after the cardiologists in Rome had given his research the thumbs down.

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Whelton

Well I think it鈥檚 a general issue of generalising from clinical trials to clinical practice and it鈥檚 not unique to blood pressure, it鈥檚 true for many trials 鈥� we do them, we do them the best we can, we try to apply the science 鈥� and then you have to be careful as a practitioner in taking information from clinical trials and applying them in practice.听 And I think if there鈥檚 anything that is coming out of this discussion around blood pressure measurement it鈥檚 maybe a wakeup call that we need to pay attention to the measurement of blood pressure.听 We know, in practice, we haven鈥檛 done as good a job in following the recommendations for blood pressure measurement as we should do.听 In fact I think if we got on a plane and the pilot said 鈥� Well I have a set of procedures for how to fly this plane but I don鈥檛 have time to fool with that, so we鈥檙e just going to take off.听 I think we鈥檇 all be horrified.

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Porter

Just to make it clear for people who don鈥檛 have a lot of experience with trials or measuring blood effect what you鈥檙e effectively saying is that you鈥檙e quite happy that the main conclusion of SPRINT 鈥� that lower is better effectively 鈥� is unaffected by the way that the blood pressure was measured because it was done the same in all of the centres.听 But what you can鈥檛 say is that let鈥檚 say the 120 millimetres of mercury recommended in the trial what that actually translates to in my consulting room when I take a blood pressure in my general practice in Gloucestershire in the UK.

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Whelton

We鈥檝e always said that, we have not gone out and made guideline recommendations.听 We鈥檝e said here is the study we鈥檝e done, here is how we鈥檝e done it, as honestly as we can tell you, and now it鈥檚 up to guidelines鈥� committees to make recommendations.听 The Canadians have changed their guidelines already, I could tell you that our guidelines will be coming out, I could you that in other countries like Australia I have heard they have a strong belief in lower is better.听 I think there is an important message in SPRINT, there鈥檒l always be debate, I think we need to see the trees for the woods.

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Porter

So Margaret, I suppose we should be concentrating just as much on how we take blood pressure as to what numbers to aim from.听 I mean 120 maybe the ideal circumstances according to SPRINT but that could equate to closer to 150 when you鈥檙e faced with a stressed and rushed GP who鈥檚 watching you as he does the blood pressure.

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McCartney

Yeah, so there鈥檚 lots of studies up and down that show this effect of white coat hypertension and that鈥檚 why now NICE recommend that you do home monitoring, where people borrow a blood pressure monitor from the surgery or buy their own and check and see what it is at home.听 Of course in the hurly burly of the consulting room you may be running late, there may be people who 鈥� babies who鈥檝e just been vaccinated and are crying in the waiting room, your blood pressure might be going up.听 Of course you might be coming in to see the doctor for something else 鈥� maybe you鈥檙e in pain and your doctor thinks oh I鈥檒l just measure your blood pressure while I鈥檓 here and of course if you鈥檙e in pain your blood pressure鈥檚 going to be going up anyway.听 So I think you鈥檙e right, I think that the circumstances in which we check blood pressures day to day are not going to be the same as the way that they鈥檙e done in trials.

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Porter

Thank you very much Margaret and we must leave it there. As ever more details on the Inside Health page of the Radio 4 website.

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Crow

Mum? Can I have something sweet because I鈥檓 hungry?听 What can I have?

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Lauren

How about some cereal?

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Crow

Okay.

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Porter

Around one in 30 boys, and one in 100 girls, in the UK are thought to have some degree of ADHD - a disorder characterised by a triad of hyperactivity; inattention and impulsivity. Or, to put it another way, children with ADHD struggle to sit to still, are into everything, find it difficult to concentrate or stick to a task, and their impulsive behaviour often gets them into trouble - at school and at home.

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Zak
Hi, my name鈥檚 Zak Crow, I鈥檓 in year seven.听 I realised I had ADHD when mum told me and I was nine.听 Before I started taking the pills I was like getting in lots of trouble.听 A lot of like just calling out answers or 鈥� I was a bit physical.听 I couldn鈥檛 sit still for like less than a couple of seconds.

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Lauren

Hi, my name is Lauren, I am Zak鈥檚 mum.听 I鈥檝e got boy, girl twins who are going to be 12 in October.听 Getting the diagnosis took about four years and we went through a whole gamut of things from sensory processing issues to speech and language difficulties to Tourette鈥檚 鈥� somebody suggested 鈥� it just seemed incredibly confusing.听 And in the end seeing an occupational therapist to see if there were sensory processing issues and she was watching Zak literally bouncing off the walls of a padded room and suggested that it might be ADHD.听 From the moment she said it it seemed incredibly obvious.

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Porter

Zak鈥檚 journey to his final diagnosis is not that unusual - and once there, not all children will need medication like Ritalin. But the number of children who do has risen dramatically over the years as awareness of ADHD has spread - among parents as well as professionals like teachers and doctors.

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Back in the early nineties one in 15,000 children in the UK were taking medication for ADHD. Today that figure is closer to one in 2,000. But new research published over the summer shows that despite this 35 fold increase over the last 25 years, numbers have now plateaued.

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

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Smeeth

Really from the early nineties, when there was almost no prescribing of these drugs, there was an incredible increase 鈥� 30, 40, 50 fold increase 鈥� in the number of children getting these drugs until about 2007-2008 when there was this incredible flattening out, it was quite a remarkable phenomenon really and then it just stayed constant.听 And it wasn鈥檛 people stopping them, it was just that the number of people initiating them was staying the same.

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Porter

The meteoric rise could be explained, I suppose, by increasing awareness 鈥� this is a condition that was probably underdiagnosed and some would say is now over diagnosed 鈥� but does that account for that massive rise?

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Smeeth

It鈥檚 certainly true that the rise was because more and more children were getting this diagnosis.听 An optimistic interpretation or a positive interpretation of this paper would be that the children who have genuine ADHD and have severe problems are not responding well to behavioural programmes are rightly getting these drugs and getting the help they need and there was a catch up, big catch up and that the level of children who were getting the drugs reached a kind of appropriate level and that鈥檚 why it flattened out.

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Porter

But the negative interpretation would be?

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Smeeth

Well the more negative interpretation would be do all the kids who are getting these drugs need them and we don鈥檛 know whether the children getting the drugs are the appropriate children, are the right children.听 We don鈥檛 know how many children who could benefit are being missed and we don鈥檛 really understand why the levels of use we see in the UK are so different from other countries where there may be underuse, there may be overuse and we don鈥檛 know where the right level of use is for a population.

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Davie

My name鈥檚 Max Davie, I鈥檓 the mental health officer for the Royal College of Paediatrics but in my day job I work in Lambeth as a developmental paediatrician.听 I only know what I鈥檝e seen and when I arrived in Lambeth and I went on my bike and went to all the primary schools and the thing that they said is they鈥檝e got these children they think 鈥� absolutely sure have got ADHD but they can鈥檛 get an assessment.听 And so what we had was an exponential rise of assessments at that point because we opened up the doors and children who鈥檇 been managed really well by schools and parents for years and years and years suddenly got a diagnosis and those were the really hard cases, the ones that had very obvious difficulties and a lot of them went straight on to medication.听 I think that鈥檚 why we had a very, very rapid rise.听 We鈥檝e come from a very, very low baseline.

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Porter

So the figures show a plateauing after this initial exponential rise, what do you think explains that from your perspective?

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Davie

We have had a degree of plateauing but I don鈥檛 think we鈥檝e had quite the plateauing that these figures show.听 You鈥檇 expect if you鈥檝e had a kind of backlog almost of cases that you鈥檇 expect after a while that the number of referrals to slightly reduce and that is what we鈥檝e found but I don鈥檛 think that can explain the degree of plateauing in these figures and what worries me about them is that it seems to be coincidental with really devastating cuts to the services for children with emotional behavioural problems which started from 2010.听 What happened was the child and adolescent mental health services were devastated, our own local one lost 40% of their funding over four years and things which are kind of between mental health and developmental paediatrics they suffered after 2010, which would chime with where the figures start to plateau.

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Porter

Getting access to specialist clinics like yours for a GP like me and parents is tricky, could that be why we鈥檙e seeing a plateau here, that we鈥檙e just not getting the children to the people that they need to see because this is a treatment that鈥檚 only initiated by people like you, it鈥檚 not initiated by GPs?

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Davie

Exactly, I fear that anecdotally I have evidence from other colleagues that children are really having struggles across the country getting these assessments.听 Paediatricians like me, embracing ADHD, is something that I鈥檓 very passionate about but doesn鈥檛 happen all over the country.

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Lauren

When he started the medication his self-esteem took a while to improve, it took a long time for him to stop saying he was stupid and for us to convince him that he just learned differently than other people.听 But he鈥檚 able to make and keep friends, he鈥檚 much more interested in what he鈥檚 learning at school and not just thinking about what he wants to think about.

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Zak

I get in a lot less trouble, a lot less physical, I鈥檓 better controlled 鈥� but yeah I don鈥檛 get in trouble anymore as much.

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Lauren

鲍鱼tv is always going to be the hardest place because every child pushes back at home in a way that they wouldn鈥檛 to anybody else, so of course I still get it but you can reason with him in a way that you couldn鈥檛 reason with him before and I think he understands consequence.

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Davie

I think nationally there are still old fashioned and out dated attitudes to ADHD, that these children are just naughty, that parents are just making excuses for them, and that is a huge shame because some children are therefore not getting the services or assessment or treatment they require.听 But conversely we do see some people making excuses for behaviour, trying to push the diagnosis of ADHD, that is, in my experience, an extremely small number and actually they鈥檙e fairly easily found out by a comprehensive assessment.

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Porter

One message you could take home from these data is that this plateauing reflects that we鈥檝e got the right level of use, are you confident that that鈥檚 the case?

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Davie

I鈥檓 not entirely confident.听 At the moment we鈥檙e prescribing for about 0.5% of the population and I think we could go above that and still be within reasonable bounds.听 But if we went up to 5% I鈥檇 be pretty uncomfortable.听 If we went up to 10%, which is what they鈥檙e doing in the US, I would be very uncomfortable about that because at that point you鈥檙e not really treating a condition, you鈥檙e medicating a section of the population.听 And one of the things that鈥檚 nice about these figures is that they really show that we are not following the American model of a continuing exponential rise in prescription of these medications.

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Lauren

There are still people who say you鈥檙e not going to medicate your son, I think the medication has gotten a very bad wrap because of how overprescribed it鈥檚 been and people using it to study for exams and things like that.听 But when I tell them that his reading age went up three years in six months they usually get very quiet very fast.

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Zak

I read better, like when I was taking my second dose of pills, suddenly after I took that I started to read, it was really weird, but that was cool.

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Lauren

It鈥檚 not that he doesn鈥檛 have issues, he still has dyslexia, he still has executive function issues but he鈥檚 now able to be an active participant in the school and is loved and admired by his peers and his teachers.

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Davie

I am concerned that practitioners are under increasing pressure to hurry assessments.听 So I鈥檓 extremely fortunate to have an hour and a half for an initial assessment and some people gasp when I tell them that and I don鈥檛 understand how you can do it in less than that because you need to talk to the family, to understand the family in the round because these things don鈥檛 happen in isolation, they happen in a social and educational and a developmental context.听 It isn鈥檛 clever, it isn鈥檛 technologically advanced work but it does require time and listening and listening requires a bit of space.

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Porter

Are you optimistic about the future, looking forwards now?

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Davie

I have my moments of optimism.听 I think that there are some really significant problems.听 I think that these children require support, both in the health service and also in education and in social care and local authority services and while health has been relatively protected these other services are really creaking under the strain at the moment and the danger is that we are going to end up applying a medical model to what is, at least in part, an educational or social difficulty for these children.

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Porter

Developmental Paediatrician Dr Max Davie. And you can find some useful links on the subject on our website.

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Just time to tell you about next week and the blood test that could change the face of cancer treatment. I will be meeting a doctor at the cutting edge of research into liquid biopsies - the technique of identifying and monitoring cancers through tiny traces of their DNA circulating in the bloodstream. Join me then to find out more.

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ENDS