Pyjamas in Bananas

Score one for Sertraline

2011-11-12T18:04:00.000Z

On the basis of some accumulating evidence of dose dependent QT prolongation with citalopram the manufacturer Lundbeck has issued new guidance on its use. The long and the short of it is that they advise the maximum dose is now 40mg (20mg in the elderly), that it shouldn't be used concomitantly with drugs that also prolong the QT interval (e.g. methadone, tricyclic antidepressants, amiodarone and sotalol), and that it should only be used with caution in those at risk of Torsade de Pointes (CCF, recent MI, bradyarrhythmias, predisposition to hypokalaemia or hpomagnesaemia, including due to medication). This risk also likely applies to escitalopram.

Citalopram is probably the first-line antidepressant in medical practice, partly due to the lower rates of interactions, but give recent evidence that sertraline is more effective, at least compared with straight citalopram (rather than escitalopram), I think sertraline is going to become the go to SSRI of choice now, particularly in the elderly (the maximum dose of 20mg is also the minimum therapeutic dose - so not much scope for increasing it).

Yet more tales of woe from the medical Gestapo

2011-11-04T19:57:00.002Z

Another affair where the GMC demonstrates how it pisses away the hundreds of pounds in fees paid by doctors to hound those self-same doctors for minor mistakes (highlights below, my emphasis in bold):

The appellant...submitted an application on 8^th December 2005 for the post of specialist registrar in plastic surgery in the Oxford and Wessex Deanery. Candidates were required to complete an application form in full.

On 17^th May 2011 the panel found that the application form submitted in December 2005 contained seven inaccurate statements which were both dishonest and misleading; that her fitness to practise was therefore impaired; and that she should be suspended from practice for 12 months. She appeals against those findings and the sanction.

Section 6 of the application form required the candidate to list her postgraduate medical qualifications. One of the bullet points states "if you are in the process of working towards a higher degree please say so, indicating expected completion date". [She]..."MD; Leeds University Medical School, UK, Thesis and Viva"; and then, in the final column, which is headed "date passed":
"TO BE AWARDED
VIVA AWAITED
Completion January 2006"
the panel's finding was as follows:
"...The truth was that far from a VIVA being awaited, your thesis had not even been completed. To imply that is was, applying the test in Ghosh, the Panel is satisfied was dishonest. In reaching its decision the Panel took account of the seriousness of the allegation and your good character. The Panel did not accept your evidence that it could have been worded better. The Panel was satisfied that it was worded in such a way to convey to the reader that your VIVA was expected and by inference your thesis completed and submitted"
Section 7 of the form required the candidate to state what relevant medical or professional courses other than those leading to a post graduate degree or qualification she had attended. [She] listed seven of these. The first was ATLS (advanced trauma life support), which she stated had been attained at the Mayday Hospital, Croydon. Under the heading "date certificate attained" she wrote "2001 C [ie completed] (recertification booked)".

...had in fact successfully completed a 3 day ATLS course at the Mayday Hospital from 13-15 September 2000. The certificate states that it expires on 15 September 2004, that is to say on the fourth anniversary of the last day of the course.

The panel found:
"...The Panel is satisfied that it was untrue to say that you completed your ATLS course in 2001. In the context of an important job application, truthfulness is expected. You knew this to be untrue. The Panel did not accept your evidence that this was a mistake. This was a certificate relevant to the application. Your application form implied that it was current when it was not. Applying the test in Ghosh, the Panel is satisfied that this was dishonest."
The last entry stated that from August 2004 to December 2005, a period of 17 months, she had worked at Pinderfields Hospital, Wakefield in the speciality of plastic, reconstructive, hand and burns surgery as a "Research Registrar" funded by Action on Plastic Surgery....Section 9 is a single line reading "time in full-time research" and seeking an answer in years and months. The answer [she] gave was 1 year, 5 months. Section 11 asks about "time in plastic surgery (do not include research)". [She] answered that she had spent 24 months as an SHO and 17 months as a registrar. In oral evidence (Day 8, page 378) she said that during this period she spent 50 hours per week on research and her clinical hours were between 40 and 90 per week.

The panel found:
"...The Panel determined that it was not true that you spent 17 months in a full time research post and spent 17 months in a full time clinical post. That is what your application form conveys to the reader. The Panel is satisfied that these are matters within your own knowledge and you must have known them to be untrue. Applying the test in Ghosh, the Panel is satisfied that this was dishonest."
Paragraph 3(g) of the list of allegations made by the GMC against [her] referred to a statement in the application form "that, during your research project, you had (1) produced 11 publications, (2) produced 21 national and international presentations". This was alleged to be dishonest and misleading. The findings of the panel were as follows [emphasis added]:
"The period of your research was from August 2004 to December 2005. There were fewer than 11 publications related to your research within that time frame...There were fewer than 21 national and international presentations related to your research within that time frame...The Panel is satisfied that these are matters within your own knowledge and you must have known them to be untrue. Applying the test in Ghosh the Panel is satisfied that this was dishonest."
In a narrative section headed "Other achievements" in the "additional information" section of the application form there were 8 sentences, the fifth of which was "I have produced medical video packages for television which was broadcast internationally on CNN". The charge in relation to this was that it was a dishonest and misleading claim.

The Panel had before it a letter from CNN dated 29^th October 2010 which confirmed that [she] "worked as an intern in the medical news department at CNN Atlanta in 1998 and was involved in writing, production and editing of medical news packages produced for CNN Health which were broadcast nationally and internationally."

In their findings after referring to this letter and the application form the Panel went on:

"...The Panel determined that it was not true that you had produced medical video packages for television that were broadcast internationally on CNN. It was not true that you were solely responsible for the production of these packages. You were involved in the production with others as part of your internship. The Panel is satisfied that these are matters within your own knowledge and you must have known them to be untrue. Applying the test in Ghosh the Panel is satisfied that this was dishonest." [emphasis added]

The findings of the appeal judge were a little more reasonable:

The above paragraphs of the judgment were circulated to the parties in draft on 1 November 2011. Counsel are agreed that in the light of their contents there would be no reasonable prospect, in the event of remission of the case to the GMC, of a Panel finding that her fitness to practise is impaired, nor of a warning being issued under section 35D(3) of the Medical Act. Accordingly the finding of impairment, the sanction of suspension and the direction for immediate suspension pursuant to section 38(1) of the Act will also be quashed. The GMC must pay the appellant's costs of the appeal, which have been agreed in the sum of £22,000.

What a farce. "Protect, promote and maintain the health and safety of the public" my arse - it's a self-perpetuating and self-interested quango which acts as a tool of the medical and NHS bureaucracy to keep the footsoldiers in line.

And yet, compare:

A GUILDFORD doctor who was suspended from medical practice for misconduct last year will be allowed to practise from next month following a case review by the General Medical Council.
Last year, the GMC found that between 1995 and 2003, Stephen Carr-Bains entered into sexual relationships with two of his patients - both of whom were vulnerable and suffering from mental health problems.

Dr Carr-Bains, who worked for the Guildowns Group Practice at the University of Surrey, got one of his patients pregnant and then helped her to arrange a termination.
Following the abortion, the doctor did not put a letter from the British Pregnancy Advisory Service into the woman's records, failed to make any record of the abortion and did not refer her for post-termination counselling.

Several years later, in 2005 and 2006, the doctor pressurised the woman not to reveal her relationship with him to her counsellor.

The 56-year-old GP had sex with the other woman while ‘staying over’ at her university accommodation.

And contrast:

The Panel is of the view that you have shown contrition for, and insight into, your actions...the original misconduct took place several years ago in the context of an otherwise unblemished record. Taking into account these matters and all of the public interests at stake, it has, therefore, determined that your fitness to practise is no longer impaired by reason of your misconduct.

I will leave a comparison of age and ethnicity to the reader. The GMC is not fit for purpose.

Medical students 1 Grumpy old GP 0

2011-09-29T20:33:00.001+01:00

Lovely rant in the Daily Mail about how these new fangled young doctors 'can't diagnose for toffee'. It contains this gem about tactile vocal fremitus:

If they had pneumonia, and therefore fluid on the lungs, the voice would sound high-pitched, and the vibrations would be reduced. Maybe not infallible, but pretty slick, right

Oh dear, we'll leave aside that vocal resonance is a better test, and that you wouldn't test for vocal fremitus if the rest of examination was normal anyway, no, the point here is that the vibrations would be increased in pneumonia!* I'd expect my medical students to know this, let alone a GP. What a clown.

* Don't give me any obfuscatory crap about a parapneumonic effusion - if that's what he meant that's what he'd have said.

Don't trust the media

2011-09-27T19:47:00.000+01:00

Words fail me:
ITV documentary can’t tell the difference between gaming and reality; mistakes Arma 2 for secret IRA film

If wishes were horses...

2011-08-03T22:03:00.000+01:00

I've talked about animal experimentation before (e.g. here and here) but I was pointed to this discussion on the Guardian website:

Dr Sebastien Farnaud of the Dr Hadwen Trust and Prof Roger Lemon of UCL debate the ethics and uses of tests on monkeys

The opening piece by Dr Farnaud contained so many anti-vivisection tropes I was moved to repeat it here (with my comments):

"I thank you very much for giving me the opportunity to start this discussion about a very controversial matter, the validity of the use of non-human primates in medical research, a subject in which, as a medical research charity, the Dr Hadwen Trust is particularly interested."

No, the Dr Hadwen Trust was set up specifically to oppose animal research.

"The first thing to consider is the aim of the Bateson report, which has just been published, its standpoint and who wrote it.
This report is an independent review commissioned by all the major research funders in the UK, to assess the quality, outputs and impacts of research carried out on non-human primates, and their benefits to human health. This review follows the publication in 2006 of the Weatherall report by a working group chaired by Sir David Weatherall that recommended that the major funding organisations should undertake a systematic review of the outcome of all their research using non-human primates (NHPs) supported over the last decade.
Interestingly, whereas the Weatherall report was unambiguously in favour of the use of NHP in medical research, the Bateson report adopts a more challenging position. Professor Bateson, who is emeritus professor of ethology at Cambridge University and president of the Zoological Society of London, is very well respected within the scientific community.
It is therefore very important that statements in his report, indicating that almost one in 10 research projects that used monkeys in the UK result in no scientific or medical benefit, are not ignored. He also states that the justification for some projects carried out over a 10-year period from 1996 was "inadequate or insufficient" and that future projects involving non-human primates that could not demonstrate plausible medical or social benefits should not be funded."

I think only 1:10 experiments showing no scientific or medical benefit is a surprisingly high proportion showing benefit. I'd imagine most scientific research is of minimal use, even medical research, and a figure as high as 90% showing benefit is amazing. Justification for most experiments, when considered outside the narrow question of what people in a particular scientific field think is interesting, is generally poor anyway. So again, I see little to criticise primate experiments over any other area of science.

"The reviewers also reported the unnecessary and unjustified repetition of work published a decade earlier."

To be fair, there are plenty of reasons to repeat experiments done a decade earlier, including replicating a study to show that the effect is robust and repeatable, and verifying that you are performing a particular technique correctly by reproducing a know effect so you can then go on to develop that further.

"These points underline that the issue is not simply an ethical issue but also a scientific one. This simply questions the scientific validity of NHP use in medicine."

No it doesn't. 10% does not equal 100%.

"The report recommends the promotion and development of alternatives to the use of NHP in research."

Well, duh! I imagine 'mom and apple pie' also get a mention.

"Since most diseases studied in NHP are human diseases that do not naturally occur in NHPs, it seems logical to try to develop models which are from the start human-relevant. Here we have to make clear that nobody is proposing we use invasive methods on human subjects. On the other hand, advanced techniques, which were barely mentioned in the Weatherall report, are highlighted in the Bateson report.. These techniques include, for example, magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS), non-invasive imaging techniques that are already in use to help us understand diseases and the needs of patients who suffer from neurological disorders. Organisations such as the Dr Hadwen Trust have promoted and funded these techniques for over a decade."

Yeah, because if fMRI doesn't have the anatomical resolution then MEG or TMS are going to do the trick. If wishes were horses...

"One very important point that the report makes concerns regulation. It emphasises the importance of and the need for a robust system of regulation for animal experiments, at a time when the Home Office is preparing the implementation of the new EU directive for the protection of animals used for scientific purposes."

Good job UK regulation is the tightest in he world (which is not to say it doesn't focus excessively on process and paperwork rather than welfare).

"To conclude I would say that although this report will not please everybody, I like to believe that it is a first step towards major changes, a different attitude that will challenge the use of NHPs in medical research."

Indeed.

FIFA fail

2011-06-01T22:00:00.001+01:00

Ha ha:

'the head of the Argentinian FA, Julio Grondona.

"We always have attacks from England which are mostly lies with the support of journalism which is more busy lying than telling the truth. This upsets and disturbs the FIFA family..."

In an interview with a German press agency yesterday, Grondona called England "pirates" and added:

"Yes, I voted for Qatar, because a vote for the US would be like a vote for England. And that is not possible. "But with the English bid I said: Let us be brief. If you give back the Falkland Islands, which belong to us, you will get my vote. They then became sad and left."'

Undercover Care: The Abuse Exposed

2011-05-31T22:14:00.002+01:00

Watch this on the BBC: "Undercover Care: The Abuse Exposed". And then reflect on the failings of the Care Quality Commission in this case* and whether they could detect or act to investigate any similar case in the future**:

"A specialist residential hospital in Bristol is being investigated by police after secret filming by BBC Panorama found a pattern of serious abuse.

"During five weeks spent filming undercover, Panorama's reporter captured footage of some of the hospital's most vulnerable patients being repeatedly pinned down, slapped, dragged into showers while fully clothed, taunted and teased.

"The programme decided to secret film after being approached by a former senior nurse at the hospital who was deeply concerned about the behaviour of some of the support workers caring for patients.

"Mr Bryan reported his concerns to both management at Winterbourne View and to the government regulator, the Care Quality Commission (CQC) but his complaint was not taken up.
Ian Biggs, regional direction of the CQC for the southwest, said an opportunity to prevent abuse was missed when Mr Bryan's complaints were not investigated."

* Headed by the former chief executive of West Midlands strategic health authority (SHA) who presided over the Mid Staffordshire scandal lest we forget, so she has relevant expertise in this area!

** Still, at least the unit concerned probably had policies for dealing with dog mess, so it can't have been all bad as far as the CQC are concerned.

Some free advice on achieving 'world class NHS productivity' McKinsey style

2011-05-20T19:52:00.001+01:00

Following on from my previous post on McKinsey's recommendations to save money in the NHS, I don't think they've been ambitious enough - where's that blue sky thinking we've come to expect from the cream of Oxford's 20-something PPE graduates?

As I mentioned before, McKinsey's approach is to list every institution in order of cost/efficiency/whatever and claim that lots of money could be saved if all those 'poor performers' performed at the level of the median. I think this technique can be taken even further, and I'll offer my advice for free!

The UK spends phenomenal amounts of money per capita on healthcare compared to most countries in the world - using some figures I had leftover from this set of posts on 'The Spirit Level' - we can see that in 2006 the UK spent some $2.5k per capita on healthcare compared to a world median of around $200! That's a potential saving of over £80bn!

What is that you say, other countries don't necessarily have great healthcare from that $200? Well McKinsey don't deal in trifles like cost-effectiveness and health outcomes, but I suppose I can stretch to looking at that if you insist - I like to think all those years at university were good for something. Using that leftover data I was talking about above we can see what sort of return you get for $200 versus $2.5k. Below is a figure plotting data for life expectancy (in 2007) versus health expenditure per capita (in 2006):

I've fitted a regression line (which is logarithmic to better reflect the shape of the data). At $2434 the UK gets a life expectancy of 79yrs (versus the predicted 81yrs) while the median spend of $218 would predict a life expectancy of 69yrs (versus a median world life expectancy of 72yrs) - countries spending around $200 include Venezuala (74yrs), Malaysia (74yrs), Kazakhstan (65yrs), Thailand (69yrs), Tunisia (74yrs), Tonga (72yrs), Gabon (60yrs), Fiji (69yrs), Guyana (67yrs), Equatorial Guinea (50yrs), Namibia (60yrs), and Swaziland (45yrs).

So there you go, save £80bn and 'cut the deficit' or bail out the banks, and it'll only cost you a predicted loss of 10yrs in life expectancy - good value I'm sure you'll agree. No? Maybe that's a bit too radical for you, but there's another approach we could take - look at that figure above again, doesn't seem like you get much of a return for you investment when your expenditure goes past around $1.5k per capita (where the graph flattens out) does it? If we cut our expenditure to $1.5k per capita we would predict a life expectancy of 78yrs and save £36n - thats a reduction of life expectancy of 1-3yrs for billions saved, an absolute billy bargain!.*

So basically I cannot see how nearly halving UK health expenditure could possibly have any down sides - I've proved it with numbers and graphs and everything! I wonder if McKinsey are recruiting?

* If you think this proposal is a joke, consider that it is the natural consequence of the putatively 'progressive' reasoning used in 'The Spirit Level' that increased health expenditure has no beneficial effect on health outcomes like life expectancy for richer countries such as the UK (I disagree) - no wonder David Cameron likes it.

McKinsey save the NHS

2011-05-19T21:32:00.002+01:00

McKinsey in shock discovery that if you put things in numerical order half of them will fall below the median. What tautology will they demonstrate next?

Via DNUK again - here's a terrifying presentation from McKinsey*:

In February 2009 McKinsey was instructed by the Department to provide advice on how
commissioners might achieve world class NHS productivity to inform the second year of the
world class commissioning assurance system and future commissioner development. The
advice from McKinsey, in the form of the following slides, was provided in March 2009.

I recommend having a detailed read to see what a bunch of 20-something Oxford graduates with no experience of the health service can come up with. Basically if everything was done cheaper and more efficiently it'd all be fine - who'd have thought?

In slide 17 we see how if we just reduced all clinical staffing levels to the median we could save a few billion - no mention of whether staffing levels have an effect on quality of care (another race to the bottom) - indeed they later go on to argue against any attempts to ensure minimum staffing ratios:

"Some Royal Colleges are recommending introduction of mandatory staffing ratios on safety
grounds that will lead to increases in staff required above the activity growth e.g ratio of
1/28 per midwife

Certain service reviews are also recommending more staff is required e.g. stroke, children"

But they argue we should "Limit introduction of mandatory staffing ratios" to save money - they can't be arguing for minimum staffing ratios for any reason, I'm sure it'll all be fine.

Highlights include slide 28 where they show how you could cut 'bed days' by 10% in mental health if only length of stay could be reduced to the median in the poor performers. I wonder whether those trusts with longer lengths of stays admit more severe patients and don't admit less severe patients, perhaps managing them in the community, and thus have already saved money over the other providers who are admitting less severe patients but getting lower average lengths of stay? Well I'm afraid McKinsey can't tell us because they are analysing data in the same way you would expect someone who has no idea of the context and a money-making axe to grind to do.

Presumably we could save money by abolishing all those specialist tertiary and quaternary hospitals with their high risk procedures because DGHs get better results for the same procedures. If only these specialist centres could be as good as those small local hospitals, the difference in performance couldn't possibly be because all the really difficult ones get sent to the specialist centres - how are we supposed to show that on our pie charts?

On slide 53 we can see some of the "procedures with limited clinical benefit" which are "relatively ineffective" or "potentially cosmetic" that we can 'de-commission' to save nearly £1 billion. Femoral hernia repair for instance, as someone on DNUK points out, the risk of strangulation is 45% at 21months in a femoral hernia, this is not a 'cosmetic' procedure!

A particular highlight is slide 60 where we find out that US physicians who do imaging (e.g. x-rays) in their offices do more investigations than those who need to refer to a radiologist. Presumably this means that we are going to massively increase the training places and consultant jobs for radiologists so we can save a few quid on chest x-rays by running each request past a radiologist first?

On slide 64 we can see that as digoxin in heart failure doesn't increase life expectancy only improve symptoms we shouldn't fund it at all. Move over NICE and the controversial QALY, if it doesn't stop you dying it isn't worth a penny.

As someone on DNUK points out, all their reasoning is based on using publicly available data to rank everyone, and then claim that £X million can be saved by making the 'worst performers' as good as the best performers. Conceptually difficult ideas such as figuring out if the factors making worse performers are actually amenable to intervention (e.g. you aren't going to make the people in rural areas all close together and nice and efficient for home visits like in a city however many graphs you draw) are just so much irrelevant detail.

I wonder how much we could have saved by getting some people who know what they're talking about to do a review instead of McKinsey and their one-size-fits-all Panglossian musings?

* This isn't new, for instance, the Ferret Fancier reported on it last year, but I think it is timely to revisit what facile idea people like this (yes Lansley, I'm looking at you)have about 'reforming' the NHS.

Nostalgia

2011-05-08T15:39:00.001+01:00

From BBC 4 - 'Movin' On Up: Pop Hits from 1991' - a look at the early nineties Indie/Dance crossover scene. I have a particular weakness for 'Can You Dig It?' by the Mock Turtles.

The GMC is not fit for purpose

2011-05-06T12:56:00.001+01:00

Via Doctors.net.uk (DNUK, the site where doctors go to bitch) I came across this story:

"A YOUNG doctor who tried to sell her staff pass for free hospital parking can only work as a medic again under strict conditions, watchdogs have ruled.

"...a foundation year doctor, put her free permit to park at Southampton General Hospital up for sale for £5 on the website Gumtree, the Fitness to Practise Panel of the General Medical Council (GMC) was told.

NHS fraud investigators found out she later claimed a senior colleague made a sexual advance in exchange for ''looking more favourably'' on the problem.

"During the meeting, on October 14, 2008, Dr White alleged she was firstly warned she could get the sack by her employers, the Southampton University Hospital NHS Trust.

"But the more senior colleague is then alleged to have gone on to say: ''I can ensure that the trust looks on your case more favourably'' and put his hand on her knee before adding: ''What will you do for me?''

But Brian McCluggage, counsel for the GMC, told the hearing in Manchester the allegation had ''no basis'' and was a ''defence mechanism'' to counteract her difficulty over the parking permit.
The doctor, who is in her 20s and qualified after completing her medical degree at the University of London in 2007, was not present or legally represented at the hearing.

She was also accused of breaking a ban on her entering the hospital and failing to attend an examination by a psychiatrist as requested by the GMC."

Now obviously what she did was naughty - you shouldn't be selling your free parking permit, even for just £5, but this is a trivial matter that should have been dealt with between employee and employer with a slap on the wrist. This is the consensus amongst the DNUK commenters.

So what are we to make of her claim that she was sexually propositioned by her educational supervisor? Most of the senior doctors on DNUK think this is highly unlikely and agree with the GMC that this is probably a "defence mechanism". Well I am not so sure. Medicine is stuck in some kind of 1950s time warp where casual racism, sexism, and sexual innuendo are commonplace. Many female junior doctors of my acquaintance have been sexually propositioned by senior doctors (usually their clinical or educational supervisors) and several have been offered inducements (e.g. authorship on publications or attendance at conferences). Even I've been questioned about my sexuality by a consultant on a ward round in front of patients.

The GMC is commonly used as a tool by hospital trusts and senior doctors to keep juniors in line (paying over £400/yr for the privilege) - how many employees making an allegation of sexual harassment against a senior work colleague are required to to attend a psychiatric evaluation? It wouldn't be possible if this was a simple employer-employee industrial dispute where this kind of punitive action would be illegal, but is just fine when it becomes a 'fitness to practice' issue.

But compare and contrast:

"...had all restrictions lifted on his ability to practise after a General Medical Council panel reviewed his case.

"The former Royal Navy surgeon was convicted at Manchester Crown Court in 2003 of making indecent photographs of children, ordered to sign the sex offenders’ register for five years and given an 18-month community rehabilitation order."

Or here:

"...admitted making inaccurate records after the operation and was slammed by the GMC panel yesterday for “significant departures from good medical practice”.

The panel cleared him, however, of serious misconduct and found that his fitness to practise was not impaired.

The panel also decided against issuing the surgeon with a warning."

Liar, liar, pants on fire!

2011-04-29T19:57:00.001+01:00

Via Dr Grumble:

Addressing the Royal College of Nursing conference in 2009 according to the New Statesman.

'Efficiency' is in the eye of the beholder

2011-04-20T21:10:00.000+01:00

From the Guardian:

One of the big debates around the NHS is whether its budget should be allowed to grow in line with "healthcare inflation", a rate above the national standard that factors in people living longer and demanding more from the service. But Sir John Oldham, the Department of Health's national clinical lead on quality and productivity, has little time for the argument.
"It's a cop out, is my response," he says. "The challenge we face is one we can't face by doing things as we do now.
"When people give that challenge to me in a room of clinicians, I ask them each to write down, if they can, one or two things in the last week, in their personal day-to-day frontline experience, with a waste. And I have never walked out of a room without everybody being able to put something down."
This view is popular with government ministers, who are increasing England's NHS budget by normal inflation and trying to obtain £20bn of annual savings through the Quality, Innovation, Productivity and Prevention (Qipp) programme. It is less popular with many staff and unions, who believe that Qipp means cuts.

Unfortunately it isn't these frontline clinicians who get to make the savings, its the managers and bureaucrats and the only way they know to save money is to sack people, they have no idea what is going on at the frontline. This is the absolutely best part of the article:

All of this would add up to a shift in care for long term conditions equivalent to that which started in mental health a quarter of a century ago, when patients went from institutions to care in the community. He says there are already examples of the openness to change required, such as Tyne, Wear and Esk Valleys mental health foundation trust, which has trained nearly 50 of its staff in use of the Kaizen method for continuous improvement. This involves often simple changes, but made promptly: for example, after staff noticed that nurses were clustering at a station rather than walking around their wards, the trust removed the station the same night. (my emphasis)

Hah, as a doctor I've already had my office taken away (an office for some six doctors or more) and given to one modern matron to twiddle her thumbs and drink her coffee in (I now have to use the nurses' station), so I'm well aware what a massive time wasting pain in the arse it is to have some moron take away your desk space which you need to complete the tedious reams of paperwork the NHS now requires. Nice efficiency saving geniuses, maybe you could ask why they were all clustering at the nurses' station, probably all filling out the mandatory risk assessment and care plans that are now required for all patients.

Heads I win, tails you lose

2011-04-18T19:54:00.000+01:00

I just learned today that the head of the Care Quality Commission (the health and social care services regulator) is the former chief executive of West Midlands strategic health authority (SHA) on whose watch the Mid Staffordshire affair occurred.

I suppose you can look at that in two ways, either it is a tacit admission that regulatory authorities cannot be expected to know what is really going on in the organisation they supervise and so bear no culpability for their failings, or, it shows how catastrophic failure is absolutely no bar to career progression for NHS bureaucrats because they take no responsibility for the direct clinical failings of their administrative decisions - heaping all the responsibility onto the front line staff because they can always hide behind the claim that ultimately everything is a 'clinical decision'*.

* I'll reproduce a comment I made on Neuroskeptic's blog:

"I love this quote:

"The Department of Health insists that although Primary Care Trusts can issue guidelines on the amount of drugs GPs prescribe, it is up to the individual GP whether he or she wants to follow them.

"Hazel's Primary Care Trust, NHS Enfield, admits it changed its guidance to GPs in January but insists doctors were not obliged to follow it."

Classic administrator response - they will relentlessly hound the GPs who don't follow their guidance to reduce script length yet when they're called out on the negative consequences of their decision they basically say it is all down to the GP and not their fault.

I'm seeing this behaviour more and more in the NHS - bean counters and other non-clinical staff make decisions that directly affect patient care, usually without any clinical input, and then when the shit hits the fan they blame the clinicians because, after all, they're the ones with clinical responsibility (but no power).

Heads I win, tails you lose."

Not the best doctor in the world

2011-04-18T19:36:00.000+01:00

Now I may not be the best doctor in the world, but I'm pretty sure I can distinguish PEA from VF - you'd think a forensic pathologist would be able to if they're going to declare VF arrest the cause of death:

"Dr Freddy Patel, the first to conduct a post mortem on Tomlinson's body, said the 47-year-old died of a spontaneous arrhythmic heart attack.
Patel reached that conclusion through a "process of elimination" after being unable to find the source of internal bleeding into Tomlinson's abdomen.

"When Tomlinson collapsed, paramedics and, later, an ambulance worker, connected him to a defibrillator. This gave ECG (electrocardiogram) readings (picture the zigzag lines you see on a beeping heartbeat screen).
Patel's view was that Tomlinson died of an spontaneous arrhythmic heart attack, caused by "ventricular fibrillation" (a fast, irregular wobble of the heart).
Patel conceded that he was not an expert, but said the ECG readings showed at times "chaotic" activity in the heart, which he said supported his theory.
The paramedic ECG charts showed Tomlinson had something called "pulseless electrical activity" – meaning electrical activity in the heart, with no pulse and no beating heart[*].
Another expert, Professor Kevin Channer, from the Royal Hallamshire Hospital in Sheffield, has produced a report on Tomlinson's ECG chart readings.
He found the ECG readings showed normal activity. Crucially though, Channer said that pulseless electrical activity was inconsistent with ventricular fibrillation (the type of heart attack Tomlinson was said to have died from)."

* This isn't true, PEA means there is 'normal' electrical activity and no pulse - the heart may still be beating but not pumping around enough blood to give a pulse, this could be due, for example, to loss of blood from massive internal bleeding.

Nurses have more balls than doctors

2011-04-13T21:54:00.001+01:00

The RCN is usually a pretty spineless union but they've shown more balls than the BMA:

...this meeting of the RCN Congress, in the light of Anne Milton's Congress address, has no confidence in Andrew Lansley's management of this Coalition Government's NHS reforms
Result
For: 98.76% (478)
Against: 1.24% (6)
Abstain: (13)

Scaring women - easy, profitable, and fun

2011-04-12T11:16:00.000+01:00

According to the Telegraph:

"Researchers say there might be no safe limit for the amount of alcohol a pregnant woman can drink without endangering her unborn child

"However, now researchers in Ireland have found evidence that women who drink up to five units a week, equivalent to two 175ml glasses of red wine, could be putting their children at risk of fetal alcohol syndrome.

"The study found three cases of fetal alcohol syndrome "one each in the low, moderate and high consumption groups". The fact there was one in the low alcohol consumption group led the researchers to question the theory that light drinking had no effect on a baby's health."

Well this is the paper, in BMC Pregnancy and Childbirth, the abstract sums it up pretty well:

"A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (> 20 units per week).

"Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake.

"High consumption was associated with very preterm birth (< 32 weeks gestation) even after controlling for socio-demographic factors adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups."

If we assume all births were single babies (since most will be, and the twins and higher number births will not affect the numbers much) that's rates of foetal alcohol syndrome (FAS) of .0023%, .016%, and .82% in the low, moderate, and high risk groups respectively. That gives a relative risk of FAS in the high alcohol consumption group of over 300x the low consumption group.

Interestingly the overall FAS rate in the study is 1/10th of the usual estimated rate, probably because this was only those infants detected in the baby check in hospital. So, in conclusion, there were only 3 cases of FAS in this study which is both very low, and also too small to really draw too many conclusions. Any claim about low alcohol consumption causing FAS is basically a case report of one child that occurred with a rate of .0023%.

Importantly, we have to remember that FAS is believed to be due to heavy drinking throughout pregnancy, and the study did not record this, only alcohol consumption early in pregnancy. If the mother of the FAS child in the low alcohol group was under-reporting her alcohol consumption or went on to drink more heavily throughout pregnancy we have no evidence for a risk of FAS in low alcohol consumption in this study.

So did the authors really cause such an unnecessary scare by claiming that low alcohol consumption causes FAS as the Telegraph reports? Well here they are in the paper:

"This suggests that the mothers of the first two infants [the low and moderate alcohol consumption cases of FAS] may have under-reported their alcohol intake at the time of booking as FAS is unlikely to occur at lower levels of alcohol intake" [my emphasis]

Apparently not. So just another PR/journalist manufactured scare because worrying women about pregnancy, childbirth, and child rearing is easy, profitable, and fun.

Read: 'The Plot Against the NHS'

2011-04-10T12:53:00.000+01:00

Read The Plot Against the NHS which rather nicely details the progressive and deliberate destruction of the NHS under Labour and now the Tories:

Prices will rise. On the one hand, the cross-subsidisation that is practised inside NHS hospitals will come to an end as the less costly activities are taken out of them, forcing them to charge more for what remains. On the other hand, Monitor will have to ensure that prices are set so that all providers make a profit. To keep the NHS budget down, what is covered by the NHS will decrease. More and more treatments will be ‘decommissioned’ and will become ‘extras’, which you can have if pay for them. This is already happening in one particular way, thanks to another New Labour measure – personal budgets, or lump sums given to patients with chronic illnesses to buy their own care with. If you want more care than the lump sum will cover you can pay for more, if you can afford it. Inequality in health care will be restored.

If you were to ask me how I thought the NHS could be improved one of the things I would emphasise is that a fundamental priority is to ensure that people brought into hospital as emergencies are treated quickly and effectively - and this means moving away from a 9-5 culture (plus massively scaled down 'on-call' emergency staffing) towards 24hr care where consultant review and radiological investigations don't keep office hours.

However, government has never been very interested in emergency care, preferring to focus on the 9-5 routine elective operations because they are easy to count and put a price on - paying hospitals fixed tariffs for these. This emphasis has been such that most general hospitals are subsidising their emergency care with routine work like elective surgery or outpatient clinics. After all, it takes a huge number of doctors, nurses, and allied staff to provide even the scaled down 24hr emergency care we have now - getting some money back from this necessary excess capacity by providing elective care is paramount to make ends meet when the remuneration for the emergency care itself doesn't cover the costs.

Unfortunately the new model of health care, initiated under Labour, and now brought forward by the Tories, envisages that everything will be broken down into its constituent parts and tendered for by various private providers. The Independent Sector Treatment Centres were the start of this - and since elective work is subsidising the huge fixed costs of emergency care there is obviously profit to be made for those who agree to take the routine elective work but don't have the same emergency care commitments. If your patients get complications after your elective surgery and you can just ship them to an NHS hospital ITU without having to cover the cost of that care from the fixed tariff paid for that operation how can you fail to be making a profit over and above the NHS?

But providing A+E services and receiving unselected acutely ill patients needs more than just A+E staff, it needs the back up of general medics, general surgeons, orthopaedic surgeons, anaesthetists, paediatricians, gynaecologists, radiologists, physiotherapists, ward nurses etc so that once A&E have stabilised and triaged them someone else can actually treat them. That means, at a minimum, all the services of your average District General Hospital - you cannot hive off A&E as an isolated service.

So what will happen as the DGH revenue streams begin to dry up as more and more of the easy and profitable work is taken over by the private sector? Well since every hospital will now be part of a Foundation Trust they will either have to save money or go bust. Saving money entails cutting services below the already bare bones one we have now - probably a return to the trolleys-in-corridors NHS of the last Tory government - and the rationalisation of services to fewer and fewer centres*.

Competition isn't going to improve emergency medical care because there can be no market in it - already it is run at a loss because NHS hospitals can cross-subsidise from other revenue streams - they do this because they aren't run to make a profit, they are still, despite Payment By Results and other market 'reforms', trying to deliver good healthcare to the local population. When the NHS becomes just a franchise for private companies to compete for provision it will remain a monopoly provider of local emergency care (if you can't financially sustain one local A+E you're hardly going to open a competing one) so the best the market can deliver is a private company taking over the running of that A+E. But since they won't be able to cross-subsidise emergency care anymore - because other companies will already have cherry-picked the profitable elective work - there will be less money available and standards will have to fall.

We are moving inevitably to a two-tier NHS where private companies cream off large profits from over inflated centrally determined tariffs for simple elective services like outpatient work and routine operations while complex and difficult or emergency care is provided by an under-resourced remnant of the old public system.

* For some services, like complex poly-trauma, a rationalisation to fewer centres would improve outcomes as more specialist teams have better results - but this would only be a fortuitous unintended consequence under the Tory plans, and for many other conditions which require less super-specialist provision the extra travel time is likely to prove detrimental.

More illness = Good practice

2011-04-08T19:54:00.000+01:00

I have had my attention drawn to this remarkable document distributed to all GP practices in London:

An Introduction to a Pan London Approach to Improve Quality, Access and Patient Experience in General Practice

It includes all manner of cunning wheezes to improve General Practice in London. On particular piece of genius includes using predicted* versus the actual GP reported prevalence of various diseases as "an indicator of general practice performance":

Organisations in the top quartile ranking within London are examples of good practice. Monitoring, intervention and support would be required for those organisations within the bottom quartile ranking in London. Monitoring and support would be beneficial for those organisations within the mid quartiles within London.

That's right. If you are fortunate enough to have a population with a lower than predicted rate of an illness then you will be judged to be an example of bad practice and failing. But if you happen to have higher rates of illness for some reason, then well done you, you're an example of "good practice"!

Now I'm no epidemiologist but population level models like this cannot be used to accurately predict the prevalence of disease at a local level** - to tell you what the real burden of disease is that those crappy GPs are failing to detect. A five variable* regression model does not capture all the variation in human disease however much you want it to. The tail is wagging the dog here.

* "Expected prevalence data are derived using expected prevalence rates provided by ERPHO which take account of age, sex, ethnicity, smoking status and deprivation score at practice level."

** They are based, of course, on taking all that local level data and then finding a best fit line between all the real data points - you can't then go back and say that those data points that don't lie on the line are now wrong. What kind of statistically illiterate fool came up with this idea?

Administrators take over the asylum

2011-04-07T21:34:00.000+01:00

I went to visit one of the low level administrators in my trust today. For reasons that are not entirely clear to me she has swipe card access to all clinical areas of the trust including secure units and happily uses it to turn up at inopportune times to bother people (much to the chagrin of the nurses).

I went to visit her today for a dull administrative reason, turns out trust policy states that doctors aren't allowed access to the administration corridor - we have to ring the person we're visiting and have them let us in.

Somehow I'm trusted with access to all clinical areas in the local general medical trust (who I don't even work for) such that I could just stroll into the ITU or paediatric ward, yet my own trust won't even let me in to see the woman who arranges leave. They truly have taken over the asylum.

Hyperinjunctions - because not talking about something makes it disappear

2011-04-03T11:28:00.000+01:00

As explained in the Telegraph - our wonderful legal system has a new concept - the hyperinjunction - not the superinjunction where a story can not only not be reported but also the fact that there is an injunction cannot be reported either - this is the next step:

...John Hemming, a Liberal Democrat MP, disclosed details of one on the floor of the Commons last week.

The hyper-injunction goes a step further. Mr Hemming told the Commons that the order, which was obtained at the High Court in 2006, prevents an individual from saying that paint used in water tanks on passenger ships could break down and release potentially toxic chemicals.

It specifically bars the person from discussing the case with "members of Parliament, journalists and lawyers", along with the US coastguard and any ship owners, and also forbids any speculation linking chemicals in the paint with the illness of any individuals.

It says: "The defendant must not communicate to the third parties any speculation that the illness of any individual (including without limitation the collapse of H) was, has been or will be brought out by the chemical composition or the chemicals present in the coating of the potable water tanks."

According to Mr Hemming, the individual was given a two-week suspended sentence after talking to a lawyer about whether he would take up the case on a no-win, no-fee basis. Mr Hemming said: "What we have, therefore, is passenger vessels trundling around the world with potentially toxic substances being released into the tanks. One of those who worked on the tanks collapsed as a result.

Now it may well not be true a true allegation about the paint - but I'm not sure that judges are the ones who should be quashing these things without any public scrutiny - and they certainly shouldn't be able to prevent people getting legal advice after they're granted.

Herbal medicines - because the government thinks you're stupid

2011-04-02T15:05:00.002+01:00

David Colquhoun asks "Why does the MHRA refuse to label herbal products honestly?"

Basically the EU regulations state that you must have the following on the label of a herbal remedy:

"Traditional herbal medicinal product for use in [insert baseless medical claim here] exclusively based upon long-standing use."

And you also get a lovely little kitemark to show that the MHRA has approved your drug:

They might be broadly safe and manufactured to certain minimum standards but the MHRA refuse to have any requirement to mention on the label that there isn't actually any evidence that this or that herbal remedy can do what the label claims, or even to mention that the evidence shows that it doesn't work at all. And then they boast about how:

"The growth of the THR scheme means that consumers will have access to a wide choice of over-the-counter herbal medicines made to assured standards.

"The current signs are that the market will be lively and competitive. The key difference for consumers is that in future they will be in the driving seat and able to make an informed choice when they wish to use these medicines."

This government (and the last one) and the MHRA think you're stupid. They don't want you to know that these herbal drugs don't work because then you might not buy them. And that would upset their friends in the multibillion pound herbal supplement industry. Because ensuring a 'lively and competitive' market in useless drugs is more important than having a real informed choice. It's just the same story at home as selling useless dowsing rods as explosive detectors abroad.

NHS reform myths

2011-03-29T20:07:00.000+01:00

Richard Blogger of the torylies blog has a good site addressing some of the 'myths' around the 'reform' of the NHS, here's an excerpt from Myth 10: Private providers will just cherry-pick the easiest cases, undercutting the NHS:

The Government's Claim:

The less complex the procedure, the less someone – including in the private sector – will be paid. Unlike Labour, we will not rig the market in favour of the private sector.

The Rebuttal

"The less complex the procedure, the less someone – including in the private sector – will be paid"

This shows a stunning lack of understanding about how Payment by Results works. Each procedure, for example, cataract removal, is paid at the same rate (the tariff). However, not every patient is the same. There will be some cases that are more difficult than others even though they are covered by the same tariff. There is plenty of evidence where this has happened with last government's Independent Sector Treatment Centre programme (ISTC).

...

The problem with the ISTC programme is that the provider was paid for referral, not for treatment. The government says that providers will be paid for treatment, but they do not say that once referred the provider must treat the patient, since there is no such provision in the Health Bill it means that once a private hospital receives a more complicated case they may refer the patient back to the NHS. The NHS has a responsibility to treat patients, private providers will never have this responsibility because they know that the NHS is always there for the more difficult cases.

...

This means that if the private providers are cherry picking we will not know about it because such data will be "commercially confidential". There is nothing in the Health Bill to prevent this, indeed, the Health Bill enables private providers to be even more secretive and apply "commercially confidentiality" clauses to their contracts with the NHS.

The Health Bill will not prevent private providers cherry picking because it does not mandate that once referred the provider must treat the patient. The Health Bill also strengthens the use of commercially confidentiality and so the public will not know whether the private sector are cherry-picking.

The fundamental priority of a national health service

2011-03-28T20:05:00.000+01:00

Read this article today from a consultant working in the ill-fated Mid Staffordshire Trust:

In my opinion a major underlying cause of the ‘Stafford scandal’ was that most of us, including politicians and healthcare professionals, had lost sight of the fundamental priority of a national health service. That is to provide excellent and immediate care to those who become suddenly very unwell. There have been tremendous improvements in many areas such as cardiac, cancer and orthopaedic care.

However, the importance of the care of sick elderly patients who make up the bulk of our medical ‘takes’ have only rarely grabbed the headlines. Care of these patients is expensive in staff time and resources, it is often difficult and tiring and can only be delivered in a high-quality way by departments which are equipped appropriately, are well staffed by motivated individuals and led by enthusiastic consultants.

Unfortunately I fear that all these wonderful new innovations in privatised 'integrated care pathways' are going to fragment care and undermine that goal, there may be winners, but it won't be the elderly patient with pneumonia and a hip fracture in A&E.

Politicians and the NHS

2011-03-27T23:24:00.000+01:00

Baroness Murphy blogs on the NHS 'reforms':

Given the recent Ombudsman’s report about the quality of care for older people, which everyone acknowledges is poor/ disgraceful in many NHS hospitals, and the lack of improvement we have seen with massive investment, I find the idea that the NHS does not need to change difficult to accept. Could it be that doctors have a vested interest in maintaining the status quo? (A doctor speaks!)

This wonderfully highlights the problems with politicians and their view of the NHS (and she's an ex-doctor). First, like so many others who utterly fail to look at the evidence, she makes unsubstantiated claims about how the investment under Labour hasn't translated to increased 'productivity nor outcomes' - this is just untrue in the latter case (and irrelevant in the former case*) - but is a standard trope trotted out to argue against increased funding of the NHS (because, you know, our health expenditure, at the mid-to-low end of the European scale, is clearly so profligate). Secondly she makes the mistake of thinking that because you think something must be done then what you're proposing to do is going to improve things - unfortunately there's just no evidence to say that the governments 'reforms' are going to do any good, and plenty of reasons to believe this thoughtless vandalism of the NHS is going to fuck it up big time, as even the most timid of GPs could tell you.

Could it be that politicians just don't know what they're talking about when it comes to the NHS?

* A large part of the increased funding for the NHS went into improving the historically low pay of employees like nurses (which by definition will adversely affect productivity) and in disastrously badly managed GP pay negotiations (which also resulted in less activity for a given amount of money, and thus decreased productivity.

Sharing the pain

2011-03-27T22:30:00.000+01:00

Vince Cable:

...has confirmed the 50p rate on tax will be abolished

He told BBC Radio 5 Live: "It moved up to 50p in an emergency because we had to have a sense of solidarity that everybody was bearing some of the pain, and the chancellor said in the budget that we're going to have to move away from that. I agree with him. The Liberal Democrats agree with him.

I guess solidarity* only goes so far.

* Talking of solidarity, it looks like MPs have finally agreed to take a pay freeze like the rest of the public sector - I'm sure the increase in their expenses is merely coincidental.

Sharing the risk - creaming the profits

2011-03-25T22:50:00.000Z

The King's Fund demonstrate their true colours again, according to the GP magazine 'Pulse':

The King’s Fund has called for entire care pathways to be outsourced to private firms, claiming GPs do not have the time to make the required service re-design in primary care demanded by the NHS reforms.

What I don't understand is what all this talk of 'risk sharing', e.g.

‘GPs can set the standards but consortia will ultimately want to commission organisations to take on the risk.’

...a risk sharing model which would see private firms take on service re-design and practice performance management in return for receiving financial incentives

Now I understand the concept of paying someone for a service, say 'service re-design' or 'practice performance management' but what does it mean to 'share the risk'? It sounds rather asymmetrical, as if you pay a company to take on service commissioning and if it goes badly, well hard luck, you've already paid them, and if it goes well they get a nice big slice of 'performance bonus' to ice the cake - 'heads I win, tails you lose' - and that model's never gone wrong before, and certainly not in the NHS. Good job there will be no financial incentives or conflicts of interest to motivate GPs to adopt that model.

Of course I have absolutely no idea what these ‘integrated pathway hubs’ even mean:

...musculoskeletal, respiratory, and frail and elderly care the first three pathways lined up to go out to tender.

Does this mean that GPs will no longer be required to know any respiratory or musculoskeletal medicine, or to deal with older patients? The patients will refer themselves to the right 'pathway' presumably ('I've got pain in my chest, I guess that's my lungs, better go to the respiratory pathway hub').

One wonders how efficient it will seem when all the respiratory or elderly care outpatient work is taken away from the general hospital to be focused in the 'integrated pathway hub' - when suddenly the acute hospital has no money to keep a respiratory team going, no one to put in chest drains, no one to give expert opinion on difficult chest cases - instead they're having to purchase services from these private providers under their 'service level agreement'. What is the ultimate goal - A&E as a glorified NHS call centre referring you to this or that private company and 'care pathway'? Each care pathway 'integrated' with itself but absolutely no flexibility to cover the messy multiple comorbidities that cross the individual pathway boundaries and make up the real cases seen in everyday medicine. Still, at least it will save money.

Or is it that a 'care pathway' in this case is just one of those referral centres we've seen implemented in areas like musculoskeletal medicine? Staffed with clerical drones who click 'computer says no' and sends the referral back to the GP to ask a physiotherapist to waste their time looking at for six weeks before these moronic box-ticking gate keepers will approve the referral being sent back again - presumably hoping the patient has died or given up in the mean time. For those interested it looks like these care pathways will be like this sort of thing - if my experience is anything to go by they will be vague, inflexible, allow referral centre drones to bounce back anything remotely complicated (because they don't know what the words mean and thus assume it doesn't matter) and ultimately end up with enormously wasted time and duplicated effort. Vive la Revolution!

Psychiatry? Orthopaedics? Same difference

2011-03-18T13:08:00.000Z

As one wag put it, psychiatry is a recruiting, not a selecting medical speciality. This year there were something like 550 applicants for 480 jobs in core psychiatry training and this was only after extending the recruitment window - locally we had exactly one applicant per job and before extending the window around one applicant for every two jobs. Although it sounds like enough people many of these applicants will be unappointable and many will have applied for psychiatry as a back-up and will get their first choice job (usually general practice, paediatrics, or core medical training) and not take up their psychiatry place. This means that lots of jobs will be filled in 'round 2' where the people who couldn't get in anywhere else and applicants from outside the EU apply (this explains why in one recent year only 6% of people taking the exam for membership of the Royal College of Psychiatrists had trained in the UK for their medical degree).

But I'm pretty sure stuff like this isn't going to help - the College published the questions to be used at interview in advance this year (although I'm informed that they didn't actually explicitly tell the candidates this) and I'm reproducing the beginning of the 'simulated patient scenario':

You are an F2 doctor on an orthopaedic ward. Jan Smith has been admitted to hospital this morning as a day case for a knee arthroscopy to be done under general anaesthetic...

Presumably recruitment for core medical training included the scenario:

Imagine you are a consultant neurosurgeon...

Maybe this is some misguided attempt to be 'fair' to those with no clinical experience of psychiatry but I'm reliably informed that locally there are more F2 jobs in psychiatry than there are in orthopaedics. Maybe the College is afraid to even mention psychiatry in their application - perhaps they think no one applying actually has any interest in psychiatry so there would be no point starting a scenario with:

You are a CT1 doctor in psychiatry...

This is not encouraging - I'm also told the psychiatrists on the interview panels had some problems following the ensuing discussions about the management of anaesthetic risks. Do these people have any idea what they are doing?

The future of the NHS

2011-03-17T13:25:00.000Z

Duck on the Badscience forums asked me to blog my concerns about the future of the NHS and how what we are about to see is wholesale privatisation.

What I was saying there is that GPs don't have the time, resources, or infrastructure to suddenly take over all the functions of PCTs next year while carrying on with their day jobs. So, naturally, they will be looking to contract out the commissioning function. But this is just one aspect of the overarching drive towards privatisation.

Something worth remembering when considering GP consortia is that these are consortia of GP practices, not individual GPs. And GP practices are no longer partnerships of equals but increasingly becoming small businesses which differ from the larger healthcare companies purely in size. The last Labour government introduced the idea that GP practices were not partnerships of GPs by removing the need for a certain number of GP partners for a given number of patients (or rather a given amount of money). Instead they were to be treated as small businesses contracted to provide GP services. This has lead to GP services being increasingly provided by salaried GPs (who are usually more recently qualified GPs) employed by the GP practices which are owned by GP partners (who are usually older GPs). Since these changes were brought in the majority of jobs available for newly qualified GPs are salaried positions and not partnerships.

So general practice has moved from being an ostensibly private but effectively collectivised system of equals (at least as far as medical staff go, the position of ancillary staff was different) to become a business like any other - the older generation of GPs have taken advantage of the new rules to become small businessmen increasingly acting as employers and screwing profit out of employees rather than acting as traditional family doctors while the newer generation of GPs become wage slaves. It won't be long before the traditional GP practice disappears (as the old partners retire and sell on their stake in the small business they own) as they are swallowed up by larger healthcare businesses - and then who is going to control the NHS budget? It won't be the workaday GPs who will just be employees of these big companies. **Poof** de facto privatisation.

The words of Liz Kendall (Labour) from the Commons debate on the upcoming NHS cluster-fuck (via Dr Grumble):

Our health and our NHS are not the same as gas, electricity or the railway. That the Secretary of State believes that they are shows how dangerously out of touch he is. What is the likely result? GPs will be forced to put local services out to tender even if they are delivering good quality care that patients choose and like; hospitals and community services will be pitted against one another when they should work together in patients’ interests; care, which as many hon. Members have said is vital as our population ages and there is an increase in long-term conditions, will become more and not less fragmented; the financial stability of local hospitals will be put at risk, and they will have no ability to manage the consequences of choice and competition in the system; and the whole system will be tied up in the costs of red tape, as GPs and hospitals employ an army of lawyers and accountants to sign contracts and fight the threat of legal challenge, huge fines and the potential of being sued. Let us also be clear that the Bill gives Monitor the same functions as the Office of Fair Trading, so it can fine organisations up to 10% of their turnover.

The more we see of the Bill, the more the truth becomes clear. The Secretary of State says that he wants clinicians to be more involved, and “no decision about me without me” for patients, but when the Royal College of General Practitioners, the Royal College of Surgeons, the Royal College of Nursing, the Royal College of Midwives, the British Medical Association or anyone else tells him that he should stop, think again and halt his reckless NHS plans, he refuses to listen. When the Alzheimer’s Society, the Stroke Association and Rethink tell him that his proposals will not give patients a stronger voice and improve public accountability, he simply tells them that they are wrong. When health experts such as the King’s Fund warn that driving competition in every part of the NHS will make it more difficult to commission the services that best serve patients’ interests, he simply puts his fingers in his ears and walks away. What makes this Secretary of State think that he is right when professional bodies and patient groups know that he is wrong?

Doctors and nurses do not support the Government’s plan, patients do not want it, some Conservative Back Benchers and members of the Cabinet do not like it, and the Liberal Democrats hate it. They had the sense last Saturday to see what the hon. Member for St Ives (Andrew George) called the potential catastrophe as far as the future of the NHS is concerned, and to ask for amendments to the Bill. I hope they have the sense to join us in the Lobby tonight.

A campaign for social science

2011-03-16T21:37:00.000Z

Via Church of Rationality I came across this little proposal:

"...I would set up a campaign for social science.
This would be a little different from More or Less or Bad Science, great as they are. Very often, they deal with the abuse of statistics. I’m thinking not just of this, but of fact-free hand-waving. What my campaign would do is insist upon more scientific standards of discussion of social affairs.

"Now, I don’t know how such a campaign would change politics. I suspect that, very often, it would reveal just how much we don’t know. But it would revolutionize the media. TV and radio would have to drop all those blowhards who just exchange anecdote and hypothesis; in proper science, no-one give a damn abot anyone's opinion - it's the evidence that matters. And it might even reverse the inequality of pay and status between columnists and reporters. "

Prescribing advice

2011-03-16T21:16:00.000Z

Just discovered the 'Prescribing Advice for GPs' blog via Black Triangle, lots of useful stuff for any clinicians out there.

Placebos in medicine

2011-03-16T20:00:00.000Z

Good short response on Comment is Free by Oxford Psychiatry Professor Tom Burns on the use of placebos in medicine and how the media exaggerates the beneficial effects*:

When researchers write, for example, that 20% of the placebo group recovered in a trial and 60% of the active treatment group did, they are not saying that placebos "have the same effect" in a third as many of the patients. They mean that (for the patients with this condition) 20% will recover in the natural course of events, but with the added treatment 60% will recover. It is this added 40% that matters. The placebo has had no effect on recovery.

This lead me to a good article he wrote in response to Richard Bentall's tedious criticisms of psychiatry:

Richard Bentall is right: psychological and social psychiatry research has been a Cinderella to biological and genetic explanations...He is also spot on about the exaggeration and hype of many of their "breakthroughs".

However, much of his article is so one-sided that those messages risk being lost.

* The seminal Cochrane review on this topic by Hróbjartsson & Gøtzsche found:

We found an effect on pain...nausea...asthma...and phobia...

There was no statistically significant effect of placebo interventions in the seven other clinical conditions investigated in three trials or more: smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, but confidence intervals were wide.

'Doctor' says screw the NHS

2011-03-15T14:14:00.000Z

Via the Jobbing Doctor, according to this BBC story:

"Dr David Bennett, head of the economic regulator Monitor, has told the BBC he expects to see many more private companies and charities treating NHS patients. If NHS services cannot attract patients they will be allowed to close.

"BMA chairman Hamish Meldrum said the full implications had been poorly understood."

As JD points out, 'Dr' Bennett is not a medical doctor*, he's an ex-McKinsey man, and was formerly Chief Policy Advisor to Tony Blair and head of the Number 10 Strategy Unit. Funny how this is not made clear in the article, yet Hamish Meldrum, GP and BMA chairman doesn't seem to warrant the 'doctor' label.

* I can't find out what his title derives from, e.g. a PhD.

Preventing access to psychological therapy?

2011-03-11T20:28:00.000Z

Interesting article in the BMJ on the Improving Access to Psychological Therapy (IAPT) initiative started under Labour and continuing under the Tories. It remains unpopular with GPs while being heralded as an outstanding success by central government:

"The impact assessment on the expansion of the programme, signed off by Mr Burstow, estimates that the cost of providing a course of treatment is £136 for mild mental health problems and £754 for moderate or severe cases. This, the assessment says, is substantially lower than the estimated costs for talking therapies before IAPT, which are quoted as £255 and £1298.

"Quite where these figures come from is a bit of a mystery because they conflict with those collected by a team led by Professor Glenys Parry of the University of Sheffield, which evaluated the first two pilot sites for the programme, in Doncaster and Newham, comparing them with neighbouring services (Wakefield and Barnsley and City and Hackney). They found that IAPT treatments cost more, not less, than those provided in the neighbouring boroughs, and that it was not possible to say whether the extra costs were justified by better outcomes."

This accords with the experience of many GPs, mental health professionals, and patients (e.g. see the Shrink here).

Service level agreements in medicine

2011-03-10T20:57:00.001Z

Apparently:

All aspects of NHS care for entire diseases are to be put out to tender under radical plans to dramatically expand the role of private companies and charities in running the health service, Pulse can reveal.

A pilot set to launch across the east of England will put entire NHS care pathways out to tender, starting with musculoskeletal medicine, respiratory care and elderly care.

As anyone who has seen their local IT services outsourced will be able to identify with, I am wondering what the response time for a chest drain will be under the 'service level agreement'?

No shit Sherlock

2011-03-09T22:17:00.000Z

Saw this paper today:

Occurrence of depressive disorder was best predicted by a combination of a history of depression and subthreshold symptoms, followed by either one alone. Occurrence of anxiety disorder was best predicted by both a combination of a history of anxiety disorder and subthreshold symptoms and a combination of a history of depression and subthreshold symptoms, followed by any subthreshold symptoms or a history of any disorder alone.

Now I realise that they were trying to make the point that:

Past episodes of depressive or anxiety disorders and subthreshold symptoms have both been reported to predict the occurrence of depressive or anxiety disorders. It is unclear to what extent the two factors interact or predict these disorders independently.

But it did just make me ask whether it was really worth the effort to show that, when all is said and done, people who have had a common mental disorder in the past, and are showing symptoms of it now, are more likely to be diagnosed with it in the future.

Clinical governance

2011-03-03T10:55:00.000Z

I've just started working in a new NHS Foundation Trust. Last night I was on-call. During my on-call I got summoned to a ward and told by the nurses to do something - something both illegal and likely to have me up in front of the GMC - 'not bloody likely' I said, 'but it's trust policy they whined'. Eventually they called in the on-call consultant, who wouldn't do it either.

'Silly nurses' I thought, 'policy indeed!' Now, officially, I'm supposed to have read all 30 of the clinical policies (and the other non-clinical ones too), I've never had the time set aside to do this but the trust have told me to do it so that's their arse covered. They're each 20+ pages long and written in a dreary bureaucratic speak that makes it impossible to easily extract the approximately one line that is actually relevant to clinical practice.

Having a few minutes of downtime I thought I'd check the relevant policy, and sure enough, there it was, an explicit instruction that in these circumstances a doctor should do something both illegal and likely to get them struck off. I looked at who wrote the policy, a nurse and an admin person (sorry, 'organisational risk lead'), no doctors seem to have been involved.

So, feeling like a good little boy, I contacted the 'Risk & Clinical Governance Department' to point out this gross oversight - 'oh yeah, someone mentioned something similar in 2008 but the policy isn't up for review until 2012 so we'll take a look at it again then'. Fantastic.

NHS Whistleblowers

2011-03-03T10:12:00.000Z

People often ask me why I spend so much time bitching about how craply run the NHS is in my area rather than submitting incident forms at work and tipping off the local press. The answer is that I want to continue to work in the NHS, and to continue to work as a doctor. The NHS hierarchy, whether that's local management or the people at GMC towers, do no tolerate dissent as seen in this via the Jobbing Doctor:

Dr Raj Mattu, a consultant cardiologist in Coventry, has finally been dismissed by his Hospital. Dr Mattu made the mistake of criticising the conditions in which patients were being treated in his hospital department.

No cuts in frontline services - whiteboards to take up the slack

2011-02-11T20:17:00.001Z

We're constantly told by the government that its squeeze on public finances will not affect frontline services in the NHS. We all know this is nonsense. I was at a meeting today where we saw what the cuts, sorry, efficiency savings, actually mean for our trust.

They have abolished several consultant psychiatrist and junior doctor posts and a great tranche of CPNs, social workers, support workers, and secretarial staff. But fear not, because this will not affect frontline service delivery. How? We all asked. By 'working smarter' we were told by the newly employed 'Team Building Manager', 'Productive Community Champion', and 'Performance Advocate'.

And what, specifically, does this 'working smarter' entail? We all asked again, because we weren't sure where the extra hours in the day were going to come from to see the same number of patients. And the answer we got was fiendish in its ingenuity. We're going to have a big whiteboard in the reception area of our CMHT community bases. Truly the NHS is safe in their hands.

The Future of the NHS

Schizophrenia in the Guardian

2011-02-05T15:21:00.000Z

A rather nice little piece on a man with schizophrenia and his father who have written a book about the experience:

"To Patrick Cockburn, it's an illness that has eaten away at his oldest child. To Henry, it has been a revelation. Father and son tell Amanda Mitchison how schizophrenia has changed them both"

Britain: leading the world in fake explosive detectors, because brown people's lives are cheap

2011-01-27T20:16:00.000Z

On Newsnight tonight how Britain's military and government promoted selling dowsing rods to third world countries for thousands of pounds. It isn't even like they didn't know about it - they banned their sale to Iraq and Afghanistan but nowhere else:

"It has been alleged that hundreds of Iraqis died in explosions in Baghdad after ADE651 detectors failed to detect suicide bombers at checkpoints.
...
between 2001 and 2004 a Royal Engineers sales team went around the world demonstrating the GT200, another of the "magic wand" detectors which has been banned for export to Iraq and Afghanistan, at arms fairs around the world even though the British Army did not consider them suitable for its own use.

The government's Department of Trade and Industry, which has since been superseded by the Department for Business, Innovation and Skills, helped two of the manufacturers sell their products in Mexico and the Philippines."

The disgusting mandarins of the British government do the security equipment equivalent of letting companies manufacture and export sugar pills to third world countries labelled as antiretroviral drugs for HIV. And they still won't ban their sale because:

The Department of Business, Innovation and Skills told Newsnight that there was little point: "The impact of any further UK action in preventing the supply of these devices from the UK would be limited if they are available elsewhere"

It makes me sick.

The Academic-Medical Establishment

2011-01-25T13:17:00.000Z

I was at a talk recently regarding the side-effects of a widely used drug, let us call it 'fictoxetine'. Now fictoxetine has long been thought to cause damage to the body, let us say the retina, leading to progressive visual loss and eventually blindness. Fictoxetine can be used for years, even decades, and so patients need to have their vision screened regularly. This talk reported their findings from a systematic review and meta-analysis that sought to find out whether the evidence actually supported this fear.

What they presented was data showing that over 1-2yrs of fictoxetine use visual acuity declined by around 10%. They also reported evidence that found that rates of fictoxetine use in people on a register of blind people were around twice those in the general population. They then concluded from this that fictoxetine doesn't really have as much of a major effect on vision as we had thought so we shouldn't be so worried about it and pontificated on how this myth had become so widespread in the medical community.

The majority of people at that talk took this message at face value and went away with that in their heads, maybe they will change their clinical practice - after all a respected academic in the field of fictoxetine research presented the evidence that showed fictoxetine doesn't have much effect on vision. Didn't he?

Well no, he didn't, the data I've just described is consistent with fictoxetine having really quite a large and serious effect on vision. If the short-term deficits of 10% in acuity over 1-2yrs continued over 10 years that would be a major loss of 40% of visual acuity. The blind register data is neither here nor there, most people would stop fictoxetine in patients with significant visual loss in the hope that they would never reach complete blindness (conversely, maybe they would be more happy to start it in people who were already completely blind than those with some vision). So the data doesn't support the narrative being given to it but few people feel qualified or confident to gainsay a big name in the field.

And this is true throughout academic medicine, and academia in general, powerful personalities are able to shape the discourse in a scientific field not only through the research they perform but also the wider influence their ideas and opinions carry.

Is low dose citalopram as effective as other antidepressants?

2011-01-24T19:18:00.003Z

From this post at the 21st Floor I found out about a study of citalopram dosing (Aursnes et al 2010) that is a sort of pre-print (apparently Webmedcentral is a kind of post-publication peer review model). It suggests that citalopram in lower doses (below 45mg per day) might not be as effective as comparator antidepressants. Citalopram is used in doses from 20-60mg for depression and an average dose is probably around 30mg so this is a significant claim*. It is actually titled "Are Regular Doses of Citalopram for Depression only Placebos? Meta-analysis And Meta-regression Analysis Of Pre-registration Clinical Trial Data" which is pretty tendentious since the study only includes two placebo controlled trials, both of which are in high doses of citalopram. Whether citalopram is or isn't a placebo at lower doses is not going to be answered by this study since, even if lower doses of citalopram are less effective than other antidepressants we don't know how they'd compare to placebo using this data.

The paper found a statistically significant relationship (p=.034) between mean citalopram dose and effect size (see Figure 1 below) and went on to split the data into doses above and below 45mg and found that doses below 45mg (but not above) had a statistically significantly smaller effect size than the control antidepressants.

Figure 1. Regression from Aursnes et al 2010

It is very unclear from the paper what methods they used - it appears that they used standardised mean difference (SMD) in change scores but it is very unclear how they computed the change scores from the data they had available. The data they show for most studies does not report change scores and you wouldn't normally be able to estimate the standard deviation of this measure (which you need for the meta-analysis) unless the study reported the correlation between baseline and final score (which is very unlikely).***

Naturally I wanted to have a look at the data and regular readers of this blog will know that baseline severity is an important predictor of antidepressant efficacy in trials and I was interested to see what effect that would have in this study. Some of the source data is conveniently provided, it was obtained from Danish medicine licensing applications for citalopram so likely to be less subject to publication bias (in a similar way to the Kirsch et al data). I was able to get final score data for the studies using the Hamilton Rating Scale for Depression (HRSD-17) as outcome but had to impute standard deviations for those using the Montgomery-Åsberg Depression Rating Scale (MADRS). I could obtain change score SMD data from their figures but I think this is a little unreliable***. I used all the studies with an active comparator (usually a tricyclic antidepressant**). All analyses were random effects unless otherwise noted, and everything was done in R.

So the first thing I wanted to do was reproduce the correlation between mean dose of citalopram and effect size. Using the data I extracted (see Figure 2 below) my meta-regression showed a slope of .038 of SMD against citalopram dose (p=.13). Then I used their numbers (SMD and standard error) and performed another meta-regression. This showed a regression slope of .037 (similar, but not the same as their .038) but it was not statistically significant (p=.20) even if I used a fixed effects regression (p=.19). This is surprising as the authors report statistical significance at p=.034! The only way I can get their data to give a statistically significant regression is to include the placebo studies so that the slope is now .041 with p=.033 but this would be completely wrong. Having placebo studies included only for high doses of 50mg and 60mg will overestimate the effect of citalopram at high doses since we expect citalopram to be better than placebo but no better or worse than another antidepressant as control.

Performing multiple regression with dose and baseline score against weighted mean difference in HRSD score and MADRS score separately**** showed slopes of .73 (p=.10) and -.047 (p=.76) for baseline severity and mean dose respectively for HRSD scores and 1.06 (p=.30) and .25 (p=.75) for MADRS scores. So no statistically significant effect of baseline severity. That isn't necessarily surprising because it may be that both citalopram and other antidepressants are all equally affected by increasing efficacy with increasing severity of depression.

Figure 2. The data I have extracted presented as weighted mean differences in RevMan 5.0

So, in summary, there does not seem to be a robust relationship between the effect size of citalopram and the mean dose used in trials - I do not think a discrepancy of this magnitude is likely to due to methodological differences and I hypothesise that Aursnes et al (2010) have made a calculation error. Therefore it does not make sense to divide the studies based on citalopram dose. If we combine all studies using the SMD as outcome (see Figure 3 below) there is not a statistically significant difference between the citalopram and active control arms of trials although the difference is borderline significant (p=.057) and includes differences up to -.46 which corresponds to scores on the HRSD up to 4 points*****. It is worth bearing in mind that not a single trial had a mean dose of citalopram less than 40mg so this analysis cannot tell us much about lower doses of 20-30mg of citalopram and, if the correlation with dose is not real, then it can tell us nothing about these lower doses. In some ways this resembles the study by Kirsch et al where the authors used a regression analysis to make claims about patients with low severity by extrapolating the line into a region where there were not actually any studies.******

Figure 3. All active control studies combined using SMD as outcome, to the left of 0.0 favours control and to the right favours citalopram

* No study had a mean dose of citalopram less than 40mg.
** Two amitriptyline, two clomipramine, three mianserin, two maprotiline, nortripyline, and imipramine. The paper seems to misreport this but looking at the original data sheets they get their numbers from I think my numbers are right and their report of five studies using mianserin is wrong.
*** This is what the authors say about their methods:

These data were fed into a tailor-made program for performing meta-analysis (Comprehensive Meta-analysis Version 2, from Biostat, Englewood, USA), which uses standard statistical procedures [9]. We filled in columns for the mean score, its standard deviation, and the number of patients in the citalopram group and in the comparator group. We added a column for correlation between before and after, Pearson’s coefficient of correlation found to be 0.48, and standardized the effect analysis with standard deviations of the differences between values before and after. We found I² to be 73.5 and performed random effect meta-analyses with the effects weighted with the inverse of their variances.

And I think they've probably committed an error in their methodology because I'm not sure what they think that correlation is for - they can't use that (the between study correlation) to estimate the correlation between baseline and final scores within studies and then use that to calculate change score standard deviations. That would be completely wrong. It is also noteable that the authors do an 'intention to treat' analysis in addition to 'last observation carried forward' but this is a flawed approach for continuous measures if you don't have access to the original data and it inflates the apparent sample size and does not capture any useful information regarding drop-outs that 'intention to treat' does with dichotomous data.
**** They can't be combined together because the baseline scores are in HRSD or MADRS units respectively.
***** You can see from Figure 2 that the studies using the HRSD did show a statistically significant decrease in the citalopram group.
****** If the regression slope were to be taken seriously an arbitrary 'clinically significant' difference of .35 (around 3 points on the HRSD) is reached around a dose of 40mg.

Pay and conditions in the NHS

2011-01-19T21:32:00.001Z

Our trust has just made a big chunk of people redundant, admin staff, nurses and doctors. Last year my pay was increased 1.5% and this year will get 1% despite a recommendation of 1.5% from the Doctors and Dentists' Pay Review Board. For the next two years doctors and many other NHS staff will have a pay freeze.

Meanwhile MPs get 1.5% as recommended by the Senior Salaries Review Board (we'll see if they decide to vote themselves another 1% next year) and the Chief Executive of my trust got 14% last year and 16% the year before, which is high even for the bloated standards of NHS Chief Execs:

All in this together my arse.

Care clusters: A race to the bottom?

2011-01-19T19:37:00.004Z

Do you think you've got severe depression? Well you're wrong, you are in 'care cluster 4':

"This group is characterised by severe depression and/or anxiety and/or other increasing complexity of needs. They may experience disruption to function in everyday life and there is an increasing likelihood of significant risks.

Likely to include: F32 Depressive Episode (Non-Psychotic), F40 Phobic Anxiety Disorders, F41 Other Anxiety Disorders, F42 Obsessive-Compulsive Disorder, F43 Stress Reaction/Adjustment Disorder, F44 Dissociative Disorder, F45 Somatoform Disorder, F48 Other Neurotic Disorders, F50 Eating Disorder

Some may experience significant disruption in everyday functioning.

Some may experience moderate risk to self through self-harm or suicidal thoughts or behaviours.

Unlikely to improve without treatment and may deteriorate with long term impact on functioning."

So you're basically the same as someone with OCD or an eating disorder. Care clusters (see Figure 1 below) are the result of the Labour government's payment by results programme. You get allocated to a cluster partly based on 'clinical judgement' and partly automatically by a computer program using scores inputed by clinicians to answer 18 questions.*

Figure 1. The 21 Care Clusters

Unlike 'acute' medical trusts which are paid by 'activity' (e.g. how many operations they do) the mental health trusts will be paid by 'need', and that is defined basically by 'care cluster', which a different local tariff for each cluster. So the local mental health trust will get paid for 20 cluster 1 patients, 30 cluster 2 etc. It isn't entirely clear at this point how that will take into account that many patients only stay on a mental health team's books for a few weeks or months.

As with my local mental health trust care providers are now going to start deciding what services they are prepared to deliver for each care cluster based on that cluster's tariff (i.e. how much they'll get paid for treating that patient) and not by the current combination of supply and need. You are not paid by activity, that is by what care (e.g. therapy sessions or meetings) you deliver, but on what cluster someone comes under - therefore there is going to be a pressure to reduce the amount of care provided within each cluster to maximise profit. You also have to wonder whether patients that seem like they'll require more work, and thus cost, than others (e.g. personality disorders) will get taken on at all.

Locally we're developing care packages for each cluster, but you have to wonder how a cluster that includes major depression, OCD, and eating disorders can really have a generic package that is actually includes the appropriate evidence based treatments for those conditions. And where is the room for a bit of clinical judgement and addressing individual patient needs?

This might not have happened if it was left to the current model where only a single mental health trust provides services to a given PCT but under the new government proposals for NHS commissioning by GPs they are subject to EU competition law and must commission services from 'any willing provider' based on price. So it seems likely there will be a race to the bottom, I may not want to deny you access to, say, psychological therapy, but if another provider is tendering for work with the GP consortium and they don't offer it they will be able to save money and come in under my quote.

This payment regime hasn't been introduced yet but the tools for implementing it are being put in place in 2010/11 ready to roll it out. Something worth looking out for.

* Bah, who says you can't quantify mental ill-health on a simple 72 point scale, and who says depression can't be nicely quantified on a 4 point scale e.g.

"Question 7. Problems with depressed mood (current):
0 No problem associated with depressed mood during the period rated.
1 Gloomy; or minor changes in mood.
2 Mild but definite depression and distress (eg feelings of guilt; loss of self-esteem).
3 Depression with inappropriate self-blame; preoccupied with feelings of guilt.
4 Severe or very severe depression, with guilt or self-accusation."

Diversifying the skill mix: or paying peanuts and getting monkeys

2011-01-17T21:10:00.001Z

This is what Alan Maynard, economist, and influence behind much government thinking on the NHS, thinks is the way forward:

"...can patient care be maintained with fewer staff or changes in skill mix?...Expensive GPs replaced by nurse practitioners, for example? Double GP list sizes and reduce the demand for such physicians by half? Expensive registered nurses could be replaced by assistant practitioners. Evidence suggests skill mix changes such as these could be cost effective. However, the potential for skill mix is limited by the power of the craft guilds, especially the royal colleges."*

That's right, the future of the NHS should be half as many GPs (so there would be half as many appointments available), or replacing GPs with nurses, and replacing nurses with kids off the street. Sounds like a recipe for success.

Funnily enough there have been some papers looking at this, by one A Maynard, doesn't look like overwhelming evidence for his plans:

"Twenty-two large studies...strongly suggest that higher nurse staffing and richer skill mix (especially of registered nurses) are associated with improved patient outcomes"

"An extensive review of published studies where doctors were replaced by other health professions demonstrates considerable scope for alterations in skill mix. However, the studies reported are often dated and have design deficiencies. In health services world-wide there is a policy focus which emphasises the substitution of nurses in particular for doctors. However, this substitution may not be real and increased roles for non-physician personnel may result in service development/enhancement rather than labour substitution. Further study of skill mix changes and whether non-physician personnel are being used as substitutes or complements for doctors is required urgently."

I must say, my experience of physician's assistants in the US and nurse practitioners in the UK to replace doctors and care assistants to replace ward nurses doesn't incline me to feel positive about the future. Currently the NHS doesn't have enough doctors delivering front line services or enough nurses delivering care on the wards. Diversifying the skill mix is just another way of saying that the magic of 'progress' and 'reform' will make up for cutting front line staff. It won't, no matter how many economists sit on their arses pontificating about how successfully managing minor self limiting ailments means that GP receptionists or your Granny can replace consultant oncologists. And who, at the end of the day, will take the brunt of these cuts, who will be ultimately responsible for what these people do? The handful of properly qualified people who are left, with their professional membership at stake and big lawsuits waiting for them as they desperately try and supervise a million under-qualified drones with no professional stake or commitment to their patient's care.

As a doctor I've spent enough of my life running around after 9-5 nurse practitioners, phlebotomists, ward clerks or whoever** doing the stuff they won't do because they can just wash their hands of it when 5 o'clock (or more likely 3pm) comes around.

* Worth bearing in mind when you hear him talking in the news recently about consultants:

"They don't always keep to their job plans and then get to do the overtime. I think there needs to be much more transparency about consultants' pay.
"The public are just not aware of the sums they can earn. If the data was published it would put pressure on them and reduce some of the figures we are seeing."

Interesting from a man making nearly £50k per year for 12 years from the NHS for chairing the board of the York NHS Hospitals Trust.

** Incidentally, one of the reasons that nurse practitioners are cheaper than junior doctors (a band 6 nurse like a nurse practitioner gets £25,472-34,189; a junior doctor's pay starts at 23,533 and goes up to 31,523 before specialist registrar level; healthcare assistants get £13,653-21,798; band 5 front line nurses get £21,176-27,534)- is that they only work 9-5, so out of hours the ever decreasing number of junior doctors has to cover the stuff the nurse does during the day but with a concomitant reduction in overall numbers to cover the out-of-hours rota and no chance to practice under the supervision of superiors whatever it is the nurse does. Medicine is now no longer 'see one, do one, teach one', it's 'read about one, do one'. That's why people die so much more at night.

Antidepressants have no more than a minor effect in Minor Depression

2011-01-07T20:58:00.002Z

Neuroskeptic reports on another paper that:

"...has added to the growing ranks of studies finding that antidepressant drugs don't work in people with milder forms of depression"

The study looked at 'Minor Depression', which is a DSM diagnosis that is similar to 'Major Depression' except that patients only have 2-4 rather than the 5 or more depressive symptoms necessary for the latter diagnosis.

Neuroskeptic reproduces the 'response rate' figure which shows no significant effect of antidepressants in this diagnosis but I think the findings from the continuous outcomes are more informative:

This shows the 3 studies that reported continuous outcomes (mean HRSD score) looking at paroxetine in nursing home residents, fluoxetine, and amitriptyline respectively. The effect size is a small* -0.93 HRSD points (95% CI: -2.27-0.41) and not statistically significant**. However, there are only about 200 patients included (which is about the minimum number to justify combining data in a meta-analysis) of which the vast majority came from one trial and I don't think there is enough evidence there to conclude that antidepressants do not work in minor depression***, although the effect size is likely to be small even if they do have a statistically significant effect when enough patients are studied.

* See my previous post for an antidepressant medication that is widely recommended and similarly shows a statistically non-significant HRSD score improvement around 1 point.
** The data presented are for random effects but fixed effects produce exactly the same results.
*** To compare with previous studies of major depression, where mean baseline severity is usually around 24 points on the HRSD in these studies they were something like 12 points on the HRSD. If you extrapolate from studies in major depression then baseline severity of this magnitude would fall well within the region of 'no effect' and so the detected effect size of around 1 point is actually larger than you would have expected.

Lamotrigine: an exciting new treatment for acute bipolar depression?

2011-01-06T20:23:00.000Z

I've talked a fair bit about the efficacy of antidepressants (or lack thereof) in treating major depression. I won't go into that again, but I did want to discuss something that has been neglected in that debate.

Bipolar depression
It's estimated that some 10% of people with a major depressive episode have underlying bipolar disorder - that is they'll go on to have a manic or hypomanic episode (if they haven't had one already) - and if the efficacy of antidepressants in straight major depression is controversial then bipolar depression is a minefield.

It is certainly considered that antidepressant usage alone gives a big risk of provoking a swing from a depressive to a manic episode so they would usually be used alongside a 'mood stabiliser' like lithium or an anticonvulsant, and even then there is considerable disagreement as to how much they help.

Lamotrigine in acute bipolar depression
Something that has got a lot of attention in recent years is the anticonvulsant lamotrigine. There is good evidence for the efficacy of lamotrigine in preventing further depressive episodes in people with bipolar disorder. But recently there has been much interest in its use for treating an acute episode of depression in bipolar disorder, and this is despite the fact that it takes a considerable time to titrate up the dose to therapeutic levels (if you go by the BNF it takes 5 weeks to get to the usual dose of 200mg).

A major paper influencing people's thinking came out of Oxford by Geddes et al in 2009. This was a meta-analysis of trials of lamotrigine in acute bipolar depressive episodes and had a considerable impact. The Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines now recommend lamotrigine as a first-line treatment for acute bipolar depression largely on the strength of this analysis.

What they did was, apparently, contact GSK (who make lamotrigine as 'Lamictal') and get hold of all the individual patient level data from all five trials performed by the drug company and used it to perform a meta-analysis. They also identified two other studies not by GSK but didn't combine them because they didn't have any individual subject data and the trials were a crossover trial (which is difficult to correctly combine in a meta-analysis) and the other used lamotrigine as add-on to lithium therapy. They excluded data from one of the trials which had used a 50mg dose as this is generally considered subtherapeutic.

I'll concentrate on their findings using the Hamilton Rating Scale for Depression (HRSD, 17-item version) which is very widely used in antidepressant trials (I've mentioned it before) which has a maximum of 54 points and a score greater than 18 is usually needed to be recruited into a trial as 'moderately' depressed. Again, I'll focus on two measures of outcome, 'response rate' (the proportion of patients in each arm who achieve a 50% or more reduction in their initial HRSD score) and mean difference in the final HRSD score.

If we look at the mean difference in the final HRSD score (this was adjusted for baseline severity in a regression) it was –1.01 (–2.17 to 0.14). That mean difference is not statistically significant (although using a different measure, the Montgomery–ÅsbergDepression Rating Scale, they did find a statistically significant effect), nor is it even suggesting a particularly large effect is possible (with the upper limit of the effect size around 2 points on the HRSD). This is smaller than the 1.8 point effect size reported by Irving Kirsch's meta-analysis of 'new' antidepressants in major depression and when I reanalysed Kirsch's data properly I (and others) found an effect size of 2.7 points on the HRSD, just short of NICE's (arbitrary) 3 point threshold for 'clinical significance'.

So a mean improvement of 1.0 points on the HRSD is not exactly impressive - certainly it wouldn't be very good if that was a uniform single point improvement across every patient. But potentially it could represent a really big, 'clinically significant' improvement for a subset of patients - and we'd be interested in a drug that could do that.

So this is why we look at 'response rates' - what proportion of patients got 'clinically significantly' better, or 'remission rates', the proportion who score sufficiently low to count as being better. Commonly the former is defined as a 50% reduction in the score on the HRSD (or other symptom scale). We can see below (Figure 1) that significantly more patients responded in the lamotrigine group than the placebo group with a risk ratio of 1.27 (95% CI: 1.09-1.47), that is 27% more patients in the lamotrigine group showed an improvement in HRSD of 50% or more - that implies 11 patients need to be treated for one additional 'response'.

Figure 1. Figure from Geddes et al - Meta-analysis of HRSD 50% response rates using individual patient data from GSK trials

As has been pointed out before, response rates in depression trials are slippery beasts. By calling a 50% reduction in HRSD score a 'response' to treatment you actually need to improve by less points on the HRSD if you are less depressed (and have a lower baseline score) so an improvement on exactly the same items of the HRSD could be classified as 'response' or 'no response' depending on that patient's initial severity. This also means that this measure is very vulnerable to small differences in baseline severity between the arms of a trial.* In practice response rates based on thresholding continuous variables like the HRSD (such as a 50% improvement threshold, or a threshold of 8 points for 'remission') are vulnerable to artefactual non-linear effects where very small improvements tip a few people over the threshold (something to particularly worry about if the threshold used seems a bit arbitrary anyway as you can easily pick one after the fact that amplifies any effect).

The response rates in this study are around 35% of patients in the placebo arm and 45% of those taking lamotrigine - so an increase of 10 percentage points due to lamotrigine. If we consider that, for the average patient, 50% improvement implies a minimum change of around 12 points on the HRSD the actual mean improvement of 1.0 points (and the standard deviation) seems a little small (in a back of the envelope calculation you could say that you would expect an average of 1.2 point improvement - thats 10% getting 12 points averaged over all the group). So a bit of a mixed bag I'd say.

Traditional meta-analysis versus individual patient data
A question that occurs to me is what extra information we gain from having the individual patient data? It is pretty rare to get hold of individual patient data when doing a meta-analysis, usually all we have is the overall results for each trial. Sometimes this doesn't make much difference, comparing the individual level meta-analysis by Fournier et al of antidepressants with Kirsch et al's meta-analysis did not reveal any major differences (and these studies looked at fairly different sets of antidepressants).

I had a quick go at performing a study level meta-analysis of the GSK lamotrigine data** and found that the response rate had a relative risk of 1.22 (1.06-1.41) (Figure 2 below) which is pretty similar to the individual level data 1.27 risk ratio.

Figure 2. Meta-analysis of HRSD 50% response rates from GSK per trial data

Looking at the mean difference in the change in HRSD scores I found an effect size of -.86 points (-1.84-.12) which is similar to the -1.0 effect using individual level data and is similarly also only borderline statistically significant (Figure 3 below).

Figure 3. Meta-analysis of mean difference in HRSD scores from GSK per trial data

This is pretty reassuring as it suggests the majority of the information is present in the trial data so we wouldn't lose too much or miss any important effect if we didn't have the individual patient data available. You have to ask why GSK didn't re-analyse the data themselves, this would have been easily done (it took me a few minutes). I think there are a few reasons for this, one intimated in the paper is that regulatory authorities do not accept the results of meta-analyses, they require two large positive trials for licensing a drug, and all but one of the GSK trials was negative so a meta-analysis would have done them no good with licensing. However, they could still have influenced the scientific literature or provided justification for a further larger trial and I wonder whether they didn't in fact do the same analysis as either me or Geddes et al and realise that this was probably a small and fairly dubious effect and reckon it wouldn't do them any favours in the long run.

Antidepressant response and the severity of depression
Like many previous studies of antidepressants Geddes et al also find that there is an interaction between the size of the antidepressant effect of lamotrigine and how severely depressed the patients in the study were at baseline. They found a significant interaction on their ANCOVA analysis between baseline HRSD severity and final HRSD score with a regression coefficient of .30 (p=.04). They go on to comment that:

"Thus, the interaction by severity was because of a higherresponse rate in the moderately ill placebo-treated group, ratherthan, for example, a higher response rate in the severely ill lamotrigine-treated group."

This statement is very redolent of Kirsch et al's claim:

"The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication."

Kirsch et al got a lot of stick for saying this, not least from yours truly, so I was interested in what a set of rather more mainstream figures in the psychiatric world (two Oxford academic psychiatrists and a psychiatrist from the GSK advisory board) were trying to say, and how this relates the Kirsch's work. Maybe I was being unfair to Kirsch?

Kirsch et al argued that the apparent increase in antidepressant efficacy with increasing baseline severity in trials was due to decreasing placebo response in more severe trials (see Figure 4 below). They further argued that this increasing efficacy was therefore only 'apparent' because the response to antidepressant was the same. I've discussed before how, on many levels, it is meaningless to claim that this effect is only 'apparent'.

Figure 4. Figure from Kirsch et al - Regression of baseline severity against standardised mean difference of HRSD score improvement for antidepressant and placebo groups using per trial data

However, when I re-analysed their data it was their finding of decreased placebo response that was actually only 'apparent', and was due to needlessly normalising the raw HRSD data using the standardised mean difference (see Figure 5 below) and in fact placebo responses remained fairly static with increasing severity while antidepressant responses increased.

Figure 5. Regression of baseline severity against HRSD score improvement for antidepressant and placebo groups using per trial data from Kirsch et al

Of course these correlations are only looking at the average baseline severity between each trial and doesn't tell us whether the relationship between baseline severity and HRSD improvement holds true within each trial for the individual patients in that trial. Fournier et al used individual level data to look at this relationship and found increases in both placebo and antidepressant responses, with the greater gradient in the latter leading to increased efficacy of antidepressants overall (see Figure 6 below) so there is actually not great evidence for a decreased placebo response with increasing baseline severity in straight trials of antidepressants in major depression.

Figure 6. Figure from Fournier et al - Regression of baseline severity against HRSD score improvement for antidepressant and placebo groups using individual patient data

So what did Geddes et al find? Well, unlike Kirsch et al and Fournier et al they primarily looked at response rates rather than mean change in HRSD, obviously you can't have an individual patient's response rate (an individual either does, or does not respond) so they divided the subjects into two groups, those with a baseline severity below 24 points, and those above. They found that only those in the 'severe' severity (>24 point) group had a statistically significant response rate greater than placebo with 46% of those on lamotrigine responding compared to 30% on placebo. In the 'moderate' (<= 24 point) group response rates were 48% for lamotrigine and 45% for placebo. Geddes and others have argued that this increased placebo response at moderate severity is due to something like inflation of baseline severity at trial recruitment (that is doctors subconsciously inflate severity for those around the lower threshold for trial recruitment and they then regress to the 'real' lower score they would have had anyway when assessed blindly as part of the trial while this doesn't happen for the more severe patients).***

Now I've outlined some of my reservations about 50% reduction in HRSD score as a measure of 'response rate' and I don't think that these numbers necessarily show what Geddes et al think it does. Let's consider a simple model of how antidepressants might work, let's say they can be modelled simply by saying that an antidepressant reduces the baseline HRSD score by X HRSD points which is the simple sum of the placebo effect (P) and a 'true' antidepressant effect (A):

X = P + A

Based on this model, as discussed above, we can see how patients in the 'moderate' severity group could be more likely to respond even if X is the same for both severity groups. This is because a lower baseline severity means less HRSD points need to be lost to reach a 50% reduction. If we take this observation it is conceivable that the lower placebo response in the 'severe' group could be, at least partly, due to pure artefact. Given that those treated with lamotrigine in the 'severe' group had a larger response rate than those on placebo you might then go on to posit that maybe P is larger for the more severely depressed patients.

The way we ideally would want to answer this question would be to look at the mean HRSD scores as we did above for the data from Kirsch et al and Fournier et al. The response rate figures alone would still be completely consistent with a relationship like that shown in Figure 5 above and suggest that the claim that "the interaction by severity was because of a higherresponse rate in the moderately ill placebo-treated group" is false.

Unfortunately Geddes et al don't show the mean HRSD data by baseline severity nor do they report the correlations between mean HRSD score and baseline severity for the lamotrigine and placebo groups separately, either of which might help to answer this question. This is a bit odd as this is one of the main areas where the individual patient data would prove very useful and answer questions that the trial only data cannot. So we'll never know whether they do or don't show that placebo responses are constant, decreased, or increased with greater severity of depression. I've reproduced the data presenting each trial below (Figures 7 & 8) but these can't really answer this question, for that we need the within trial data.

Figure 7. Simple regression of mean baseline severity against 50% response rates from GSK per trial data split by lamotrigine (blue) and placebo (red)

Figure 8. Simple regression of mean baseline severity against mean change in HRSD score from GSK per trial data split by lamotrigine (blue) and placebo (red)

Amusingly, if you consider Figure 8 in the same way as my Figure 5 and attempt to determine a severity 'threshold' above which the NICE 3 point 'clinical significance' criteria is reached then you find that you never actually reach it.

Summary
So, what should we conclude? Well a few things:

Lamotrigine is not very effective for acute bipolar depression
Individual patient data in these trials doesn't tell us much more than a classical meta-analysis
The effect of lamotrigine, like other antidepressants in major depression, increases with greater baseline severity of depression, but never reaches the NICE 'clinical significance' criteria
It is unclear exactly why antidepressant efficacy increases in this way but it is far from established that it is due to "higherresponse rate in the moderately ill placebo-treated [patients], ratherthan, for example, a higher response rate in the severely ill lamotrigine-treated [patients]"

So what next?
So what medication should be used for acute treatment of bipolar depression? Well I think the data from quetiapine is pretty promising and certainly a lot more convincing and impressive than for lamotrigine monotherapy. Perhaps lamotrigine will be synergistic when added to quetiapine and the first author, John Geddes, is heading up the CEQUEL trial looking at just this question.

* I think a better measure might be a fixed improvement in HRSD score, call it a 'clinically significant response', this would avoid the assumption that antidepressants somehow cause an X% reduction in HRSD score rather than say improving Y number of symptoms, and thus the problem I've mentioned above about how mildly depressed patients need less improvement to 'respond' than more severely depressed.

** I got the response rate data from the Geddes et al paper and the HRSD mean difference data from the GSK trials register (since it wasn't presented in the paper). I used mean change scores rather than final HRSD scores (although this shouldn't make much difference), I had to estimate standard deviations for trial SCA40910 and the means for trial SCA30924 were already adjusted for baseline severity. Data are for fixed effect models but random effects makes minimal difference to the results.

*** Interestingly this explanation would only be tenable if trials of greater severity showed the same within-trial effect as trials of lower severity, since this effect should take place at the recruitment threshold irrespective of what that threshold is. So therefore within a trial the less severe subjects around the recruitment threshold should show a greater placebo response whereas there would not necessarily be any relationship between average baseline severity and average response between trials. This means that my regression data from Figure 5 above doesn't necessarily argue against this model - what we need to know is whether this relationship holds within the trials, something that even the individual subject data from Figure 6 doesn't rule out because we'd ideally have data separately plotted for each trial since the recruitment thresholds for each trial may have differed.

BMA Idiots

2010-12-18T22:58:00.000Z

From the GP magazine 'Pulse':

"Dr Andrew Dearden, chair of the BMA’s pensions committee, said...the NHS Pension Scheme was running a surplus of around £1bn a year...How do you justify increasing contribution rates?’"

Ah, 'the most selfish generation' in demonstration yet again.Why should they pay enough money to provide their gold plated pensions, retiring at 60, when they can get the next generation to pay for their nice long life expectancies and take massive cuts in what they can expect when they're allowed to retire at 70+, if they even live that long.

Levelling the spirit - pt 2.5

2010-11-22T21:33:00.000Z

From the comments to part 2 Christopher Snowden notes that:

"...since the only plausible mechanism is through stress and CVD, what W & P really need to show is a correlation between inequality and CVD incidence. This, they never do."

What he's saying is that as Wilkinson & Pickett (W&P) in the Spirit Delusion are claiming that income inequality influences health via the biological effects of psychological stress, and as the evidence from research on individuals suggests that any relationship between inequality or stress and health are likely to be through effects on cardiovascular disease (CVD), you would expect them to demonstrate that differences in inequality between countries are in fact associated with cardiovascular mortality specifically (rather than mortality overall).

Well W&P may not do that, but I thought it was worth looking at. I obtained 2004 mortality data from the WHO. Obviously this data is confounded by the relative population structure so I took data for the over 60s since this is an at risk group for CVD and less likely to be confounded than the 15-59 age group. I'll just look at the countries W&P include in their analyses and use their measure of inequality. The measure of cardiovascular disease I'll use is ischaemic heart disease and cerebrovascular disease deaths (per 1000 over 60s) combined.

So what do we find? Well I've plotted the correlation below:

Not very convincing. That's a minimal correlation of r=.06 (not remotely statistically significant). If we just look at ischaemic heart disease (r=-.012) or cerebrovascular disease (r=.119) alone these are also small correlations and not statistically significant. I'm obviously still concerned about differences in the age structure in the over 60 populations between these countries but using other cause mortality as a covariate (which might pick up some of these population differences) doesn't make the relationship any stronger (doing a similar analysis using 15-59yr olds we find a correlation of r=.107 which is only marginally improved by using other cause mortality as a covariate, and which remains not even remotely statistically significant).

Levelling the spirit - pt 2

2010-10-21T14:04:00.000+01:00

This is the second part of my discussion of Richard Wilkinson and Kate Pickett's The Spirit Level. In part 1 (and the updates parts 1.5 and 1.75) I covered their use of international comparison data and the limited consideration they give to potentially confounding factors such as material differences between high and low equality countries and their arbitrary and suspect looking decisions to exclude various countries or measures that upset their arguments.

I'll reiterate at this point that I'm all for reducing income inequality (as well as other forms of inequality), I think it is responsible for a number of pernicious and harmful effects in our society. However, I think the specific take on this problem by Wilkinson & Pickett (W&P) is both objectively unproven (and speculative) and potentially counterproductive.

Neo-materialism and income inequality

Cards on the table, I would probably favour more of a 'neo-materialist' explanation for the ill effects of inequality on society (and particularly on the poor), that is inequality largely has negative consequences through physical and material differences between the lives of the rich and poor. A nice summary of that position is given here:

The neo-material interpretation says that health inequalities result from the differential accumulation of exposures and experiences that have their sources in the material world. Under a neo-material interpretation, the effect of income inequality on health reflects a combination of negative exposures and lack of resources held by individuals, along with systematic underinvestment across a wide range of human, physical, health, and social infrastructure. An unequal income distribution is one result of historical, cultural, and political-economic processes. These processes influence the private resources available to individuals and shape the nature of public infrastructure—education, health services, transportation, environmental controls, availability of food, quality of housing, occupational health regulations—that form the “neo-material” matrix of contemporary life.

This leads me to object to the core thesis of the Spirit Level - Wilkinson & Pickett go to great pains to claim that far from it being life's material inequalities that underlie the detrimental effects of income inequality in richer societies, it is in fact the psychological impact of this inequality that causes all the problems. Indeed they claim that material inequalities actually have no effect on health or other outcomes! We saw a little of this in part 1 where I discussed W&P's argument that expenditure on health in rich countries actually has no effect at all on life expectancy, infant mortality, or other commonly used measures of health outcome.

Psychosocial effects on health

Although it is a little more vague and spread out in the book, in their interviews for the radio (e.g. Pickett on More or Less, or W&P on Analysis) W&P make it very clear that they are proposing a rather bold version of 'status anxiety' such that the stress of an unequal society directly causes ill effects via the physical consequences of stress hormones on health.

I should be upfront and say that this is far from biologically implausible, we know that chronic stress affects the hypothalamo-pituitary-adrenal axis and can therefore alter hormone levels, and we know high levels of the 'stress hormone' cortisol have been associated with increased cardiovascular (but not other) mortality**. But what is so appealing about the psychosocial hypothesis over the neo-materialist explanation for the relationship between income inequality, health, and other bad stuff?

In the Spirit Level W&P say:

As societies have become richer...so the diseases we suffer from and the most important causes of health and illness have changed...During the greater part of the twentieth century, the predominant approach to improving the health of populations was through 'lifestyle choices' and 'risk factors' to prevent these chronic conditions. Smoking, high-fat diets, exercise and alcohol were the focus of attention.

But in the later part of the twentieth century, researchers began to make some surprising discoveries about the determinants of health. They had started to believe that stress was a cause of chronic disease, particularly heart disease. Heart disease was then thought of as the executive's disease, caused by the excess stress experienced by businessmen in responsible positions. The Whitehall I Study, a long-term follow-up study of make civil servants...expected to find the highest risk of heart disease among men in the highest status jobs; instead, they found a strong inverse association between position in the civil service hierachy and death rates...Further studies...in Whitehall II, which included women, have shown that low job status is not only related to a higher risk of heart disease: it is also related to some cancers, chronic lung disease, gastrointestinal disease, depression, suicide, sickness absence from work, back pain and self-reported health.

So was it low status itself that was causing worse health, or could these relationships be explained by differences in lifestyle between civil servants in different grades?..these risk factors explained only one-third of their increased risk of death from heart disease. And of course factors such as absolute poverty and unemployment cannot explain the findings because everybody in these studies was in paid employment. Of all the factors that the Whitehall researchers have studied over the years, job stress and people's sense of control over their work seem to make the most difference.

The Whitehall II Study

Ah, the Whitehall II study - it all comes down to this. It is important for W&P to point towards studies like this because, for all their emphasis on comparing countries, because there are so many confounding factors comparing a few dozen heterogeneous countries, no one is going to believe that there is an association between inequality and health unless it can be shown at the individual level within a society.

Putting aside the rather poor history of associations between 'stress' and ill-health*, as W&P say, the finding that cardiovascular disease (CVD) showed an inverse association with job grade in the Whitehall studies was indeed a revolutionary moment in epidemiology. A huge number of publications have emerged from the Whitehall data and the central message has been, as W&P state in the book, that the relationship between job grade and CVD is mediated directly via job stress and control. These findings from the Whitehall II study form the core of the psychosocial explanation for the relationship between income inequality and health. Back in 2001 Wilkinson was saying:

The Whitehall II study showed that low control in the workplace predicted coronary heart disease independent of social status,and that low control in the workplace accounted for about half of the social gradient in cardiovascular disease

Now the Whitehall II study is something I've covered before, but I think it is clear that my observations merit repetition in the context of the argument over the Spirit Level.

As W&P say, the Whitehall II built on the findings of the Whitehall I study to show that employment grade and health outcomes, in particular coronary heart disease (CHD), are associated***. While risk factors such as smoking do account for a lot of this association it has been claimed that the strongest predictor of CHD incidence, even taking risk factors into account, is 'low control at work'. Job control is supposedly associated with CHD independent of job grade (and so presumably socioeconomic status), leading to the conclusion that low job grade is associated with heart disease because low job grade is associated with low job control - that is, it is the psychosocial strains of being in a low grade job that cause CHD. It would be difficult to overstate just how influential this conclusion from the Whitehall II data has been - although there have been other studies in other populations and looking at other psychosocial factors this is the core of the evidence for the role of psychosocial factors in causing disease.

So just what constitutes coronary heart disease?

The question I want to ask is how robust is this association between CHD and job control? There have been a number of studies looking at the Whitehall II data and job control (e.g. Bosma et al 1997, Kuper & Marmot 2003) and all have found the same thing - low job control is associated with higher incidence of CHD whatever job grade you are in.

But all is not quite as it seems - coronary heart disease (CHD) is quite a broad term, it covers a spectrum from fatal myocardial infarction (MI) to cardiac chest pain (angina), but all of these are the result of ischaemia in the heart. Most studies of the Whitehall II data have tended to lump all CHD together, combining MIs with angina to create the broad category of CHD. If we look at the findings from these studies we can see something very interesting, once we take into account confounding factors (like age or health related behaviours such as smoking) the association between CHD and job control is driven by angina rather than MI.

So in the paper by Kuper & Marmot they looked at two outcomes, all coronary heart disease and myocardial infarction (fatal or non-fatal). They actually found no effect of job control for women, but for men there was a highly significant effect of job control on all CHD even adjusted for coronary risk factors (smoking, cholesterol, hypertension, exercise, alcohol, BMI). However, there was no effect of job control on the rate of MI. And there wasn't even a relationship when the comparison was unadjusted for coronary risk factors. This is a puzzling result - if job control causes CHD then we would expect this to be reflected in all forms of CHD, in rates of MI just as much as angina since it is the same underlying biological process (furring up of the coronary vessels in the heart) that underlies both angina and MI.

If we look at the earlier study by Bosma et al we can begin to see why this anomaly might arise. In the same way as Kuper & Marmot they found an association between job control and all CHD - but they also split the data up into those with angina detected on a questionnaire (the Rose angina questionnaire) and those with CHD diagnosed by a doctor. What they found was that if you controlled for age, sex and coronary risk factors only questionnaire detected angina was associated with job control (with about twice the rate of angina in those with low job control versus those with high control) whereas in those with physician diagnosed CHD there was no statistically significant relationship (and around 1.3x the rate of diagnosed CHD in the low job control group).*4

Since the majority of patients classified as having CHD in the Whitehall II studies had Rose questionnaire diagnosed angina it is these patients driving the association between job control and CHD - those patients with harder end-points, actually having an MI or having a doctor diagnose them with CHD, didn't seem to show this relationship. So why might that be?

Diagnosis by questionnaire

The Rose angina questionnaire used in the Whitehall II study is a self reported measure of chest pain. All studies that have looked at the association between psychosocial factors and CHD in the Whitehall II data have classified anyone with a positive angina questionnaire as having angina and thus having CHD. The use of this questionnaire reminds me of a (possibly apocryphal) study I heard about where they gave healthy people a checklist of life threatening symptoms (chest pain etc) and asked them to keep a diary for a few days recording them - at the end of the study everyone had recorded 1 or 2 potentially life threatening symptoms per day.

The question is, does everyone with a positive Rose angina questionnaire have true angina and thus CHD? Now obviously a questionnaire that asks about chest pain is going to pick up people with angina (angina being, by definition, a form of self-reported chest pain that meets certain criteria) but it appears that some 70% of people diagnosed with CHD via the Rose questionnaire in the Whitehall II trial did not have a formal diagnosis of angina - that is they had not been diagnosed by a doctor with angina and did not have documented CHD through any other means. The risk here has to be that at least some of those 70% did not have angina at all - only about 12% of these people had an abnormal ECG, 5yrs later 80% still hadn't been diagnosed with CHD by a doctor, 15% didn't even report any further anginal symptoms, and 50% still didn't have any evidence of CHD other than via the Rose questionnaire.*5

So most studies have tended to find associations only between subjective reports of psychosocial factors (such as job control but similar problems are found in studies of other 'psychosocial' risk factors) and subjective measures of cardiovascular disease (the Rose questionnaire), rather than objective measures (like documented MI). We really have to entertain the possibility that people report more symptoms of chest pain when they feel less in control of their work (causality here may be direct, or via third factors like personality) without necessarily actually having increased rates of CHD - that is they report more chest pain for psychological reasons without necessarily having increased rates of dodgy coronary vessels in the heart. Without an effect on objective coronary endpoints we can only assume that an explanation of this form is most likely.

Just as we discussed in part 1, this criticism of the Whitehall II results is far from a novel observation, in 2005 epidemiologist George Davey Smith noted the results from one of his own studies using the Rose angina questionnaire:

"The large apparent influence of stress on incident angina was probably seen because the people who reported high stress also reported other forms of discomfort in their lives, including chest pain. This was obviously not due to there being any actual stress-related coronary disease, otherwise it would have been revealed in incident ischaemia and cardiovascular disease mortality.
...
We could have published the 2.5-fold increased risk of angina independent of confounders and reporting tendency, because studies of stress have got into major journals reporting on just this outcome with similar effect sizes...Rather than this, we reported these results as demonstrating how it is possible to get misleading findings on stress and disease from observational epidemiology. It is interesting to compare our results...with the Whitehall II study findings for job control...The two studies got very similar results with a subjective measure - Rose angina. In both studies there was no association between job control and the non-subjective measure of electrocardiogram (ECG) ischaemia. There is a remarkable parallelism between the findings."

A question of emphasis

To sum up part 2 - Wilkinson & Pickett rely very much on a psychosocial explanation of how inequality can impact on health and other aspects of quality of life without being mediated via material mechanism such as wealth or healh expenditure. While superficially plausible the basis for this explanation remains, at the very least, unproven. My concern is that if you purely emphasise the psychological impact of inequality then you are choosing to ignore or minimise (and in places W&P explicitly do this) material inequality and will encourage the rejection of more concrete concerns such as addressing smoking behaviour or increasing healthcare expenditure - things which will have a real impact on health and quality of life and which are probably going to be easier to provoke the necessary political will to address directly than tackling the hypothetical ill-effects suffered by people's perception of status inequality.

So what is my overall conclusion from reading the book? Well I said when I started out writing these two posts that I avoided reading the book for a long time because I both (a) sympathised with the authors aims and broad policy recommendations and (b) suspected that the actual data and methods used would make me cringe and then rant. I think I was proven right in my (b) but I also think that exposure to the arguments of W&P has undermined my belief in (a) - not that I now think inequality is good but rather that maybe I was wrong about sympathising with W&P's aims, because I wonder whether they are really quite so similar to mine after all.

As I concluded at the end of part 1, I don't think the Spirit Level deals with confounding factors at all adequately - and I think this it driven by a desire to undermine any causal role of material factors in explaning the relationship between inequality and health or other societal ills. This leads to W&P making what seem to be arbitrary and suspect looking decisions to exclude countries from their analyses or to use specific data sources rather than others precisely to undermine the relationships between material factors and these important outcomes.

They rely heavily on the unproven psychosocial hypothesis to provide a causal underpinning to the associations they describe despite this model being derived from a flawed interpretation of studies such as Whitehall II. I think that there is a real danger that the Spirit Level will lead people who genuinely recognise the social ills caused by inequality in society to neglecting real material changes that could be instituted in the here and now, and encourage politicians to ignore those changes because we all know that it isn't things like relative poverty or lack of access to healthcare that causes these societal problems, it is the psychological trauma of perceiving that you are lower status than someone else. In this regard I think that the Spirit Level may actually have a rather pernicious effect in undermining the very measures that we should be championing to address the inequality we see in our society today. This leads to my concern that perhaps I don't subscribe to (a) above because the authors aims and broad policy recommendations could actually conflict with those I would advocate from a neo-materialist perspective.

A worrying further point that I haven't discussed (largely because W&P simply do not provide much evidence to elaborate on it)*6 is that the Spirit Level, particularly in its media guise, has also set itself up for failure - W&P have framed the debate in such a way that they argue that inequality in society leads to worse outcomes for the whole of society, not just those at the bottom of the socioecenomic gradient. Now that may well be true for a number of social ills, but it may also not be for a number of other outcomes. By framing the debate as one of selfishness rather than altruism it provides a get out clause for those better off in society from supporting increased equality if they come to find that inequality is not always disadvantageous for them personally.

* The story of the discovery of the relationship between H. pylori and peptic ulcers is rather well know but it is a salutory lesson that spending too much time worrying about stress as a cause for disease can lead us to neglect rather stronger and more easily remedied physical causes.

** However there is actually only pretty equivocal evidence for an effect of the psychosocial environment on cortisol levels:

"In the 23 studies addressing association between cortisol in serum or urine and the psychosocial working environment, no consistent results were found: 11 showed no association, nine showed a positive association and three showed a negative association."

*** The latest data from the Whitehall II study show that, while those in the lowest employment grade compared to the highest group had 1.6x the death rate, once all health related behaviours (e.g. smoking) were controlled for, and crucially, taking into account how these behaviours varied over the course of the study, there was no statistically significant increase in the overall death rate in the lowest grade compared to the highest. However, overall there was a 1.85x rate of death from CVD in the lowest job grade, but no increased rate of non-CVD mortality. Therefore the main focus of those studying the relationship between inequality and health is on cardiovascular disease, and this has indeed been associated with levels of the 'stress hormone' cortisol as I noted above.

*4 The specific figures from these two studies are reproduced below with the more objective CHD outcomes in bold:

In Bosma et al 1997 (from Table 6) odd ratio (OR) of new CHD at follow-up comparing low job control versus high job control: all CHD 1.93 (95% confidence interval 1.34-2.77) and adjusted for coronary risk factors (CRFs) 1.99 (1.36-2.91), angina 2.09 (1.29-3.37) and adjusted for CRFs 2.02 (1.22 to 3.34), diagnosed IHD 1.49 (0.81 to 2.74) and adjusted for CRFs 1.26 (0.67 to 2.39).
In Kuper & Marmot 2003 (from Table 2) hazard ratio (HR) of new CHD at follow-up comparing low job control versus high job control (men only): all CHD 1.55 (1.26-1.90) and adjusted for CRFs 1.43 (1.15 to 1.78), fatal CHD and non-fatal MI combined 1.14 (0.82 to 1.59) and adjusted for CRFs 1.01 (0.70 to 1.45).

*5 There was also no increased risk of death in these people but since there was no increased risk of death in those diagnosed with CHD by a doctor I don't think this tells us anything.

*6 For instance, they don't consider how things like murder rates differentially affect each end of the income distribution, assuming they're just a bad thing for society overall - which may be true but I'm pretty sure you'll find individuals doing rather well out of inequality.

Levelling the spirit - pt 1.75

2010-10-15T15:45:00.003+01:00

Following on from part 1.5, here's my final set of analyses. I've had quite some trouble reproducing the analyses from the Spirit Level. This time I'm going to source my data from somewhere other than the OECD, the UN Human Development Report 2009 - this gives data for income inequality (average Gini 1992-2007), life expectancy at birth (2007), and government health expenditure (2006 in $PPP).

I've specified my data set in advance, I'm going to look at all countries (where data is available) shown on Wilkinson & Pickett's (W&P's) figure below which have greater national income than Porugal (the poorest country included in W&P's analyses). I'll also look at all those countries excluding those with a population less than 3 million (a specification made by W&P in their reply to critics). Finally I'll just look at those countries included by W&P in their analyses.

So, I'm throwing out Luxembourg, Liechtenstein, Hong Kong, and Andorra at the start because they aren't on the graph. This leaves me with 36 countries, all the usual ones plus Singapore, Korea, Israel, Slovenia, Brunei, Kuwait, Cyprus, Qatar, UAE, Czech Republic, Barbados, Bahrain, Hungary, and the Bahamas. Of these I have no Gini data on Iceland, Brunei, Kuwait, Cyprus, Qatar, UAE, Barbados, Bahrain, and the Bahamas. So I start with 27 countries - and the correlation between Gini coefficient and life expectancy is r=.13 (p>.5). The relationship between health expenditure and life expectancy was r=.37 (p=.06), so 'trend significant' as we say in the trade.*

Ok, population size, well the lack of data got rid of most of the small ones, but it's bye bye Slovenia with its 2m population, and unsuprisingly it makes little difference to the relastionship with life expectancy not significantly correlating with Gini (r=.12, p>.5) and the relationship with health expenditure even less significant than before (r=.35, p=.08).

Finally we'll look at W&P's subset of 23 countries: that means farewell to Hungary, the Czech Republic, and Korea, but we get to keep Singapore and Israel in addition to the usual crowd of Anglo-Saxon and Western European countries plus Japan. In this sample the correlation between life expectancy and Gini is still not significant at r=-.13 (p>.5) but now there is no correlation with health expenditure (r=0). Below I've reproduced the scatterplot of this relationship:

Compare this chart with the one by W&P in the Spirit Level reproduced below:

The two graphs don't look massively different, yet W&P report that they found a statistically significant relationship between income inequality and life expectancy, whereas I didn't find much of a relationship at all. Why would this be? Well, as I've been discussing in the two previous posts the exact composition of countries in the subsample is important, but that can't be the issue here since we've used exactly the same arbitrary sample of countries as W&P. I've also discussed how data source is important, which is why I've sought to do my analyses using different sources to W&P to check how robust they are. But even then the two graphs look pretty similar, and life expectancy estimates are not likely to differ by enormous amounts between sources.** But one areas where my data in all my analyses differ from those of W&P is in how we estimated inequality. This is important because if you look at the two figures an important differences between them seems to be that Japan in the top left hand corner and the USA, Singapore, and Portugal in the bottom right hand corner seem more extreme in the scatterplot from W&P than they do in my graph.

So how did I estimate inequality? Well I just took Gini data from a UN report as a stated above. What is the Gini coefficient? I'll let W&P explain:

"Other more sophisticated measures include one called the Gini coefficient. It measures inequality across the whole society rather than simply comparing the extremes. If all income went to one person (maximum inequality) and everyone else got nothing, the Gini coefficient would be equal to 1. If income was shared equally and everyone got exactly the same (perfect equality), the Gini would equal 0. The lower its value the more equal a society is. The most common values tend to be between 0.3 and 0.5."

Sounds like quite a good measure of inequality then. So why didn't W&P use it in the Spirit Level? Well here they are to explain:

"To avoid being accused of picking and choosing our measure, our approach in this book has been to take measures provided by official agencies rather than calculating our own. We use the ratio of the income received by the top to the bottom 20% whenever we are comparing inequality in different countries: it is easy to understand and is one of the measures provided ready-made by the United Nations. When comparing inequality in US states, we use the Gini coefficient: it is the most common measure, it is favoured by economists and it is available from the US Census Bureau. In many academic research papers we and others have used two different inequality measures in order to show that the choice of measures rarely has a significant effect on results."

Gosh, if only there was a way to obtain Gini data for the countries they studied. Never mind, since they've told us it doesn't make any difference I'm sure their selection of income ratios rather than the more commonly used and academically accepted Gini coefficient was just for convenience.

It seems that to both find no relationship between wealth or other markers such as health expenditure and life expectancy, whilst simultaneously finding a relationship between income inequality and life expectancy requires an exquisite balance between exactly which data source, subsample of countries, and measure of inequality you choose to use. Can it really be the case that W&P just stumbled onto this analysis first time and didn't think to check how robust it was to slight variations? Or could it be that there is some intellectual dishonesty at work?

* For 'trend significant' read 'not statistically significant'

** As Neuroskeptic points out in the comments there is a big difference between the life expectancy data in my graph and in the one from the book. Having downloaded the data from the Equality Trust website it seems that their data is about 3yrs older (from 2004) but from the same source. However, reanalysing the data using the Gini coefficients from this post and the life expectancy data from the book I get a stronger correlation (r=-.34) but this is still not statistically significant (p=.12). Re-analysing the data using their inequality measure confirms their analysis with r=-.44 (p<.05). So my failure to reproduce their analysis is partly about which year the life expectancy data is taken from and partly about the choice of inequality measure.

Levelling the spirit - pt 1.5

2010-10-14T19:54:00.007+01:00

Just a quick update to my previous post: Levelling the Spirit - pt 1 inspired by the discussion with Neuroskeptic in the comments.

He suggests that Wilkinson and Pickett (W&P)* are correct in regarding the 'flat' part of the national income-inequality curve (the figure below) as being different from the rest of the curve, and thus W&P are justified in their very selective choice of which countries to include in their analysis:

So I went back to my 2007 OECD data I've been using** and selected just those countries with greater (or equal) national income per capita than Portugal (the poorest country W&P use in their analysis). As you can see from the graph above I still get to keep Hungary, the Czech Republic and Korea, and I'm not including Israel or Singapore because they aren't OECD and that's where I get my data from***. So what is the relationship between inequality and life expectancy in this sample? Well, as you can see from the figure below, essentially there is no relationship (the correlation coefficient is tiny and is not statistically significant).

Well presumably this is something to do with range restriction or small sample sizes as we discussed in part 1? Well maybe not because if we look at the relationship between health expenditure and life expectancy (the data for Portugal are estimated from another source but inclusion or exclusion makes no difference) there is a strong r=.56 statistically significant relationship. If we look at the relationship between Gini inequality and life expectancy when we control for health expenditure the correlation is a statistically significant r=.46, that is higher inequality is associated with greater life expectancy!

Now I'm not trying to argue here that inequality really leads to greater life expectancy, or specifically that inequality isn't related to life expectancy, or even that health expenditure is more important than income inequality for life expectancy, although all of these would be conclusions you could draw from the data I've presented. No, what I'm trying to point out is that the choice of both which specific source is used to derive the data and which countries to include or exclude when running these analyses has very important consequences for the relationships that are detected - and I am having trouble seeing what non-arbitrary criteria could be used to select the particular collection of countries used by W&P when it seems so very important to their claims that just this very specific sample are used.

* Is it just me that always thinks of this when they hear 'Wilkinson and Pickett'?

** I always exclude Luxembourg even though it is in the OECD because W&P pretty much exclude it from any analysis even though it's rich, and I think most people would agree with them given that it is a tiny (under half a million) country, and also the OECD don't have Gini or health expenditure data for it.

*** If this is upsetting you I also derived some 2007 data from another source for Israel and Singapore (from the UN Human Development report 2009) and the findings were the same with these two countries included. When I just looked at those countries used by W&P in their analyses (using OECD data plus the above data for Israel and Singapore) I also found no relationship between Gini and life expectancy (r=-.11, p=.61) which highlights just how important the exact combination of data source and subsample of countries is for W&P's claims. I haven't included UAE, Kuwait, Brunei, Qatar, Bahrain, Barbados, the Bahamas, or Cyprus in any analyses, just as W&P haven't, although they are richer than Portugal on that curve.

Levelling the spirit - pt 1

2010-10-13T18:02:00.006+01:00

I listened to an episode of Radio 4's Analysis programme about the ubiquitous book 'The Spirit Level' today (it has also been covered on More and Less). I resisted reading the book for a long time because I both (a) sympathised with the authors aims and broad policy recommendations and (b) suspected that the actual data and methods used would make me cringe and then rant.

I was right.

So in order to fulfil the 'rant' part of that reaction I'm going to share my thoughts on the evidence behind the Spirit Level in two parts trying not to associate myself with some of the attacks on the book from the right (but note that criticism hasn't come only from the right). I'll start with a discussion of the scatter plots that form the core of the book.

Bivariate scatter plots - playing dot-to-dot with the data

Now I'm just not a fan of 'ecological' analyses at the level of countries - even if you do multivariate analyses trying to control for confounding variables you're still taking a dozen heterogeneous societies and drawing straight lines through the data in a simplistic fashion. But in this book the authors, Richard Wilkinson and Kate Pickett, aren't even doing that, they're just plotting bivariate scattergrams, which doesn't bring the level of the analysis much above the level of a blog post (and I should know, I've written just such posts).

What the authors do is basically print a large number of scatter plots which show a relationship between 'inequality' (largely represented as income inequality) and something bad (e.g. murder rates, overall mortality, subway sandwich bars per capita, etc*) - they promise that the scientific literature shows that any potential confounding factors don't matter.

So just how robust are the correlations in the Spirit Level? Well lets look at one of them - the book makes considerable hay with the relationship between (income) inequality and worse life expectancy so that is what I will focus on (see Figure 1 below). It seems that the worse the income inequality in a country the lower the life expectancy.

Figure 1: Income inequality versus life expectancy (from the Spirit Level)

Well first let's sense check the data** and look at the relationship between income inequality (here represented by the mid-2000s Gini coefficient) and life expectancy at birth (see Figure 2 below). There's a big relationship with a correlation of -.41 (that is, the higher the GINI coefficient, and the more unequal the society, the lower the life expectancy) just as we would expect from the Spirit Level data.***

Figure 2: Income inequality versus life expectancy (OECD figures)

So what is causing this relationship between income inequality and life expectancy? Wilkinson & Pickett would say that it is psychosocial factors (such as chronic stress caused by the status anxiety of an unequal society - more on this in part 2) but we can't really reach the conclusion that it is inequality per se causing the lower life expectancy without considering some alternative explanations - that is, we need to ask what other factors are correlated with both inequality and life expectancy that might actually causally mediate the relationship and show that they don't, in fact, do this.

Confounding variables - assessing alternative explanations

I've previously talked about the relationship between health expenditure and health outcomes including life expectancy (in these five posts here) and this would represent a good first proxy for those material factors that could underlie this relationship. Wilkinson & Pickett (W&P) say that health expenditure cannot be the causal factor, and produce this little graph to illustrate why (see Figure 3 below).

Figure 3: Health expenditure versus life expectancy (from the Spirit Level)

In this scatterplot they find no relationship between the expenditure on health in these developed countries and life expectancy. Could this really be true? The US could reduce its expenditure from nearly $6000 per person down to the Portugese level of nearly $2000 and have no effect on life expectancy? That is quite a bold claim to be making with really very far reaching potential consequences if it is true.

So let's sense check this data, we'll get our data from the OECD again, looking at total expenditure on healthcare in dollar purchasing power parity equivalents (see Figure 4 below).*4


Figure 4: Health expenditure versus life expectancy (OECD figures)

Strangely I seem to get quite a strong relationship between health expenditure and life expectancy, the correlation is .56 (that is, the more money spent the longer the life expectancy). In addition the correlation between Gini and expenditure is -.30 - so it might be plausible that rather than being mediated via psychosocial stresses maybe more unequal societies just don't spend as much on healthcare which leads to material deficits in the healthcare for that country - is it the case?

Well there are statistical methods to think about (although maybe not resolve) this question - a partial correlation looks to control for a third variable using regression analysis and then to then look at the relationship is between the two other variables assuming that third variable is the same across the sample. If we look at the relationship between Gini and life expectancy where we partial out the effect of health expenditure there is a correlation of .3 between Gini and life expectancy - that is, if we assume that expenditure is equal between all countries then increasing inequality actually predicts longer life expectancy (but this is not actually statistically significant).*5

Choosing your sample - or picking those cherries?

So why does the graph from the Spirit Level show no relationship between health expenditure when my scatterplot shows a strong relationship? Well we can see from the two charts that in the bottom left hand corner of mine there is a little bunch of countries that I have included and W&P have not - these include Hungary, Poland, the Czech Republic, Slovenia, Turkey and Mexico - I also don't have Singapore in my chart since it isn't in the OECD (while the others are).*6 So why aren't these countries in the Spirit Level? The book says:

"All the data come from the most reputable sources - from the World Bank, the World Health Organization, the United Nations and the Organization for Economic Cooperation and Development (OECD), and others."

Which isn't particularly enlightening. But in their 'response to critics' W&P say:

"In The Spirit Level analysis the authors took countries among the 50 richest in the world with populations of more than 3 million, for which there was comparable income distribution data. They did this because they wanted to look at the countries where life expectancy and other outcomes have ceased to be related to economic growth. Peter Saunders adds in Chile, Argentina, Mexico, Venezuela, Turkey, Trinidad & Tobago, Malaysia, Russia, Estonia, Lithuania, Latvia, Poland, S. Korea, Romania, Slovenia, Hungary, Croatia, Czech Republic, Slovakia. In Figure 1.1 (in The Spirit Level ) it can be seen that all these countries are on the rising part of the curve indicating that for them, unlike the richest countries, economic growth remains beneficial. Saunders' later demonstration that economic growth remains beneficial is entirely a result of including these poorer countries."

That figure they refer to is this one (Figure 5 below):

Figure 5: National income (per person) versus life expectancy (from the Spirit Level)

What they are arguing (and indeed argue in the book) is that for poorer countries there is a relationship between life expectancy and economic development - the richer the country the longer the life expectancy - but this relationship then disappears when you get to a certain threshold of wealth. We can see from their graph that there is certainly a steep portion of the scatterplot (below $10,000) and the region they want to concentrate on is the flatter part (above $25,000) but I think it is pretty misleading to claim that we can see no relationship between wealth and life expectancy once we move beyond the steep portion of the curve - certainly to my eye there is a less steep but still linear relationship between wealth and life expectancy in the region above $10-20,000.*7

Even by W&P's standards if we look at countries by PPP adjusted GDP or by nominal GDP per capita they should have included countries like Hungary, the Czech Republic, Slovakia, Poland or Croatia which all come in the top 50 and have populations over 3 million. I took my data (without trying to decide on countries a priori) by just looking up what OECD data was available, and using that directly including where the numbers were indicated to be estimates (since we're interested in trends not exact numbers here). I'm somewhat concerned as to what exact grounds W&P have used to justify excluding those countries which fall at the bottom left of the scatterplot and thus will contribute most to the correlation between wealth (or health expenditure, or whatever measure of material difference we're using) and life expectancy.

At this point I think we need to talk about range restriction. If there is a correlation between two variables (say, for example, height and weight) then, despite the scatter (since not every heavy person is tall, and not every tall person is heavy, it is a relationship that holds on average) there will be a correlation and you can draw a nice regression line showing the relationship - but what happens if you just look at one part of the range (say only those above average in height)? well the relationship (as measured by the correlation) gets smaller, because the scatter noise now begins to mask the relationship. If you keep restricting the range eventually you'll end up with no relationship at all (say looking only at those in the top 10% of heights) even though we know that there is a relationship when we consider the whole range (have a look here for a visual example).

What this digression means is that you have to be careful about insisting on only looking at rich countries because you may not be showing that there is no relationship between expenditure and health in those countries, you may simply have restricted the range so much the relationship gets lost in the noise. And a good sense check for that is to see what happens when you add in a few countries at the bottom of the range - if there really is not relationship it shouldn't make much difference, and if it does you might want to think about just why you're excluding them - a point that is think is highly relevant if you're thinking about keeping in, say, Portugal (population 11m, nominal GDP per capita $22k) but excluding, say, the Czech Republic (population 10m, nominal GDP per capita $18k). Looking at W&P's argument above you also have to be very careful you don't begin some circular reasoning ("these countries are on the rising part of the curve...economic growth remains beneficial") where the very fact that a country has low health expenditure and low life expectancy, so that if it is included in the analysis there will be a relationship, it therefore must be excluded from the analysis - i.e. if there is a relationship we'll eliminate these countries until there is no longer a relationship! (see part 1.5 for further discussion of just how important the specific selection of countries by W&P is for their claims).

So, I think my take home message from part 1 is that the Spirit Level doesn't deal with potentially confounding factors in a satisfactory way, ignoring or dismissing material differences between high and low equality countries that could be the actual causal mechanism for the relationship between inequality and life expectancy (or other measures).*8 It also contains some fairly arbitrary and suspect looking decisions to exclude various countries that upset the arguments W&P are making.

Nothing new under the sun

It is probably worth noting that these shortcomings are not accidental - Wilkinson has been working in this field, and making these sorts of arguments, for many years and others have been questioning the assumptions he makes for just as long.

Take a look at some figures from literature published in the BMJ in 2000-2001 on this topic of wealth and inequality:

Figure 6: GNP per capita versus life expectancy (from Marmot & Wilkinson 2001)

The authors of this figure (Figure 6 above), one of whom is Richard Wilkinson, report that:

The figure shows the relation between life expectancy and gross national product per capita at purchasing power parities for the 25 richest countries for which the World Health Organization holds 1998 data.There is a slight negative relation between the two (r=−0.107). For the 30 richest countries, the correlation is 0.064. It is only when poorer countries are included that the association with mean income emerges.

This article is in response to one which produces the figure below:

Figure 7: GDP per capita versus life expectancy (from Lynch et al 2000)

The authors of this graph (Figure 7 above) are criticising Wilkinson's previous claims that there is no relationship between wealth and life expectancy:

Wilkinson's demonstration that absolute income was unrelated (r=0.08) to health among developed countries has been important in staking a claim for this psychosocial theory of health inequalities.Figures...show the association between gross domestic product per person and life expectancy...for the 33 countries where gross domestic product was greater than $10000—the cut-off used by Wilkinson. Our results, however, include data for all the countries above $10000, not a selection of some countries in the Organisation for Economic Cooperation and Development as used by Wilkinson. The correlation between life expectancy and gross domestic product per person in the complete sample is r=0.51 (P=0.003). Thus the association between absolute income and life expectancy among wealthier countries depends on which countries are included.

This is an argument that started a long time ago, the points being made now by the critics of W&P are not new, while I'm sure we're not going to resolve this debate any time soon it would be grossly misleading to pretend that these criticisms are purely politically motivated. Many researchers in this field were unimpressed when Wilkinson first made these arguments and those objections still stand largely unanswered.

I think that's enough for today - in part 2 we'll discuss the evidence for those psychosocial mechanisms W&P postulate to provide the causal connection between inequality and health (and various other 'bad things'). If yiou just can't wait until then 'Levelling the spirit - pt 1.5' should tide you over.

* I may have made up one or more of these examples.

** I'm going to use OECD data on OECD countries as my sample - the Spirit Level uses a lot of data from them and they largely represent what people would consider developed high income countries, I'm using 2007 which is the most complete set of data I have available. I've included all OECD countries I could get data for directly from the OECD so I don't include Chile because there was no Gini data or Luxembourg and Portugal because there was no health expenditure data, the US and Korea lack infant mortality data but are included in the life expectancy analysis.

*** All correlations are statistically significant at least to p<.05 unless I specifically note otherwise.

*4 This means that instead of adjusting expenditure between countries by the exchange rate between their currencies you look at what that expenditure would actually buy within the country concerned (so in a poor country your dollar is likely to go a lot further than in the US, and the purchasing power parity equivalent conversion reflects this). This seems to be the same thing that they do in the Spirit Level (see, I don't just make this stuff up).

*5 Note that if you partial out Gini from the relationship between expenditure and life expectancy you still see a partial correlation of .50 - more expenditure means longer life expectancy.

*6 This is a similar finding to that made in this person's blog post except, for some reason (perhaps selection of source for Gini coefficients) they don't find a significant relationship between Gini and life expectancy (whereas I do) but they do find the reversal of this relationship if you include covariates (in their analysis per capita GDP).

*7 An interesting comparison to W&P's claim that income (or expenditure) has no effect on life expectancy (or other health outcomes) can be found in the Spirit Level itself - in a figure from the book (Figure 8 below) W&P compare the relationship between the mortality rates in individual US counties and median household income in those counties:

Figure 8: Median household income by US county versus standardised mortality rate (from the Spirit Level)

What W&P want to do is compare the steepness of the slope indicating the relationship between income and mortality between those counties from the 25 most equal states and the 25 least equal states. That more equal states have a less steep relationship between income and mortality doesn't concern us here, what is interesting is that there is a relationship between income and mortality at the county level within the US at all - this is contrary to what W&P are arguing at the level of individual nations where they dismiss a relationship between national income (or health expenditure) and life expectancy (or other health outcomes) and you have to wonder why this relationship would hold within a rich country but not between them.

*8 Looking at infant mortality, another measure often used to estimate a country's level of health, we find that there is a correlation between the Gini coefficient and infant mortality of .77. Health expenditure correlates with infant mortality with a coefficient of -.64. However, unlike with the relationship between Gini and life expectancy, the partial correlation between Gini and infant mortality, controlling for health expenditure, the coefficient is attenuated to .62 - that is the relationship between income inequality and infant mortality is not likey to be mediated purely through the relationship between health spending and infant mortality - so it is more complicated than just claiming that the relationship between inequality and any health measure is simply mediated by health spending.

Catholic balls

2010-09-17T10:11:00.000+01:00

From the Daily Mash:

POPE Benedict was congratulated on the sheer heft and girth of his testicles last night after the former Hitler Youth member said atheists were Nazis and accused Richard Dawkins of plotting a new holocaust.

Looking as if he believed every word of it, the Pontiff claimed it was the Nazis' atheism that drove them to kill millions and warned that the smart arse you argue with in the pub about religion will eventually gas you in a camp near Watford.

Stephen Hawking rules modern art is rubbish after all

2010-09-02T17:59:00.001+01:00

I love the idea that the world was basically waiting with baited breath for Stephen Hawking to make a ruling on the existence of God:

There is no place for God in theories on the creation of the Universe, Professor Stephen Hawking has said.
He had previously argued belief in a creator was not incompatible with science but in a new book, he concludes the Big Bang was an inevitable consequence of the laws of physics.

The Daily Mash:

"And - though it probably goes without saying - if the creation did not involve chocolate or monkey balloons, then who made your so-called 'physics'? Thrust and parry!"

Professor Hawking had previously argued that a 'grand unified theory of everything' could offer a glimpse inside the mind of chocolate but now accepts that such a discovery would finally make chocolate irrelevant, except for maybe Aeros and Wispas.

Depression severity

2010-08-13T21:10:00.000+01:00

Interesting post on neuroskeptic about the HAMD:

"The APA use the terminology "Very Severe", which doesn't even appear on other scales...But where did the APA get their system from? This is the most extraordinary thing. Here's the paper they based their approach on. It's an 1982 British study by Kearns et al...You'll recognize the APA's categories, kind of, but they're all shifted. Why? We can only guess. Here's my guess. The scores in that Kearns et al graph were the average HAMD scores of people who fell into each severity band. The APA must have decided that they could use these to create cutoffs for severity."

Could I care less?

2010-05-24T22:20:00.004+01:00

Sadly this is something that really bugs me too.

A thought for our new Tory overlords

2010-05-09T21:17:00.005+01:00

I hope when the cuts fall they remember that those without much are least able to tolerate losing it, when you have lots there's plenty to cushion the blow. But I don't think that this is a message that they'll be receptive to.

Panorama and migration

2010-04-19T21:29:00.001+01:00

Vaguely watching this dull Panorama, sensationalised and tabloid as all Parorama documentaries have become, about population pressures in the UK, concentrating, it will not surprise you, on blaming it all on immigrants: "there's a widespread belief that migrants get preferential access to housing...[insert glaring lack of any attempt to actually answer whether this is the case or not]"

But I was struck by the figure of immigration benefiting the UK by "only 60p per person per week" (contrast this with Migration Watch's previous figure of 4p) apparently sourced from this Lords report (although I can't find that specific figure), and contrasted with the 'misleading' government use of the benefit to GDP of immigration.:

The total size of an economy is not an index of prosperity. The focus of analysis should rather be on the effects of immigration on income per head of the resident population.

The report makes an interesting point about how while in the short term migrants fill vacancies in he economy but in the long term the economy proportionately expands (increasing vacancies again). But in emphasising the raw monetary figure of per capita increase in GDP I think it is equally if not more misleading than the government approach. In particular I take issue with their rejection of the argument that a large proportion of the UK population are not of working age, whereas new immigrants are largely young or working age such that they swell the (shrinking) working age population which contributes (proportionately) the majority to the economy and state coffers - so that dividing immigrant contributions over the whole population is unfair because they are largely not addding to the dead wood of the non-working populace (who actually cause most of the costs to the state). The report says:

Arguments in favour of high immigration to defuse the “pensions time bomb” do not stand up to scrutiny as they are based on the unreasonable assumption of a static retirement age as people live longer and ignore the fact that, in time, immigrants too will grow old and draw pensions. Increasing the retirement age, as the Government has done, is the only viable approach to resolving this issue...

Lord Turner argued that as people live longer, it is reasonable to assume that the extra years of life are divided between working years and retirement so as to keep roughly stable the proportions of life spent working and retired. Under this assumption, half of the projected increase in the dependency ratio disappears, when compared with the simplistic case in which the retirement age stays unchanged.

First of all I'd like to make clear that it is generally considered that for every additional year of life expectancy you can expect at best 6 months of relative health and 6 months of ill-health such that the policy of incrementally increasing the retirement age with life expectancy is basically aiming to work the populace until they are sick and to erode the few years of healthy retirement they might otherwise have expected*. It is also worth noting that immigrants can have a tendency to return to their country of origin after a few years. So while it is true that increasing the working age population will increase the number of retired people eventually (although to a lesser extent in the first generation due to decreased life expectancy compared to the UK population as a whole) it is still more sustainable in the short term than increasing the retirement age until people are being worked right to their death beds (in order to pay for the current older generation's nice early retirements at 60-65yrs old with over 10 yrs of life expectancy).

In this vein, if we're going to talk about how much immigrants add in 'per capita GDP' we have to compare them to other members of the population - old people or the unemployed for instance - what do they cost in per capita GDP? Averaging over a homogeneous UK 'indigenous' population is completely misleading because compared to significant proportions of the UK population immigrants use much lower poroportions of national expenditure. The question should be how many 'indigenous' people does each immigrant support? And 'per capita GDP' can't answer this.

To look at it another way, if we consider a British person who contributes exactly the average per capita GDP to the country, are they having zero effect on the country or a net benefit? According to the 'per capita GDP' measure of economic contribution they are giving nothing to the country - despite working, paying taxes etc. - whereas common sense shows that they are helping to pay for those people who are a net cost to GDP (the economically inactive like the old, the young, the sick, the unemployed).

* Another gift from 'The Most Selfish Generation'

BBC distorting the news

2010-04-13T21:20:00.000+01:00

This story was widely reported in the news today:

Preventable diseases in children are reaching epidemic proportions that could see a generation dying before their parents, doctors at a leading children's hospital have warned.

But this story is obviously related to this BBC documentary:

With unprecedented access to Alder Hey Children's Hospital in Liverpool, Panorama meets the kids and the paediatricians treating them, and follows them home in an attempt to uncover the root cause of their problems. Reporter Richard Bilton soon discovers that some of the basic health messages from the doctors are not getting through to the parents.

So either Alder Hey have been sending out press releases to coincide with BBC documentaries or the BBC have done so themselves, either way it is a real distortion of the news agenda for the day to present this story without pointing out the BBC's role - unfortunately this seems to be more and more common. A particularly stark example can be seen when the Today programme interview someone then the news bulletin seconds later reports a throwaway comment (often the result of bizarre questions and extensive badgering all designed to get a specific response) as if it is some groundbreaking announcement (normally quoting it out of context).

So today's health news was dominated by essentially an advert for a BBC documentary. Maybe there was something worth saying but the media really need to be more transparent about what is driving the news agenda.

Gotta persecute me some Christians

2010-04-05T20:46:00.002+01:00

Amusingly partisan documentary on the 'persecution' of Christians. Damn those 'New Atheists', still at it. Of course I have some form, after all, 'ultimately you are either for or against baby Jesus', oh why do I hate the baby Jesus so?

"It is true that a number of muslims have failed to win the right to wear the full veil at work, but even so..."

Serotonin hypothesis of depression

2010-03-30T22:58:00.000+01:00

A post from The Twenty-First Floor on the serotonin hypothesis of depression:

The main aetiological explanation for depression in the public consciousness is undoubtedly the “serotonin hypothesis”. This probably manifests more popularly as the idea that depression is somehow the result of a “chemical imbalance” in the brain, and therefore that sufferers of depression (whose suffering is not in question) are somehow the passive victims of an organic condition, like victims of diabetes, for example, and that this can be righted with medication. It’s a neat explanation, which, I guess, is why it’s so appealing. However, the evidence, as it so often does, suggests that depression is nowhere near this simple.

While I agree that the evidence for the serotonin hypothesis of depression (or even the rather wider monoamine hypothesis) is fairly weak, he links to this study finding mixed evidence for an association between suicide, impulsivity, and depression and serotonin metabolite levels. It is worth noting that a review by Mann et al (1989) is often taken as demonstrating that serotonin (or its metabolites) are reduced in the brainstem (source of serotonergic projections in the brain) in suicides, independent of underlying diagnosis. Although this actually only shows reduced serotonin in depressed suicides (if you look at the individual studies) that would actually make it stronger evidence for the hypothesis.

Treating depression in general medical patients

2010-03-26T21:59:00.250Z

As a doctor with an interest in psychiatry currently working in general medicine the issue of depression in general medical patients is one that interests me. We commonly see overdoses secondary to depressive illness and depression in patients with terminal diagnoses but also in many other conditions, particularly chronic disease. While we have access to specialist psychiatric or palliative care services for the former conditions that still leaves a substantial number of depressed patients to care for, and that is something of a treatment dilemma.

Physical illness is strongly associated with depression and some 10-20% of general medical inpatients or outpatients have a depressive disorder. This is particularly marked for people with chronic disease where rates range from 11% of diabetics to 20% of people after a heart attack. Depression is a a risk factor for poor prognosis in physical disease, being associated with worse mortality, at least partly mediated via decreased adherence to treatment. Yet evidence shows that physically ill patients receive less antidepressant prescriptions than other depressed patients.

There are some specific challenges in recognising and treating depression in general medicine, early in an admission somatic symptoms of depression can difficult to distinguish from symptoms of physical illness and later on during treatment low mood can be considered 'understandable', with a natural resistance on the part of clinicians to medicalise normal emotional reactions. The inpatient environment is also unusual and stressful and it is unclear whether patients will maintain a low mood or improve when discharged home. Practically, the onset of antidepressants is generally believed to be delayed over two weeks which means that any effect may not be seen during an acute admission and psychological therapies such as CBT are just not available in general medicine.

In recent years the risks of self-harm and discontinuation syndromes with antidepressants have received significant coverage and since Irving Kirsch's 2008 paper much doubt has been raised about overall antidepressant efficacy in any other than the most severe patients. A recent Cochrane Review has addressed the question of antidepressant usage for depression in physically ill patients:

Rayner et al 'Antidepressants for depression in physically ill patients' Cochrane Database of Systematic Reviews 2010, Issue 3.

They looked at studies of depression quite broadly defined (major depressive disorder, adjustment disorder, dysthymia) and found 51 studies (mostly in SSRIs but also in tricyclics and a few less common antidepressants), with fluoxetine (Prozac) the drug most commonly studied (12 trials). The physical diseases studied included stroke (11 studies), HIV (7), Parkinson's disease (6), cancer (4), COPD (chronic bronchitis and emphysema; 3), diabetes (3) , heart attacks (2), and renal failure (2). At the two follow-up periods of most interest (6-8 wks and 9-18 wks) there were around 1,000-1,500 subjects included in the analysis.

Overall they found that antidepressants were similarly effective at all follow-up durations (ranging from 4 to greater than 18 weeks) as seen in the summary figures on the right. We can see an odds ratio of around 2, that is antidepressants roughly double the chance of a 50% improvement in outcome score (most studies used the Hamilton Rating Scale for Depression) or showed a standardised mean difference of around 0.5*

Looking at other aspects they found that there were more people dropped out of the study from the antidepressant group than the placebo group (this was marginally significant) with an odds-ratio of 1.3 (95% confidence interval 1.0-1.8). Looking at side-effects, dry mouth and sexual dysfunction were both significantly more likely to be reported by those in the antidepressant group, the latter being primarily driven by those taking SSRIs. So overall antidepressants had side-effects sufficiently bad to lead more people to drop out of the study.

The study didn't find any striking differences between the efficacy of SSRIs and other antidepressants, nor differences between taking a narrow (major depressive disorder only) or broad definition of depression.

Looking at the I-squared statistic for trial hetrogeneity we can see that for dichotomous outcomes differences between trials were not very large but for the mean difference outcomes there was very large heterogeneity. However, this seems to be due to two studies with stonkingly big effect sizes (improvements greater than 10 points on the HRSD) and excluding these from analyses drops the I-squared right down without massively affecting the results.

Overall this is quite an interesting finding and it suggests that antidepressants can be really very effective for depression in physically ill patients. But there are some limitations to bear in mind:

Most studies were pretty small, almost all with less than 100 subjects and we know that small studies are more likely to overestimate the size of the beneficial effect
Trial quality was actually pretty low, and low quality trials are known to overestimate effect sizes (more on this below)
Publication bias was apparent in the studies (more below)
The effect of baseline severity has become a hot topic since Kirsch et al and this study didn't look at this (more below)
They looked only at the 10 most common side-effects but not overall adverse event rates, or specifically serious adverse events, and this prevents detection of less common but serious complications (stuff like death or suicide)
No subgroup analyses were performed to see if antidepressants were more effective in specific physical illnesses (say in stroke rather than HIV)
They did not look at studies with co-morbid psychiatric illness, this is important because mixed disorders, particularly with aspects of both depression and anxiety, are very common

Looking at a funnel plot from the study we can see apparent publication bias (see right), the gap at the bottom left of the pyramid represents missing small trials (or rather, trials with a large standard error) with a large negative effect of antidepressants. This suggests that some negative trials (which we would have predicted would exist based on the effect size we are finding) are missing from the literature included in the review. This is an example of how small positive trials are much more likely to get published than small negative trials which disappear into the file drawer. Publication bias is a known problem in antidepressant trials. When Turner et al analysed data submitted to the FDA before approval** they found that 37/38 positive trials were published but only 14/36 negative trials were published, and 11 of these actually claimed a positive result!

Trial quality was disturbingly low, the authors used the 'Risk of Bias' table from the Cochrane Handbook to score as 'low risk', 'unclear risk', or 'high risk' of bias on six items:

Sequence generation
Allocation concealment
Blinding
Incomplete outcome data
Selective outcome reporting
Other issues

Only three studies scored as 'low risk' of bias on four or more items*** and only something like 13 on three or more items. The authors find that by looking only at these 13 odd studies the effect size is not grossly different to looking at all the studies. If we just look at the three best quality studies (see right, data from 9-18wks) there is a large effect that is not statistically significant for the mean difference in HRSD scores (but it is significant looking at SMD) that suggests that it isn't purely low quality trials driving the beneficial effect of antidepressants seen in this study.

Not looking at the effect of baseline severity in the wake of Kirsch et al and its widespread impact is curious. Kirsch et al, looking at the same FDA data as Turner et al, found that the NICE threshold for 'clinical significance' (an improvement of 3 points on the HRSD or 0.5 SMD) was reached around a baseline severity (as measured by the HRSD) of 26 points, which is classified as 'very severe' by NICE and the American Psychiatric Association (see right). Similar results were found by Fournier et al looking at individual subject level data.

I made a back of the envelope attempt to plot the meta-analysis data against baseline severity**** and we find that the NICE threshold is actually reached at quite low baseline severity (18.5-21.5) which falls in the upper range of moderate through to severe severity.

In summary, studies of antidepressant use in physical illness indicate a large effect size that is 'clinically significant' in the 'severe' depression range, and there is a disparity between the large effects sizes in this review and in other studies of depression. Although I have some criticisms of Kirsch et al it seems most likely that this disparity is due to publication bias in the Cochrane meta-analysis. There are some interesting issues regarding the way that studies in general depression usually have a more severe major depression population and any extrapolation to less severe patients is on the basis of few studies whereas the Cochrane review includes a number of less severe conditions and it is possible that this makes it therefore more sensitive to beneficial effects at the lesser degrees of severity. It is also possible that physically ill patients may be more responsive to antidepressants but I'm unconvinced.

This study looked at largely outpatient populations with chronic illness and it isn't clear whether the results are directly applicable to inpatient populations but it certainly supports the use of antidepressants in inpatient depression and suggests that at the very least they are likely to be as effective in this population as in the general population of depressed patients.

Finally it is worth noting that NICE has a guideline on treating depression in chronic physical illness which makes recommendations which are broadly similar to those they make for depression in general:

For low persistent subthreshold depressive symptoms or mild to moderate depression:

Low intensity psychosocial intervention (e.g. computerised CBT etc.)
If symptoms persist, previous severe depression, or symptoms compromising care consider either:

SSRI (citalopram or sertraline first line)
High intensity psychosocial intervention (e.g. individual CBT etc.)

Severe depression

Antidepressant and individual CBT

Be aware of drug interactions

* Standardised mean difference is the difference between the mean outcome scores for the antidepressant and placebo groups divided by the standard deviation, this corresponds to something like a difference of 4 points on the HRSD. Since many studies don't report dichotomous 'improvement' measures, or use different definitions, and these have to be 'imputed' using the mean difference data (making assumptions about how the data is distributed), I prefer mean difference data, ideally using the raw HRSD figures rather than the standardised mean difference (since this can create odd distortions in the data, e.g. in Kirsch et al's study). Almost all studies use the original 17-item HRSD but the few studies that instead use, say, the Montgomery-Åsberg Depression Rating Scale means that the authors have used the SMD so that this data can be combined (the SMD is supposed to allow you to combine data from different scales that are intended to measure the same thing).
** This data should be free from publication bias because the FDA legally mandates the pharmaceutical companies to supply all studies performed on the drug.
*** Cochrane actually discourage adding these up to produce a scale but I can't think of a better way to see which studies are more or less biased.
**** Only including those studies with HRSD data, and those trials where I could access the article and extract it. Since I didn't try too hard to check everything it is quite possible some scoring from scales other than the 17-item HRSD crept in there.

UPDATE

In response to neuroskeptic in the comments, here's the baseline severity data split by antidepressant and placebo groups (as seen in Kirsch et al's analysis), the regression is weighted by sample size, the baseline severity is mean HRSD score, the improvement is mean baseline severity minus mean HRSD score at 6-8 weeks. We can see that increasing baseline severity leads to increasing response to antidepressant with placebo response fairly flat. This was pretty much what we found when we looked at HRSD outcome data from the Kirsch et al study.

Summary Care Records

2010-03-13T20:54:00.000Z

Frontier Psychiatrist has a good post on summary care records, not a fan it appears. I'll share my comments:

I've elected to remain opted in (although I do have a very dull medical history). In my everyday practice on acute medical and surgical takes I have seen many patients who would have benefited from us having access to their SCR - most patients, surprisingly I think, seem to know remarkably little about their past medical history, particularly their surgical history, and in my trust it takes a day or more to get a patient's medical notes (the notes stored for that trust only, anything from elsewhere is very difficult to obtain, including GP data) assuming they haven't been misplaced or lost somewhere on the way. I can think of at least one death in the last few months that might have been avoided if details of past medical history were known.

I have no doubt that, as with many other big government IT projects, there will be massive cost overruns and huge useability issues, but in theory I think it is a good idea.

Popular political science

2010-03-13T19:28:00.001Z

Interesting piece of popular political science on PoliticalBetting.com:

A new measure by researchers at the University of Manchester shows a significant problem for Gordon Brown: the mood of the country is against Labour on policy competence.
Green and Jennings argue that it is important to study the public mood across a large number of issues: public ratings of party policy competences move together.
This graph shows the authors’ measure, “macro-competence” over six incumbent governments, annually, from 1950 to 2010 (the final data point is February 2010 – the most recently available).

The Tories and medical blogging

2010-03-13T15:16:00.001Z

It has come to my attention that over the last year or so the Tories have been checking out the medical blogosphere and making discrete contact with influential medical bloggers. I haven't heard of Labour or the Lib Dems making similar overtures. This may reflect the Tories' cutting edge online strategy or just that Labour have completely conceded the ground to them.

What is interesting is the pattern that has seemingly emerged. Rather than outright endorsement of the Tories* there is just explicit condemnation of Labour and what it has done with the NHS. This chimes rather well with the attitude amongst doctors within the NHS. Although naturally leaning towards the Conservatives as upper middle class high earners doctors also have something of an old fashioned public service ethos and are understandably concerned with public service provision (being public sector employees, directly or indirectly, themselves). However, in recent times, after the euphoria of the early years died down, doctors have been fairly vocally critical of Labour's 'reform' agenda, from PFI to patient 'choice'. This is an attitude that you can see daily being expressed by doctors to patients, and this must have a real influence on regular health service users.

But it is only half the story and there is a danger that by failing to spell out what an alternative to Labour's unpopular policies would entail doctors are giving tacit endorsement to the Tories who, in many ways, want to extend and entrench exactly those policies which have proved so unpopular and unsuccesful. I wonder whether the Tories have already figured this out.

* Although perhaps a little nearer the election this will change, with nose peg style 'change' rhetoric.

A case study in nurse practitioners

2010-02-28T11:21:00.001Z

Let us consider a hypothetical district general hospital, we will call it Fairylandshire NHS Trust (FNT), they have identified a suitable area for the creation of a new nurse practitioner role to help facilitate clinical care and free up the time of doctors to do other tasks. Sounds great doesn't it?

What the managers and senior types at FNT had noticed was that a very large proportion of new referrals to the Medical Admissions Unit (MAU) were suspected DVTs. These took up a lot of doctors time but were generally fairly straightforward to deal with - so much so that a nice little flowchart for how to manage these cases was created.

So how did the MAU work before? Well the triage nurse (a sister/charge nurse) would take a GP referral* and then the patient would, eventually, come in to the unit to be triaged by said nurse (including taking bloods). Once triaged** the patient is seen by a junior doctor who takes a history and examines the patient and then arranges any additional tests that may be needed (x-rays, venous ultrasounds etc.), usually after having waited a little while for the blood results to come back. Once this is done the junior doctor decides on a diagnosis and management plan, then at some later point*** the on-call consultant comes and reviews the patients and management plan.

For suspected DVTs the more experienced juniors (SHOs and registrars) may decide to discharge the patient without consultant review if they do not suspect anything sinister going on and the tests are negative (FY1 doctors can do the same if they discuss it with a more experienced junior doctor first). Once all the management has been decided and if the patient can go home the doctor then writes a discharge summary for the GP, medical notes, and patient, and prescribes any necessary medications to take home and arranges any follow-up. If a patient has a pulmonary embolism (a blood clot that has gone to the lungs) the consultant will need to see them anyway, and all the findings and management plan will be discussed. If it isn't a DVT and isn't serious the junior doctor will discuss the findings and management with the patient and send them home or back to their GP's care. All this takes place on a severly overcrowded ward with a single triage room and a single assessment room (the latter for the junior doctors to use to see the patients), a spare bed may or may not be available on the ward if more than once doctor needs to see a patient at the same time (there are usually 1-4 junior doctors available to see patients depending on the time of day and whether they are needed in A+E or on the wards).

So, what is the wonderful new innovation that will speed up this process? The 'Thromboembolic Nurse Practitioner' (DVT nurse to you or me). She will see any suspected DVT instead of the triage nurse (and see them in the single assessment room usually used by the doctors), take bloods and do obs as the triage nurse does and then...measure the calf circumference on each side. There is a lovely long pro-forma for DVTs with lots of wonderful sections for the doctor to then fill out once the DVT nurse has seen the patient, they have to take a full history, they have to examine the patient (there is even a section for rectal examination findings!), they then have to reach a provisional diagnosis, calculate a Wells score (assessing the pre-test probability that the patient has a DVT), they then have to interpret the D-dimer test (a blood test for DVTs) based on the prior probability, they then have to arrange further investigations such as venous ultrasound if indicated by the 'DVT pathway', then finally they have to interpret all these tests and reach a final diagnosis (most of these patients do not actually have DVTs). If the patient is short of breath or has chest pain then a pulmonary embolism has to be considered and ECGs, x-rays and even lung perfusion scans arranged by the junior doctor (and a much more detailed history squeezed into the tiny history box on the DVT pro-forma).

After all this, if it does turn out to be a DVT the doctor then needs to prescribe low molecular weight heparin for the patient and start warfarin. At this point the DVT nurse will then talk to the patient about the treatment they will be receiving, adds them to a database for 'audit purposes' and arranges a clinic follow-up for them. If if is a PE the patient will be seen by the consultant and if it isn't a DVT then the same process as above will happen with the DVT nurse playing no further part.

So what does the DVT nurse (or rather what do the two DVT nurses) bring to the table? Well she only works 9am-5pm, costs about £10,000 per year more than the triage nurse, she clogs up the single treatment room usually used by doctors to see patients thus slowing them down, she gets an extra office on the same corridor preventing that being used for something more useful (the doctors office has, of course, be converted into bedspace), she harrasses the junior doctors busy seeing sicker patients to see her suspected DVTs as soon as possible, she does some minor counselling and arranging of follow-up for the few patients with DVTs, she does some follow-up clinic work and she undertakes audits and other ephemera to do with 'thromboembolic prophylaxis' around the hospital (note that there are two DVT nurses to do this extra work, one doing the assessments, the other doing the other ephemera). She saves maybe 10 minutes per confirmed case of DVT.

An FY1 doctor could nearly double their salary doing a DVT nurse practitioner role, I wonder if there are any locum jobs going?

* This is madness in itself, massively inflating the number of accepted referrals, having a doctor take the referral would allow them to refuse unsuitable referrals at an early stage decreasing the overall workload - but that isn't my focus here.

** In this unit triage actually means the presenting complaint is briefly noted and bloods are drawn and perhaps a cannula is inserted, and basic observations are taken (blood pressure etc.) No actual triage of severity is undertaken and the patrient is then seen by the next junior doctor available, whether they be FY1 house officer or registrar.

*** This can be very many hours later, and is also madness, since very sick patients can be seen by the most junior doctors without any review by more experienced seniors, and this may even include patients referred from A+E being seen by the FY1 doctors.

The drugs do work?

2010-01-31T16:43:00.000Z

An interesting article in the NY Times by psychiatrist Richard Friedman:

Last week, The Journal of the American Medical Association published a study questioning the effectiveness of antidepressant drugs. The drugs are useful in cases of severe depression, it said. But for most patients, those with mild to moderate cases, the most commonly used antidepressants are generally no better than a placebo.
...the authors of the new analysis gave themselves an additional handicap: they decided to exclude a whole class of studies, those that tried to correct for the so-called placebo response.
...
Another drawback of the study is that its conclusions are based on studies that included only two antidepressants — when there are 25 or so on the market. By contrast, when the Food and Drug Administration wanted to investigate the safety of antidepressants, it analyzed data from some 300 clinical trials, with nearly 80,000 patients, involving about a dozen antidepressants.
...
Every once in a while, a landmark study comes along and overturns everyone’s cherished ideas about a particular treatment. But the current study is not one of them. So it would be a shame if it discouraged depressed patients from taking antidepressants.

Neuroskeptic has blogged about this study before (Fournier et al 2010 JAMA 303(1)), but it is worth noting that, despite my criticisms of Irving Kirsch's meta-analysis of the FDA data on antidepressant efficacy, even when I reanalysed the data I found that the NICE threshold for 'clinical significance' was met at around a baseline severity of 26 points on the Hamilton scale. In this study by Fournier et al the threshold was met around a baseline severity of 25 points.

My analysis could only correct for baseline severity on a per trial basis whereas the above study was a patient level meta-analysis which is a better approach when available. So while the above study did include only two antidepressants (one of which was the older tricyclic class, although these are thought to be similarly effective to the newer SSRIs, just with more side-effects) it is consistent with the study by Kirsch et al, even given the criticisms of it I've previously raised.

So I don't think Friedman's criticism holds up, I think a more sensible attack is that the NICE threshold is entirely arbitrary, an argument I made at the time of Kirsch's paper.

30-year old women only able to conceive 30,000 times

2010-01-27T20:57:00.000Z

Scientists have discovered the reason why women find it difficult to conceive later in life - they have used up 90 per cent of their "ovarian reserve" by the age of 30.
...

The new research by the Univeristy of St Andrews and Edinburgh University is the first to colate the actual decline of the "ovarian reserve" - the potential number of eggs women are born with - from conception to the menopause.

It shows that on average women are born with 300,000 potential egg cells but this pool declines at a much faster rate than first thought.

By the age of 30 there is only 12 per cent left on average and by the age of 40 just three per cent. Dr Hamish Wallace, the co-author, said: "Our research shows that they are generally over-estimating their fertility prospects.
...
The researchers said many women make the mistake of thinking that because they are still producing eggs that their fertility remains constant. But this new research shows that it delcines rapidly.

Oh dear. I haven't read the original research, maybe it does demonstrate what the authors claim, but not on this evidence. Given that the average woman has 4-500 menstrual cycles in her lifetime then losing 90% of these eggs hardly makes a dent. Over 90% of eggs formed in gestation are lost by birth, does this explain why newborn and pre-pubescent children are infertile?

Dick swinging braggadocio

2010-01-15T20:34:00.001Z

As I noted last year:

If swine 'flu turns out to kill a lot of people this Autumn then Jenkins should really be forced to confront his words. Of course, it probably won't, further inflating his dick swinging braggadocio, until we finally do get a pandemic viral illness (which we will eventually) - when he'll be clamouring to know why more wasn't done. Ah, the privilege of consequence free comment pieces, the life of a journalist is so easy - you get to feel so important while doing fuck all.

As I feared the colossal arsehole has taken the fortunate avoidance of a pandemic flu as further proof of his omniscience:

This is why people are ever more sceptical of scientists. Why should they believe what "experts" say when they can be so wrong and with such impunity? Weapons of mass destruction, lethal viruses, nuclear radiation, global warming … why should we believe a word of it? And it is a short step from don't believe to don't care.

Why indeed should anyone pay attention to scientists and doctors when our always right Dr Simon Jenkins is there to keep us informed. What was that about AIDS again Simon?

"Aids has been confined largely to homosexuals and drug abusers, whose activities put them at risk of blood contamination and leave them vulnerable to lethal disease. There are some Aids cases outside the “high-risk” groups, but numbers are tiny: 60 at most in Britain. As far as Britain is concerned, the plague appears to be passing."

Iceland, a morality play

2010-01-14T20:49:00.004Z

Quoted for truth as they say on teh internets:

There really, really is no case to be made for the "plucky lickle Icelanders". It's notorious in the Nordic region for being a boastful little country with a selfish streak a mile wide, and when they elected successive governments of neoliberal chancers, they knew what they were doing.

From D-squared digest. The grown-up version is at Crooked Timber.

2010-01-03T20:53:00.003Z

Just found this in my email:

The IPA launched the Diagonal Thinking Self-Assessment last September and as we approach its first anniversary we are carrying out a review to assess its progress, the results of which will be used to further develop the Diagonal Thinking Self-Assessment.

As one of the 3,500 people who have completed the Self-Assessment, we would be very grateful if you could take a few minutes to give us your feedback on your experience and subsequent use of the results. As a small incentive to you we will holding a prize draw for an i-pod nano (8gb) among those who send back their completed questionnaire by 18th September 2009.

The questionnaire should only take you a few minutes to complete and all replies that we receive are much appreciated.

The link to access the survey is:

http://snaponline.snapsurveys.com/surveylogin.asp?k=125240289817

Many thanks for your help

Roger XXXXXX

Finance Department Research Consultant

I can't believe that I failed to share my views on the 'Diagonal Thinking Self-Assessment' with them - to recap:

One might be inclined to think that people in advertising know fuck all about logic and linear thinking, they certainly appear unable to figure out that despite physicists being a subset of scientists we can't tell whether any of them have high levels of intellect (and thus lack interpersonal skills) from these statements. Diagonal thinking my arse, smug self-congratulating tosspots more like.

Don't blame the system for winter travel chaos. Stay put

2009-12-23T20:10:00.002Z

Simon Jenkins says:

Hypermobility is now the opium of the people, an obsession that wrecks communities and planet. There are no free trips.

My solution to winter travel chaos? Don't travel. Stay indoors. Build a fire. Live and shop within walking distance of civilisation. Associate with neighbours. See distant relatives some other time of the year. Above all, do not complain if you insist on laying siege to motorways, stations and airports and the weather or the labour force let you down, as they do every year. It is not their fault, it is yours for being there.

I really don't know why people insist on not being London based journalists telecommuting from home.

If a hospital visit requires a drive of 50 rather than five miles, the NHS does not pay but someone does; indeed everyone does.

On the plus side, when you get to the 50 miles away hospital the economies of scale that entails mean that there might actually be some doctors and services there to provide you with at least a minimally effective service...that's if the doctors are allowed to get to work despite the fear of offending metropolitan pseudo-intellectuals.

Don't get sick this Christmas Dr Jenkins...and if you do don't you dare come to my hospital and screw up my already crappy Christmas day.

Newtongate

2009-11-22T19:22:00.001Z

Brilliant:

If you own any shares in companies that produce reflecting telescopes, use differential and integral calculus, or rely on the laws of motion, I should start dumping them NOW. The conspiracy behind the calculus myth has been suddenly, brutally and quite deliciously exposed after volumes of Newton’s private correspondence were compiled and published.

Are glutamatergic drugs the future for the treatment of schizophrenia?

2009-11-14T16:56:00.003Z

Just found this on my PC, I wrote it some time ago, before the latest news on the failure of the LY2140023 trial was known (I altered it a little around the time to reflect this). I started it with the intention of doing an updated meta-analysis of glutamatergic drugs in schizophrenia but it became apparent that the quality of the data was so low that I wasn't going to be able to carry out any sensible analysis. I wrote the following as a summary of what I'd wasted my time doing, it isn't really publishable quality but I thought people might be interested if psychiatry is their area (I could have put it on a pre-print server like Nature Precedings but they don't like clinical treatment data).

Abstract

There is growing evidence for the role of glutamate in the aetiology of schizophrenia and a number of glutamatergic drugs are being developed and trialled. This systematic review finds that there is evidence for beneficial effects on symptoms in schizophrenia for both adjuvant NMDA glycine binding-site agonists and monotherapy with a type II metabotropic glutamate receptor agonist (LY2140023). LY2140023 represents the first successful placebo controlled clinical trial of non-dopamine based antipsychotic therapy for schizophrenia but the evidence for its greater efficacy over glycine binding-site agonists is tentative at best. It is unclear why the apparently antagonistic effects of post-synaptic NMDA co-agonism and reduced glutamate release via pre-synaptic inhibition from type II metabotropic agonism both appear to have beneficial effects on schizophrenic symptoms, nor why the latter is so much more successful than direct NMDA antagonism. Ongoing trials should help to clarify the promising results found to date.

Introduction

All existing antipsychotics work via the dopamine D2 receptor (1) but this class of medication has several important limitations. Although effective at treating ‘positive’ symptoms of schizophrenia (such as hallucinations and delusions) antipsychotics have limited impact on ‘negative’ symptoms (such as emotional blunting) or cognitive deficits, and it is these that are thought to have most relevance for prognosis (2). Side-effects are significant and range from considerable weight gain and hyperprolactinaemia to movement disorders such as extra-pyramidal effects and tardive dyskinesia. Although clozapine, and the atypical antipsychotics have been considered superior to typical antipsychotics any advantages appear to be fairly marginal (3).

While pathophysiological investigations of schizophrenia have traditionally concentrated on the dopaminergic system (4, 5) there is increasing evidence from gene association and neuropathological studies for an involvement of the glutamatergic system (6). For some time there have been hopes that medications which interact with the glutamatergic system may be able to ameliorate some of the negative and cognitive deficits of schizophrenia. In this review I appraise the current clinical evidence in a narrative systematic review of double blind randomised controlled clinical trials of adjuvant or monotherapy with glutamatergic drugs in schizophrenia.

Methods

Glutamatergic drugs were defined as those primarily acting via glutamate receptors or the glutamatergic system (e.g. re-uptake inhibition). Medline was searched via PubMed using the ‘broad’ and ‘therapy’ clinical study filters and the Cochrane Central Register of Controlled Trials (CENTRAL) was also searched up to January 2009. Search terms were ‘schizophrenia’ AND either ‘glutamate*’ or the names of specific glutamatergic compounds discussed below (glycine, d-cycloserine etc.). Unpublished trials from the CENTRAL database were not included in the results because no data was available, this may produce a degree of publication bias in the studies considered. Following from previous reviews I concentrate on overall symptoms as determined by the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS), negative symptoms as determined by the PANSS negative subscale or the Scale for the Assessment of Negative Symptoms (SANS), and positive, cognitive, and general symptoms from the relevant PANSS subscales.

Results

Searches produced 522 records from Medline and 102 records from CENTRAL with 18 trials previously covered by a Cochrane review and a further 18 new studies identified. Trials were generally of good quality although small in size and of short duration. Reporting of blinding methods was poor, and outcome measures and statistical methodology were well validated but varied between trials making comparisons difficult. The initial goal to perform a meta-analysis using the additional data from newly identified studies was abandoned due to the difficulty in extracting usable data. All trials mentioned in this review are placebo controlled unless stated otherwise.

Glutamatergic stimulation

One model for pathology in schizophrenia is a hypoglutamatergic state or N-methyl-d-aspartate (NMDA) receptor dysfunction. Consistent with this proposal blockade of the NMDA receptor with phencyclidine or ketamine produces a psychotic syndrome similar to schizophrenia, including negative and cognitive symptoms. In pre-clinical trials, the use of co-agonists at the glycine binding-site of the NMDA receptor has been shown to modify some of the effects of NMDA antagonism (7).

The genes G72 and d-amino acid oxidase (DAAO) have been implicated in the genetics of schizophrenia (8) and are involved directly in neurotransmission at the NMDA receptor glycine binding-site, with DAAO metabolising the endogenous agonist d-serine.

These findings suggest that glycine binding-site agonists may potentially act to facilitate NMDA neurotransmission and correct underlying glutamate hypofunction in schizophrenia.

Adjuvant therapy

There have been a number of reports that augmentation of antipsychotics with agonists at the glycine binding-site preferentially improve negative and cognitive symptoms (7). A Cochrane Review has looked at the endogenous agonists glycine and d-serine and the partial agonist d-cycloserine as adjuvant therapy in schizophrenia (9). From data published up to 2003 they found 18 double blind randomised controlled trials, all short (≤12 weeks) with small numbers (358 subjects randomised in total).

d-cycloserine appeared to be ineffective on all measures, with trends towards harm compared to placebo. Glycine and d-serine were effective on some global measures and symptom scores. These comparisons all involved few patients (<150)>

Three further adjuvant studies of daily d-cycloserine have since been published and none of these found a beneficial effect on symptoms confirming the negative findings from the Cochrane review (10-12). However, an 8-week study of once weekly d-cycloserine adjuvant therapy in 38 patients found a statistically significant effect on mean negative scores but not 20% improvement rates or mean positive or cognitive scores (13).

Several studies of full glycine binding-site agonists have also been published since the Cochrane review. A 16-week trial, with 104 patients in the glycine and placebo groups combined, looking at adjunctive glycine found no difference from placebo for mean difference or 20% improvement in negative symptom scores, or for mean differences in cognitive or positive symptom scores (12). Conversely, a cross-over study of 17 patients using high dose glycine added to atypical antipsychotics resulted in a significant decrease in mean negative, cognitive, and positive symptom scores at 6-weeks. There was not a significant increase in 20% improvement rates for overall symptoms but there was for negative symptoms (14).

Similarly, in a cross-over study of 39 patients with adjuvant d-serine and atypical antipsychotics there was a significant decrease in mean negative, cognitive, and positive symptom scores, and also extra-pyramidal side-effects at 6-weeks, with 20% improvement rates significant for overall symptoms and negative symptoms (15). However, in a trial of d-serine added to risperidone, with 44 patients with acute exacerbations of schizophrenia in the d-serine and placebo groups combined, there was no statistically significant mean difference in overall or negative symptom scores at 6-weeks (16). Another small cross-over trial of 12 patients on clozapine also found no difference in mean overall, negative, positive, or general scores at 12-weeks (17).

Finally, d-alanine, another glycine binding-site agonist, has been tested as a adjuvant therapy in a 6-week study of 32 patients which found a significant benefit in mean scores on overall, negative, positive, and cognitive symptom scales (18).

The Cochrane review and later studies suggests that the partial agonist d-cycloserine is ineffective as adjuvant treatment in schizophrenia but the balance of evidence is still equivocal for the full glycine binding-site agonists. A reasonable estimate of the NNT for a 20% improvement in symptoms would be of the order of five patients but there is an obvious need for better and more consistent reporting to facilitate comparisons between trials and meta-analysis, particularly for cross-over trials. From the evidence these drugs appear to be well tolerated but they are not very practical to use, requiring fairly high doses diluted in liquid. Most trials have been fairly short, except for one 6 month trial of d-cycloserine, so estimates of long-term efficacy and tolerability are needed.

An alternative method of promoting agonist activity at the glycine binding site is the use of glycine re-uptake inhibitors. The glycine transporter-1 inhibitor N-methyl-glycine (sarcosine) has been examined in three studies. A 6-week trial of sarcosine with 38 patients showed benefits on mean differences in overall, negative, positive, cognitive, and general symptoms. These results were dependent on the analysis method, but mean differences at 6 weeks appear robust for overall and general symptoms (19).

Another 6-week study of sarcosine added to risperidone in acute exacerbations of schizophrenia, with 44 patients in the sarcosine and placebo arms combined, found significant changes in mean overall, negative, cognitive, and general symptom scales (although these depended on the analysis method used), with a significant difference in the rates of clinical response (defined as a 30% reduction in overall symptoms) (16). However, in a 6-week study of sarcosine added to clozapine with 20 patients there was no significant effect on mean difference in overall, negative, positive, cognitive, or general symptom scales (20). Pooling 6-week mean differences from all three studies will not result in significant effects because the statistical differences in the original studies largely depends on using regression to control for baseline imbalance in severity.

There has been some suggestion that use of glycine agonists with clozapine results in lower efficacy, perhaps because clozapine already has some glutamatergic activity. The Cochrane review found no evidence of differential efficacy of these drugs when used with typical or atypical antipsychotics, or with clozapine, and later studies have not provided any strong evidence to contradict this finding.

The compound CX516 is an ‘AMPAkine’ and allosterically binds to the ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor prolonging channel opening. It has been studied as an adjuvant therapy in schizophrenia with no significant benefit found in mean overall, negative, positive, cognitive, or general symptom scales (21, 22). A tiny trial of eight patients also failed to find evidence of benefit for CX516 as monotherapy (23).

Monotherapy

Recently a small trial of 20 patients was published looking at 6-weeks of sarcosine monotherapy for acute exacerbation of schizophrenia. This was not placebo controlled but rather compared high and low doses of sarcosine. There were no significant benefits of a higher dose on mean overall, negative, positive, or general symptom scales, but on the dichotomous outcome of 20% improvement in overall symptom score there was a significant benefit over the lower dose, and this was found in those subjects who were antipsychotic naïve (24). Although the dichotomous data suggests a NNT under three patients, in the absence of a change in mean symptom scores it seems unlikely that this finding reflects a true clinical benefit.

Glutamatergic inhibition

In contrast to the above proposition that glutamate hypofunction contributes to the symptomatology of schizophrenia, there has been some suggestion that glutamate hyperfunction may also play a role. Although superficially contradictory there is evidence that NMDA receptor hypofunction preferentially affects inhibitory interneurons causing disinhibition of pyramidal cells and increased glutamate release in prefrontal cortex (25).

Adjuvant therapy

Given the known effects of NMDA receptor antagonists such as phencyclidine in producing psychotic symptoms there has been little focus on these drugs as therapy. However, memantine is an NMDA antagonist used for the treatment of the cognitive symptoms of Alzheimer’s disease and has been investigated in an 8-week clinical trial of 138 patients as an adjunct to atypical antipsychotics. This study found no significant effect of memantine on global scores, or on overall, positive, negative, or cognitive symptom scales (26). There was also no significant difference in response rates (10% reduction in overall symptom score) but an increased rate of adverse events, including 6% of patients experiencing auditory hallucinations. Another study published only in abstract form has also found no effect of adjunctive memantine on cognitive measures (27).

Monotherapy

In 2007 a glutamate agonist trial was published that caused some considerable interest. This was a 4-week trial of 196 patients with poorly controlled chronic schizophrenia given the compound LY2140023 (versus olanzapine or placebo) (28). LY2140023 is metabolised to LY404039, a selective agonist at metabotropic mGluR2/3 glutamate receptors. The gene for mGluR3 has previously been associated with schizophrenia (6). As an agonist at type II metabotropic autoreceptors LY2140023 would be expected to antagonise rather than potentiate glutamate transmission, a mechanism that contrasts with the NMDA glycine binding-site agonists. However, LY2140023 has been shown to ameliorate the effects of NMDA antagonists in pre-clinical studies. Significant reductions were seen in mean overall, negative, and positive symptom scores for both LY2140023 and olanzapine, but LY2140023 did not show the weight gain associated with olanzapine. The reduction in symptom scores was greater for olanzapine than LY2140023, particularly with positive symptoms, but this difference was not statistically significant. With the dichotomous outcome of improvement (25% reduction) in overall symptoms there was a significant benefit to both LY2140023 and olanzapine compared to placebo suggesting a NNT of less than three patients for olanzapine and around 3.5 for LY2140023.

It is worth noting that while commentators have been quick to hail the advent of a new antipsychotic agent without the extra-pyramidal side-effects of dopamine blockade this study did not find any evidence for a difference using a variety of rating scales for these side-effects, although there was a significant difference in prolactin levels between the two drug groups. A substantial number of patients dropped out of the study (40%, primarily due to lack of efficacy), significantly more in the placebo group although the LY2140023 group also had more dropouts than the olanzapine group.

Discussion

The study of LY2140023 represents the first successful placebo controlled clinical trial of non-dopamine based antipsychotic therapy for schizophrenia* and the results suggest that this and similar compounds represent a promising avenue for developing antipsychotics with a different side-effect profile to that of current medication and the potential for efficacy in patients resistant to current treatments. This study does not establish that LY2140023 is better than olanzapine for negative symptoms, an early hope for these compounds, nor that it has a lower incidence of extra-pyramidal symptoms (since there were few of these in this short study) although prolactin levels were lower and weight gain less. There is an outstanding issue regarding the optimum dosing regime with LY2140023 and it is possible that higher doses could result in a greater antipsychotic effect and more marked effect on negative symptoms. A dosing study has just been completed but the manufacturers have recently announced that this failed to show a benefit of LY2140023 over placebo with no dose response effect – this failure has been ascribed to the large placebo response in the trial and further studies are awaited with interest.

It is worth comparing the NNT in the 2007 LY2140023 study with the evidence from glycine binding-site agonists as adjuvant treatment. The Cochrane review found a NNT for 20% reduction in symptoms of three patients (including evidence from later studies a more reasonable estimate would be five) and high dose sarcosine monotherapy produced a NNT of less than three patients (compared to a low dose of sarcosine). These effects are not markedly dissimilar to the results of LY2140023 and mean differences in negative symptom scales (the main outcome used in the adjuvant studies) for glycine binding-site agonists are of a similar magnitude to LY2140023. However, the difference in mean overall symptom scores is much larger for LY2140023 than the glycine binding-site agonists, and the sarcosine monotherapy trial produced no significant differences in mean symptom scores at all.

These comparisons suggest that, while LY2140023 has evidence for somewhat greater efficacy than glycine binding-site agonists this is a tentative conclusion at best, and may prove to be premature when the results of the latest trial of LY2140023 are published. We are still awaiting the outcome of placebo controlled trials of glycine binding-site agonists as monotherapy, but it is conceivable that use as adjuvant therapy may have underestimated the full antipsychotic effect of these compounds. Similarly, trials of LY2140023 as an adjuvant therapy may show an additive therapeutic benefit over-and-above the effect of conventional antipsychotics, which may be similar to or greater than that of the glycine binding-site agonists.

It is not entirely clear why both NMDA glycine binding-site agonism and reduced glutamate release (via type II metabotropic receptor agonism) appear to have beneficial effects on schizophrenic symptoms, nor why the latter is so much more successful than direct NMDA antagonism. Presumably differential and complex effects on neural circuits underlie this apparent paradox but it highlights how poor our understanding of the glutamatergic pathology of schizophrenia still is. Glutamatergic drugs may still not prove to be the future of schizophrenia treatment, but they are currently offering some hope.

References

* Although the original study found no evidence that LY2140023 or LY404039 interact with dopamine receptors it has been proposed that there may be some action at high-affinity state dopamine D2 receptors (29), and there are considerable interactions between the glutamatergic and dopaminergic systems (6).

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2. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153(3):321-30.

3. Tandon R, Belmaker RH, Gattaz WF, Lopez-Ibor JJ, Jr., Okasha A, Singh B, et al. World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia. Schizophr Res 2008;100(1-3):20-38.

4. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987;44(7):660-9.

5. Matthysse S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Fed Proc 1973;32(2):200-5.

6. Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005;10(1):40-68.

7. Javitt DC. Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 2004;9(11):984-97, 979.

8. Li D, He L. G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies. Genetics 2007;175(2):917-22.

9. Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 2006(2):CD003730.

10. Duncan EJ, Szilagyi S, Schwartz MP, Bugarski-Kirola D, Kunzova A, Negi S, et al. Effects of D-cycloserine on negative symptoms in schizophrenia. Schizophr Res 2004;71(2-3):239-48.

11. Goff DC, Herz L, Posever T, Shih V, Tsai G, Henderson DC, et al. A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology (Berl) 2005;179(1):144-50.

12. Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 2007;164(10):1593-602.

13. Goff DC, Cather C, Gottlieb JD, Evins AE, Walsh J, Raeke L, et al. Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study. Schizophr Res 2008;106(2-3):320-7.

14. Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry 2004;55(2):165-71.

15. Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry 2005;57(6):577-85.

16. Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry 2005;62(11):1196-204.

17. Diaz P, Bhaskara S, Dursun SM, Deakin B. Double-blind, placebo-controlled, crossover trial of clozapine plus glycine in refractory schizophrenia negative results. J Clin Psychopharmacol 2005;25(3):277-8.

18. Tsai GE, Yang P, Chang YC, Chong MY. D-alanine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 2006;59(3):230-4.

19. Tsai G, Lane HY, Yang P, Chong MY, Lange N. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 2004;55(5):452-6.

20. Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, et al. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia. Biol Psychiatry 2006;60(6):645-9.

21. Goff DC, Leahy L, Berman I, Posever T, Herz L, Leon AC, et al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 2001;21(5):484-7.

22. Goff DC, Lamberti JS, Leon AC, Green MF, Miller AL, Patel J, et al. A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology 2008;33(3):465-72.

23. Marenco S, Egan MF, Goldberg TE, Knable MB, McClure RK, Winterer G, et al. Preliminary experience with an ampakine (CX516) as a single agent for the treatment of schizophrenia: a case series. Schizophr Res 2002;57(2-3):221-6.

24. Lane HY, Liu YC, Huang CL, Chang YC, Liau CH, Perng CH, et al. Sarcosine (N-methylglycine) treatment for acute schizophrenia: a randomized, double-blind study. Biol Psychiatry 2008;63(1):9-12.

25. Homayoun H, Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 2007;27(43):11496-500.

26. Lieberman JA, Papadakis K, Csernansky J, Litman R, Volavka J, Jia XD, et al. A Randomized, Placebo-Controlled Study of Memantine as Adjunctive Treatment in Patients with Schizophrenia. Neuropsychopharmacology 2008.

27. Lee JG, Kim Y-H, Lee SW. Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: A 12-week, double-blind, placebo-controlled trial (abstract). International Journal of Neuropsychopharmacology 2008;11(Suppl 1):141-2.

28. Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 2007;13(9):1102-7.

29. Seeman P. Glutamate agonists for schizophrenia stimulate dopamine D2High receptors. Schizophr Res 2008;99(1-3):373-4.

Call of Duty: Modern Warfare 2

2009-11-14T12:04:00.005Z

Off to get the new Call of Duty today (because at heart I'm just a little boy). I was watching the review of it last night on Newsnight Review - it was rather bizarre, while I haven't seen the controversial level that's got so much coverage, most* of the reviewers (who also appeared to be unfamiliar with computer games in general) seemed to object to the overall violence (in a first person modern warfare shooter!) because, as far as I could tell, killing people 'is like bad, m'kay?'

Now I totally agree that killing people is bad, but I'm pretty unclear how computer simulated violence has quite the same moral ramifications as actually killing someone**, particularly when our reviewers didn't extend their objection to all those films about killing people, or films with other morally dubious things like rape, or infidelity***, or just being mean.

I suppose you could make a more specific objection that in computer games you are taking on an active role rather than being a passive observer - this seems to have been behind some of the objections to the controversial level in Modern Warfare 2 - but the reviewers didn't actually seem to make that point. But if that was the direction you were going, arguing that taking part in simulated violence has some negative impact on an individuals moral integrity (does that include paintball, laser quest, archery even?) then why should we not extrapolate that out to other immoral acts as I've intimated above? And why are actors not faced with such opprobium for playing roles in films about, for example, incest - roles where they are getting a whole lot more involved that someone bashing the plastic controller on their games console?

At one point Paul Morley bemoans that there has been this divide between gamers and non-gamers with the latter dismissing the condemnation of the former because they 'just don't get it' - sadly I think the latter are correct, non-gamers seem to be condemning something they don't understand and fear because of that - Morley seems to be making a pretty penny watching and writing about X-Factor at the moment, I wonder does he feel morally degraded through his complicity in that nasty piece of voyeurism?

ETA: This is hilarious:

Video games depicting war have come under fire for flouting laws governing armed conflicts.
Human rights groups played various games to see if any broke humanitarian laws that govern what is a war crime.
The study condemned the games for violating laws by letting players kill civilians, torture captives and wantonly destroy homes and buildings.

Hmm, perhaps the authors ought to concentrate on having real life violations of humanitarin law prosecuted first, before defending out pixelated friends.

* Admittedly one of them thought it was great

** You also have to wonder whether the thousands of people being blown to bits in wars around the world might be worthier of our defence before we start helping out the little pixelated pretend people from being killed by by teenage boys

Dowsing for IEDs

2009-11-08T10:53:00.003Z

So unbelievably fucking disgusting it makes my skin crawl. The Halliburton of woo. Not entirely unlike the use of pointless lie detectors by the British government only this time it leads to lots of people dying - arrogant and ignorant morons in power will never cease to piss away millions of pounds on magic beans because they sound cool.

Tedious psychological turf wars

2009-09-01T11:59:00.004+01:00

Richard Bentall has a new book out so it was only a matter of time before he made his way into the British press. I don't have time for an indepth critique but here's a few selected highlights:

"Many studies have also reported an association between trauma in early life and psychosis. These effects are large: one recent study estimated that individuals who had been sexually abused in childhood were 12 times more likely than others to suffer from serious mental illness, and another calculated that the population-attributable risk of a diagnosis of schizophrenia associated with an inner-city childhood was 15% (that is, there would be 15% fewer cases if we all grew up in the countryside). The risk associated with having a parent with the diagnosis is 7% (ie, there would be 7% fewer cases if patients stopped having children)."(my emphasis)

Note that what this segment subtly doesn't point out is that the evidence suggests that schizophrenia in particular isn't actually associated with childhood abuse (unlike, say, depression).

The whole piece is a depressing blow in a pointless academic turf war where psychologists seek to undermine 'biological' psychiatric research (which, is to some extent justified) only to posit even weaker little barely-theories to replace it:

These effects are understandable in the light of psychological research. For example, early trauma seems to disrupt the process by which we distinguish between our own thoughts and our perceptions, leading to a specific risk of hallucinations. Disruption of early relationships with caregivers, coupled with victimisation, create a tendency to mistrust others and to anticipate threats, leading to paranoid delusions.(my emphasis)

I mean, seriously, what is the highlighted sentence even supposed to be telling us? That there is an association between trauma and hallucination? But he's just told us that, what does 'psychological research' tell us on top of that? What are the useful therapeutic insights that this research igives us?

To date, about 30 trials of cognitive therapy for psychosis have been completed; by comparison, in the period 2001-3, nearly 400 drug trials were published in the five leading American psychiatric journals. There is therefore an urgent need to develop a less drug-based, more person-centred approach to understanding and treating mental illness, which builds on the recent scientific findings and which takes the experiences of patients seriously.

CBT is similarly effective to antidepressants (but of little use in psychosis compared to anti-psychotics) but if psychologists think the recent success of psychological therapies supports their approach then they are going to have to look very hard at why their therapies are little better (and often worse) than the 'biological' therapies they seek to undermine.

The problem wth Bentall (and I've read Madness Explained) is that he makes valid but somewhat overstated arguments against things like psychiatric labels or the efficacy of psychoactive drugs but then thinks that he has somehow completely demolished existing medical understanding of mental illness and its treatment (rather than having slightly deflated its claims) and then goes on to make 'psychological' theories that are often much worse supported that the 'biological' theories he has just tried to undermine and also to present them as radically opposed to existing understanding rather than being complementary (which is what they are).

This is really just a slightly more sophisticated vesion of Oliver James - if mental illness doesn't have a genetic component then drugs don't work, if mental illness is associated with childhood abuse then we need psychological therapies. That mental illness is probably both partly genetic and partly associated with envronmental factors including childhood abuse (a) tells us nothing about whether drugs or therapy work, and (b) that the evidence tells us that both drugs and therapy work (depending on the diagnosis) is just too complex and nuanced for this pathetic dick-swinging Sunday supplement debate.

Dr Simon Jenkins

2009-07-22T14:32:00.009+01:00

Dr Jenkins shares his well informed views of how trivial swine 'flu is:

...a condition correctly diagnosed by a Dulwich 12-year-old during the initial outburst of hysteria in May as "like a cold"

...the one thing not to take is Tamiflu...People should take an aspirin.

After all, who are you going to trust, doctors and scientists who have dedicated their lives to studying and treating disease, trying their best to plan and advise based on incomplete information, or some bloke in the pub?

If swine 'flu turns out to kill a lot of people this Autumn* then Jenkins should really be forced to confront his words***. Of course, it probably won't, further inflating his dick swinging braggadocio, until we finally do get a pandemic viral illness (which we will eventually) - when he'll be clamouring to know why more wasn't done**. Ah, the privilege of consequence free comment pieces, the life of a journalist is so easy - you get to feel so important while doing fuck all. Reminds me a little of the greatest intellectual struggle of our time.

EDIT: Heh, Gimpy got there first, pointing out that aspirin shouldn't be used in children, although there are plenty of other errors tackled in the comments to Jenkins's article. Also jonnyhead covers it and the Times's Mark Henderson.

* I really hope it doesn't, not least because it'll mean I have to deal with the consequences at work as everyone in the NHS goes off sick or to look after their children, leaving me with a massive workload and lots of really sick patients trying their hardest to infect me.

** And, I'd be willing to bet, making demands that health workers and/or other people (e.g. patients or healthy people depending on whether he's caught it) risk their own health to preserve his.

*** According to Gimpy, it would appear he's already been wrong about another viral epidemic - so it looks like it probably wouldn't bother him. Here's Jenkins on AIDS/HIV:

"Aids has been confined largely to homosexuals and drug abusers, whose activities put them at risk of blood contamination and leave them vulnerable to lethal disease. There are some Aids cases outside the “high-risk” groups, but numbers are tiny: 60 at most in Britain. As far as Britain is concerned, the plague appears to be passing."

'New Vegetarianism'

2009-06-17T12:16:00.004+01:00

I was all ready to make the above joke after reading this article:

The worst thing about not eating meat isn't the limp salads - it's the other vegetarians

But I was beaten to it by the second comment:

"New Vegetarianists" are so shrill.

NICE infiltrated by Berties

2009-06-05T02:18:00.006+01:00

As they say on teh interwebs, quoted for truth:

First the MHRA lets down the public by allowing deceptive labelling of sugar pills (see here, and this this blog). Now it is the turn of NICE to betray its own principles.
...
If NICE does not reconsider this guidance, it is hard to see how it can be taken seriously in the future...

David Colquhoun on NICE, low back pain, and the Woo-sters here, here, and here.

I think D^2 has an interesting, but ultimately flawed take on it:

Similarly, in the early days of the evidence-based medicine movement, when they were the Young Turks or punk rockers, shaking up a complacent medical establishment that had got out of touch with the cutting edge of medical research, they had the potential to do a lot of good. But now they are the establishment, and as a result of that, the very evidence that they rely on, is shaped by the fact that it needs to appeal to them. The fact that a movement which begun by trying to bring science back into medicine, has now ended up putting its imprimateur on some obvious pseudoscience, ought to worry us more than it does, because this is only the most obvious manifestation of the general problem.

I think he is wrong here, in fact I'm not even sure exactly what he's trying to say is the institutional weakness of Evidence Based Medicine - the strength of EBM is that it has relatively objective and impartial methods to decide questions like this - which is why this failure to adhere to those standards has caused such outrage.

Also, see the guy in the comments lamenting that these EBM enthusiasts have no way to combine data from multiple trials and other misapprehensions.

Simon Singh

2009-06-05T01:58:00.003+01:00

Simon Singh is to appeal and fight on against the ridiculous libel action brought by the British Chiropractic Association for his article accusing them of promoting 'bogus' treatments. I urge you to sign the petition about this abuse of the overly harsh libel laws of England & Wales:

We the undersigned believe that it is inappropriate to use the English libel laws to silence critical discussion of medical practice and scientific evidence.
The British Chiropractic Association has sued Simon Singh for libel. The scientific community would have preferred that it had defended its position about chiropractic for various children's ailments through an open discussion of the peer reviewed medical literature or through debate in the mainstream media.

Singh holds that chiropractic treatments for asthma, ear infections and other infant conditions are not evidence-based. Where medical claims to cure or treat do not appear to be supported by evidence, we should be able to criticise assertions robustly and the public should have access to these views.

English libel law, though, can serve to punish this kind of scrutiny and can severely curtail the right to free speech on a matter of public interest. It is already widely recognised that the law is weighted heavily against writers: among other things, the costs are so high that few defendants can afford to make their case. The ease and success of bringing cases under the English law, including against overseas writers, has led to London being viewed as the "libel capital" of the world.

Freedom to criticise and question in strong terms and without malice is the cornerstone of scientific argument and debate, whether in peer-reviewed journals, on websites or in newspapers, which have a right of reply for complainants. However, the libel laws and cases such as BCA v Singh have a chilling effect, which deters scientists, journalists and science writers from engaging in important disputes about the evidential base supporting products and practices. The libel laws discourage argument and debate and merely encourage the use of the courts to silence critics.

The English law of libel has no place in scientific disputes about evidence; the BCA should discuss the evidence outside of a courtroom. Moreover, the BCA v Singh case shows a wider problem: we urgently need a full review of the way that English libel law affects discussions about scientific and medical evidence.

Putting any reservations I might have about SaS to one side, this is an important fight - libel law should not be used to shut down scientific disagreements.

Atheists: No God, just whining

2009-05-30T16:26:00.003+01:00

This is amusing reading:

"I can't stand atheists – but it's not because they don't believe in God. It's because they're crashing bores...and their fixation with the fine points of Christianity.

The problem with atheists – and what makes them such excruciating snoozes – is that few of them are interested in making serious metaphysical or epistemological arguments...

What primarily seems to motivate atheists isn't rationalism but anger – anger...So, atheists, how about losing the tired sarcasm and boring self-pity and engaging believers seriously?"

Eight out of ten cats prefer...Boots

2009-04-29T00:36:00.015+01:00

Via badscience forums I see that there has been a placebo controlled randomised clinical trial of an anti-ageing creme that found a positive effect of the product - expect to hear about it:

Scientists say they have clinical proof that a face cream available on the high street does reduce wrinkles.
Five months' worth of stock of the leading brand sold in a day after Professor Chris Griffiths announced in 2007 it appeared to combat sun damage.
Two years on from the BBC Horizon programme showcasing his work, his team has shown the cream visibly smoothes out the skin.
Boots predicts boom sales of its No 7 Protect & Perfect Intense Beauty Serum.

Now it is certainly good that Boots has conducted a clinical trial, published in the British Journal of Dermatology no less, but it is, I'm afraid, bollocks.

I'm going to ignore everything in the paper other than the clinical trial as they are, to be blunt, irrelevant. So what did they do? Well they randomised 60 adults to placebo or the face cream in question to apply to their hands and face for 6m -and they looked at four measures, clinical scales for fine lines and wrinkles, dyspigmentation, and the overall clinical grade of photoageing and tactile roughness at baseline, 1m, 3m, and 6m.

So what did they find? Well they report that at 6m there was no statistically significant difference on any of the measures - including improvement in facial wrinkles (compared to baseline) where 43% who had used the product improved and 22% of the placebo group (that's a relative improvement of 1.89 times, 95% CI .86-4.0, with a p-value of .11*). As the paper says:

"the test product did lead to a noticeable clinical improvement in facial wrinkles...in 43% of treated individuals after 6 months, compared with only 22% of those treated with the vehicle...In a comparison between groups, this improvement was not statistically significant" (my emphasis)

Huh? Yes, that's right, no differences. So why is this supposed to be a positive study? Well that's because they were rather sneaky, after 6m - at which point their were no significant differences remember - they stopped doing a blinded placebo controlled trial and put all the subjects on the face cream. They then extrapolated (using linear regression, and presumably the 1m, 3m, and 6m response rates) the placebo response to 'guess' what the 12m response rate might be. They found that 70% of the 60 people now getting cream had improved facial wrinkles (not improved hand wrinkles, or improved dyspigmentation, photoageing, or tactile roughness of the hands or face**) while they estimated that only 33% of the extrapolated placebo group would have improved.

Now we don't know anything about this regression because they don't tell us any data from baseline***, 1m, or 3m, but you might argue that 33% seems a rather low rate, and, since we might want any regression to go through 0,0 (since at baseline there can have been no improvement) and only have data from 6m presented we could suggest that 44% would be just as reasonable a 12m response rate for the placebo group.

This is an inherently dodgy way to go about analysing the data (and it gives free additional sample size artificially inflating the power of the study) which is now not even from a blinded randomised trial but instead a open label trial (everyone now knows they're on the cream, not placebo) but if we look at what the results give we might find that, assuming the placebo group is 30 (and, of course, that group doesn't really exist) and the cream group has 60 people we get a response rate of 70% for cream and 33% placebo (2.10 times relative improvement 95% CI: 1.23-3.58, p=.006****) - if we assume my 44% placebo response it is 1.62 times 95% CI: 1.04-2.51, p=.03).

However, we've also forgotten that they made a lot of statistical comparisons, we'll let them off the comparisons at 1m, 3m, and 6m (they're not independent anyway, if this had been a pain relief trial, say, they might have tried to make something of them if they had proven to be signficant early in the trial and then became non-significant later on - but that is unlikely here) but they did do 4 measures on each of the hands and face - that's 8 sets of statistical tests - so our error rate of p=.05 will get inflated with all those tests (which each have a 5% error rate) so we need to correct for that - a simple Bonferroni correction implies that we need to multiply the p-values by 8, which makes the 70%-33% comparison barely significant (p=.048) and the 70%-44% comparison non-significant (p=.24).

It is worth noting that although only 13/30 showed an improvement with 6m treatment when the placebo arm was added in and another 6m of treatment given, assuming the original 13 sustained their improvement, a whacking great 29 further people showed an improvement (i.e. we might think that a second 6m had the same response rate as in the first 6m, doubling the response rate for that first 30, plus an extra 30 people have that same 6m response rate). I find that pharmacologically unlikely*****.

Take home message - they did a randomised blinded clinical trial for 6m and found no statistically significant effects of the Boots cream (or even remotely nearly significant given the necessary multiple testing correction). They then did a non-trial where they essentially made-up placebo control group results and gave the cream to all the real patients in a non-blinded fashion. And then, maybe, they have a borderline statistically significant result.

The data is sufficiently badly presented, and given that the clinical trial is what, ultimately, they'll use to sell it, that I'd say they have deliberately done dodgy stats to hide the negative nature of the data. God knows what the Manchester researchers were thinking, and I despair of the British Journal of Dermatology and its peer review.

I wonder what the following were thinking when they said:

"Nina Goad of the British Association of Dermatologists said: "Approximately one in five people using the cream will get something extra for their money over plain moisturisers. "It is an interesting step forward in research although the long term benefits are unknown. "The main preventable causes of skin ageing are sun exposure and smoking, so if you're worried about wrinkles, limiting these factors is sensible."
Dr Nick Lowe, clinical professor of dermatology at UCLA School of Medicine, said: "The previous rapid study reported from this group measured fibrillin a substance that predicts the formulation of collagen. More collagen should result in skin rejuvenation. "This latest longer study over six months appears to confirm skin rejuvenation as measured by dermatology examination."
Dr Richard Weller, senior lecturer in dermatology at the University of Edinburgh, said: "This is, as far as I am aware, the first properly conducted placebo controlled, double blind trial of an over the counter cosmetic product. Boots are to be congratulated for doing this."

I wonder if they actually read it (it was published on the 28th - the same day as the BBC article - the media have a habit of asking for quotes before anyone gets to read the article).

NHS Behind the Headlines has also covered this story.

Acknowledgements to the observations of willowtree and BenFranklin in the thread.

UPDATE
We can see here from the press release from Manchester that there was specific misrepresentation:

"The study, published online in the British Journal of Dermatology today (Tuesday, April 28), showed that 70% of individuals using the beauty product had significantly fewer wrinkles after 12 months of daily use compared to volunteers using a placebo." (my emphasis)

* Maentel-Haenszel assuming 30 in each group - we can only assume because they give no details of numbers in each group or if any dropped out - looking at the 22% placebo response rate I think that either the two groups were not of equal sizes or there were dropouts because that figure does not give a whole number for number of responses if you assume a sample size of 30 - in the actual study they report p-values derived from Wilcoxon rank tests which doesn't make any sense given the data they present.

** I'll get back to these in a bit

*** IT would certainly be nice to know baseline scores because, since they report improvement over baseline, differences between the two groups in baseline scores (these happen by chance often in trials, particularly small ones like this) could lead to differences in improvement (say, because those who start out less severe have less opportunity to improve because their skin was pretty good already).

**** Obviously these are make believe stats since this would really be a cross-over design and I'm assuming independence, and because, obviously, you just can't make up placebo responses like this.

***** Would have been nice to be able to judge that by showing the 1m, 3m etc data.

The test of liberalism

2009-04-26T17:46:00.004+01:00

Via butterfliesandwheels and the comments at aaronovitch watch - Terry Eagleton on CiF tells us:

"There is no quarrel about how to treat those whose scorn for liberal values takes the form of blowing the legs off small children. They need to be locked up. But socialists as well as Islamists reject the liberal state, so what is to be done about them? Are they to be indulged only until they successfully challenge the state...?

"Liberalism holds that the state should tolerate any opinion that does not seek to undermine that very tolerance. It is an ironic kind of politics.

"If the test of liberalism is how it confronts its illiberal adversaries, some of the liberal intelligentsia seem to have fallen at the first hurdle. Writers such as Martin Amis and Hitchens do not just want to lock terrorists away. They also tout a brand of western cultural supremacism. Dawkins strongly opposed the invasion of Iraq, but preaches a self-satisfied, old-fashioned Whiggish rationalism that can be wielded against a benighted Islam. The philosopher AC Grayling has an equally starry-eyed view of the stately march of Western Progress. The novelist Ian McEwan is a freshly recruited champion of this militant rationalism. Both Hitchens and Salman Rushdie have defended Amis's slurs on Muslims. Whether they like it or not, Dawkins and his ilk have become weapons in the war on terror. Western supremacism has gravitated from the Bible to atheism.

"There is also an honorable legacy of qualifying too-absolute judgments with an awareness of context: the genuine liberal is appalled by Islamist terrorism, but conscious of the national injury and humiliation that underlie it. None of the writers I have mentioned is remarkable for such balance.

"For the liberal state to accommodate a diversity of beliefs while having few positive convictions is one of the more admirable achievements of civilization. But such neutrality, once under pressure, can easily slide into superiority, as sitting loose to other people's faith comes to look like rising disdainfully above it. It is then only a short step from superiority to supremacism."

I think this is a rather confused piece. I don't buy the claim that liberals are necessarily obliged to not tolerate opinions that seek to undermine the liberal state - but if that is, in fact the case, then how is intolerance of Islam to fail 'the test of liberalism'?

Note that Eagleton rather sneakily slides from the dodgy views of Amis to claiming that Dawkins's rationalism can be wielded against Islam and that he is a 'weapon' in the 'war on terror' - I mean, so what? I'm sure the findings of academic psychology can be wielded in the 'war on terror' - should we abandon the practice of psychology?

But what intrigues me is how the socialist is supposed to fit in. After all, as Eagleton points out:

The left objects to the liberal case not because it believes in crushing those who differ, or dislikes the idea of a partisan state, but because this case rules out the kind of partisan state that socialism requires. It rules out, for example, a state that would not be neutral on whether cooperation or individualism should reign supreme in social and economic life.

Socialism is no friend to Islam, sure it seeks to defend the oppressed, and Eagleton is right that Muslims have been the target of some unpleasant demonisation, but fundamentally socialists reject most religious belief. In fact, I'm not entirely clear how the SWP and Richard Dawkins differ in this regard.

Martin In The Margins notes that:

Eagleton is a master of the classic pseudo-leftish 'guilt by association' move. If you can get your audience to see your opponents as part of a wider, sinister movement - the war on terror, neoconservatism, late capitalism, imperialism - this relieves you of the necessity of engaging with their arguments.

El Gordo

2009-04-26T17:16:00.000+01:00

It seems I may be one of the few people in the UK who thinks Gordon Brown's performance was a perfectly creditable piece of public speaking. I guess my ability to detect mental illness through hand gestures just isn't up to the standards of the rest of the population - I must be in the wrong job.

Are the new antidepressants any better?

2009-03-07T09:33:00.004Z

You may recall that the Kirsch et al study showed a trend (that was not statistically significant) for venlafaxine to be superior to other antidepressants. But there are a number of newer antidepressants, how do they compare to the vanilla SSRIs?

A new meta-analysis in the Lancet tried to find out:

"Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1·39, 1·33, 1·30 and 1·27, respectively), fluoxetine (1·37, 1·32, 1·28, and 1·25, respectively), fluvoxamine (1·41, 1·35, 1·30, and 1·27, respectively), paroxetine (1·35, 1·30, 1·27, and 1·22, respectively), and reboxetine (2·03, 1·95, 1·89, and 1·85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine."

I haven't read it yet, so I can't speak for its veracity.