All too predictable

From the Guardian:

"Doctor who criticised NHS reforms is threatened with disciplinary action...
...

Prof John Ashton, county medical officer for Cumbria, received a letter from his PCT last week after he joined 22 other signatories to a letter in a national newspaper criticising Lansley's health and social care bill. The letter read: "You are bound by the NHS code of conduct and as such it is inappropriate for individuals to raise their personal concerns about the proposed government reforms." Ashton will have to "explain and account" for his actions at the hearing."

Score one for Sertraline

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

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

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.

The GMC is not fit for purpose

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."

Not the best doctor in the world

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.

Scaring women - easy, profitable, and fun

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.

Administrators take over the asylum

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.

Psychiatry? Orthopaedics? Same difference

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?

Prescribing advice

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

Placebos in medicine

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

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.

Service level agreements in medicine

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

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.

NHS Whistleblowers

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

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

The Academic-Medical Establishment

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?

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

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?

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."