29 January 2012

In which I have a fight with an Australian lady on the radio

Well, today was certainly an interesting one. Hot on the heels of the recent report in the Lancet about how cells derived from embryonic stem cells have safely integrated into the maculae of patients with macular degeneration, I was on BBC Radio Ulster defending the ethics. Quick summary - these cells were injected into the eyes of patients with degenerative disorders of the retina; the cells have integrated, and are apparently functioning well. This is exciting and promising research, for people with visual disorders, and many other degenerative conditions.

I think Embryonic Stem Cell Research (ESCR) is a highly ethical avenue of research, but my opponent thinks otherwise. She is Josephine Quintavalle from a lobby group called "Comment on Reproductive Ethics" (CoRE); they take a fairly hard-line embryo-is-a-full-human-person tack, pretty much in accordance with the official position of the Roman Catholic Church (which I find wholly ridiculous, but I may post on that some other time).We had a very polite discussion, expertly chaired by the indomitable William Crawley, but I'll leave the listener to decide whether I did a good job or not.

In retrospect, I wonder if I should have been a little more aggressive. The arguments against ESCR are pretty weak, and are based around a fundamental misunderstanding (or downgrading) of what it means to be a human person.

Anyway, have a listen - our bit starts at about 33 minutes: http://t.co/V0Rr94dP

Please leave any comments below - I would love to hear 'em.

25 January 2012

Human Genomics Strategy Group releases report

Here's the skinny:
This is a topic dear to my heart, so expect more blogging about it
soon. I've had a quick look at the document, but this sort of thing
requires Deep and Ponderous Consideration. From the press release (25
Jan 2012), the main recommendations are:

• [Government] to develop a cross-cutting strategic document, to set
out the direction on genomic technology adoption in the NHS;
• [Government] to develop a national central genomic data storage facility;
• NHS Commissioning Board should lead on developing genomic technology adoption;
• to work to develop a service delivery model for genomic technologies;
• NHS should continue to develop genomics education and training;
• to raise public awareness of genomic technology and its benefits.

These are OK as far as they go, and I think the UK is already in a
great position to bring these objectives and their attendant benefits
to realisation. Whether we would be able to do that with Mr Lansley's
proposals to "reform" the NHS in England is another question (I
respectfully differ with the government on this issue - I think the
proposals in the forthcoming NHS Bill are utterly wrongheaded, and
will actually harm the harnessing of genomic advances, but that's
another story).

The first point is important; the second is a very welcome proposal -
we need to set up such a unit as a "Trusted Third Party" repository of
genetic and genomic information. Third point - yes; fourth - yes -
Clinical Genetics Units can form the nucleus of this model. Points 5 &
6: of course - these are no-brainers. Perhaps the most important thing
we need to add to these is a strategy for rigorously gathering
evidence to see how much our greater genomic capabilities actually
influence the health of real patients. Everything about Medicine must
keep an eye to the evidence.

We have 23 established centres of genetic (and increasingly genomic)
excellence in the UK, namely the Regional Clinical Genetics Units.
These units already work closely with other medical and surgical
specialties to bring the fruits of the genetic/genomic revolution to
patients and families with both rare diseases and common diseases, so
a fantastic infrastructure already exists. We are already
"Mainstreaming". If we develop and resource that infrastructure
appropriately, great things are possible, and the UK can continue to
lead the world in both the research and translational aspects of

[The link to the full report on the DH website doesn't appear to be
working yet, but I'm sure that'll be fixed soon].

I would love to hear folks' thoughts on this - this is a major plank
in the future of Medicine.

19 January 2012

Some thoughts on prescribing

Those of you who know me will know that I am no shill for Big Pharma. I conservatively reckon that you could strip our pharmacopoeia down to maybe 30 drugs, and still be able to successfully manage the large majority of medical conditions that come our way. OK, 30 may be a bit tight, but even so, it seems that we as doctors are bombarded with ever more snippets of trial data that supposedly demonstrate the superior efficacy of Fuckitol over Bollexin and such like.

Every now and then I like to remind our medical students of a few salient points when deciding whether a patient needs a certain drug, or whether their medication needs changed at all. These are in no particular order; they are not meant to be comprehensive, nor are they meant to replace the Ten Commandments of Prescribing that I've mused on previously. However, they may help in that decision-making process when you're weighing up the findings of studies.

  1. Statistical significance is not the same as biological significance.
    Just because you see a really impressive p value, this does not mean that prescribing drug A will be much more effective than drug B (or even nothing at all). You need to ask yourself: what is the size of the actual effect that is being measured? Is this a clinically relevant distinction - i.e. will your patient be much better off on drug A than they would be otherwise?
  2. Relative risk is clinically meaningless - you need absolute risks.So what if drug A has twice the risk of complication X than drug B? If the complication only arises in 1% of patients on A, that means that only 2% of patients get the complication on B. That's still not a lot. Furthermore, for rare complications, the numbers are typically very low indeed, so calculating this relative risk is difficult, and the confidence intervals tend to be large.
  3. Trial results are very different from real world results.
    Drugs are trialled on relatively standardised patients being monitored in standardised ways, and the subjects and researchers are typically super-motivated to make sure they're taking the drug properly and doing everything by the book. So even if the superiority of drug A over drug B is truly demonstrated in a trial in a certain group, it is very rare that the same degree of superiority persists in the Real World, which is where your patients live.
  4. Trials rarely include elderly patients on polypharmacy with multiple co-morbidities.
    This is important, because very often these are precisely the people in whom you will be prescribing drug A or B. It's related to the point above - patients are complex. If you are going to start a patient on a drug, be aware that it is very likely that they would not have made the entry criteria for the study that assessed its efficacy in the first place, so exercise appropriate scepticism that you're doing any damn good at all.
  5. A percentage improvement in a surrogate marker is not the same as effect on underlying disease.
    Perhaps one of the most important points. All young doctors have it drummed into them: treat the patient, not the blood result. Lowering someone's cholesterol from (say) 6.0 to 4.5mmol/l is of no value whatsoever unless you can show that you have reduced their risk of heart attack (and not increased their risk of other problems). It does not matter what the rates of heart attack are in the population for patients with cholesterols of 6.0 vs 4.5 - the relevant measure is: what is the rate of heart attacks in patients whose cholesterol has been lowered from 6.0 to 4.5. These are not the same thing.
  6. Differences between treatment and control groups in trials do not equate to the probability of improvement if you treat your individual patient.
    This is a slightly more complex one. Say you have a drug A which has been shown in a trial to be effective against The Purple Heebie-Jeebies (PHJ). In a big trial the group of patients on A showed improvement in 50% whereas the control group had a 25% rate of improvement. In walks wee Mrs Miggins, and you confidently diagnose PHJ. Now you might think that if you start her on drug A she will have a 50% chance of getting better, whereas if you didn't, her chances are only 25%. Sounds good. However, let's assume that the trial data are correct, and she fits the bill. You have 4 Mrs Migginses, and you start them all on drug A; 2 of them get better, whereas only one would have got better otherwise. But you have treated FOUR patients in order to get a clinical improvement in one. Suddenly this doesn't look so impressive, even if the data are correct. This concept is the "Number Needed to Treat" (NNT), and it is perhaps the hardest yet most important concepts in all of therapeutics.
  7. Numerical difference between groups is not the same as individual improvement score.
    If 50% of patients on drug A show an improvement, whereas 25% of controls show improvement, that is very much not the same as saying that the patients on the drug do twice as well as the patients in the control group. This sounds obvious, but all it means is that a greater number of patients show improvement, not that all the patients show a greater improvement. Subtle, but important.
So there you go - just a few little items among many to get us thinking about whether we are doing the right thing with Mrs Miggins when her Purple Heebie-Jeebies start flaring up. Please add your thoughts to the comments below. Am I being unfair? Go to it.

09 January 2012

Is it time to reclaim the word "Spirituality"?

The shorties: probably not.

Here's why I think in such a churlish way. "Spirituality" is one of those nicey sounding words that carries a huge amount of baggage. It seems so benign, so uplifting, so positive. How can anyone not love it?

Well, groups like the Templeton Foundation (more on those punters later) love to point at the "Spirituality" of scientists, and in the simple sense, many (if not most) scientists experience a sense of awe and wonder at the vastness of the universe or the complexity of molecular pathways or the differentiation of cells. And many people feel perfectly happy to call this experience a "sense of spirituality". So far, so labelly.

However, then we run into the problem of disingenuous religious apologists identifying this sense with some sort of recognition of the divine - an appreciation of some sort of transcendence that necessarily (in their wee heads, bless 'em) means that there has to be a god to make this all hang together. The ever-entertaining Christian apologist - sorry - analytic philosopher - Alvin Plantinga likes to link this to a "sensus divinitatis" - an innate "sense of the divine". This is a weird concept dreamt up by the lunatic theocrat of Geneva, Mr John Calvin - a nasty piece of work if ever there was one, but more on that Johnny anon. Alvin thinks that with Atheists, their "sensus divinitatis" is defective, and this is a "spiritual" flaw. Maybe he's right, but I would regard it as a sublime virtue. He might want to sort out his moralisations.

Anyway, using this and other methods, some people take the word "spirituality" from a context where it is meant to denote that entirely human feeling of awe and wonder, and subtly shift the meaning, so that we get the gods in by the back door. That is pretty greasy, and indeed dishonest.

So my suggestion is that we just let this word go. Lose "spirituality" altogether from our science-life-lexicon. Just stick with awe and wonder, and don't let it become a Trojan Horse for those whose agendas are far from noble.

08 January 2012

Good news! (P)Residents of South America, relax.

Venezuelans send good wishes to Uncle Hugo.
(Image linked from BBC News website)
Anyone who has followed the marvellous career of Venezuelan president Hugo Chavez knows that he's a bit of a loose cannon. I can't go too hard on the chap because he has been treated for some unspecified cancer, but the apparent rate of cancers among South American leaders has led him to suggest (perhaps jokingly) that there was a US plot to encancerate left-wing presidents in the continent.

Well, happily it turns out that at least one of those cancers can be removed from the list - President Cristina Fernandez de Kirchner of Argentina turns out to have benign thyroid disease, rather than papillary cancer of the thyroid as had first been suspected.

It rather looks like Hugo has been overselling his conspiracy theories, but sure I told you that before - even when President Fernandez was still thought to have a cancerous tumour. I'm delighted that President Fernandez is OK, but the egg on Hugo's face will not last very long - we can be sure of that.

07 January 2012

Integrated Care: some clarity?

Over at the Nuffield Trust, Dr Judith Smith tries to get us enthused about Integrated Care. It would seem that Integrated Care is a good thing, particularly for vulnerable and frail patients in the NHS. In principle I am happy enough with that, and for certain definitions/specifications of "Integrated Care", I would be delighted to see a greater emphasis on this.

However, I see a problem. "Integrated Care" is far too easy to say. It trips off the tongue and sounds like it carries significant import. It sounds like something everyone should want, and, moreover, if you say that the NHS needs to implement Integrated Care, it implies that a/ this is a radically new idea, and b/ that it's not already being done.

Now, I accept that the care of many patients could do with being a LOT more joined up than it currently is, but we need to be clear about some things. Most doctors and other health professionals in the NHS are already aware of the need for a patient's overall care to be considered in the round. We already have very dedicated GPs and others who try to take an overview of the patient and the decisions that need to be made at certain points to help them navigate towards the best outcomes possible.

So Integrated Care is not a new idea - at best it is just a new label for  what we (largely) try to do already, and indeed is arguably a core principle of the National Health Service. It can be improved, and possibly it can be improved a lot. What is needed to achieve improvements in the integration and linkages of healthcare needs for individual patients (not as snappy a title, I'll grant you that, so from here on, if I use the term Integrated Care, that's what I mean) is not diktat that this radical new policy be implemented, but better targeting of resources to build on what is currently going on.

If one were cynical, one might think that this is a softener - a pre-emptive strike by the government to address one of the key objections to their ill-conceived Health Bill in England - that demoting health care services to "Any Qualified Provider" will inevitably lead to fragmentation and a loss of the Integrated Care that already exists structurally (if imperfectly) within the NHS. How better to grease  the pill than to pretend that the NHS is not doing Integrated Care, then put it (only as words, mind you) at the forefront of the proposals to destroy the NHS?

Making sure patients receive joined-up care is a well-duh. Let's not allow politicians to pretend that they've only just come up with the concept, and let's make the case for support for health professionals to continue to deliver an excellent service for the benefit of their patients.

06 January 2012

The New Therapeutics: Ten Commandments

Read, learn, implement. This is the best medical advice you will receive all year.

  1. Thou shalt treat according to level of risk rather than level of risk factor.
  2. Thou shalt exercise caution when adding drugs to existing polypharmacy.
  3. Thou shalt consider benefits of drugs as proven only by hard endpoint studies.
  4. Thou shalt not bow down to surrogate endpoints, for these are but graven images.
  5. Thou shalt not worship Treatment Targets, for these are but the creations of Committees.
  6. Thou shalt apply a pinch of salt to Relative Risk Reductions, regardless of P values, for the population of their provenance may bear little relationship to thy daily clientele.
  7. Thou shalt honour the Numbers Needed to Treat, for therein rest the clues to patient-relevant information and to treatment costs.
  8. Thou shalt not see detailmen, nor covet an Educational Symposium in a luxury setting.
  9. Thou shalt share decisions on treatment options with the patient in the light of estimates of the individual's likely risks and benefits.
  10. Honour the elderly patient, for although this is where the greatest levels of risk reside, so do the greatest hazards of many treatments.

Originally formulated by Prof J Yudkin, From:
- it's well worth reading the full article.

    Tweet people love playing "Divide and Rule"

    Dianne Abbot MP may not be stupid in general, but her famous tweet*
    was a stupid thing to say, and, yes, it was a racist thing to say. But
    seriously, is this a major problem? Kick her arse and move on; let her
    move on too.

    One of the most tedious things about Twitter is the number of people
    prepared to get enormously outraged at every silly wee thing; if you
    had listened to Twitter, you'd have thought the Alternative Vote was
    in the bag. You'd have thought that the NHS Bill would have foundered
    in the early stages. You'd have thought that no-one would be stupid
    enough to re-tweet "I'm doing an experiment to prove to my wife how
    great Twitter is" crap.

    Twitter, I am sorry to say, is a *shite* barometer of the wider
    Zeitgeist, and people (including @shanemuk - pls RT my wife thinks I
    waste too much time LOL FTW w00t etc etc #inaneCrap) need to get over
    themselves a bit. A lot.

    [*: "White people love playing Divide and Rule"]