Richard Lehman’s journal blog, 17 June 2009

Richard Lehman Richard is in Prufrockian mood as he picks out items of interest in the latest major medical journals. As well as quoting T S Eliot, he also pens his own ditty about a zika virus outbreak on the island of Yap.

JAMA 10 Jun 2009 Vol 301
Lipoprotein (a) is present in atherosclerotic arteries but not healthy ones, and it is a perfect candidate for causing plaque, since it contains both cholesterol and a prothrombotic glycoprotein (apolipoprotein [a]).

However, it is very difficult to study its association with myocardial infarction; and since we have no tolerable drugs which reduce LPA, such an association has no obvious practical consequences anyway.

So I was strongly inclined to pass over this Danish study, but I’m glad that I didn’t. It is quite an intellectual tour de force as well as a logistic feat, combining three types of study within the population of Copenhagen, and it shows how the deft use of genomics can obviate the need for a randomised controlled trial.

The key element here is mendelian randomisation, the reshuffling of genetic material which happens each time we make a baby. I won’t go into further detail here, but if you are interested in such cutting edge stuff, I would strongly recommend a look at this paper and its accompanying editorial (p.2386).

Cardiac computerised tomography exposes patients to large amounts of radiation for large sums of money and often negligible clinical benefit. In the USA, you can apparently get it done in “small community hospitals”, which were lumped together with larger centres in this exceedingly unsophisticated before-and-after study.

Before these centres participated in the Advanced Cardiovascular Imaging Consortium in Michigan, they used twice the dose of X-rays that they did afterwards. But if you really need to know how furred-up your coronary arteries are, and want much smaller doses of radiation, it’s best to wait for the arrival of prospectively triggered sequential scanning in your area, or even better, single heartbeat acquisitions.

Most of my readers, I know, do not rush about putting in central venous lines and intubating people and doing all sorts of exciting televisual things that result in pools of blood on the hospital floor. But one or two do, and for your sakes I mention this useful systematic review of corticosteroids in the treatment of severe sepsis and septic shock in adults. Heroic doses are not required: I will merely quote the conclusion – “Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.”

NEJM 11 Jun 2009 Vol 360

Like so many diabetic trials, this one tries to do a bit too much with its painstakingly assembled cohort of patients (2368 in all), but I do think it sends out an important message about the management of type 2 diabetes with stable coronary heart disease. Do as you like. Treat them with insulin provision – either by injecting it directly or by flogging the beta-cells with a sulfonylurea – or else try insulin sensitization, by metformin or a glitazone: it will make no difference to outcomes. Similarly, choose revascularization or medical management: again, it will make no difference. The only subgroup which fared appreciably better consisted of those for whom coronary artery bypass grafting was “deemed the preferred method of revascularization”. Note that patients with left main coronary artery disease were excluded from this trial, called BARI-2D.

Wow: could this be a trial which gives a clear message about the treatment of locally advanced prostate cancer? The headline message is that if the chosen initial treatment is external-beam radiotherapy, then survival will be improved if androgen suppression is continued for three years rather than six months. This was an important fact to establish, since androgen suppression has a lot of unwelcome side-effects. However, the effect size is modest and the statistics only just reach significance.

Here is what you wanted to hear: a large database study from Israel confirms earlier observational evidence that metoclopramide in early pregnancy is not associated with adverse fetal outcomes. There were more than 78 000 controls to compare with 3458 cases where mothers had been prescribed metoclopramide in the first trimester, and there were no significant differences in fetal anomalies, preterm delivery, birth weight, or perinatal death.

Zika virus outbreak on Yap Island! Avoid Micronesians! Actually, the first statement is true, but the second is false, because although the inhabitants of Yap are Micronesians, it’s their mosquitoes and not themselves that are thought to transmit this virus. Micronesia is the name given to a cluster of 607 Pacific islands, and the mystery here is how this rare virus ever got there. The previous 14 reported cases were from Africa and Asia, whereas Yap Island in the middle of nowhere can now claim 49 confirmed and 59 probable cases. The traditional money of the Yapese consists of carved stones up to 4m in diameter: no change given; stop yapping. Fortunately for them, Zika is no deadly killer plague virus, but something that causes conjunctivitis, rash, fever and arthralgia for a few days.

The Island of Yap
Is a speck on the map:
But it’s slightly easier
To detect Micronesia.
A virus called Zika
Made some Islanders sicker,
But they all got better,
And there’s an end to the metter:
Let’s twist no knicker
For a virus called Zika.

Lancet 13 Jun 2009 Vol 373

EURODIAB has capital letters like an acronym, but surely it’s just an abbreviation. Anyway, it does what it says on the tin: here it reports that alarming numbers of Eurochildren are getting diab. It’s called a multicentre prospective registration study and the good thing is that ascertainment rates are higher than 90%, so it’s pretty reliable. Less reliable, perhaps, is its estimate that new cases of type 1 diabetes in children under 5 will double in Europe by 2020. Let’s hope that between now and then, a vaccine to prevent the disease will be developed.

If you are going to do a proper randomised trial of something, you need to do a proper literature review first; best of all, do a meta-analysis. By the time you have done that, and filled out the funding bid forms, you will probably have lost the will to live; or at any rate the will to do the study. But never mind. If you persevere, you can publish the meta-analysis and your own RCT as a single paper, like these British investigators of progesterone for the prevention of preterm birth in twin pregnancy. Progesterone does not prevent preterm birth in twin pregnancies; it does not prevent adverse outcomes either, which is a subtly different question. The acronym of the trial is STOPPIT. Do not prescribe progesterone for twin pregnancies; do not come up with silly acronyms. Stoppit at once.

For an account of the life of James Parkinson, man of God, ardent child-beater and author of An Essay on the Shaking Palsy, you will have to go to a Lancet of some years back for an excellent piece by Druin Burch. For an account of the shaking palsy itself, this seminar on Parkinson’s disease is worth reading for a wealth of useful information, though the three professors who write it seem a little unconnected with the shop floor.

The most characteristic feature, without which the diagnosis cannot be made, is bradykinesia: slowness of initiation of voluntary movement with progressive reduction in speed or amplitude of repetitive actions. Since the diagnosis is entirely clinical, you might as well try and elicit the right signs.

If you love airports and can drop everything at a moment’s notice to get free flights to all sorts of exotic destinations, then flight medicine is the thing for you, and pays handsomely, according to a colleague I was talking to a while back. This nice practical review goes into the medical issues associated with commercial flights and is of interest to all of us who get put on the spot by patients who wish to travel by air and ask us for advice. It’s probably a bit basic for hardened flight medics who are sent out to accompany those taken ill abroad.

BMJ 13 Jun 2009 Vol 338

Only ten years ago, the words “stroke” and “TIA” (not a real word, but never mind) induced a sort of sad shrug in most British doctors. Now stroke medicine is a specialty in its own right and alone among medical conditions, stroke demands “hyperacute” care (see p.1419): 999 ambulance, immediate scan, thrombolysis, wham, bang. TIA demands a clinic appointment the same week, carotid ultrasound, and carotid endarterectomy within two weeks if there is a suitable lesion, according to the NICE guideline. How does real life in our dear NHS compare? According to this study, achievement is about 20% and there are no figures for how many strokes occur in the 80% of patients who have to wait longer.

Do you dare to do a TYM? I am old, I am old, and I shall wear the bottoms of my trousers rolled, but I am not sure I can bear to find out. People are so kind when I forget their names. It is great fun to go to places for the first time and then be told I have been there before. I think I have just the right amount of Alzheimer’s. No need for a baseline score, thanks. If you feel differently, visit the website and do the self-administered cognitive screening test. It is almost certain to be the instrument of choice from now on, however much people quibble about its predictive characteristics, because it performs better than the MMSE and is available without copyright restrictions (see the Lancet comment piece, Taxing Your Memory, p.2009).

Another quick pointer for readers who spill blood on hospital floors: a nice little (longer on the website) piece by some Army doctors about damage control resuscitation for patients with major trauma. Carry on, Major; and good luck.

Archives of Internal Medicine 8 Jun 2009 Vol 169

I like the Archives for its wide range of topics, but this week’s is full of weak studies from which I have plucked this one merely for personal interest. If you sleep badly, your blood pressure is more likely to rise. This is one of many studies under the umbrella of CARDIA (Coronary Artery Risk Development in Young Adults) which has followed a cohort of 5115 from 1985. In 2002 it invited some of them to participate in this study: they had to be normotensive and non-pregnant. The upshot is that if you sleep badly – as assessed by various questions and three nights of actigraphy – your BP is more likely to go up. The authors even claim that this explains the difference in BP between blacks and whites in their cohort, and that measures to improve sleep may help hypertension. Cognitive behavioural therapy for everything, say I.

Plant of the Week: Paeonia “Garden Treasure”

The genetic modification of plants is the basis of civilisation. Sumer was founded on the breeding of wheat, and China on the breeding of rice. We don’t know how exactly which garden flowers the Sumerians bred five thousand years ago – the names are mostly obscure – but we do know that the Chinese have been breeding peonies for at least 1,600 years.

When they were first brought to Europe, they caused a sensation, especially in France, where new kinds were bred soon after their arrival. These were from the two basic categories of peony, the herbaceous kind and the so-called tree peonies, which are really just moderate sized sprawling shrubs. Both sorts abound in the colours pink and white and purple and red, but yellow has always been rare, confined to a few tree peonies and a couple of herbaceous species which are unsuitable for hybridizing.

The French breeders took this as a challenge. They tried to interbreed yellow tree peonies with various herbaceous varieties, but ended up declaring that this was impossible. They concentrated instead on producing a number of hybrids between the tree species lutea and the various tree peonies arriving in shipments from China and Japan. Some of these yellow-flowered Lemoine tree hybrids are becoming available again, and they are exquisite, especially “L’Espérance” and “Argosy.”

In the USA and Japan, one or two peony breeders challenged the French orthodoxy that you couldn’t get a tree to mate with a herbaceous peony. With enormous patience and a huge failure rate, they produced a tiny number of viable offspring. Here were slightly woody low plants with flowers of beautiful clear yellows, often with central flashes of crimson. When one of them, called Bartzella, first came on sale in 1998, it was offered at $1,000.

“Garden Treasure”” came soon after, and was judged by the very picky American Peony Society to be even better than Bartzella. Now it has begun to arrive in England. We saw it in flower at Wisley less than a fortnight ago, blazing with beauty from 100 metres away, and bought one last week in Shropshire for £80. A lot for a plant? Not really. Once in the ground, it will flower for 50 years or more. Admittedly for only one week of the year. But what a thing to look forward to! Worth the price of a nice meal for two, any day.