Richard Lehman’s journal review, 4 January 2011

Richard LehmanNEJM  30 Dec 2010  Vol 363
2588   A sizeable multinational study seeks to find out whether providing free daily anti-retroviral drugs as well as free condoms might help to reduce the transmission of human immunodeficiency virus in men who have sex with men. The majority of the subjects were recruited in Peru, with smaller groups from Ecuador, Brazil, Thailand, the USA, and South Africa. It’s highly likely that if all at-risk men took the antivirals every day (as offered), they would achieve very high levels of protection; but in this randomised trial, the reduction in infection was only 44%. Blood tests to check for compliance showed detectable antiviral levels in 51% of those who remained seronegative but only 9% of those who became positive for HIV.

2611   This trial announces itself as testing the value of collaborative care for patients with depression and chronic illness, but as is too often the case with papers under such broad titles, it actually looks at a much narrower issue, and in a way that doesn’t at all mimic real life. The “chronic illness” here is type 2 diabetes and/or stable coronary artery disease: these are labels for largely asymptomatic raised-risk states, as opposed to conditions such as COPD or generalised osteoarthritis which are constantly symptomatic and restrictive. The nice thing about diabetes and CHD is that they have associated surrogates for risk which you can easily measure over a short period – 12 months in the case of this trial. These are blood pressure, glycated haemoglobin and LDL-cholesterol. Depression measurement was by Symptom-Checklist-20, and this was the only thing that really fell by a clinically significant amount in the intervention group. And why? It’s impossible to tell. So many things were thrown at the patients – not just the book (The Depression Helpbook) but also the DVD, self-monitoring equipment, and a chat with a nurse every 2-3 weeks, who then conferred with a physician, a psychiatrist and a psychologist. Whereas the control group got “usual care”. In a properly controlled trial, they might have got a book of short stories, a Harry Potter video, and a visit every 2-3 weeks with a friendly person who then conferred with a zookeeper, a butcher and an accountant. Who knows if that might not have worked even better?

2621   Note for all Sarah Palin imitators in eastern America: when going out prayerfully shooting white-tailed deer with your family, take care that your little loved ones do not nick their fingers when removing the deer hides. Otherwise they may be struck down with a novel parapoxvirus. No fatalities have been recorded from this infection, merely a self-limiting papulonodular lesion, identical to the one we see in those who handle sheep and goats. “Mommy mommy, Trig’s skinning my deer!” “Just mind that hunting knife, Bristol; and Willow, get orf!”

2638   In several places, John Donne compares sleep to death, most famously in his Holy Sonnet 6, “DEATH be not proud”, where he foresees pleasure from death :
From rest and sleepe, which but thy pictures bee,
Much pleasure, then from thee, much more must flow
Moreover, Donne has a sense of the superiority of artificial sleep over death:
And poppie, or charmes can make us sleepe as well,
And better than thy stroake;
“Poppie” is of course a reference to opium, used as a sedative: the equivalent is fentanyl in modern anaesthesia. “Charmes” is interesting: perhaps a reference to an early form of hypnotism, because

Donne is clearly referring to something that really did send people to sleep. Anyway, all this metaphysical poetry is but an introduction to an interesting paper about the varieties of induced sleep as caused by various agents, and how it differs from natural sleep or coma. We know remarkably little more than Donne did about how anaesthetic agents work, and there are many more possible mechanisms we could tinker with, short of death.

Lancet  1 Jan 2011  Vol 377
31   Peter Rothwell’s aspirin-prevents-cancer paper is already so last-year, having appeared electronically in early December and been fiercely debated ever since. His meta-analysis of individual patient data from seven trials shows a significant lowering of mortality from several cancers in people who have taken several years of low-dose aspirin. The effect is strongest in cancers of the gastrointestinal tract and strongest of all for bowel cancer, as we already knew. The significance of these findings is discussed in two editorials: one on p.3 of The Lancet, and a much better one on p.5 of the BMJ, which looks in more detail at the robustness of this analysis and casts doubt on whether we should embark on a policy of dosing the population with a drug which is bound to cause a dramatic increase in the number of gastrointestinal bleeds.

63   The last time I discussed the correct pronunciation of Clostridium difficile in these columns, there was a mini-storm of correspondence in which the central arguments were “How on earth can you know anything about how Latin was pronounced 2,000 years ago? And why should that matter anyway?” The first question is relatively easy to answer: consider, dear child, how in every modern language derived from Latin, “C” becomes a different sibilant sound before certain vowels, while remaining hard before others; consider how Greek words were transliterated into Latin; consider also… et kaytera, etsetterer. But the second objection is unanswerable, because in language, usage is all. And in biological Latin, usage is all over the place. Cicero would be hard put to understand the standard modern English pronunciation of Hydrangea petiolaris, for example: as for Clostridium difficile, it hardly existed in the Roman bowel until we came along with antibiotics and encouraged its evolution and its massive spread; especially in hospitals, as this Europe-wide study shows. As long as we are liberal in our use of antibiotics – as we should be – this bug will be common and tricky to deal with, and we will need to call it something: and fortunately everyone in the English-speaking world agrees on Seediff.

74   Are you sometimes impulsive? Do you get moody, even to the point of self-destructive behaviour at times? Do you often bridle at authority? Welcome to the diagnosis of borderline personality disorder (DSM-IV), which entitles you to SSRIs, olanzapine and/or dialectical behaviour therapy. If you exhibit lesser versions of these traits, the next edition of DSM may perhaps include subclinical borderline personality, and so allow you access to such treatments in the future. If, on the other hand, you exhibit none of these things, you may be suffering from very boring personality disorder and so require treatment with amphetamines and Ritalin and assertiveness training, so that you can drone on more loudly and for longer. If you think I am exaggerating, or need help, read this German/American seminar on BPD.

BMJ  1 Jan 2010 Vol 342
34   Until recently, it was common practice to transfer two embryos following in-vitro fertilisation, resulting in a high rate of twin pregnancies. Firstborn twins, we know, usually need Caesarian delivery, and are often small-for-dates and carry higher risks for maternal and neonatal morbidity. This painstaking multinational meta-analysis of individual patient data comes up with the unsurprising conclusion that it is better to rely on single embryo transfer, followed by another single embryo implant if the first is unsuccessful.

35   Safe births require obstetricians, but this noble and shrinking body of women and men do tend to meddle at times. Intrauterine growth restriction at term is a weasel phrase: it sounds grand and alarming but in reality it is largely unmeasurable. The standard management is induction at term on the grounds that such babies are at higher risk of intrauterine death if left in the womb. The dubious science behind this is exposed in the Dutch DIGITAT study: the question is really quite open, and women should be aware that there is nothing to choose between induction and leaving alone.

36   The last decade began with high hopes that B vitamins and omega 3 fatty acids would dramatically reduce the incidence of cardiovascular diseases. That period did indeed see a dramatic fall in CVD, but almost all due to statins, smoking cessation, and the better treatment of high blood pressure. B vitamins and fish oils are indeed excellent things when eaten as vegetables, eggs and fish, but taken as pills they do nothing for cardiovascular prevention, as shown by many trials including this French one (SU.FOL.OM3 should you need to know).

39   The last decade has also seen dramatic advances in the management of rheumatoid arthritis, which are described in a Clinical Review here by five Dutch rheumatologists. Workmanlike and reasonably comprehensive, but flat – like a Dutch winter landscape by a minor artist hanging in a corner of the gallery.

Lament for Daphne

Early in November I wrote my usual paean to Daphne bholua, finest of shrubs, as it was beginning a period of abundant fragrant flowering that usually lasts to March. But since then there has hardly been a night without frost, culminating in temperatures of minus 12C and heavy snow. Now, with the snow melted, the daphne is a dismal wreck, surrounded with black and blighted leaves and hanging with dead and shrivelled flowers.

But all is not lost. The last time this happened – though not to the same extent – the shrub broke back into new leaf around May, and has flowered as generously as ever each winter since. Our prayers must ascend (or is it descend?) to Gaia, or perhaps the river god Peneus, who are variously credited with turning the nymph Daphne into a tree, to avoid the lascivious pursuit of Apollo. To be on the safe side, we will sacrifice to Apollo as well.

This tale formed the subject of the first opera in the German language, written by Heinrich Schütz after he returned from his first Italian journey. Alas, the music of Dafne has been lost, and we will never know how he managed to turn his principal singer into a tree on stage.