Richard Lehman’s journal review, 18 October 2010

Richard Lehman JAMA 13 Oct 2010 Vol 304

Cardiac surgery was once considered too bloody even to contemplate: now it is commonplace. But there is still no agreement in practice about how much blood should be transfused following heart surgery – rates of transfusion vary between 8% and 93% in similar units across the USA (p.1586). The Brazilian TRAC trial randomised heart surgery patients to be transfused to achieve a target haemoglobin level of 10.5 g/dl in one group and 9.1 in the other. Outcomes were identical. An accompanying editorial is entitled “Blood Transfusion as a Quality Indicator in Cardiac Surgery.” Enough said.

Opioid dependence would be a straightforward and fairly minor medical problem if society so decided: we know that substitution therapy works, so it is largely a matter of giving it to people. “Diversion” and “illicit use” are artefacts of the legal system. Subdermal buprenorphine implants can’t be “diverted” to the drug market and according to this phase 3 randomised controlled trial they reduce illicit use of other opioids (now mainly prescribable drugs rather than heroin in the USA). It was quite a painstaking study, requiring 3 urine samples per week, all of them warm. Because buprenorphine is a partial antagonist of the opioid receptors, it reduces the pleasure of taking extra drugs. Like all opioid substitution trials, this one had a huge drop-out rate especially in the placebo group (69%) and only a 12% difference in the main end point, which was the detected use of illicit opioids.

I gave up real general practice a few months ago. By the time you have done it in the same place for 31 years, it has turned largely into the title of this article – Managing Medications in Clinically Complex Elders. Not that we use “elders” in quite that way in Britain. And we are privileged with a financial reward system for undertaking regular reviews of repeat medication – one that involves ticking a box now and again. Our community pharmacists are already empowered to question our decisions and make medication reviews of their own. If this article is to be believed, all this should improve the care of our clinically complex elders; but somehow I didn’t get that impression when I was still at the clinically complex coal face.

NEJM 14 Oct 2010 Vol 363

The good news is that we have a really effective new drug for painful arthritic knees. The bad news is that we will probably never be able to use it. Further trials of tanezumab have been suspended, because it can cause joint failure in some recipients. As its name implies, it’s a humanised monoclonal antibody, and as its name doesn’t imply, it is targeted at nerve growth factor. Inside the worn and torn knee, nerve growth factor sensitizes peripheral neurons by activating tropomyosin-related kinase A (TrkA), and it’s been known for decades that blocking this action (by antisera in animal models) has a marked analgesic effect. But alas, pain from arthritic joints is sometimes a warning against overuse, and blocking it so effectively has led to joint collapse in this and two other trials: hence the FDA’s decision to put them on hold.

Hyperemesis gravidarum is one of those strange mixtures of Greek and Latin which our medical ancestors loved to use in order to cover complete ignorance. Judging from this article, we still don’t really know what causes nausea and vomiting in pregnancy, but at least we have lots of ways to treat it. Most anti-emetics are safe in pregnancy, including the old mixture of vitamin B6 and doxylamine which used to be marketed as Debendox. The main thing I learnt from this paper is that you can precipitate Wernicke’s encephalopathy in some women if you replace fluid intravenously with dextrose solution without giving vitamin B1 (thiamine) at the same time, because after 3+ weeks of vomiting women are already B1 deficient, and the dextrose uses up the rest, leading to permanent neurological damage.

Standing on the ramp at Auschwitz-Birkenau a few weeks ago, I was awed at the madness of the Nazis who deemed it worth collecting all the remaining Jews of Europe (after 4 million had been murdered by more personal methods) and killing them here by cyanide asphyxiation or by starvation and unproductive overwork, at a time of war when transport and labour were invaluable resources.

Nazi “racial science” (Rassenwissenschaft) would have hated genomic medicine for revealing that most human beings are Mischlinge, a jumble of ancestral DNA from various places. Africa has by far the most genetic diversity, supporting the “out of Africa” theory of human origins, and humans as a whole have far less genetic diversity than the great apes, who haven’t been through so many evolutionary bottlenecks. This article on ancestry and disease in the age of genomic medicine is beautifully clear, and a must-read for anyone with the least spark of intellectual curiosity.

Lancet 16 Oct 2010 Vol 376

A nice clear NHS-based study shows that the results of renal transplantation are equally good from kidneys donated after cardiac death as from those donated after brain death. The most important factor is not the mode of death but the cold ischaemia time.

I often force myself to wade through papers simply in order to conclude that they are not worth writing about, such is my devotion to you, my dear readers. Which, alas, is the case with these two studies on the genetic variants which determine response to clopidogrel in acute coronary syndromes, based on TRITON-TIMI 38 and PLATO. If you happen to be interested in such things, you will no doubt be intrigued to learn about the significance of polymorphisms of ABCB1 and CYP2C19; not that you will leave it there, but you will also refer to the Florentine editorial on p.1278, giving chemical formulae for clopidogrel, prasugrel and ticagrelor plus a few more allelic variants which might affect the metabolism of one but not the others. For the rest of us, it’s time to move on.

BMJ 16 Oct 2010 Vol 341

Reboxetine is an antidepressant drug which has never really caught on, and does not deserve to. In two published trials sponsored by Pfizer, it was shown to be more effective than placebo and as effective as serotonin reuptake inhibitors. In two unpublished trials sponsored by Pfizer, it was shown to be as effective as placebo and less effective than SRIs. This had already come to light elsewhere but is thoroughly analysed here in a systematic review and meta-analysis. Elsewhere Robert Steinbrook and Jerome Kassirer call for complete trial data to be made available routinely to medical journals, citing the deplorable RECORD trial of rosiglitazone, but they get lukewarm backing from the three commentaries that follow. Fortunately the BMJ is not going to let the matter rest, as you can see from Trish Groves’ editorial, Evidence-debased medicine.

In medicine, there are scores of different scores but one that scores among the best was devised by Apgar in 1953. Like all good scores it’s simple and it’s predictive. In this paper, countrywide Apgar scores were read off the Norwegian Birth Registry and compared with the Registry of Cerebral Palsy in Children. The odds ratios show an awesome degree of predictive value.

The Doctors for Choice section of the Dignity in Dying campaign was launched last week, and every doctor who supports voluntary euthanasia should join. Dying people need to have better choices about the mode and place of death, and evidence from Oregon and the Netherlands suggests that this goes hand in hand with better palliative care and an actual decline in people requesting assisted death from doctors. The evidence from Flanders in Belgium is unfortunately incomplete due to under-reporting, as demonstrated in this paper. But it doesn’t alter the argument for legalised euthanasia as a final kindness to our patients.
I don’t understand much about eyes, least of all uveitis, so I was delighted to read through this excellent clinical review and find that some of my ignorance is shared by ophthalmologists, who label 50% of acute anterior uveitis as idiopathic. For those of you doing exams, there are nice lists of the known causes, which include multiple sclerosis and Lyme disease. Apparently some specialists with an itch to try new treatments are using biological agents by intraocular injection but this remains an experimental treatment of last resort.

Arch Intern Med 11 Oct 2010 Vol 170
A decade ago, much hope centred on the fact that levels of homocysteine correlate well with cardiovascular risk, and so it followed (we thought) that using B vitamins to lower homocysteine was bound to be a simple and effective way to reduce the population risk. One person I talked to years ago about possible primary care studies was Robert Clarke, now principal author of this meta-analysis of 8 big randomised trials. Every trial succeeded in lowering Hcy but utterly failed to make any impact on cardiovascular outcomes, cancer, or all-cause mortality. You can’t push some risk curves the other way by known interventions – as we’ve also found with a wide range of blood sugar.

The Women’s Health Initiative is a data mine for the effects of oestrogen-only and combined hormone replacement therapy in postmenopausal women, and the latest data concern conjugated equine oestrogens and the risk of nephrolithiasis. This type of oestrogen replacement was associated with an absolute increase of risk of kidney stones from 34 per 10,000 person-years to 39 per 10,000 person-years. “These findings should be considered in relation to decision making regarding postmenopausal estrogen use.”

Plant of the Week: Ceratostigma willmotianum

This autumn stalwart belongs to the same family as the lovely climber Plumbago auriculata, which brings pale blue joy to the ochre walls of Rome at this time of the year. Alas, no genetic engineer has yet bothered to create a hardy version of this delightful plant, which is therefore confined to conservatories around the isles of Britannia. Outdoors here, however, the sharp blue flowers of ceratostigma are produced from late August to the middle of November, their piercing brilliance set off by reddening leaves and low shafts of autumn sunlight.

During the winter, you need to be harsh with the massed twiggy stems of this essential garden plant. Cut them off near the ground and leave a tidy nest of stumps. Maybe dig the odd rooted bit from the periphery to give to friends. This simple, cheering, hardy shrub takes up little room and should be seen everywhere.