Richard Lehman’s journal review – 12 July 2012

Richard LehmanNEJM  5 July 2012  Vol 367
11    Eltrombopag is a name which has moved me to poetry in the past, and there is a grave danger of this happening again. It is, you remember, an orally available thrombopoietin mimetic which can be used to treat thrombocytopenia. In this phase 2 trial it was used to treat aplastic anaemia which had failed to respond to immune suppression and was therefore likely to be fatal. The logic for giving it a try was that some lines of haematopoietic cells respond to thrombopoietin by rapid multiplication and differentiation. Happily, eltrombopag had the same effect in this trial—but only on 11 out of 25 patients, and not on every lineage of cells. The responsive patients continue to take eltrombopag, with results that remain to be seen.
When your counts begin to flag
In anaemia aplastic
Don’t allow your hopes to sag –
There may be a cure fantastic:
It is called eltrombopag!

Eltrombopag! Eltrombopag!
O keep it in your doctor’s bag!

20     The great advantage of estimating glomerular filtration rate using cystatin C rather than plasma creatinine is that the result is unaffected by race, sex, age, protein intake, or body mass. But for most purposes this is unimportant, since early intervention in “chronic kidney disease” is of very dubious benefit. So the editorial accompanying this study of combining measurement of cystatin C with creatinine is largely taken up with wondering how it will affect clinical practice. I would suggest one possible scenario, which may seem far-fetched: in determining the prognosis of elderly breathless patients. Patients like this go from one hospital readmission to the next and hardly ever receive proper end-of-life care: their hearts fail, their lungs fail, and their kidneys fail, and nobody wants to discuss with them and their families that all this is connected and inevitable, and that the proper aim of treatment may be symptom relief and preparation for death. One way of breaking through this barrier of prognostic paralysis and tunnel vision might be to use a biochemical score, consisting of BNP, to assess strain on the heart, cystatin C, to assess renal dysfunction, and co-peptin, which measures vasopressin activation and is the best overall marker of prognosis. My hypothesis is that use of these “expensive” diagnostic blood tests—perhaps sequentially—would save far greater expense from the use of other futile diagnostic and therapeutic procedures, and might result in better end-of-life care.

30    The title of a paper should tell you what is in it. The label on the can should say Campbell’s Tomato Soup, not just Soup. Cognitive Trajectories after Postoperative Delirium is a misleading title, because it covers only patients undergoing cardiac surgery, an unspecified amount of which was done using a cardiac bypass pump; and it uses a very blunt assessment instrument—the Mini Mental State Examination—which you and I are forbidden to use on pain of copyright infringement. Nearly half of these patients from three Boston hospitals had an episode of delirium after their cardiac surgery, and on the whole they had slightly worse cognitive outcomes in the short term and at one year, as you might expect.

40    There are all sorts of reasons you might want to take vitamin D: to reduce your cardiovascular risk, to prevent your unborn child getting multiple sclerosis, to make your muscles feel suppler, to lift your mood: none of which have a sound evidence base, still less any information to guide dosing. This study combines individual participant data from 11 RCTs to see if it can find good evidence for a dose of vitamin D to prevent fracture. “High-dose vitamin D supplementation (≥800 IU daily) was somewhat favourable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older.” But much depends on where you are starting from—a complex subject in itself, discussed in outline in the editorial.

Lancet   7 July 2012  Vol 380
29    After a couple of above-average weeks, The Lancet returns to usual form with an Offline by Horton consisting of the usual ad hominem London medical school gossip, and a paragraph about the latest highly important person he has met, Prof Anne Glover, Chief Scientific Adviser to the President of the European Commission. She invited him to an elite gathering and is rewarded with a final sentence saying “She needs our assistance.” The special theme this week is, yawn, Sport. Sport and exercise as contributors to the health of nations is the grandiloquent title of one paper, which claims that playing games is associated with a 20-40% reduction in all-cause mortality. Oh yeah. And the first research paper? A phase 2 study of an unnamed antibody to proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) which reduces LDL-C in patients with heterozygous familial hypercholesterolaemia. Wake me up in ten years when there are some hard end-points. Except that I shall probably be dead from hyposportia.

37    Tell you something—if you go to Scotland you will find a lot of multimorbidity. As the rain sweeps from the grey skies down the narrow granite streets, you will everywhere perceive the bent coughing figures of elderly Scots shambling towards their doom; aye, their doom. Fortunately, they still have a National Health Service to turn to, like the one we used to have in England, including a fine contingent of general practitioners who often remain in the same place for their entire working lives. Moreover, they actually want to do this—see Margaret McCartney’s excellent blog.

This survey looked at 314 Scottish practices, containing 1,751,841 registered patients. Over 40% of them have more than one thing wrong with their organs! Above the age of 65, nearly everyone has, and you can knock ten or 15 years off this if the area is socioeconomically deprived. So: “Our findings challenge the single-disease framework by which most healthcare, medical research, and medical education is configured. A complementary strategy is needed, supporting generalist clinicians to provide personalised, comprehensive continuity of care, especially in socioeconomically deprived areas.” Funny, I don’t seem to see a lot of that happening, in England, Scotland, or the USA.

44    Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial. Nice acronym: shame the magnesium doesn’t work.

BMJ   7 July 2012  Vol 345
Before the cultivation of cereals began about 10,000 years ago, people had been living and evolving on a diet which consisted largely of animal protein, fat, and small quantities of fruit and grains. Whatever else this diet may be, you can’t call it unnatural. Viva Atkins, say I: it encourages you to eat lots of nice-tasting things, and lose weight at the same time. But it does not conform to decades of dietary teaching, and therefore any study discouraging it will get publicity: and publicity is a stated aim for BMJ papers. Low carbohydrate diets kill Swedish women is a good headline: as far as I can see, there is no evidence (worth the name) that it is true, or indeed untrue. This study administered a single dietary questionnaire to women aged 30-49 and followed them up for an average of 15.7 years. After adjusting for everything they could think of, the authors found a slight difference in survival between those who once said they did and didn’t eat carbs. I rest whatever case there is to rest, and move on.

Risk scores came into their own with the introduction of statins, highly effective interventions for the secondary prevention of cardiovascular disease, at a time when these drugs were new and expensive. For this particular mode of treatment, some have coined the slogan “treat to risk and not to target,” since statins will reduce the risk of cardiovascular events whatever the underlying mechanism. With osteoporotic fracture, however, the situation is somewhat different. We don’t know to what extent bisphosphonates reduce fracture risk in many groups, or even how long to use them for; so an updated risk score doesn’t necessarily tell us how to treat patients. The indefatigable Julia Hippisley-Cox has updated her previous QFracture algorithm and validated it in this cohort study. So… use it as best you can.

Ever since the invention of the photocopier, journal article reprints have been an anachronism: since the arrival of the internet, a simple absurdity. And yet orders for reprints remain a huge source of income for medical journals, as this study is able to prove thanks to the openness of two journal groups, both British. The American journal editors remain completely secretive. In the BMJ and Lancet groups, the highest reprint order (835,100 copies of a single paper!) was netted by The Lancet and brought in over £1.5 million. These orders are, of course, usually placed by the pharmaceutical companies who ran the trials, or in the case of other types of article, otherwise influenced the content. This paper, I am told, is a toned-down version of the original: the words scam and disgrace do not appear. But they should. This practice is simply indefensible, and for once I am cheering Richard Smith in the Rapid Responses.

Plant of the Week: Grass
I am at a loss to name a plant that looks good in our current English summer. But now and again, when you can see it through the gloom and rain, the grass looks greener than usual.