Centre for Evidence-Based Medicine - Journal Watch

JAMA - 3 March 2010, Vol 303

Wed, 03 Mar 2010 12:00:00 GMT

841 O willow, willow, willow. Willows weep, and grow by water. Willow bark is bitter and acrid with an acid which, when acetylated, yields us aspirin. Despite its melancholy associations, aspirin is generally thought of as a very good thing. Everybody who has had a stroke or coronary event gets to take it, and its effectiveness in those contexts has led us, by extrapolation, to offer it to other people at increased risk, for example because of diabetes, hypertension and/or peripheral artery disease. But it seems peculiarly reluctant to yield its benefits until after something nasty has happened. In this randomised controlled trial carried out by a horde of international salicylophiles, 29,000 people with a reduced ankle/brachial pressure index were randomised to 100mg aspirin or placebo and all that happened is that they had more bleeds. O willow, willow, willow.
http://jama.ama-assn.org/cgi/content/abstract/303/9/841

849 Last week, JAMA informed us that elderly people who get admitted to hospital, especially to intensive care, show greater cognitive decline than those who don't. Now it brings us news that elderly people who have been admitted to ICU die more quickly in subsequent years than those who haven't. Especially in the first few months after mechanical ventilation. Ah well. I suppose it's a basic tenet of science that you must never assume that something is obvious until you have proved it.
http://jama.ama-assn.org/cgi/content/abstract/303/9/849

857 Erythropoietin treatment for the anaemia of chronic renal failure is one demonstration of how you can't assume that anything is simple in science - medical science, anyway. CRF depletes erythropoietin and causes anaemia: give them an erythropoietin analogue, and a healthy ruddiness returns to their cheeks. Then people started noticing that the more you gave them, the faster they died. This study takes a look at what really happens in all the haemodialysis centres covered by Medicare in the USA. If the haematocrit is 33% or less, mortality is high and is reduced by giving good doses of epo and iron. Above that, you do more harm than good. Give it to the pale and weary but stop before their cheeks glow.
http://jama.ama-assn.org/cgi/content/abstract/303/9/857

NEJM - 4 March 2010, Vol 362

Thu, 04 Mar 2010 12:00:00 GMT

779 I hadn't seen a patient in shock for many years until one turned up during an out-of-hours session a couple of weeks ago. I bundled her off rapidly to the arms of doctors who know what to do in such circumstances, and I don't know if she got dopamine or noradrenaline (norepinephrine) or neither. In the casual talk I overhear from these blood-covered hero-doctors who use vasopressor agents, I catch the word "dopamine" most often. But the word I should be catching is "norepinephrine", which is equally effective with fewer adverse effects, according to this European trial. It's called SOAP-II. The daftest acronym of the year competition is hotting up already, and it's only March.
http://content.nejm.org/cgi/content/abstract/362/9/779

790 The last time I read the name ethosuximide, a drug which came out in the 1950s, I was swotting for Finals in 1975. Now it reappears with honour in a study of childhood absence epilepsy, for which it seems the most specific and harm-free treatment when compared with lamotrigine and valproate. Lamotrigine is not very effective, and valproate blunts attention during the learning years, which is no petit mal in itself.
http://content.nejm.org/cgi/content/abstract/362/9/790

800 The majority of cardiovascular events take place against a background of impaired glucose metabolism, usually below the standard threshold for diabetes. You can measure this by fasting glucose or by glycated haemoglobin (gHB, preferred to HbA1c which involves finding subscripts on your computer). The risk curve for coronary heart disease and stroke climbs fairly evenly from any level of gHb over 5%. The authors of this study based on ARIC suggest that we may need to redefine the term "diabetes" using gHb. No! no! Bin the term diabetes until patients become symptomatic. Consider gHb as just another cardiovascular risk factor and treat the total risk; and never use any antiglycaemic drug except metformin unless you really have to.
http://content.nejm.org/cgi/content/abstract/362/9/800

Lancet - 6 March 2010, Vol 375

Sat, 06 Mar 2010 12:00:00 GMT

807 The Stent Wars have become terminally boring, but the Clot Wars are hotting up and becoming cosmic. The current heroes in the Battle of the Clot are the orally available direct thrombin antagonists and the factor Xa inhibitors. It's a great feature of these wars that the heroes fight each other as well as the Clot, and to excite spectators they are given names like warriors from Astérix or Assyrian battle lists. Apibaxan versus enoxaparin. Well, you know enoxaparin isn't going to win because he's an old injectable and this is a drug company funded study in The Lancet. Bring on dagibatran. We want dagibatran v apibaxan! We want to see a real fight with some blood in it! But no clots, please.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/abstract

834 I'm not going to be put off praising this systematic review of clinical features which identify serious infection in children merely because I know some of the authors. It is exactly what we need. I had it on my desk to read last night but I was interrupted by a constant flow of febrile children in the out of hours centre. "Parental concern" and "clinician instinct" were there by the bucket load, and these are important discriminators in this analysis. I ended up sending one child to the paediatricians (albeit less experienced than myself) and a dozen others home to their parents with advice and safety netting. I hope the nets held. This is not relaxing work, we do not do it sufficiently thoroughly, it still scares me at times after 30 years, and this paper is just a beginning towards better triage of sick children.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62000-6/abstract

846 Bacterial septic arthritis in adults. That's scary too, but pretty rare in Britain - much commoner on the eastern fringes of Europe and further afield. It's a "never miss this" condition, like Kawasaki's disease (which is similarly rare) or subarachnoid haemorrhage (which isn't rare at all). Perhaps I'll retire altogether from clinical medicine after all. It's just too dangerous.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61595-6/abstract

856 I seem to remember mocking The Lancet more than ten years ago for publishing a review of sun exposure in November. Now, amid the March frost of the longest English winter for decades, comes this review of the health effects of hot weather. How we look forward to them. O take me out of the baking heat into some dark room where warm breezes blow through open, curtained windows, where I must rest and drink litres of iced fluids. Kennst du das Land, wo die Zitronen blühn? ...O Vater, lasst uns ziehn!
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61711-6/abstract

BMJ - 6 March 2010, Vol 340

Sat, 06 Mar 2010 12:00:00 GMT

518 One of the key issues in the Lancet review on triaging febrile children was how we might safely devolve responsibility on the parents. For a long time, we have been giving adult asthmatics supplies of prednisolone for emergency self-administration. In children of school age, there might be concern that parents would overuse the steroids, but that is something we could easily monitor. No schoolchild is going to come to harm from having a couple of 30mg doses of prednisolone as soon as their asthma gets bad and the salbutamol isn't helping. In fact they stand to benefit, as this trial shows: also read the excellent editorial by Duncan Keeley (p.488).
http://www.bmj.com/cgi/content/full/340/mar01_1/c843

520 For a couple of days last week, I shared the experience of CSF/ME. If I lay down, I felt vaguely awful but my mind seemed normally active; as soon as I got up, my legs felt weak and achy; as soon as I set down any of my thoughts in e-mails, they began to break up and developed an introverted, whingeing tone; and after about half an hour my brain gave out and I had to lie down again. In the wake of this study and the related personal article by Cathie Sudlow on p.510, there was a river of Rapid Responses from ME/CSF sufferers all reporting and exhibiting the same features as I had in the wake of two trivial viruses. Except that for them it had lasted for years. Clearly this is a neurocerebral problem involving reinforcement effects in something the brain usually overcomes rapidly by internal negative feedback. It is neither conscious (and so amenable to cognitive therapy) nor somatic (and so amenable to exercise). Some day we may find the right cerebrally active drug for it. Finding a purported viral cause is never likely to help anyone, except in their desperate quest to be believed. In case you're interested, xenotropic murine leukaemia virus-related virus is unlikely to play a part.
http://www.bmj.com/cgi/content/full/340/feb25_1/c1018

521 Haven't we had enough meta-analyses? The answer, sadly, is no. The Cochrane Collaboration has so far only covered 10% of the medical literature. This is drudgery, but useful drudgery, and it needs to be done well if it is to inform clinical practice accurately. Samuel Johnson in his Dictionary defined a lexicographer as "a harmless drudge", but a bad meta-analyst is a harmful drudge. The most accurate and informative meta-analyses are of individual participant data, and if you are going to become an effective, helpful drudge, you need to read this paper. As for me, my drudging days are done.
http://www.bmj.com/cgi/content/short/340/feb05_1/c221

526 The high quality and practical focus of the BMJ's recent Clinical Reviews is maintained in this one on age related macular degeneration. Particularly good on the merits and pitfalls of intra-ocular vascular endothelial growth factor inhibitors.
http://www.bmj.com/cgi/content/extract/340/feb26_1/c981

Ann Internal Med - 1 March 2010, Vol 152

Tue, 01 Mar 2010 12:00:00 GMT

287 When did you last measure a leg? Not that easy, is it? In this study they didn't use orthopaedic surgeons fumbling about with tape measures but radiologists with sophisticated and reproducible measuring devices. The aim was to determine whether something as simple as leg length discrepancy could lead to osteoarthritis of the knee. Above a centimetre, it does.
http://www.annals.org/content/152/5/287.abstract

307 We're running out of vitamins to try out for reducing cardiovascular risk. I've seen them all come and go - anti-oxidants like C&E, homocysteine lowerers like folate and B12 - and now will it be the turn of my new favourite, vitamin D? According to abstract of this systematic review, it's not looking too good: "Conclusion: The association between vitamin D status and cardiometabolic outcomes is uncertain. Trials showed no clinically significant effect of vitamin D supplementation at the dosages given." But the last sentence of the actual paper is more upbeat: "Vitamin D remains a promising, although unproven, new element in the prevention and management of cardiometabolic disease."
http://www.annals.org/content/152/5/307.abstract

315 And in fact the next paper is another systematic review showing some evidence of cardiovascular benefit at the top end of the vitamin D dose range, i.e. at least 1000iu/day. I went into a health product shop to buy mine this afternoon. All the vitamins and minerals of proven cardiovascular uselessness are there, still promoted for the purpose, whereas vitamin D, which might be useful, is not trumpeted at all.
http://www.annals.org/content/152/5/315.abstract

Plant of the Week: Daphne kamtschatica

Mon, 08 Mar 2010 12:00:00 GMT

This is the northernmost daphne out of a little group with fragrant yellow flowers in late winter: the others are jezoensis and koreana. Few people have seen one, because they are amongst the most miffy members of this very miffy genus. Miffy was a favourite word of Reginald Farrer, and although I don't know for certain what it means, from the contexts he uses it in I think it's "easily miffed". A plant that is miffed, or miffy, tends to die, or if it stays alive, it is in a resentful sort of way. At work, I collect miffy patients, and at home, I collect miffy plants, so that when the opportunity came to lay out £25 on Daphne kamtschatica, sure to miff and/or die within a season, I seized it with both hands.

I hardly thought that four months would go by without a single day fit to plant it, so I left it in its pot all winter, with its roots frosted on most nights. It seems to have loved it. It is covered with yellow flower buds and one has even opened. Its leaves are presently a healthy green, and abundant. But as summer approaches, they will all fall off. This is not miffiness: it's how this plant likes to organise its photosynthesis. They will come back in the autumn.

This is a plant from the furthest reaches of north-west Russia, where once prisoners would die in the gold mines of Dalstroi and Magadan. These were the worst places in the entire Gulag, where millions of tons of rock would have gold crushed out of them, and hundreds of thousands of prisoners would have hope and life crushed out of them. Perhaps, as they stumbled over the bleak slag heaps in late winter, they would catch a gleam of another gold - the flowers of Daphne kamtschatica, and pause for some brief moment of comfort and delight.