This week, Richard ponders a multitude of topics, including the usefulness of prognostic markers for heart failure, the pros and cons of aspirin, and the ins and outs of climate change, while boldly stating that, to his knowledge, no one has ever died of crumbly toenails.
JAMA 13 May 2009 Vol 301
A few years ago I was putting together the first book about heart failure and palliative care and decided to write the chapter about prognostic markers. There is a widespread myth that the course of heart failure is terribly difficult to predict, whereas we now have two biochemical markers – B-natriuretic peptide and co-peptin – which are more predictive than most cancer biomarkers. What I found as I was compiling this neglected masterpiece (buy it at once for your practice library) was that were in 2006 already more than a hundred different prognostic markers and scoring systems in the literature – most of them somebody’s doctoral thesis done with stored sera and/or a convenient database. I still get regular free updates on the heart failure literature through amedeo.com and still there’s a new prognostic association bruited nearly every week – here it is circulating estradiol in men with systolic heart failure. The late and much lamented Philip Poole-Wilson is among the authors. I’m sure that were he still alive he would be the first to admit that finding higher mortality in the top and bottom quintiles of serum estradiol is not going to change a great deal. “Charming but irrelevant, dear boy,” I picture him saying. Though I only met him a couple of times, I really will miss his kindness and wisdom.
Another figure who enlivened my days in the heart failure arena was John Cleland, a fervent campaigner against aspirin. I don’t know if a willow bough fell on young John’s jam-jar when he was fishing for sticklebacks by some boyhood Scottish brook, but his ardour against salicylates is remarkable. And gradually the medical world is having second thoughts on the subject. Two or three years ago, we were suggesting daily 75mg aspirin to everyone with diabetes, hypertension and/or peripheral vascular disease, and indeed to most patients with heart failure, but the evidence is remarkably thin. In this meta-analysis the effect of aspirin and or dipyridamole on cardiovascular events in PAD does not reach statistical significance. For nonfatal stroke alone, there is a protective effect.
NEJM 14 May 2009 Vol 2006
It seems that the more you inhibit platelet aggregation, the more you prevent strokes, while leaving total cardiovascular mortality relatively unaffected. This is true of the ACTIVE A study reported here; combining aspirin with clopidogrel in atrial fibrillation achieved a 28% reduction in strokes but the rates of vascular death in the aspirin-only and the combined group was identical. Also, while the difference in fatal strokes between the groups was 23 in favour of combined treatment, the difference in fatal bleeds was 15 against. So this study doesn’t quite show the clear advantage that might inspire you to audit all your AF patients unsuitable for warfarin and urge them to take clopidogrel with their aspirin.
This interesting Canadian study randomised 800 babies presenting to an emergency department with bronchiolitis to receive nebulised epinephrine (adrenaline), high dose oral dexamethasone (1mg/kg), neither or both. The oral steroids and the nebulised adrenaline did nothing on their own. But combined with each other, the effect was to reduce hospital admissions. This is nicely illustrated in the cumulative admissions plot in Figure 3, but alas, when the statisticians got to work adjusting for multiple comparisons, significance was no longer achieved. Even bigger studies are needed.
As far as I know, nobody ever died of crumbly toenails, but apparently people have been known to die from liver failure due to oral terbinafine. This article on fungal nail disease mentions this but doesn’t quantify it, and doesn’t even come off the fence completely about liver function testing. Cost is no longer a barrier to terbinafine prescribing, but I don’t know that I could face harming a patient to treat a harmless condition, so I think I will insist on LFTs before treatment and at 6 weeks. All other treatments are a waste of time.
Lancet 16 May 2009 Vol 373
I never grudge orthopaedic surgeons their expensive cars, because on the whole they do more obvious good to my patients than any other group of specialists. Whatever they may lack in communication skills and thinking outside the operating theatre, they make up for by fixing stuff. It took them a while to notice that immobile legs can get deep vein thrombosis, but now that realisation has dawned, thromboprophylaxis following total knee replacement has become routine. The nurses go round giving enoxaparin every 12 hours; but that may soon be a thing of the past. Each morning, as the orthopaedic surgeon throws his suit jacket into the back of the Porsche, the drug trolley will rumble round the ward laden with rivaroxaban, a fixed-dose oral factor Xa inhibitor, which proved superior to enoxaparin in this randomised trial (RECORD4).
Much of this week’s Lancet is taken up with high-level hand-wringing about climate change. Anthropogenic climate change needs an anthropogenic answer, and since anthropes rarely change behaviour in favour of greater discomfort and lesser wealth, this needs to go beyond mere exhortation. Non-anthropogenic climate change is even scarier; a mere 15,000 years ago the place where I am typing this was the terminal moraine of a vast glacier covering northern Europe. What worries me most is the fact that all the scientific solutions seem to be proposed by grey-heads of my age or older, while the youths who ought to be coming up with the goods are too busy flying off around the world career-building.
BMJ 16 May 2009 Vol 338
When the great Peter Medawar collected together his essays attacking bad science, he called the book Pluto’s Republic, after a malapropism attributed to an American lady of his acquaintance. PLUTO, the king of the underworld, also gives his name to this study – a “pragmatic multicentre randomised controlled non-inferiority trial” of the kind that Medawar might well have consigned to his infernal republic. I am inclined to be kinder, because it is difficult to study an intervention like ultraviolet B phototherapy for mild to severe psoriasis taken out into the community except in a fairly pragmatic, non-inferiority-seeking sort of way. The main point you need to establish is that patients can give themselves this therapy safely and effectively at home rather than having to come up to hospital all the time – and in this Dutch study, they could.
Fifteen years ago, a paper appeared from Dundee showing that levels of the then newly-discovered cardiac hormone B-natriuretic peptide were more predictive of heart failure and death following myocardial infarction than measurement of the systolic ejection fraction. This led me on a long wild-goose chase which ended when an MRC-funded pilot study showed that it was impossible to titrate individual treatment on the basis of BNP. Here a French study of elderly patients following MI confirms that BNP is a good prognostic marker: that’s the easy bit. What to do with that knowledge is still the problem – as discussed in the accompanying editorial.
I draw your attention to this short paper on streptococcal perianal infection in children not (heaven forbid) because it’s by me, but as a tale of perseverance akin to Robert the Bruce and his spider, designed to inspire you to write for the BMJ. In 1996, our then registrar Sarah Pinder did a nice little awareness and case-finding study of this topic, which showed that most local GPs had never heard of it, despite the likelihood that they were probably seeing it twice a year. We urged Sarah to write it up for the BMJ at the time, but instead she got married, had babies and moved to Australia. Not long after, a new serological test appeared that for the first time made it easy to diagnose coeliac disease, and I urged Harold Hin to do a case-finding study for that, as I’ve told you oft and anon. Meanwhile I was working with less effect on BNP. All this gave me the idea for a BMJ series called “Commoner than you think”, which I proposed to them in 2002. Sorry, too ill-defined, was the reply. Then in 2006, Fiona Godlee asked if I’d like to write something for her new-look journal, and I proposed the same idea again, but now as part of a bigger series on Diagnosis at Presentation. Eventually, with the invaluable help of Anthony Harnden and Mabel Chew, this bit became “Easily Missed”. Then I finally had to track down Sarah in Australia and produce draft after draft of this little piece, known in our household as “bums”. And now, 13 years on, it appears in print, complete with a picture of a bum. If you hadn’t recognised this condition before, you will now: and if that’s the case, it was all worth it.
Arch Intern Med 11 May 2009 Vol 169
The Beginning of a New Era for the Archives and the Nation, declares the new editor, Rita Redberg, modestly placing herself by the side of Barack Obama. Those interested in American health care reform ideas will have a lot of important reading in her journal and in the other two I report on, but I shall try to keep to my general rule of not commenting directly on matters of politics. I shall simply slave on here in Egypt, making bricks without straw under the rule of Lord High Darzi until he is replaced by another Pharaoh who knew not Joseph.
ALLHAT is one of those trials which will not go away, like UKPDS. Both of them could be said to have too many interventions and too many end-points, and have been the subject of much special pleading and unwarranted extrapolation. But both have unexpected and important lessons for clinical practice, confirmed by subsequent trials. In the case of UKPDS, it’s that blood pressure control is more important than tight glycaemic control, and that metformin is the most beneficial drug. In the case of ALLHAT, the message is that all drug classes for hypertension are equally good at reducing most cardiovascular end-points, and that thiazide diuretics may be the best because they prevent heart failure, and the hyperglycaemia they induce does not produce any adverse cardiovascular consequences.
Various medical conditions have from time to time been known as Syndrome X, indicating general mystification, and none is more mystifying than cardiac chest pain on exertion in women with normal coronary arteries. The Women’s Ischaemia Syndrome Evaluation Study (WISE) followed up women with ischaemic symptoms but normal coronary arteries for a mean of 5.2 years and compared them with a cohort of asymptomatic women from the St James Women Take Heart Study. The 540 “WISE women” (as the study describes them) did markedly worse than the Take Hearters. In women with 4 or more cardiac risk actors, their annual event rate exceeded 25% while it was 6.5% in the asymptomatic.
Pre-scientific medicine developed some pretty effective rituals for pain relief, the most impressive and persistent being acupuncture. This study, like many others, shows that it works well for a lot of people, whether you follow the traditional points or do it at random. To perform acupuncture, you just need a set of sterile long thin needles and an impressive manner. Exhibit charts of ancient Chinese pricks on the walls of your room. Enquire about the exact nature and location of the chronic low back pain and perform a slow and meticulous examination. It may help to insist that the patient comes in a loin cloth. After a period of serious contemplation, proceed to introduce the needles wherever you like. Make sure you charge a high fee. This increases your reputation and allows you to wear finer robes.
Plant of the Week: Iris “Black Swan”
All bearded irises are lovely, and with most the scent seems to complement the colour: a rich fruit salad smell from the pink and brown ones, something more exotic from the blues, and chocolate and liquorice from this almost black one. Definitely a flower to turn heads, especially when planted where the sun can shine through it, producing an effect like very dark stained glass.
I imagine that all the many iris varieties with “black” in their name are very similar. Split them regularly and give bits to admirers.