Richard Lehman’s journal review – 8 November 2010

Richard LehmanJAMA 3 Nov 2010 Vol 304
There is no suggestion in any of the numerous works of PG Wodehouse that Jeeves might have suffered from Alzheimer’s disease, and we may attribute this to the fact, attested by Bertie Wooster, that he wore a size 14 hat and ate tons of fish. But whereas there is some evidence that a high intake of fish might prevent Alzheimer’s disease, this trial shows that once you have it, fish oils will not slow cognitive decline. Just over 400 subjects with mild-to-moderate Alzheimer’s were randomised to capsules containing docosahexaenoic acid (DHA) or placebo and the two groups showed no difference in cognitive decline, or indeed hat size as measured by CTs of brain volume. (N.B. a simple test for cognitive decline: learn how to spell “docosahexaenoic” and test yourself in a few minutes’ time).

This week’s JAMA is devoted to the problems of old age, which seldom arrive singly. I think that one of the many reasons that most GPs retire soon after reaching 60 is to avoid being reminded all day long of what is in store for them. But I also have to say that in my working life as a doctor, treatment of the elderly has become much more humane and thorough. “Nobody rushes you through” is the subtitle of this piece on comprehensive primary care for older patients with multiple chronic conditions. Now that can’t be said of British primary care, which is the art of working in ten-minute slots; but it can be said increasingly of geriatric assessment in hospital outpatient departments. The models of assessment described here are called GRACE, PACE, and guided care. Sounds good to me, though I hope it’s another 20 years before I need them.

I tried to do some heart failure research in the mid-1990s, and was baffled to discover that a lot of elderly patients with obvious clinical heart failure had high levels of B-type natriuretic peptide but a normal systolic ejection fraction. When I pointed this out to British cardiologists, I was generally told to shut up: there is no such thing as “diastolic heart failure” and treasonable talk of this kind would stop people having echocardiograms and taking the maximal doses of ACE inhibitors and beta-blockers that real heart failure requires. I slunk away and eventually came to a provisional understanding of this kind of heart failure, which is not based solely on events in diastole but also to stiffening of the main capacitance arteries. It is extremely common in people over 75 and we don’t know how to treat it, partly because cardiologists and drug companies remain uninterested; as this short commentary on “age disparities in heart failure research” points out.

NEJM  4 Nov 2010 Vol 363
The New England Journal describes itself as the world’s leading medical journal and I wouldn’t argue with that. Every now and again, though, its papers are of such a rarified nature that a mere GP cannot hope to apply their undoubted wisdom and excellence to his personal practice. You and I shall never use recombinant activated Factor VII in a heavily bleeding patient, which is probably just as well, because it might kill people; we shall never have the satisfaction of seeing the subependymal astrocytomas of tuberous sclerosis shrink under the influence of everolimus; nor indeed are we likely to use brentuximab vedotin in relapsed CD30-positive lymphomas; while advances in haemodialysis we leave in the capable hands of our learned friends, the nephrologists. I have no objection to such rarefaction on the part of the NEJM editors because these are life-and-death matters for many people around the world. Moreover, I can’t fault the journal’s stance on many of the important debates in medical politics, including criticism of the role of some major pharmaceutical companies, such as GSK in relation to rosiglitazone. But in one of his latest blogs, Richard Smith reminds us that high-faluting does not come cheap, and 32% of papers published by the NEJM relate to studies paid for by drug companies, who then pay the journal up to $1M for reprints. It is this sort of thing that led Marcia Angell to her depressing conclusion that “it is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of the New England Journal of Medicine.”

Lancet  6 Nov 2010  Vol 376
You only have to look as far as The Lancet for a classic example of a promotional trial run by a drug company (Abbott) with the flimsiest of end-points. Typically, it involved 60 centres in 10 countries to recruit 281 patients with type 2 diabetes and albuminuria. There must be that number in every small town in the developed world. The end-points that are important for these patients are the usual ones in diabetes – death, cardiac ischaemia, loss of an extremity, blindness, and renal failure. We try to avert these by prescribing RAAS-inhibiting drugs and statins, controlling blood pressure, and getting the glycated haemoglobin below about 9. Now most patients in the Northern hemisphere with diabetes (or anything else, for that matter) are vitamin D depleted, and can be treated with a vitamin D analogue paricalcitol manufactured by Abbott, which costs £70 per month, or £140, for the doses used in this trial. Alternatively, anyone can go and buy vitamin D3 25 mcg daily for about £3 per month. So if you wanted to know whether paricalcitol is a beneficial and cost-effective treatment for T2DM with albuminuria, you might recruit a couple of thousand patients, randomise them to paricalcitol, or vitamin D3, or placebo, and follow them for 5-10 years looking for hard end-points. Oddly enough, that is not what Abbott did here. They measured the urinary albumin-to-creatinine ratio (UACR) in response to paricalcitol 1 mcg or 2mcg daily, and found that it went down and stayed down for 24 weeks. End of trial. Now there is an observational association between UACR and adverse events in diabetes. But there have also been trials (such as AVOID) where reducing UACR has actually been associated with harm. UACR is not a valid surrogate end-point for any trial, let alone one that would have us spending up to £1,800 a year extra on every diabetic patient with protein in their urine.

Next to Marcia Angell’s point about authoritative medical guidelines. This meta-analysis of three studies of out-of-hospital cardiopulmonary resuscitation concludes that chest compression only is superior to chest compression with rescue breathing. Just before this review appeared on the Lancet website, another nicely conducted study appeared, showing a twofold improvement in survival with compression-only CPR. But the International Liaison Committee on Resuscitation had already made up its mind, and its 2010 guidelines were already with the printers. Result: a declaration in favour of rescue breathing. The more “trusted physicians” you have on any guideline panel, the less you should trust them, particularly if the evidence dictates the abandonment of some cherished practice. Because the more eminent you are, the harder it is to eat your words in public.

Next to the now-famous paper by David Nutt, who was sacked by the outgoing government for disagreeing with their policies on controlled drugs. I fear he does himself no favours with this “multicriteria decision analysis” which puts the harms of alcohol way above those of anything else. This may or may not be true, but if you want to find out, there is absolutely nothing in this paper that will help you. All modelling is suspect, but expert consensus scoring is stark rubbish: it reminds me of Wolfgang Pauli’s famous outburst, “This paper is not right! It is not even wrong!”

BMJ  6 Nov 2010  Vol 341
Faecal occult blood screening for bowel cancer is a crap test, and the more you inform people about it, the less they take it up. This is the welcome conclusion of an Australian study of a decision aid aimed at adults with low education. The paper inspires a mummy-knows-best editorial from Hilary L Bekker – our aim should be “informed uptake rather than informed decision-making”. I am sure that Pope Urban VIII said something very similar to Galileo, as he showed him the instruments of the Holy Inquisition.

“But it’s for their own good!” cries the inner health visitor in each of us, especially as the people who get bowel cancer tend to be adults of low education, with their deplorable lifestyle choices. They’re fat and lazy and they smoke and drink and eat rubbish instead of fruit and vegetables. This Danish cohort study confirms that each one these things increases your risk of bowel cancer. The more reason, you’d have thought, to opt for a screening policy that actually detects most cancers, like flexible sigmoidoscopy.

For half of my professional life as a small-town GP there were moves afoot to close down our local consultant-led obstetric unit (1,600 births/year) and replace it with a midwife-led facility. On first principles, this seemed like a dangerous idea, since the nearest alternative obstetric unit is an hour away. So I unwillingly set about finding out the evidence about the safety of low-risk midwife deliveries and was appalled (a) at what evidence there was, but even more (b) at what evidence there wasn’t. In the UK, this is a delicate topic: the Birthplace Cohort Study of Low Risk Birth was supposed to report 14 months ago but still hasn’t managed. In the mean time, the Dutch system, long held up as a model of safe midwife-led care with lots of home births, has come under scrutiny for its alarming perinatal mortality and severe morbidity statistics. Basically, birth outside hospital is much nicer for the mother and much riskier to the baby. If things start going wrong in labour and require transfer from a midwife to an obstetrician, the risk of neonatal death is trebled.

A succinct and practical summary of the diagnosis and management of psoriasis from SIGN, the Scottish guideline manufacturers. My dear fellow-GPs, thrown into the brave new world of the insolvent NHS as sole rationers and commissioners of care, consider this: “Resources are needed in primary care for an annual review of patients that fully evaluates the impact of these diseases on quality of life, identifies those patients with more severe disease who require specialist services, and assesses comorbid conditions such as depression and vascular disease. In secondary care, clinical time needs to be made available for multidisciplinary care that optimises patient outcomes over the longer term, in the face of pressures to prioritise new patients. The increased resources required for phototherapy, systemic treatments, biologic treatments, and inpatient treatments are substantial.”  Oh dear.

Ann Intern Med  2 Nov 2010  Vol 153
With stockings, the longer the better. This is not merely a fetishist preference, but carries the imprimatur of the Medical Research Council of the United Kingdom, the Chief Scientist Office of the Scottish Government, and Chest Heart and Stroke Scotland, the funders of the CLOTS trail collaboration. This clottish acronym is derived from Clots in Legs Or sTockings after Stroke. The subjects were 3114 patients in 112 hospitals (no, they don’t have that many in Scotland – the trial covered 9 countries) immobilized by stroke. They were randomised to have below-knee or thigh length compression hose. The latter had fewer clots in their proximal deep veins.

Eight Italian meta-analysts go to work on the trials of prophylactic implantable cardioverter-defibrillators. These expensive devices often malfunction with shocking consequences but they probably save a few younger patients from sudden death. But in people of sixty and over – called “elderly” by these authors, perhaps through a limited knowledge of the English language – there is no clear evidence of benefit. Purchasers of care, take note, and do not be duped by interventional cardiologists: biventricular pacing saves lives but putting in an ICD at the same time is usually wrong.

Plant of the Week: Euphorbia characias subsp wulfenii “Emmer Green”

The euphorbias are a vast and various plant family, ranging from huge tropical rain-forest trees to the little annual milk-weeds that come up in every English garden. One common feature is that they all tend to exude a milky sap which is highly toxic and usually irritant to the skin, making them unpopular with dermatologists. But there are three of four shrubby euphorbias that should form part of every garden plan, even where dermatologists lurk; though not where small children are likely to fondle and eat them. Of those hardy in England, “Emmer Green” is the most spectacular.

Its foliage is milk-white with barely enough grey-green to support its metabolism, for which reason it is a plant that needs lots of sunshine, and is prone to mope, or die out altogether. A miffy subject, as Reginald Farrer would have said. The reason it is called “Emmer Green” is not because it is green, but because it was raised in the worthy suburb of Reading that bears that name. In fact it is anything but green. It looks absolutely resplendent at the foot of our front porch, with great sprays of leaf shining a permanent white against the contrasting leaves of Trachelospermum jasminoides Wilsonii, which are turning a deep wine purple after a couple of light frosts.

This is a plant that’s definitely worth seeking out and paying a fancy price for. Some nurseries even run a waiting list for it. Like most such, it may die on you at any time, though ours survived deep frost and snow last winter. It has cymes of typical euphorbia flower in mid-to-late summer, but these are nothing to the leaves. Put it in bad soil – as limy as you like – against a warm wall, and hope for the best. Its best is very good indeed, especially in the gloomiest times of the year.

P.S. Come on now, spell out the full name of DHA, without looking back