Richard Lehman’s journal review, 25 October

Richard Lehman
JAMA 20 Oct 2010 Vol 304
What do fish oils and Mozart have in common? Answer: both have been proposed as ways to enhance neurocognitive development in utero. But I am afraid the claim is untrue in both cases, and had Mozart lived he would not have gone on to write The Magic Herring. Or perhaps he would – it’s rather a good title, and according to Google, still up for grabs. Anyway, the magic of herring does not inhere in the enhancement of early life development, or indeed prevention of postnatal depression, according to this study of docosahexaenoic acid (DHA), which was given as fish-oil capsules and tested against vegetable oil capsules in pregnant women. If DHA does anything for this group, it’s to prevent premature delivery and this of course may be a great good in itself.

Few trials have caused so much embarrassment to well-intentioned doctors as the Women’s Health Initiative randomised study of conjugated equine oestrogens with medroxyprogesterone versus placebo for menopausal women. On the basis of observational evidence, we had been encouraging every woman to experience the benefits of HRT: suddenly in the middle of 2002 we started warning them off, in large part due to the added risk of breast cancer. Here are the latest WHI data about the risk at a median of 11 years after cessation of the trial. Women randomised to HRT all those years ago continue to get 25% more breast cancers and these tend to be of a more aggressive type. So we now know a lot about the risk of breast cancer in relation to this particular form of HRT but perhaps less about other oestrogen-progesterone combinations.

When I was a medical student the professor of surgery didn’t know the names of his immediate juniors, and I later encountered surgeons who regularly made their nurses cry and threw instruments in theatre. For a few young men, these became heroic role models: the rest of us were put off surgery for life. “There is insufficient information about the effectiveness of medical team training on surgical outcomes,” according to this study of team training in US Veterans’ hospitals. They found that such training brought about a 50% fall in mortality rates. Further studies should include Kleenex counts among operating room staff.

Does it really matter if deafness is detected in the neonatal period rather than at nine months? This study looks at developmental outcomes at ages 3 to 5 in children who went through a gradual transition of public screening policy in the Netherlands earlier this decade. As the change was introduced region by region, outcomes could be compared in similar cohorts, and the results definitely favour hearing tests at birth.

NEJM 21 Oct 2010 Vol 363
You’ve probably got at least one patient with aortic stenosis who is considered too poor a surgical risk for open valve replacement and who will therefore become increasingly symptomatic and die within a couple of years. In the future, such patients will face a difficult choice: whether to go for trans-catheter aortic valve replacement, which involves a bovine valve being implanted via a femoral artery catheter and expanded with a balloon. This is as tricky as it sounds and carries a 5% risk of stroke and a 16% risk of major vascular complications; on the other hand, in this randomised study (TAVI) 70% of the patients randomised to catheter valve replacement were alive at one year compared with 50% of those randomised to standard treatment (which could include balloon valvuloplasty).

About ten years ago, the Lancet (less pompous in those days) published a picture of a piece of glass at an angle of 45 degrees with trickles of blood running down it. This was a patient’s way of measuring his own INR while taking warfarin on a trip to remote China. Nowadays there are expensive home testing kits which do the same thing. Here is a trial that compares weekly home testing with monthly standard lab testing in patients taking warfarin for atrial fibrillation or valve replacement. Fortunately it was funded by the Department of Veterans Cooperative Studies Program, rather than a diagnostics company, and it concludes quite simply that “These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy.” I bet if a testing kit manufacturer had paid for it, this would have read “Self-testing shows significant benefits in time within target INR range and patient satisfaction, with no increase in stroke, major bleeding episode or death.”

In the UK, there is a strange association between the right-wing popular press and stories of cancer breakthroughs (always British) that will make all cancer a thing of the past in a couple of years. The New England Journal is more cautious, and usually tells us about tiny incremental advances in particular types of cancer: but maybe this paper heralds the beginning of a true and general breakthrough by demonstrating that a wide range of cancers have a strange kind of receptor on endothelium of their blood vessels. It’s normally only found in some gonadal cells of the adult human and it binds to follicle stimulating hormone, of all things. Wouldn’t it be great if this led to the rapid invention of all sorts of FSH-targeting anti-tumour agents for a huge range of cancers including prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary?

Lancet 23 Oct 2010 Vol 376
I groaned when I saw the title of this paper: A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. I knew I would have to read right though it, because the abstract is of little help. “Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event.” But what the Finnish investigators discovered was a difference of 70% between the lowest and highest quintiles in their gene-carriage score, which is not the same thing at all: it probably means a risk increase of about 30% compared with the mean. And, as I suspected all along, factoring in these SNPs adds nothing to existing cardiovascular risk scores. The vast amount of work these investigators put in to this analysis of the FINRISK and COROGENE cohorts was doomed from the start: as the accompanying editorial states, “it seems unlikely that genomic risk prediction alone will attain the discriminatory resolution to predict individual disease-risk for many common diseases with only modest heritability.” In other words, if a disease isn’t already strongly predictable from family history, trawling through billions of gene pairs to identify candidate SNPs and doing case-control studies to achieve p values of less than 10-6 is likely to be a waste of time.

Here is an awe-inspiring account of Escherichia coli O157 written by a single retired bacteriologist, Hugh Pennington. You won’t easily find a better monograph on a single pathogen – though I have to confess that I haven’t often tried. There is reasonable evidence that Shiga-toxin producing E coli is a new phenomenon, causing haemolytic-uraemic syndrome in sporadic outbreaks from 1983 onwards. It lives harmlessly in the bowels of ruminants and gains little by jumping to humans, who cannot carry it for more than a couple of weeks. Once a child has it, we know of nothing that will prevent the development of haemolytic-uraemic syndrome. After so magisterial an account, I was looking forward to a stirring final peroration, but we have to be satisfied with “In this regard, the South Wales Public Inquiry report from 2005 recommended investigation of supershedders.”

BMJ 23 Oct 2010 Vol 341
I am old enough to remember a time when tricyclic antidepressants were used almost entirely to treat depression: quite good they were too, and much less dependence-forming than SRIs, though we’re not supposed to mention that. Nowadays tricyclics are prescribed mainly for chronic pain, including headache. Most patients I referred to a headache clinic came back with a little bag containing amitriptyline tabs 10mg x 27, which they placed reproachfully on my desk. “The doctor told me to take these and I did but the next day I felt, it was so dreadful oh I can’t tell you, so you can have them back for all the use they are to me.” But there are others who persevere and say that they really help: and in fact this meta-analysis appears to confirm that TCAs show an increase in effect over time for both chronic tension headache and migraine.
The next systematic review deals with interventions to promote cycling. I have a keen personal interest in these, because I cannot ride a bike. The intervention I need is free cycling lessons in a safe padded environment where nobody is looking. This is not a laughing matter. When Russian soldiers poured across eastern Europe at the end of WW2, they left heaps of broken bicycles in their wake. Having stolen the bikes, they tried to ride them, fell off, and then took revenge on the machines (see After the Reich by Giles MacDonoch, 2007).
A clinical review of pyrexia of unknown origin shares authorship between experts from India, the USA and England. A list of common diagnoses of PUO from the three places would make an interesting comparison, but instead we get an account so generalised that I didn’t find it very useful. Not that this should trouble a mere GP: the definition of PUO now includes failure to find the cause after 3 days in hospital or 3 or more outpatient visits. Strictly for House fans.

Ann Intern Med 19 Oct 2010 Vol 153
Nurse care management is now standard practice in type 2 diabetes, but the designers of this trial suggest that “many patients with diabetes would benefit from self-management assistance between clinic visits.” They selected 244 male patients with a mean HbA1c of 8.02 and randomised them to continued nurse care management or telephone-based peer support between paired diabetic patients for six months. During this time there was a small fall in the HbA1c of the peer-support group and 8 of them started insulin, compared with a small rise in HbA1c in the usual care group and only one insulin conversion. A success! Except that there is no evidence that this shift of HbA1c has any clinical significance, and those converting to insulin would be swapping a 7 in 1000 lesser chance of having a heart attack in the next five years with a 47 in 1000 chance of being admitted to hospital with hypoglycaemia, with no clear benefit to their eyes or kidneys. I’m indebted to John Yudkin for those figures. It’s time we got real with what we are trying to do when we treat type 2 diabetes: watch this and other spaces.

Plant of the Week: Mahonia x wagneri “Moseri”

I’ve plugged this shrub before, but people don’t seem to be listening. It remains something of a rarity, while mahonias of far less worth are seen in every garden centre. I bought it from one of the few specialist nurseries that offer it because I read that it has foliage interest in every season, and this is absolutely true. At present its leaves are turning a red brick colour. In spring the new foliage will be yellow, turning to coral and pale green.

With such dysfunctional means of photosynthesis, this shrub is never going to get big. But it is always pretty, and like most hardy mahonias it will grow anywhere, even in deep shade. However, it’s important with Moseri to choose a place in full sun on poor soil to get the full range of leaf effects. As a bonus, it has yellow highly scented flowers, usually in spring; but in this peculiar autumn a spray of them has already appeared.