Richard Lehman’s journal review – 6 December 2010

Richard LehmanJAMA  1 Dec 2010  Vol 304
Eicosapentaenoic acid – which one is that? That’s right, the fishy one: all that spelling homework I made you do is paying off. More accurately, it is the omega-3 fatty acid that fish get from eating algae and deposit as liquid fat. And docosahexaenoic acid? The same again: only commercial preparations tend to be made directly from plant sources. These fatty acids have some anti-arrhythmic properties, but it is very hard to translate these into any demonstrable clinical benefit. Here is the latest in a series of negative omega-3 trials: a study which proves that they do not reduce recurrences of atrial fibrillation in people with symptomatic recurrent AF.

Sharing decision-making with patients can be a tough act, especially when you have to say “We know you have a sort of cancer but it’s probably not a good idea to treat it just now, so we’ll do regular blood tests and keep an eye on it.” Think of chronic lymphocytic leukaemia, or in this case of low-risk prostate cancer. The patient has the deadly label of cancer, and will never again be the same person. Now you expect him to share in a decision not to treat it – whatever “it” is. This paper tries to help: “We constructed a state transition model analyzed using Monte Carlo simulation with TreeAge Pro Suite 2009, version 1.0.2, to estimate health benefits (QALE) accruing to men with low-risk, clinically localized prostate cancer (PSA <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). In the model, men are treated at diagnosis or undergo active surveillance.” To be fair to the authors, they do actually provide the assumptions of their modelling method in an e-appendix. But to be fair to me, do you really expect me to spend half my weekend interrogating it? And that is the problem with all modelling studies – the busy clinician has to take them on trust. And the patient who has to live with this uncertainty? It’s your job to work that one out.

Here’s a perfectly straightforward study which adds to the available stock of human reality, as RP Blackmur said of great poetry. Not that ANCA-positive vasculitis is a poetic subject: it is nasty, it shortens life, and still often bears the name of Friedrich Wegener, a high ranking Nazi military doctor who worked adjacent to the ghetto at Łódź (survival rate 4.9%). For years the mainstay of treatment has been azathioprine, and this large open-label European study sought to discover whether mycophenolate mofetil  would work better. It did not – there were more relapses and similar rates of adverse effects.

And here by contrast is a study which does not add to the sum of human reality, but simply generates a vague and unsatisfactory hypothesis. Take one ill-defined group – children labelled as autistic – and take another miscellaneous collection of cytological phenomena called mitochondrial dysfunction. Compare the two and you find a correlation. Or do you? There were ten autistic children and ten controls. What is this study doing in JAMA?

We’ve mentioned localised prostate cancer and CLL: now it’s time for multiple myeloma precursor disease. Another nasty label, because once you have multiple myeloma you will die painfully within 5 years. So how precursive are these precursors? In the case of multiple gammopathy of uncertain significance (MUGA) the risk is 1% per year; in the case of smouldering myeloma it is 5% per year, decreasing the longer it goes on smouldering. And it seems from this review that we have no means of dousing the myelomatous smoulder: all we can do is wait for overt disease, and start the five-year clock.

NEJM  2 Dec 2010 Vol 363
Yet another large population study examines the relationship between body mass index and mortality. I like the ones that show that it’s good to be slightly fat at the age of 60. This one doesn’t, so I immediately question its validity. If it’s a typical sample of the American population, why is the median baseline BMI 26.2? I guess it’s because the 19 cancer-related prospective studies in this aggregate cohort were enrolled any time from 1970. And a sample size of 1.46 million does suggest adequate power. Less winter comfort-eating for me, then.

All doctors resemble five-year old children in their daily need to talk about poo and snot. This review of airways mucus is the first I can remember in the NEJM over the last 12 years (I can’t remember any at all about faeces, that “neglected organ” containing more living cells than all the rest of the body many times over). Phlegm is important stuff: think of what happens to the lungs in cystic fibrosis, or in severe asthma when plugs of rubbery mucus can block enough of the airways to cause rapid death. Abnormal amounts of mucin play their part in the progression of COPD too. The effectiveness of the mucociliary apparatus in the healthy lung is astounding, but we don’t have all that many drugs to help it when impaired: this paper contains a useful list of those we do and those in development.

Lancet  4 Dec 2010  Vol 376
The largest group of healthy patients we treat with several medications for life are people with high blood pressure, and we rarely succeed: we may bring the BP down but we do not abolish the added risk completely; or else we simply fail to bring the BP down sufficiently to do any good at all. This bugged me a lot at one time, but once I had mapped the area I decided there was no fruitful way forward for primary care research, except perhaps in the detection of primary aldosteronism. But what have we here? An intervention which reduces office BP by 33/11 mm Hg between groups at 6 months. Yes, rub your eyes. Typically a new intervention reduces BP by a few mm Hg if that (see CPAP in last week’s BMJ), and adding drugs in people already on three medications seldom works at all. But renal sympathetic denervation may actually cure hypertension in some people. Forsooth, is this verily the True and Holy Grail which Sir Perceval doth bring unto us? “The jury is still out” says the commentary on p.1878, but it can’t disguise its excitement over the potential revealed in the Symplicity HTN-2 trial.

GREACE is not a very flattering acronym, but it’s wittily apposite for a Greek study about blood lipids. It stands for Greek Atorvastatin and Coronary Heart Disease Evaluation and this post-hoc analysis looks at whether people who get raised liver enzymes on a statin need to stop treatment. Emphatically not: ignore the LFTs and carry on and get as much risk reduction from the statin as if the LFTs were normal.

BMJ  4 Nov 2010  Vol 341
The pseudo-marketisation of UK health care was an idea thought too radical by Margaret Thatcher, who nonetheless allowed Kenneth Clarke to go ahead with it. Amongst its disastrous effects is to consolidate the artificial division between primary and secondary care, and indeed to put a price, and therefore a penalty, on every move of a patient from one to the other. In the guise of fundholding in the 1990s, this led directly to the disgraceful under-referral of suspected cancer which gave the UK the worst survival statistics in Europe at that time. Yet greater – perhaps terminal – calamity threatens the NHS when GPs cease to become patient advocates and instead act as the agents who will ration all spending on secondary care over the next few years. This cohort study, based on the Health Improvement Network (anonymised data from Vision system users), provides no reassurance whatever as it seeks to explain variations in referral from primary to secondary care. Actually the data probably aren’t good enough to draw any conclusions about anything, but if it really is true that only 61.4% of women with postmenopausal bleeding are referred to secondary care, then 38.6% of British GPs shouldn’t be allowed near postmenopausal women. The best result of this study is a very clear editorial by Moyez Jiwa on the limitations of referral analyses.

A Swedish Clinical Review of oesophageal cancer maintains the high quality of this series. Barrett’s oesophagus is mentioned just once and the section of screening is clear and minimalist. This is a cancer which presents too late for curative attempts in 75% of cases. Adenocarcinomas are getting much commoner  for reasons we can only guess at. We don’t know whether chemoradiotherapy should be pre-operative, peri-operative or post-operative, and successful surgery may still leave a trail of problems in its wake. No more comforting than the average episode of Wallander (Swedish version), but with equally high production values.

Plant of the Week: Rumex acetosa


Very common and widely distributed . . .it is called Sorrow . . .in some parts of Worcestershire

Memory worsening — let it go as rain
streams on half-visible clatter of the wind
                            lapsing and rising,
that clouds the pond’s green mistletoe of spawn,
seeps among nettlebeds and rust-brown sorrel,
perpetual ivy burrowed by weak light,
makes carved shapes crumble: the ill weathering stone
salvation’s troth-plight, plumed, of the elect.

This poem by Geoffrey Hill was sent to me by a young Yale English graduate called Peter Behrman-de Sinety, who started a correspondence about these reviews some years ago. He finally came to stay with us last Monday, on the way to hear Geoffrey Hill’s inaugural lecture as Professor of Poetry in Oxford the next day.

Peter didn’t know how this poem would resonate with us – the personal sorrow we associate with Worcestershire, where my wife’s parents died; or how my own parents used to gather sorrel for soup when I was little and we were desperately poor, and how it now grows on their windswept Pennine grave.

To celebrate our meeting I cooked up a Sorrel Feast, using the last of the culinary sorrel (Rumex scutatus) from our garden, gathered before the frosts. 

Sorrel, tomato and prawn soup

Oysters with sorrel and wild mushroom cream

Sorrel salad (although we forgot to add the sorrel)

Quails without sorrel (basil and pine nuts instead)

Sorrel, persimmon and physalis sorbet

Partridge breasts with port and sorrel butter


It was nice. The next day we explored Hill’s childhood Worcestershire and heard his thunderous lecture.