Richard Lehman’s journal review – 7 February 2011

Richard LehmanJAMA  2 Feb 2011  Vol 305
487   Most of us have never come near a vial of bevacizumab, though we’ve read plenty about it, especially over recent years in the context of eye disease involving vascular proliferation. This monoclonal antibody targeting vascular endothelial growth factor A was initially developed as a treatment for solid cancers and this remains its only licensed indication: an ironic situation given that it works so well for eye disease but fails to improve overall survival in all the cancers for which it has so far been used (see editorial on p.506). The meta-analysis here shows that this is probably because it kills as many patients as it saves, the numbers being small in either case. Which raises the important questions of whether we can identify the patients who are going to benefit and those who will be harmed: or whether in fact the use of VEGF inhibitors is a false turn in cancer therapeutics.

502   A short Commentary piece raises more questions about how to get the balance right in treating advanced cancer – it’s called Mind Matters in Cancer Survival. In a trial published last year in the New England Journal, patients with metastatic non-small-cell lung cancer who received 4 visits to discuss their end-of-life attitudes and preferences lived longer than those who received standard anti-cancer treatment. The piece cites a number of other examples, usually in cancers for which there is little effective treatment for advanced disease. In other words, by giving too much aggressive chemo and too little supportive care, we are not only worsening such a patient’s journey towards death but also hastening it.

504   My unfortunate colleagues who haven’t been able to take their pension and get out of UK general practice in time will soon be faced with monitoring outcome measures in their local hospitals and imposing their own fines and incentives for things like length of stay and readmissions. They will quickly learn how dirty these indicators are, dependent as they are on case-mix and local support systems in social and primary care, for which they will also be responsible. Poor dears: I counsel them to read this commentary on the American situation, and sharpen their staves for an all-out confrontation with the government which seeks to dump this unmanageable task on them, along with real cuts in funding.

NEJM  3 Feb 2011  Vol 364
401   Males produce fewer antibodies to human papillomaviruses than females, and so get more overt warty infections: on the other hand, the cancers of the penis, anus, and oropharyngeal tract that men get as a result are far outweighed in total by  cancer of the cervix in women. Look at it whichever way you like, it is still highly desirable to cut down the amount of HPV circulating in males, particularly of the dangerous subtypes 6,11,16 and 18. This can be done with a quadrivalent HPV vaccine, though only to a limited degree. The reduction was 90% for overt warts carrying these subtypes, or 48% for detected viral DNA.412   A rigorously executed histopathological study helps to determine the importance of occult metastases in node-negative breast cancer, and in fact finds that they hardly matter. “Node-negative” means that the sentinel lymph nodes were found to be free of metastases larger than 2mm. The clinical question that this trial sought to address – and which amazingly was first raised in 1948 – is whether it is worth examining every lymph node in detail for micro-metastases in order to give a prognosis for the cancer. And the answer is a no: 94.6% of patients with micrometastases are alive at 5 years, compared with 95.8% of those without.

422   Oh dear, it’s that difficult time again. I shall have to mention Clostridium difficile, but without discussing its pronunciation. The last time I did that, my comments found their way to doc2doc where they produced a long stream of comments and even a survey offering 4 different ways of pronouncing difficile, none of which would have cut the mustard with any ancient Roman. A majority of 60+% of doctors prefer the modern French “diffiseal” and so does the poshest person at the BBC, Corrie Caulfield, so vox populi, vox dei is what I say (pronounced as you wish). Though if you regard Corrie Caulfield as God, then it would be vox deae, and I defy you to pronounce that. Enough: the best drug to get rid of Seediff may now be fidaxomycin which in this RCT showed non-inferiority to vancomycin for initial cure and a lower rate of recurrence

453    Percutaneous coronary intervention is the treatment of choice for myocardial infarction, but PCI can also cause MI. If you look hard enough, you can find biochemical evidence of MI occurring in between 5-30% of PCIs: but this interesting review shows that the great majority of this is unlikely to have clinical significance. If you happen to be an interventional cardiologist, you’ll need to read this in all its detail, and the take home message be that you mustn’t do more PCIs than are strictly necessary: take COURAGE and use medical treatment for stable angina.

Lancet  5 Feb 2011  Vol 377
469    In the early 1990s, when the Heart Protection Study was set up, there was a lot of interest in C-reactive protein as a marker for cardiovascular risk. It also seemed plausible that some of the vascular protective effects of statins were due to anti-inflammatory actions, so the study stratified patients prospectively by their baseline CRP. But in fact this study found that the protective effect of simvastatin is the same whatever the level of CRP: which is what we have now come to expect in relation to all CV risk factors and statins.

487   I have never read an account of prions that I could understand, which perhaps proves I have bovine spongiform encephalopathy from eating too many British steaks in the mid-1980s. Or it may mean that we are up against something like Hilaire Belloc’s Microbe (I have quoted this before, including in a bacteriology exam, but I can’t resist misquoting it again):

THE PRION is so very small
You cannot make him out at all,
But many sanguine people hope
To see him through a microscope.
His jointed tongue that lies beneath
A hundred curious rows of teeth;
His seven tufted tails with lots
Of lovely pink and purple spots,
On each of which a pattern stands,
Composed of forty separate bands;
His eyebrows of a tender green;
All these have never yet been seen–
But Scientists, who ought to know,
Assure us that is must be so…
Oh! let us never, never doubt
What nobody is sure about!
(from More Beasts for Bad Children, 1912)

The leading Scientists of the MRC Prion Unit have devised a blood test for the prions they associate with variant CJD of bovine origin – a disease which has nearly disappeared and whose epidemiology is strikingly dissimilar to that of other brain diseases attributed to prions.

BMJ  5 Feb 2011  Vol 342
320   How do you score in the use of scores? I’m afraid I did rather badly when I was still a jobbing GP, though my computer made up for some of my deficiencies. Prescribing statins, I relied on personal hunch, strongly biased in favour of universal use (see the discussion piece on p.313); but for giving out a life-long poison like warfarin for atrial fibrillation, such slovenliness will not do. We used to have the CHADS score, the we had CHADS2 and now, heaven help us, we have CHA2DS2-VASc. It performs just a bit better than its predecessors particularly in selecting people at low risk, and I guess it should therefore go on every NHS computer as soon as possible, until the day arrives when we can stop using warfarin altogether.

321   Last week I directed your attention to an editorial in the NEJM which suggested that it was time a trial of cardiopulmonary resuscitation with and without chest compression – claiming that there was no evidence one way or the other. This is hotly contradicted in the editorial which accompanies this paper, affirming conventional belief that any CPR is better than none. So we’re left with the old debate – with or without rescue breathing? The latest of many observational studies – nationwide from Japan – comes out in slight favour of including the kiss of life, though a brain-fuzz meta-analysis of the papers I’ve read over the years would suggest no difference overall, and the editorial agrees.

322    The effect of pay for performance in British primary care has attracted much transatlantic interest, and this examination of the impact of QOF on hypertension has authors from Harvard and Alberta as well as Nottingham, UK. British levels of hypertension control are amongst the best in the world, thanks to a robust system of primary care. The improvement line remained completely straight in response to QOF. While in diabetes, you may remember, it kinked and flattened as GPs realised they were hitting the targets without any need for more effort. It’s time to bin the whole idea: a massive diversion of money and organisational effort which has largely made no difference to outcomes, or in the case of the lower HbA1c target for diabetes, has probably done harm.

Ann Intern Med  1 Feb 2011  Vol 154
152   We paid our first visit to New York a few weeks ago: a city impossible not to enjoy, but with a confusing Metro system which led us to getting out at the wrong one of three stations with the same name. This meant that we had to cross a tiny part of Harlem just north of Central Park, where the glitz suddenly gives way to a squalid blankness in which young crippled black men wander on improvised crutches and dishevelled psychotics sing hymns and beg for money. I guess many Americans are hardened to the way that their health system treats poor black people. The US journals often carry papers demonstrating poorer outcomes for hospitalized black adults, without any real suggestion of a solution: but here is a notable exception. Black Americans with stroke do better than whites, in the short term at any rate. In New York City, they are 22% more likely to be given life-sustaining treatment and 13% less likely to die.

160   From the other coast of America comes news that expensive hospitals have lower inpatient mortality. This was a careful analysis of 6 common medical conditions in 208 Californian hospitals from 1998 to 2008. The headline conclusion in a big observational study like this is rarely as interesting as dabbling among the data subsets: but for that you will need a subscription, or a handy library. But by and large it does seem that the more you spend on hospital care, the better the survival: not a welcome message for today’s NHS hackers and slashers.

Plant of the Week:
Teucrium fruticans

There is a certain irony in my praising this plant, since ours, newly bought last autumn, looks in definite peril of its life. But for years we had a great big straggly one, which eventually outgrew its space and had to be sacrificed. Though a good plant for leaf and flower for most of the year, it was particularly welcome in February when it first shows its curiously shaped sky-blue flowers, the token of many to come.

It’s one of those Mediterranean plants that will usually survive in England, liking a sunny spot with poor rubbly soil like a Cretan hillside. Its leaves are grey and felty and its stalks almost white. It has a sweet sage smell if you brush against it. Although you can prune it hard, it will never look tidy, with branches that fall down to soil level and grow at zany angles however you try to tame it. Delectable, but not respectable.