Richard Lehman’s journal review – 11 June 2012

Richard LehmanJAMA  6 June 2012  Vol 307
2269    As I near my fifteenth year of writing comments on the medical journals every weekend, I sometimes envy columnists who can write their copy ahead of time and take the odd week—or even month—off. I don’t have any prepared store of fine phrases or worked up indignation, but depend for inspiration entirely on the material spread out fresh and steaming before me each week, if you understand the metaphor. I refer to a fine meal, of course. Unfortunately there is little fine food on the menu this week. Negative studies are worthy and must be published: it is important for those who look after small children with cystic fibrosis to know that it makes no difference whether the inhaled saline they are given is isotonic or hypertonic. And this was a well-powered study which measured exacerbations over four years. It deserves to be in JAMA.

2278    The medical device in widest use today was invented by Alexander Graham Bell and patented in 1876: it is, of course, the electric telephone. There has been a fair amount of telephone-smashing in the journals over recent weeks. Studies have appeared showing that close telemonitoring is associated with huge increases in mortality in patients with bad COPD or complex comorbidity in the elderly. Mr Bell himself wisely avoided having a telephone near him in his old age. But then he probably did not require cognitive behavioural therapy, being a wealthy man with a productive mental life. Those who need CBT often have to wait a long time for appointments which may involve travel and time off work. In this trial, 325 patients who presented with depression to primary care doctors in the Chicago area were randomised to 18 (!) sessions of CBT delivered either face-to-face or by telephone. Results were identical, and there were fewer drop-outs in the telephone CBT group.

2295   If you want to get a paper in a major journal, go for something about prognosis. It couldn’t be easier. Take some bloods—or better still, use some that have already been taken and stored—and measure something that is bound to be associated with overall mortality: B-type natriuretic peptide, rise in creatinine, cystatin C, copeptin, or, as in this case, troponin T (TnT). Pick a clinical scenario: in this case non-cardiac surgery. Then shock horror: overall predictor of mortality predicts mortality in this population! A million people die every year within 30 days of surgery: measuring the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery will allow you to identify some of those at highest risk. Compared with what other clinical characteristics or biochemical markers? And what are you going to do with this information?

NEJM  7 June 2012  Vol 366
2151    Delamanid, a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. This manufacturer-funded trial shows that it produces faster sputum clearance than standard regimes for MDR-TB. The scale of this important global health problem is highlighted by an epidemiological study of MRD-TB in China showing that one in ten cases of TB there is resistant to first-line treatment and that most of this is due to person-to-person transmission of resistant strains. There will need to be a concerted global effort if this epidemic is to be contained, as a very good editorial explains.

2171    The distinguished English conductor Sir Thomas Beecham (1879-1961) once declared that “the noise made by a harpsichord reminds me of two hedgehogs copulating on a tin roof.” Taking a draw on his cigar, he was careful to add, “I do not thereby mean any disparagement towards that estimable quadruped.” The hedgehog is indeed an estimable fellow, and no gardener would seek to disrupt a hedgehog pathway, whether the creature be proceeding to a tin roof in search of nuptial bliss, or a garden bed in search of delicious leaf-eating insects and gastropods. For oncologists, however, the hedgehog pathway is associated with basal cell proliferation, and hence (when upregulated) it can produce out-of-control basal cell carcinomas. These are mercifully rare, since we spot early basal cell carcinomas every week and excision usually results in cure: but for the unlucky few with unresectable local spread or metastasis (rare), an oral hedgehog pathway inhibitor promises to be the first effective treatment. Vismodegib is the name bestowed upon drug which produced results in the two trials reported here. It was usually effective and sometimes curative, but at the price of severe and common adverse effects such as loss of taste, loss of hair, and muscle cramps. This path to success is clearly a prickly one.

Lancet  9 June 2012  Vol 379
The dear old Lancet is in one of its global moods this week, and there is much to ponder on in articles about child mortality and its determinants, preterm birth rates, measles mortality, and possible ways to improve health outcomes in children in Sub-Saharan Africa. I have, alas, nothing useful to say on these subjects. The only piece I would comment on is a paper on the advantages of urban walking and cycling in the UK, written, among others, by Andy Haines. In the darkest days of the Cold War, Andy and I used to go on marches as members of the Medical Campaign Against Nuclear Weapons. Now he and his colleagues claim that “Within 20 years, reductions in the prevalences of type 2 diabetes, dementia, ischaemic heart disease, cerebrovascular disease, and cancer because of increased physical activity would lead to savings of roughly UK£17 billion (in 2010 prices) for the NHS.” I don’t believe a word of it. The longer people live, the greater the cost to society. Economically, the fewer people there are in the world, and the shorter their lifespan, the more there is to go round for the rest. The same applies to the NHS. If the aim of global health is greater wealth, rather than social justice and a better life for everybody, then maybe we should be campaigning for nuclear war to reduce population. Personally I would rather campaign for contraception. This, however, is just a rant to fill space. I am in favour of walking and need to learn to ride a bike.

BMJ  9 June 2012  Vol 344
The English are a rum lot. About 25% of the population feel tired all the time and about the same proportion feel dizzy. I suspect that there is a lot of overlap: so if a patient comes in complaining that they feel dizzy, it’s best not to ask if they feel tired all the time, and vice versa. You only have ten minutes to diagnose and treat them, and nothing to treat them with. It’s no good doing tests of vestibular function, since about 50% of Brits over 60 will fail, and about 25% of those younger. So here is the British answer: give them a booklet. Give them a cup of tea. Tell them to live with it. To take more exercise. Look on the bright side of life. That sort of thing. Next please!

Did I say take more exercise? Here’s the already notorious study showing that in a population offered good usual care for symptoms of depression, which could include exercise on prescription, the offer of assistance from a physical activity facilitator made no difference to depression-related outcomes at one year. The facilitators did succeed in increasing levels of exercise, but not to an extent that resulted in an improvement in mood. “Exercise does not help depression” was the inevitable headline that followed in the media. Worse still, it was echoed by one of the professors who helped to run the study. It’s enough to make anyone despair of accurate medical reporting. But despair is a symptom of depression: best go for a run; avoiding facilitators.

DESMOND was a nice idea. A new diagnosis of type 2 diabetes is a warning call to people that they are at high risk for a range of vascular events, and there is reasonable evidence that lifestyle changes can be of benefit. A diabetes education and self-management programme (which allegedly contains the letters comprising DESMOND) seems a self-evident good. This UK-wide cluster randomised trial, however, showed no change in biochemical or lifestyle measures at three years. The average age of the patients was 57, and fewer than 5% were from ethnic minorities. Back to the drawing board.

Long before it came into routine primary care use, D-dimer testing struck me as a potentially very useful way of diagnosing deep vein thrombosis. When it finally became available, though, I found that it wasn’t all that good. No patient over the age of 60 who had an “elevated” D-dimer ever seemed to have a DVT, and a lot of them were given LMW heparin for no good reason while they waited for an ultrasound the next day. This Dutch study shows that this may be due to a the low one-size-fits-all threshold level of 500µg/l. Add 10 µg/l for each year of age and go for 750 µg/l over the age of 60 – that way you can safely rule out many more DVTs.

Ann Intern Med  5 June 2012  Vol 156
767   If in the year 2012 you sent a leading medical journal a case series describing the results of treatment for pneumonia using sulfanilamide, you might expect rejection – followed by an immediate visit from a disciplinary officer, perhaps accompanied by a psychiatrist. For therapy, we require that the most effective modern treatment be used, and that any new treatment should have a good chance of being shown to be more effective in a blinded randomized controlled trial. And taken alone, observational data are seldom enough. But as I’ve already hinted, it is so very different when the study is about prognosis. Here, it seems, the best is never the gold standard: any available combination of data will do. This Canadian study of mortality following acute heart failure crunches data relating to various emergency room measurements such as heart rate, creatinine, BP, oxygen saturation and troponin, and finds that you can derive a multivariate index which is somewhat predictive for mortality. Of course you can: but why ignore the best marker for mortality in heart failure, which is B-type natriuretic peptide? There are few clinical uses for BNP in real life, but the one that has been firmly established for 15 years is predicting death.

Plant of the Week: Rosa “Graham Thomas”

We don’t actually grow this rose ourselves, primly shunning all such modern inventions, but we did see it on a New England wall recently and had to admire its fragrant yellow apricot blooms amidst good dark healthy leaves. It was raised by David Austin in 1983 and has become extremely popular: its habit is perhaps best described as “semi-climbing.”

Graham Stuart Thomas (1909-2003) was the greatest English writer on roses and one of the best on all types of garden plants from alpines to large shrubs. The only class he never covered systematically was trees. When writing these columns in England, I would always take down a volume or two of his: they are all worth having. So, I think, is this rose.