Richard Lehman’s journal review – 6 February 2012

Richard LehmanJAMA  1 Feb 2012  Vol 307
    We of a physicianly disposition may not like to admit it, but throughout history surgeons have been well ahead of physicians at looking critically at their outcomes. For example, rates of re-operation have appeared in case series reports for well over a hundred years, so this paper on re-excision in breast-conserving cancer surgery is less innovative than it might seem, except that it goes further and looks at variability between centres and surgeons.

And actually that is nothing new either – James Simpson and Florence Nightingale were doing it in the 1860s. I’m not sure we have got all that much further in understanding this wild variation: in this survey of 4 US centres it isn’t associated with caseload at all, and isn’t even all that much to do with completeness of excision. For example, reoperation rates on patients with negative margins varied from 0% to 70% (?!) among individual surgeons, and from 1.7% to 20.9% among institutions. What is going on?

483   Shock horror: Americans are not getting fatter. We can no longer console ourselves that however bad the obesity epidemic may be in the UK, it will always be worse in the USA. Mind you, we are quite a way behind; and Americans still cherish their obesogenic environment by never serving portions that are less than twice the amount required. It’s just that nowadays in middle class circles it tends to contain a lot of unidentifiable greenery and some grated carrot. A plateau has been reached at every age group in the US, according to the latest figures from NHANHES (National Health and Nutrition Examination Survey). The 2010 obesity level was 17% overall in children and adolescents, and 36% in adults, with higher levels in black and Mexican Americans. The awful fact is that for those already obese, this is virtually irreversible by any non-surgical intervention, individual or societal.

NEJM  2 Feb 2012  Vol 366

399    Hodgkin’s lymphoma in its earlier stages became a curable cancer several decades ago, through a combination of combined chemotherapy and radiotherapy. Now we are witnessing a gradual finessing of treatment aimed at minimising the harms of curative therapy: a noble effort, where success is measured in small differences in outcome at 12 years’ follow-up. This trial was initiated in 1994 and proves by the narrowest of statistical margins that using modern staging and chemotherapy, stage IA and IIA non-bulky Hodgkin’s lymphoma survival is better if you omit the radiotherapy. Great news for people with early Hodgkin’s and a great example of patient research, in both senses of the word.

409   And now to two trials on fibroids. I don’t know why that should seem vaguely odd in the NEJM, but the editorial seems to feel the need to apologize (Uterine Fibroids and Evidence-Based Medicine — Not an Oxymoron, p.471). I suppose the point is that although there are plenty of evidence-based treatments for fibroids, most women still end up with a hysterectomy. These trials looked at the effect of ulipristal acetate, an orally available progesterone receptor modulator, in women waiting for fibroid surgery; in the second trial ulipristal was pitted against leuprolide, a GnRH agonist already in use for shrinking fibroids prior to surgery. Ulipristal certainly shrinks fibroids and may have fewer side-effects than leuprolide:  “Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes.” I recently caused hot flashes in Neville Goodman by using the term “non-inferior,” for which there is unfortunately no technically suitable alternative in the English language. Alas, Nev, the medical world has few places left for us ageing pedants and purists. It is heartening to see Jeff Aronson’s learned letter on the word “surrogate” in this week’s BMJ; but the reprinted JAMA piece on Fossil Medical Words (1912) is full of the most beastly howlers in Greek spelling. The rot may have set in 100 years ago – in America, of course.

Lancet  4 Feb 2012  Vol 379
Fuddy-duddies wishing to enjoy hot flashes of rage at bad English generally go to two places in the medical literature: the poetry section in JAMA and Offline by Richard Horton. The JAMA offering this week is beyond human endurance, while Offline reverts to being merely dotty, with the odd bum note that most readers would hardly notice, such as “his stunning musical career took off—aged 8.” While praising Donizetti, Horton begins his section by disparaging a plate of brains he saw in an Italian restaurant. This is most unfair. Brains are a great delicacy and the Italian way of preparing them in batter is delicious. And those over 60 need hardly worry about Creutzfeldt-Jakob disease with its incubation period of around 50 years (possibly shorter if you eat squirrel brains).

413   The Bill and Melinda Gates Foundation funded this study of malaria mortality between 1980 and 2010 – all part of the noble effort that we Microsoft users put into global disease eradication (what have you trendy Apple users got to say for yourselves? Eh?). As you will have read by now, the adult death rate may be around twice what we previously thought, hovering around a million a year. Previous attempts at global malaria eradication foundered on Cold War competition to produce genocidal weaponry and land a man on the moon. Now it might be worth addressing this before sending a man to Mars.

432    Here is another massive effort: Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. The conclusion of the editorial sums it up perfectly: “The EBCTCG meta-analyses continue to show that polychemotherapy saves lives (and that it can, on average, reduce breast cancer mortality by about a third). Clearly, the actual benefit and harm of polychemotherapy will be determined by the individual future risk of relapse and coexisting comorbidities. The challenge now is not only to save more lives, but to reduce the number of women given polychemotherapy unnecessarily. It is with such hope that the results of ongoing oncomolecular trials are awaited. We look forward to the day when treatment of fewer women with a personalised approach achieves more.”

453    Even better is the editorial on this study of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC). State-of-the-art cardiac MRI is pretty amazing at spotting coronary atheroma, and better than state-of-the-art CT (SPECT); but that is no reason to rush to adopt the new technology. Robert Bonow’s words have resonances far beyond cardiac imaging: “Enhanced diagnostic accuracy of CMR must be balanced against availability and cost-effectiveness, and there is a need for evidence of measurable improvements in patient outcomes. Diagnosis of coronary artery disease alone is not sufficient to determine the need for revascularisation. To show value, advances in imaging must be coupled with enhanced patient well-being or a reduction in unnecessary downstream testing and procedures.”

461   For your further intellectual nourishment this week The Lancet offers seminars on Lyme borreliosis, hereditary angio-oedema and low back pain. Hereditary angio-oedema is caused by C1 esterase deficiency, and if you have a patient with it the chances are that he or she will be able to tell you all you need about it (including tales of relatives who died from laryngeal involvement). About low back pain you already know as much as anyone else. This seminar on Lyme disease, however, has already come in handy as it was already on the Lancet website last July, when my wife and I hired a car and passed through Old Lyme, Connecticut, on our way to a highly recommended coastal nature reserve. This consisted of reedy marshland and woodland areas full of bracken and stagnant pools of water. After two hours we emerged covered from head to toe in insect bites which became gross and sometimes haemorrhagic, spreading out in large erythematous circles over several days. But we took no antibiotics, and after a few hot nights, rendered sleepless from itching, the spots settled. I don’t think we have Lyme disease, though thousands of Americans believe that they have the chronic form and rage incessantly at anyone who disbelieves them. If we eventually become delusional, you’ll all regret we didn’t just take some tetracycline in good time.

BMJ  4 Feb 2012  Vol 344
Three papers in this week’s BMJ examine the decline in mortality from myocardial infarction in European countries. The first is England, a part of the United Kingdom which was oddly missing from the European MONICA study in the 1980s and 1990s. This record linkage study shows an astonishing fall in standardized mortality from myocardial infarction of one half between 2002 and 2010. This is unevenly spread across England, as most things are, but in this case there is no evidence of a clear North/South divide. Nearly half of the drop is attributed to improved survival at 30 days. Most deaths from MI in England are now sudden deaths outside hospital.

In Denmark, a similar decline has occurred, but measured over 25 years rather than 8.

The investigators from Poland prefer to measure their halving of cardiac mortality from 1991: “Over half of the recent fall in mortality from coronary heart disease in Poland can be attributed to reductions in major risk factors and about one third to evidence based medical treatments,” they conclude. By means of different kinds of modelling, they attribute this to “socioeconomic transformation”, ie liberation from the yoke of socialism. Perhaps we in England should attribute ours to Tony Blair, though I would rather not.

A somewhat worrying report from five Scandinavian countries suggests that taking serotonin reuptake inhibitors during pregnancy may double the risk of persistent pulmonary hypertension in the newborn. This is billed as a population cohort study but is really a case-control study. The risk seems greatest when SRIs are taken in the last weeks of pregnancy – unfortunately just when one would least wish to discontinue them.

Plant of the Week: Rubus cockburnianus

Basking in temperatures of 5 degrees and more here in New England, we think anxiously about you left in old Britain as it snows and freezes. Often the plants that look best in such conditions are the brambles that we love to hate all the rest of the year. Covered in rime, their stems and even their leaves can take on a sort of hoary magic. Once the ice has melted, you can go back to cursing and bleeding as you struggle to extirpate them. Here in New England there are curiously few wild brambles, or even nettles, making its woods a delight to wander in (so long as you avoid poison ivy).

If you want a bramble that looks good all the year round, this one is worth trying – but only if you are prepared to give it about fifty square yards of ground, or fight a losing battle to contain it. The white stems look wonderful all winter, and there are various varieties with goodish leaves for the rest of the year. R cockburnianus is not quite as invasive as the common bramble, and when we finally decided to extirpate our bank of it, it only took about five goes and less than a pint of blood.