Richard Lehman’s journal review—26 November 2012

Richard LehmanJAMA  21 Nov 2012  Vol 308
OPERA is the quintessential Italian art-form: devised as a return to the classical past, it is a brilliant transitory display of music, costume, and painted stage sets; an escape to a heightened form of existence and emotion. Palpitations are to be found everywhere: in fact the aria Di tanti palpiti from Rossini’s Tancredi was a great nineteenth century favourite. Oily fish, on the other hand, play but a small part in the operatic repertoire, to the best of my knowledge. Were I sufficiently versed in the full range of Italian musical drama, I might be able to cite the odd eel or mackerel. Perhaps there may be a herring in Lucia di Lammermoor. The climax of Maria Stuarda probably involves a salmon. Alas, I am an infrequent visitor of the opera house, and no sound guide on this important topic: all I am trying to do is to relieve the tedium of reporting on an Italian trial of fish oil in post-operative atrial fibrillation, called OPERA. “In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF.”

2020   Here is an open-access article on Nonpharmacologic Management of Behavioral Symptoms in dementia. This is a problem which many of us have to deal with, but the paper offers no short cuts; just a variety of labour-intensive suggestions.

NEJM  22 Nov 2012  Vol 367
1979   When Felix Hoffmann, working for the Bayer company in 1897, acetylated salicylic acid and produced aspirin, he produced a drug that we are still learning new uses for. The ASPIRE trial looked at the effect of low dose aspirin (100mg) on events following the discontinuation of anticoagulation for a first episode of venous thromboembolism. The enteric-coated aspirin was provided free by Bayer (they still make plenty); the study was publicly funded in Australia and New Zealand. They had recruitment problems despite using 56 sites in 5 countries, but they did manage to conduct a double-blinded trial on 822 patients over 4 years. As far as thromboembolic event prevention went, the benefit did not reach significance—though taken with the results of the WARFASA trial, there is a definite signal for protection. But if you add in stroke, myocardial infarction and cardiovascular death, there was a significant reduction of 34%. It looks as if people who have had any episode of VTE might be well advised to take 100mg of Bayer enteric-coated aspirin daily: with this preparation, there was no increase in bleeding events.

1988   When you are trying to share decision making with patients, you need reliable data from a representative population, and you need it presented in a form that the patient can understand. Imagine that you are a man who has to decide on surgery for aortic abdominal aneurysm: you have a time-bomb ticking in your belly; it may never go off; if it does you may well die. Better have it repaired, then, but that too carries a small but significant risk of death, amounting to 3% if you have an open operation (in this study) or 0.5% if you have endovascular repair. In the long term, though, the mortality figures are equal, as this 881-strong trial shows. There is also a fine balance between major harms and complications. Here is a perfect example of a major preference-sensitive decision which requires an option grid. Don’t know what an option grid is? Look them up here.

1998   I had the pleasure of meeting Peter Gøtzsche for the first time this week: the Great Dane is probably best known for his sceptical writings (including an entire book) about screening mammography, though he has made many other notable contributions to rational medicine. Another leading mammography sceptic is Gilbert Welch of Dartmouth, and it his work which appears in the New England Journal this week: quite a coup, given the American culture of furious enthusiasm for all types of cancer screening. This analysis by Bleyer and Welch calmly traces the incidence of late presenting breast cancer, before and after the introduction of screening mammography in the USA thirty years ago; and remember that over there it is often done annually from the age of 40. There has been a decrease of 8 per 100,000 women annually presenting with late cancer, but an increase of 122 per 100,000 diagnosed early, using mammography. It is a fair assumption that 30+% of these represent overdiagnosis, and that mammography has done very little to decrease the burden of breast cancer.

2006   I am quite an authority on criminality in Sweden, having watched all the native television episodes of Wallander at least twice. I can tell you that there are only two swear words in Swedish, that murder is very common, and that almost everybody has seasonal affective disorder throughout the year. No wonder a study of Swedish criminals with so-called attention-deficit hyperactivity disorder shows they commit less crime when they are taking methylphenidate, amphetamine, or atomoxetine. Probably all persons living at that latitude should take these drugs; then they would be less inclined to kidnap children, kill their love rivals, import narcotics, and generally misbehave in gruesome and inventive ways while looking miserable. They would just kick the odd birch tree and go fishing.

Lancet  24 Nov 2012  Vol 380
1819  Alemtuzumab has been hailed as the best drug so far for relapsing-remitting multiple sclerosis, and it should be cheap too, as it has been around a long time for the treatment of leukaemia. But the sole manufacturer, Genzyme (Sanofi) has now withdrawn it so as to apply for a new licence for use in MS. The workings of capitalism can be disgusting, but we are told there is no other way. And to be honest, it is not entirely clear from the two trials in this week’s Lancet what all the fuss is about alemtuzumab; it is not all that effective as first-line therapy, failing to reduce disability scores in this trial. It increases infection rates and can cause thyroid dysfunction, possibly including papillary carcinoma.

1829  Slightly better results here in this trial of alemtuzumab as second line treatment in MS. Both trials compared this anti-CD52 antibody with interferon beta 1a. It is better at reducing relapses, but as a patient you could notice nothing much except the side effects.

BMJ  24 Nov 2012  Vol 345
General health checks are useless: it’s official. Peter Gøtzsche and his Nordic Cochrane colleagues have looked at the trials and there is no evidence of any benefit in total mortality, cardiovascular mortality, or cancer mortality. One study found a 20% increase in new diagnoses, which suggests that checks are dangerous for healthy people; who should therefore avoid doctors.

This has been a great week for the cause of data sharing in medicine, with the promise of a parliamentary enquiry on undisclosed trial data in the UK, and a lively European Medicines Agency workshop on transparency. But how willing are clinical researchers themselves to share data? Joe Ross at Yale encouraged a medical student there to send out a questionnaire to triallists who had published studies in the major journals over the last year, and the results are encouraging. The response rate was 46% and the proportion of respondents in favour of data sharing was over 70%. That still leaves a substantial number of academic researchers who may be, or are, sceptical, and who believe that having collected the data, they in some sense own it. There are battles ahead in academia as well as in industry.

Call me old-fashioned, but I think that if you want to compare two interventions, you have to do a randomized controlled trial of one versus the other. You can do indirect comparisons but only to generate hypotheses or give interim guidance to clinicians. It would be nice to believe this direct and indirect meta-analysis which claims that all novel oral anticoagulants are equivalent to warfarin in the management of venous thromboembolism, but I doubt whether it is as simple as that.

Resistant hypertension is the subject of this week’s BMJ Clinical Review, and the evenly high quality of the series continues. It really is worth taking some trouble over these patients. Poor compliance is often cited as a cause, but a person who is willing to keep coming back for BP checks is not likely to be non-compliant with therapy in my experience. There is more likely to be an underlying reason such as hyperaldosteronism. Forget QOF and look carefully at these high-risk people, and let this article be your guide.

Ann Intern Med  20 Nov 2012  Vol 157
681   When I still did normal hours general practice, erectile dysfunction was quite a common complaint—in other men, of course. I would usually check their testosterone level and give them an androgen supplement if it was low. Almost all of them would then come back for Viagra. Here’s a study comparing the effect of sildenafil alone or sildenafil with testosterone replacement in men with low levels and impotence. There was no difference in success rates: testosterone levels are rarely worth checking.

Plant of the Week: Euphorbia robbiae

In the dark, claggy days of late November, as the leaves desert your favourite shrubs, you begin to notice the odd evergreen euphorbia which you may have chanced to plant and forgotten about. This one, with rosettes of dark shiny leaf, is a must for all the half-neglected shady areas of the garden periphery. It may get a bit invasive but I have found it quite easy to control and it seems imperturbably hardy with us. It is really a very handsome foliage plant with decorative green flower shoots in the spring.

There are many showier euphorbias, of course. In fact this genus of 2008 species has something for every habitat, and if you go into a great tropical plant house like the Eden Project you will find huge trees that are called by this name. Large and small, they all exude a milky sap which can be a powerful irritant and may have a thunderous effect on the colon. This is how they got both their common English name, spurge (which later became purge, a treatment resulting in urge and splurge) and their botanical name:

“The botanical name Euphorbia derives from Euphorbus, the Greek physician of king Juba II of Numidia (52–50 BC – 23 AD), who married the daughter of Anthony and Cleopatra. He wrote that one of the cactus-like Euphorbias was a powerful laxative. In 12 BC, Juba named this plant after his physician Euphorbus in response to Augustus Caesar dedicating a statue to Antonius Musa, his own personal physician. Botanist and taxonomist Carl Linnaeus assigned the name Euphorbia to the entire genus in the physician’s honour.” (Wikipedia)

Alas, gone are the days when physicians can win immortality in the plant kingdom by opening the bowels of a royal patron.