Richard Lehman’s journal review – 3 May 2011

Richard LehmanJAMA  27 Apr 2011  Vol 305
1625    Obedience is no longer a fashionable concept, though it was once prized as the most essential virtue in religion and society (see Psalm 119 vv1-176, Dante’s De Monarchia, Hobbes’ Leviathan; look up the meaning of the Arabic word islam). Nowadays we go to endless lengths to persuade ourselves that everyone is making a free and informed choice about everything from the Prime Minister (though not of course the British head of state, whose future identity will depend on the marital joys of the two dear young people being joined in wedlock as I write) to the pills we give our children. If these children have newly diagnosed epilepsy, we explain to the parents which drugs are available, which we think are most likely to prevent further fits, what adverse effects they might have, and then expect them to agree with what we prescribe. Actually, as mere GPs we do not do this ourselves: we leave that to paediatric neurologists and we then obey them, and expect parents to do likewise. This process is known as “achieving concordance”. Concordance is then supposed to achieve compliance, or adherence as we must now call it. But this carefully conducted US study finds that in real life, not everyone concords, complies, adheres or obeys. Judged by an electronic chip that monitors medication-giving, just 42% are perfect citizens of the Dantean/Hobbesian/Burkean monarchy and obey their paediatric neurologist to the letter. Another 26% have a reasonable stab but often forget a dose or two. About 13% start off not trying and never obey, and 7% start by trying and then give up. I am afraid that these last people come from the lower socioeconomic strata, as Edmund Burke would have foreseen. Bring back the beadle.

1677    Obedience features in evidence-based medicine too, and is measured in outcomes research. Here is a very good teaching example from Sweden, based on analysis of their whole-population database of ST elevation myocardial infarction between 1996 and 2007. This was a time of revolution in the management of STEMI as immediate percutaneous intervention supplanted thrombolysis as the treatment of first choice. Sweden’s success in providing this for 61% of its population by 2007 is impressive given the spread of its population, its climate and its geography. Door-to-balloon time increased initially but then went down again. The use of secondary preventive drugs went up steadily. Mortality declined, both in the short and the long term. But readers of Wennberg will not be surprised to learn that the one thing that did not change was the disparity between performance in individual hospitals. It seems that the hardest thing to change in medicine is the culture of individual institutions.

1695   For contrast, here’s an example of the kind of “outcomes research” that sets my teeth on edge. Take two poorly defined concepts – heart failure and health literacy – match the two, and follow the patients up by mail for 1.2 years, response rate 72%. “Health illiteracy” is defined by 3 questions and is present in 17.5% of respondents. They die the fastest. So do we try to improve health literacy? Use the questions to target community nurse input? Make better use of real prognostic markers such as BNP? Or just forget this whole health literacy concept as simply the latest way of bundling together old things such as social class, poverty, intelligence, non-adherence and the rest.

NEJM  28 Apr 2011  Vol 364
1607   One of the delusions of general practice is that you acquire wisdom from experience. The trouble is that your sampling errors are enormous, and so is the cognitive bias produced by your wish to believe that you have snatched people from the jaws of death. For example, I looked after two youngish diabetic patients with heart failure, both of whom were going through episodes of decompensation and appeared likely to die within months. Enthused by the latest reports, I insisted that they both have coronary angiography, and this was duly followed by coronary artery bypass grafting to reperfuse hibernating myocardium. Many years later, they remain in full time employment, proof of the life-saving potential of CABG for hibernating myocardium, not to mention its economic benefits. But these complacent presumptions may well be wrong, according to the STICH trial, in which patients with systolic HF and coronary heart disease were randomized to receive either CABG or maximum medical therapy. Overall mortality was the same in both groups, though the CABG group had somewhat fewer cardiovascular events.

1617   So what about the whole concept of “hibernating myocardium” and sophisticated tests for myocardial viability in ischaemic left ventricular dysfunction? A subset of the patients in the STICH trial were put through single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of prespecified thresholds. The presence of viable (“hibernating”) myocardium was associated with better overall survival, but the difference lost significance after adjustment for other baseline variables.

1626   As a medical student in Oxford I used to spend a lot of my time hitch-hiking to London, and on one occasion I was given a lift by a distinguished professor of bacteriology whose special interest was Mycobacterium leprae. We had an interesting conversation, though there is a limit to the comfort one can give to a man whose only laboratory subject is the armadillo. Some remote recess of my brain must have stored this encounter for the last 40 years, because when I saw the title of this paper, Probable zoonotic leprosy in the Southern United States, the image of an armadillo immediately filled my sight. And yes, the investigators found that the genotypes of M leprae bacteria isolated from 50 US leprosy patients and those found in the local wild armadillo population were an exact match. Blame this remarkable mammal, Dasypus novemcinctus, for all non-imported leprosy in the USA, and look out for more cases as it spreads slowly northwards, unopposed by any natural predator.

1634   Now the armadillo is most famous among mammals for its degree of vertebral protection, while the human female stands at the other extreme. Her suffering when vertebral collapse occurs is often extreme, and these events are common, in men as well as women. Some episodes require hospital admission, and most require strong opioid analgesia for several weeks. Early reports of benefit from vertebroplasty or kyphoplasty have not been borne out by some well-designed sham-controlled trials. This article is a good summary of current practice but it does not raise my spirits at the thought of next visiting an elderly patient with agonizing back pain of rapid onset.

Lancet  30 Apr 2011  Vol 377
1506    I’ve several times pointed out the tendency of high-impact journals to publish industry-sponsored trials that can generate large sums from reprints, while at the same time publishing damning editorials about the same studies, in order to satisfy their intellectual conscience. As usual, I have no idea whether the sponsors of this trial, Alkermes, intend to buy up lots of reprints from The Lancet, although they acknowledge that they paid someone to help write it up. And the trial has already resulted in FDA approval of their product Vivitrex, a once-monthly injection of extended-release naltrexone for the management of opioid dependence. Reading the abstract of their paper, you can see why: their six-month placebo-controlled trial in Russia produced opioid discontinuation rates an order of magnitude better than for most other interventions in this addiction. But then read the editorial: it is entirely damning about the ethics of the trial design and warns that similar interventions have in the past resulted in high rates of death due to unintentional opioid overdosage. The authors here are saying that this trial should never have been conducted and that FDA approval should not have been given. A great – and greatly depressing – teaching example of the ways of medical journals and much else besides.

1495    The countries where most new tuberculosis infections arise tend to be those with the poorest diagnostic facilities – not just for confirming active TB but also for tracking drug resistance. The Xpert MTB/RIF test is much simpler and faster than culture and conventional drug sensitivity testing, and it performed very well in this admirably thorough study in several resource-poor countries. But the editorial by Katharine Kranzer points out the problems: a diagnostic sensitivity of 90% sounds good but would miss a million cases per year of a life-threatening curable infection; and the lab time and facilities required for the test still far exceed the means of most countries with high TB incidence.

BMJ   30 Apr 2011  Vol 342
960    Drospirenone is not a name familiar to all but the most dweebish prescriber. We prescribe it – if at all – under its trade name Yasmin, in combination with ethinylestradiol, as a contraceptive pill for those who get acne or breakthrough bleeding with other pills. But Bayer got into trouble with the FDA for promoting this combination in the USA, because it had failed to carry out sufficient research on its risks compared with levonorgestrel-containing contraceptive pills. The chief allegation is an increased risk of non-fatal venous thromboembolism, seemingly borne out by a case-control study from the Boston Collaborative Surveillance Program here.

961   And here is some more evidence of from the UK General Practice Database to the same effect. The increase in VTE is 2-3 fold in the two studies, but these are promptly questioned by the editorial. Who to believe? Whom to believe? Don’t waste time on this: there are plenty of other oral contraceptives.

962   Here is a systematic review indicating that calcium supplements with or without vitamin D produce a modest increase in the risk of cardiovascular events. Hang on, I hear you say, are you reviewing the right issue of the BMJ? We read about this before Christmas. And so you did, dear reader: this is just a confirmatory analysis by the same people, adjusting for factors that were brought up in the discussion which followed their original paper. The waters are murky. Who to believe? Whom to believe? I cannot tell you, dear reader: I take my vitamin D with cheese rather than chalk.

968   The standard of clinical reviews in the BMJ is usually as high as that in the leading US journals, and this one about the management of paracetamol poisoning is no exception. Except that in the USA it would be the management of acetaminophen poisoning. The antidote, acetylcysteine, is invariably effective if given in time. Other antidotes may be on the way. But people will still die from paracetamol because its therapeutic range is quite narrow and toxicity is affected by hepatic enzyme induction and small degrees of undernutrition which deplete liver stores of glutathione.

Arch Intern Med  25 Apr 2011  Vol 171
744    Quite soon I shall be off to the USA for several months, hoping, amongst other things, to preach the joys of medical generalism. The words one must always use are “internal medicine,” though this is but one part of what we do in British general practice. I don’t fully understand what Americans mean by “primary care” and how internal medicine fits in with that. So much to learn. But while US “primary care” languishes unloved, despite the passionate embraces of Don Berwick, internal medicine is enjoying a small revival amongst medical students in the USA, according to this study of career choices between 1990 and 2007. So much to do.

750   The byways of heart failure research are full of strange sights and sounds. The fattest people survive the longest, perhaps because they have to do more exercise just getting about: for those who could not even do that, a team in Hull devised electric shorts to stimulate the thigh muscles. They did not work. Here the trick is Tai Chi, about which I know nothing but which I presume is some sort of exercise programme with added mumbo-jumbo. The comparator was not ordinary exercise but sitting down being educated for the same length of time. Well, would you believe it: the exercised group showed better exercise tolerance and quality of life. All due to a better balance of Yin and Yang and other energies.

770    Plant of the Week: Laburnum x watereri “Vossii”
The reason the laburnum is squeezed in here is that its alkaloids were the precursors of varenicline, and a trial here shows that this nicotine-receptor competitor combats nicotine addiction best when started 4 weeks before smoking cessation. As for this ubiquitous garden hybrid, I enjoy seeing it in other people’s gardens with two-foot trusses of yellow scented flowers covering the entire plant: especially good in massed plantings or as laburnum tunnels. We don’t have room.