Richard Lehman’s journal review – 30 July 2012

Richard LehmanJAMA  25 July 2012  Vol 308
This was the week of the XIX International AIDS Conference held in Washington DC, where the catchphrase everywhere was “an AIDS-free generation.” That forms the title of the first piece in this week’s JAMA, which is given over entirely to HIV-related matters. So also is a large part of this week’s Lancet, which singles out the issues of HIV in men who have sex with men. And in Offline, Richard Horton very sensibly points out that “With 2.5 million people acquiring HIV in 2011, the notion of a generation free of AIDS is manifestly ridiculous.” The JAMA pieces are of specialist interest only, while the Lancet is largely about epidemiology and social factors. Some of it is interesting and important, but as usual I won’t comment as a backwoods British GP has nothing useful to say about these issues.

NEJM  26 July 2012  Vol 367
289    This week’s New England Journal begins with an engrossing piece called Olympic Medicine, reflecting on the changing meanings of the “Olympic ideal” over the last century. “In July 1912, the Boston Medical and Surgical Journal celebrated “American Supremacy,” noting that the “overwhelming success of the American athletes at the current Olympic games in Stockholm is as interesting physiologically as it is nationally gratifying…” The United States “is more mixed of all races, and we should therefore be able to select the best strains and breed the best mixtures.” American athletes were “better nourished and conditioned” than their competition, “which again should conduce to racial physical superiority.”’ It’s very curious to see how eugenics could be used to cut both ways. For Hitler, the Olympics were an opportunity to showcase the supremacy of the pure Nordic races, while for the Americans in 1912, it was hybrid vigour that won the day. But the awful fact is that the Olympics validate the most ghastly eugenic experiment in history, when British slave traders captured millions of fit young Africans, chained them side by side in the hot stinking holds of their ships for several weeks, took out the ones who were still alive, sold them for hard labour, and let British and American slave owners breed from the ones who were still left. Result: awesomely strong sports champions from America and the Caribbean. I can’t help finding something queasy about these trials of physical strength and endurance, with their loud rhetoric of fierce nationalism mixed with bombastic internationalism. They’re just about survival of the fittest, as crude as it comes.  As for the realities of real “Olympic medicine” as practised in London 2012, do follow the often hilarious tweets of Trish Greenhalgh, an incurable sportsperson who has taken time out from her professorial duties to be a humble Olympic medic. Very humble indeed, in the eyes of some of her clients.

299   ROMICAT stands for Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography, and this is the second trial so far—hence ROMICAT-II. The primary end-point was time to discharge from hospital and this 1,000 person randomized trial shows that you can cut it from a median of 26.7 hours to 8.6 if you do immediate CT scans on all patients presenting with possible cardiac chest pain. At least that’s what Table 3 says. In the Abstract the figure given is a mean reduction of stay by 7.6 hours. A good illustration of the difference between the median and the mean, and a rare example of a study underselling itself. But questions remain. Part of the rationale of the study was that reliance on ECG biochemical markers in acute chest pain can leave residual diagnostic uncertainty, yet the rate of adverse cardiovascular events within 28 days in the two groups was exactly the same—zero. Moreover, those who had immediate coronary CT had more downstream diagnostic tests, not fewer. They only thing they gained was earlier discharge home; costs were identical, and on the down side, the CT group notched up a sizeable dose of ionizing radiation. Given that we can’t quantify the harm from this, here’s a situation where patients with acute chest pain have a very difficult choice to make as they arrive in the emergency room, wondering if their end has come. “Do you want a high radiation scan or would you be willing to stay here a bit longer to avoid it?” I wonder how many ER doctors would even ask them.

309   The acronym for the next trial is ORIGIN, and it looked at two things which were thought promising to prevent cardiovascular events in 12,536 subjects with dysglycaemia: n-3 fatty acids and/or basal insulin. In fact, neither of these had any effect on CV events. But maybe this is a good moment to remind you of the three categories of “dysglycaemia” as currently defined. There is type 2 diabetes, defined by a persistent fasting blood glucose of 7.0 mmol/L or more. There is impaired fasting glucose, defined as a fasting glucose level between 6.1 and 7.0; and there is impaired glucose tolerance, defined as a rise in blood glucose to between 7.8 and 11.1 two hours after a glucose load. All of these states confer some additional cardiovascular risk.

319    So let’s move on to the second and more interesting part of this 2×2 factorial trial which tested the hypothesis that reducing fasting glucose to 5.3 or lower by means of injected basal insulin glargine will lower cardiovascular events in all these patients. The logic of this must be familiar to all of you: 5.3 is the level of fasting glucose that represents the threshold for increased macrovascular risk. So let’s see what happens if we try to lower everyone’s sugar to 5.3 with insulin. I’ve already told you the answer—nothing. And this is important. Firstly because it is one more bit of evidence that pushing down sugar levels below quite a high level (perhaps above 8 mmol/L) is a futile strategy for risk reduction, and secondly because it shows that exogenous insulin itself does not increase cardiovascular risk. It does however increase the risk of severe hypoglycaemic events, from 0.3 to 1.0 per 100 person-years.

340    Ee, it were grim up North in my day; and few places were grimmer than the Chest Clinic at Chesterfield, on the edge of the Derbyshire coalfields, where a line of wheezing men would sit in a dim corridor with peeling paint awaiting the attentions of my beloved boss the local chest physician, and my humble self, his SHO. Chronic obstructive pulmonary disease had not been invented at that time: instead we worked with a variety of diagnostic terms, among which “emphysema” and “chronic bronchitis” were prominent. You tried to avoid mentioning the former, because “having the emphysmia” was considered a death sentence within mining communities. In those days the only treatments we had were theophylline, aminophylline and antibiotics. And, despite changes of fashion in nomenclature and treatment, there has been no real progress in treating COPD since the 1970s, except to define the macrolides as the best antibiotics for long-term use in damaged lungs which are prone to infection. Azithromycin accumulates in lung tissue to levels which are highly bactericidal, and it has local anti-inflammatory effects too. In those days, we usually only used long-term prophylactic antibiotics during the “bronchitis season,” but the recent trials have given them all year round. A 250mg dose of azithro twice a week is probably all you need to reduce exacerbations by 30-50%: it’s well worth looking out this review for further details.

Lancet  28 July 2012  Vol 380
349    Some ideas seem so good that they just keep on being tested, to repeated destruction. Stem cells for cardiac repair; HDL raising for lowering cardiovascular events; neuroprotective drugs for better stroke outcomes. We would all love them to work, but in trial after trial, they bomb. Here, in a multi-centre European trial, citicoline, which works in animal models of stroke, fails to have any effect in 2298 patients with moderate-to-severe acute ischaemic stroke, though it’s already got a licence in several European countries. In The Marriage of Heaven and Hell (c.1793) William Blake has Isaiah over for dinner and asks him, “does a firm perwasion that a thing is so, make it so?” The prophet replies, “All poets believe that it does, & in ages of imagination this firm perwasion removed mountains.” Alas, what may be a fine rule for poets and prophets is not a very good one for drug licensing bodies and medical practitioners.

358    Dabrafenib in patients with BRAFV600E-mutated metastatic melanoma. Does this sound familiar? It should, somewhat, as we’ve already been this way in two dose-finding studies published earlier this year in The Lancet, and a similar trial in the NEJM. For the occasional patient, this drug might even induce lasting remission, but for most it buys about 3 months of progression-free survival. This is frequently accompanied by skin-related toxicity, fever, fatigue, arthralgia and headache. A modest advance then, though perhaps offering the glimmer of a major breakthrough in the future.

BMJ  28 July 2012  Vol 345
An editorial with an authorship that includes Julian Tudor Hart reminds us that multimorbidity is not just a problem of old age: in Scotland, people under 65 account for more than half of it. Social deprivation brings it forward by 10-15 years, and Julian’s famous inverse care rule applies more now than ever, in the UK as elsewhere.

Another thing that never seems to change is public misperception of high blood pressure as something that is caused by stress and which gives rise to symptoms. Here is a systematic review of qualitative studies from a total of 16 countries—more of these please!—and everywhere the myth is the same. Lay people of all nations share the delusion that if you take away the stress, down goes the blood pressure and the symptoms disappear, so you can stop taking the tablets. Not that doctors are free of myths about hypertension either, but that is another matter, and deserves a similar level of qualitative enquiry.

Nowadays when I do out-of-hours shifts, I try to remember to record capillary filling time, respiratory rate, temperature, and pulse in every febrile child. Now obviously these are connected, and in an ideal world one would adjust each one for the others. Here’s a step towards that: a chart using specific levels of respiratory rate and temperature to predict lower respiratory infection in different age groups. A nice refinement, but I’m not sure I shall be using it in the hurly-burly of real life triage.

Still, I hope to do better than Afghan practitioners with their febrile patients, nearly all of whom get antimalarials, though very few of them really have malaria. Those who have falciparum malaria get the wrong treatment anyway. Depressing.

And another risk score I won’t be using much is QRISK2, because it is so rare for me to initiate long-term treatment these days, and I tend to be of the “statins for everyone” persuasion anyway. But if you care deeply about better discrimination of risk, this external validation study shows it’s better than Framingham for the UK population—by 5% in men and more in women.

I’m haunted by memories of my daughter’s severe eczema in childhood—such a misery at the time, though happily leaving few traces now. I read this very comprehensive review with interest, but with dismay at the widespread lack of evidence—stretching from the most basic treatment with moisturisers (avoid Aqueous cream, which can be allergenic) to the small case series which inform treatment with immune suppressants.

Arch Intern Med  23 July 2012  Vol 172
1078    When love, with one another so
Interinanimates two soules,
That abler soule, which thence doth flow,
Defects of lonelinesse controules.
Wee then, who are this new soule, know,
Of what we are compos’d, and made,
For, th’Atomies of which we grow,
Are soules, whom no change can invade.

So John Donne, in one of his greatest poems, The Extasie, describes the fusion of souls achieved by sexual love. Some think the poem was addressed to his 17-year-old wife, Anne; and certainly when she died after giving birth to their twelfth child at the age of 33, he became obsessed with his own death, which he believed might re-interinanimate their souls. When he eventually sickened at the age of 58, he duly prepared his tomb, and had himself depicted lying within it before he rose to preach his last sermon. Loneliness in older persons is a predictor of functional decline and death, as this study confirms. In the paper following, this is also found to be broadly true of people over the age of 45 who have atherosclerosis and who are living alone.

1096   In the Heart and Soul Study, “Distance walked on the 6 Minute Walk Test predicted cardiovascular events in patients with stable coronary heart disease. The addition of a simple 6MWT to traditional risk factors improved risk prediction and was comparable with treadmill exercise capacity.” Interesting: and I bet if you look in five years’ time, cardiologists will still be doing as many treadmill tests and as few six minute walks as they do now.

1104   When questioned, patients with heart failure often rate better quality of life as more important than longer duration of life, but they are seldom offered the choice. Implantable cardioverter-defibrillators improve overall survival figures in patients with systolic heart failure and QRS prolongation, but few patients are aware that they are therefore more likely to experience a slow death from breathlessness than a sudden death from ventricular arrhythmia. This survey of AHA physicians (12% response rate) shows that cardiologists don’t, by and large, discuss this with their patients. They know best: ICDs save lives, and earn fees.

Plant of the Week: Geranium sanguineum var striatum

This is one of the best of our native perennials, commonly called the Bloody Cranesbill, but without any hint of asperity. Put in the front of a sunny border and it will flower beautifully for the whole summer, in pinks or purples above excellent dark cut foliage.

Although there are so many good hardy geraniums for every place in the garden, I would say this species is the most valuable of the lot. It flowers for ever, and never outgrows its space or spreads seedlings where you don’t want them. I’ve never seen one growing wild, which is just as well, as I’d be tempted to dig it up and take it home.

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