Richard Lehman’s journal review—15 April 2013

Richard LehmanJAMA  10 Apr 2013  Vol 309
I try my best, dear Reader, oh I do. When I see an issue of JAMA devoted to Genomics, I don’t just sigh deeply: I brew the coffee and get stuck in. This is the future and it needs to work; the doctor of tomorrow will see this as the dawn of a great new age. Or so they tell us: but I defy you to find a scrap of immediate clinical relevance to hang on to in this batch of research papers which have held me in detention for the last hour:

1447   This news and perspective article starts promisingly: “When the Human Genome Project revealed that human chromosomes encode a paltry 21 500 genes, far fewer than anticipated, scientists began to think outside the genome to find additional factors that could be involved in the complexities of human health and disease.” You can read on for free, but unfortunately it turns out to be mostly a heap of old microbiome.

NEJM  11 Apr 2013  Vol 368
1379   When it became clear about ten years ago that immediate percutaneous coronary intervention was the treatment of choice for myocardial infarction, I advised readers to have their MI on a Thursday morning in a large city where there was a sporting chance that there might be a fully staffed cardiac catheter suite ready to receive them. The treatment of first choice remains very challenging to provide: so how much worse is the treatment of second choice—immediate (prehospital) fibrinolysis, followed by PCI at relative leisure (6-24hrs later)? The answer is that the two strategies are equally good when judged by a composite end-point of death, shock, congestive heart failure, or reinfarction up to 30 days. The only drawback was a greater incidence of cerebral haemorrhage in the primary thrombolysis group, due to their cocktail of tenecteplase, clopidogrel, and enoxaparin. Dose adjustment helped to reduce this in the later stages of the trial. Overall, this is very good news for those working out how best to provide safe MI services around the world.

1447   Pain is the commonest cause for people to see doctors, and taking a history of pain is one of the commonest things we do. But doctors don’t like dealing with things they can’t see or measure “objectively,” and it has proved uncommonly difficult to find a means to observe pain directly. The investigators of this functional MRI study are pretty certain they have found a way of measuring pain caused by frying the forearms of healthy volunteers. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal grey matter, and other regions. It’s a complex signature and they claim to be able to identify it in other kinds of pain, including social pain, and to demonstrate blunting by an opioid. “Imagine how all fields of medicine would be altered if pain could be objectified by a measure that did not require direct patient reporting” says the accompanying editorial. I’m trying to, and I can’t make it work. “So you want another sick note for your back pain, do you, Mr Shirker? How do I know you have any pain at all? But we have your number, matey. Just come through into my functional MRI suite and we’ll soon be able to tell whether you are pulling the wool over our eyes.” Brave new CCGs should negotiate with Atos to order in their scanners now and help sort out those pain-claiming scroungers once and for all. Think what it would save society in benefit fraud.

1398   In the 1980 there grew up a vogue for attaching a label of “asthma” to any child who ever wheezed, or even coughed at night. Salbutamol was prescribed for everything, and also beclomethasone, and cromoglycate, sold by the same firms who ran all the training courses for practice nurses. Parents of perfectly healthy children were advised to keep them on corticosteroid inhalers and double the dose at the first sign of a cold. A lot of this still seems to go on today. But gradually we’re beginning to sort out what makes children wheeze and may one day even be able to treat the various syndromes rationally. Now read carefully and you will see me praise genomics. Yes, that’s right: genomics can actually help to sort out the mass of wheezy kids who crowd our waiting rooms all winter. Many of them will have particular variants at the 17q21 locus which predispose to a wheezy reaction to viruses, and the commonest trigger is the commonest virus, good old human rhinovirus (HRV). These are not the same kids who get early wheezing and bronchiolitis from respiratory syncytial virus. HRV activates two genes at this locus: if we could stop this happening, these kids would not wheeze every time they get a cold. Genomics would have emptied the winter waiting room. Bring it on.

1417    Here is an article which should not be read by those who oppose assisted dying, because it challenges all their prejudices by laying out the facts of how it works in real life at a comprehensive cancer centre in Seattle. “Of the 40 participants who, after counselling and upon request, received a prescription for a lethal dose of secobarbital (35.1% of the 114 patients who inquired about the program), all died, 24 after medication ingestion (60% of those obtaining prescriptions). The participants at our center accounted for 15.7% of all participants in the Death with Dignity program in Washington (255 persons) and were typically white, male, and well educated. The most common reasons for participation were loss of autonomy (97.2%), inability to engage in enjoyable activities (88.9%), and loss of dignity (75.0%). Eleven participants lived for more than 6 months after prescription receipt. Qualitatively, patients and families were grateful to receive the lethal prescription, whether it was used or not.” That’s how it works in Washington State: what would happen in the UK if we went down this slippery slope can only be imagined by bishops and baronesses.

1450   You can take a free ringside view—or even contribute to—the debate about physician-assisted suicide in the United States by linking to this NEJM case scenario. Don’t forget to switch to Option Two when you have read the responses to Option One. Much of it has a familiar ring, especially the arguments from a religious fixed position dressed up as concerns about societal values. I worry about the lack of compassion shown by doctors who should know the reality of unmitigatable suffering at first hand. Nobody is asking them to do anything against their principles, and they can die as best suits them when their turn comes. It is denying others the choice that seems so strange to me.

Lancet  13 Apr 2013  Vol 381
1260 ‘”How many ‘global health’ conferences are needed each year?” So asked Gabriel Scally, justly perplexed about why the Swedish Medical Society was holding Global Health beyond 2015 last week.’ That’s the first sentence of this week’s Offline column from Richard Horton. However many such conferences there are, Horton is determined not to miss a single one. Last week he was at a High-Level Panel of Eminent Persons in Bali. He must have the carbon footprint of a Chinese power station. “The last word should go to the young professionals in Stockholm. ‘Stop global whining,’ urged Renzo Guinto from the Philippines,” Horton reports. But perhaps he misheard, and the young man was actually telling him to stop global wining.

1277   “Simple aspiration and drainage is a standard initial treatment for primary spontaneous pneumothorax, but the rate of pneumothorax recurrence is substantial. We investigated whether additional minocycline pleurodesis after simple aspiration and drainage reduces the rate of recurrence.” Well, here’s a nice example of good practical low-hanging-fruit clinical research from Taiwan. Bung in the minocycline and you reduce recurrences by a third.

1302   The two hundredth anniversary of John Snow’s birth has triggered various celebrations by epidemiologists, some of whom regard him as the founder of their discipline. The best piece about this in The Lancet is an editorial by Fine, Goldacre (yes, our Ben), and Haines, advocating the teaching of epidemiology in schools; while here for your leisure reading is an assortment of more-or-less oblique short pieces celebrating, disputing, or taking off from Snow’s famous pump-action precedent.

1312   The Lancet’s Health in Europe series has been long on windy rhetoric and generalities, but also contains islands of useful quantitative information. I dipped into this piece on Ageing in the European Union in case it contained any hints on where to move to if the British climate continues to grow more intolerable. It doesn’t: but it does contain a long and useful discussion of the effect of an ageing population on future health expenditure. The forecasts are very optimistic: an extra 1.5% of GDP by 2060, reduced to 0.7% if improvements in quality of life continue at their present rate. So I am OK to the age of 110, perhaps. And should we be thinking southern France? Or a Greek island?

BMJ  13 Apr 2013  Vol 346
I would be more enthusiastic about the teaching of epidemiology in schools if grown-up epidemiologists were not so given to outrunning their evidence in various efforts to force “health” on people. Salt reduction is a typical example. Everybody agrees that a reduction in the salt content of food is a global health priority. Well they shouldn’t: there is no hard evidence one way or the other. Oh, you say, but lowering sodium intake lowers blood pressure! Yes it does, over a short period: it also raises plasma renin activity, aldosterone, and noradrenaline. That is demonstrated in this updated Cochrane review, in which the duration of studies reached a median of 5 weeks in hypertensive subjects and 4 weeks in normotensives. The reviewers conclude that “These results support a reduction in population salt intake, which will lower population blood pressure and thereby reduce cardiovascular disease.” This gets a nice response from the Nordic Cochrane reviewers: “we think that general recommendations based on one single outcome (a small blood pressure effect) without knowing the consequences of this effect and possible accompanying side effects on morbidity and mortality is potentially hazardous.” For “side” effects read long-term effects on real outcomes.

As if to drum in the point, the BMJ goes on to publish a systematic review of the effect of lower salt intake on health. The conclusion dutifully states, “Lower sodium intake is also associated with a reduced risk of stroke and fatal coronary heart disease in adults. The totality of evidence suggests that most people will likely benefit from reducing sodium intake.” In Thatcher week, should we reply “Rejoice!” or “No, no, no!”? I suggest the latter. The summary in the printed BMJ says it all: “Low and very low quality evidence suggest that lower sodium intake is associated with reduced risk of stroke, fatal stroke, and fatal coronary disease in adults.” Again, there is a good response from Copenhagen. “The conclusion of the analysis is not justified by the data, but that is not the issue. The interesting question is why BMJ use 20 pages on the publication. The answer may be that the science of salt is not scientific, but political.”

But potassium is probably good. I’m not saying the evidence is perfect—it never can be—but this systematic review concludes “High quality evidence shows that increased potassium intake reduces blood pressure in people with hypertension and has no adverse effect on blood lipid concentrations, catecholamine concentrations, or renal function in adults. Higher potassium intake was associated with a 24% lower risk of stroke (moderate quality evidence).” Eat bananas and tomatoes. Drink fruit juice. Accentuate the positive.

Speaking of imposing low-grade evidence on the population, I’m appalled that Britain’s Quality and Outcomes Framework persists as a yoke upon our terminally overburdened primary care system. It must be abolished, and the RCGP should make that its most urgent goal. A commentary by Stephen Gillam and Nicholas Steel makes valuable points, but lacks militancy, probably because they are too worn down by trying to collect QOF points.

JAMA Intern Med  8 Apr 2013  Vol 173
Don’t confuse this journal with JAMA. This is the interesting one with sparkling content and discussion.

506   “We have followed too much the devices and desires of our own hearts… And there is no health in us” says the General Confession at Anglican Evensong. The devices in question might be vena cava filters, much desired by certain American physicians, but probably incapable of imparting any health to the recipient. Over there, they were adopted enthusiastically for the prevention of pulmonary embolism from the mid-1980s onwards. I can remember my incredulity on encountering my first one in a returning patient who had spent time in the USA around then. As with most devices, you don’t need to have any evidence of efficacy; you just need some evidence of safety. And as with all such fashions, there is a fantastic pattern of variation in their use. Some of it is mapped here: and a couple of other articles discuss complications, and how this can still happen in the era of evidence based medicine. Oh, but you device diggers ain’t seen anything yet…

534   Safety and efficacy depend on what you are looking for. If safety is what happens in the first year, and efficacy consists of reducing blood sugar, then exenatide and sitagliptin are safe and effective treatments for type 2 diabetes. Just a shame that they double the incidence of pancreatitis, as this database study shows. And again, you ain’t seen nothing yet, my friend. What about cancer of the pancreas? Other long term harms? The signals are sounding nasty.

Plant of the Week: Erythronium dens-canis

The so called “dog’s tooth violet” is named from the shape of its bulbs—quite brutish looking big brown canines. In early March (read mid-April this year) these produce a beautiful furl of mottled leaf and a high stem bearing lovely pendent flowers a week or two later. In this species they are highly reflexed and come in shades of pink, with black and white stamens hanging vertically down. Plant and forget, and then have the surprise of recognition when spring brings them to light.