Richard Lehman’s journal review – 16 April 2012

Richard LehmanJAMA  11 April 2012  Vol 307
1489   The new editor of JAMA feels that his worthy journal needs a bit of livening up, and who can disagree? He has borrowed an old idea from the BMJ, in the form of head-on for and against articles. “Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature CHD be treated with a statin?” This is an awful question for several reasons. It implies that the doctor is the one who should decide, and the “patient” is the object who should, or should not, “be treated”. But in what way is this man a patient?  Why is he “otherwise” well? Is his illness being 55, having low blood pressure, or having a total cholesterol of 250 mg/dL? In this exchange of views, three doctors think he should “be treated”, and two doctors (one the editor of Arch Intern Med) think he shouldn’t. I would argue that it is none of their business: give him the evidence and let him decide.

1497   Gah, this is so boring! Are major and minor ECG abnormalities associated with coronary heart disease events? Yes. Does this mean that everybody should have a regular ECG? No. And why? Oh for goodness sake don’t bother me—just go back to medical school or read Overdiagnosed.

1506   Next a Danish nationwide database study looking at everyone over 45 admitted with heart failure for the first time and treated with an angiotensin receptor blocker. Does it make any mortality difference whether they are given candesartan or losartan? No, provided they are given a decent dose (100mg losartan).

1513   If you aren’t in America, why should you read a paper on eliminating waste in US healthcare? Two reasons—first it’s by Don Berwick, and anything he writes is worth reading (though if you only have time for one piece, make it The Epitaph of Profession); second it has lessons for all health systems. Especially the NHS, as it becomes a feeding trough for all those nice private providers that MPs and Lords have shareholdings in. Failure to deliver the most effective care, failure to coordinate care properly: on these counts the NHS does very well compared with the US, but will improvement continue? Overtreatment, administrative complexity, and fraud and abuse: what can we look forward to on these fronts? Surely the noble guardians of our legislature will protect our healthcare system from any such taint.

1517  The Rational Clinical Examination series may be struggling to maintain the standards of its glory days, chiefly because it is running out of topics: but blunt intra-abdominal trauma is a great topic and gets a great discussion. When I last worked in an emergency room, handheld ultrasound hadn’t even been invented, but it now comes out top in investigative usefulness, though it can’t entirely rule out a damaged viscus. If you deal with this kind of scary emergency, this paper is a must-read: and you also ought to be thinking about designing some on-the-ground research, since more is clearly needed.

NEJM  12 Apr 2012  Vol 366
1382   Another week, another drug which prolongs progression-free survival by about 4 months in an incurable cancer. This week it is the turn of olaparib, an orally available PARP inhibitor, for maintenance therapy in platinum-sensitive relapsed ovarian cancer. But the tale does not end with AstraZeneca taking this drug to the FDA for approval for ovarian cancer, and marketing it at the usual price of about $10k per month gained. Instead the company has recognized that there was no overall mortality benefit and has dropped the drug for this indication. Is this a welcome sign that “progression-free survival” is losing credibility as a meaningful end-point in cancer trials?

1393   Coronary computed tomographic angiography (CCTA) is a high-radiation procedure which is very good at ruling out significant coronary artery disease. This important study from the Commonwealth of Pennsylvania shows that it can be used in emergency departments to rule out coronary ischaemia at the cause of chest pain in patients with low-moderate probability. That way more patients can go home more quickly. But I can see drawbacks. For a start, CCTA picks up coronary artery disease in 9% of these patients, as opposed to a 3.5% pick-up rate if CCTA is not used. A lot of this will represent overdiagnosis of asymptomatic disease, and may lead to further (radiation- and cost-intensive) investigation. Secondly, the routine use of CCTA to save an average of 6 hours waiting for biochemical tests will drive up costs and increase the “defensive” use of radiation, meaning that in some instances patients going to different hospitals with recurrent non-cardiac chest pain and getting pretty massive cumulative X ray doses. I think this is a development to be welcomed with caution.

1404   Vorapaxar is a novel antithrombotic agent which works by preventing thrombin binding to platelets, by blocking the protein-activated receptor (PAR-1). To test such agents these days requires enormous trial sizes—this one recruited 26,449 subjects with a history of myocardial infarction, ischaemic stroke, or peripheral artery disease to see how well it prevented further events. The prize for Merck would have been a new blockbuster drug for the whole secondary prevention market. But fate, bleeding fate, intervened and the trial was halted. There were fewer ischaemic events in the group who got vorapaxar rather than a thienopyridine, but more cerebral haemorrhage. Vorapaxar is an interesting drug which may have some kind of future, but blockbuster it is unlikely ever to be.

Lancet  14 April 2012  Vol 379
1393    In 1998, when I first started writing these brief notes on the journals for a few friends and colleagues, I decided that coronary artery stents were an interesting new development that I should tell people about whenever they cropped up in the literature. How dearly I (and you who have followed me) have paid for that decision! Paclitaxel, sirolimus, everolimus, zotarolimus… I have tried to make them interesting by pretending they were creatures from Star Wars, or minor characters from Antony and Cleopatra, or members of a zany family called Olimus, whose next son will no doubt be called boralotimus. And now it turns out we may have been looking at the wrong thing all along: what matters in the Stent Wars is not the drug these things elute, but the metal they are made of. According to this “comprehensive network meta-analysis” of 49 trials with 50,844 randomly assigned patients, the clear winner is a cobalt-chromium stent which elutes everolimus. For the first time in 14 years, my remarks on stents will actually be read by some interventional cardiologists, thanks to their appearance on the CardioExchange website run by the NEJM. OK you guys, start quarrelling about this study: the rest of us are off for a nice snooze.

1403    Now children, what happens if you give somebody with type 2 diabetes a drug which increases endogenous insulin secretion? Their sugar levels go down, yes. If the drug is a sulfonylurea like glimepiride, they also have a risk of hypoglycaemia, and they may lose beta-cell function more rapidly. And don’t forget that UKPDS tells us that if you combine a sulfonylurea with metformin, you end up with increased mortality—but that is by the way. In the phase 2 trial reported here, the investigators aren’t interested in crude measures like coffin counts. Takeda have produced a new diabetes drug which works by activation of the free fatty acid receptor 1 (FFAR1), and it seems to stimulate insulin production and reduce blood sugar without any serious risk of hypoglycaemia. That’s about it for now. The drug TAK-875 doesn’t yet have a name and needs some phase 3 trials. Let’s hope that these are double-blinded trials of this single drug, of sufficient power and duration to determine real microvascular and macrovascular end-points. Let’s hope that the licensing authorities insist on such evidence, even though it may take five or more years to gather, and disregard all surrogates such as HbA1c, creatinine/albumin ratio, lipid fractions, rate of retinal changes, doubling of creatinine, etc etc. That way, for the first time in the history of type 2 diabetes, we might actually know what a specific treatment does to patients.

1412    Adolescence is a state from which most of us eventually recover. In some youths it is characterised by periods of chronic fatigue, and if these persist for a long time, they become chronic fatigue syndrome. I suspect that many factors often conspire to perpetuate CFS in adolescence, which can have devastating results for social development and education. The sensible Dutch have now devised a web-based cognitive intervention called FITNET, and in this trial it achieved spectacular success at six months: 75% school attendance and 85% absence of severe fatigue, compared with 16% and 27% respectively with usual care.

BMJ  14 April 2012  Vol 344
Health literacy is the subject of this survey of English adults. It’s a term which has spread widely in recent years. In the grim judgemental days of my youth in Yorkshire, where everything carried its due apportionment of blame, people were graded according to intelligence, and separately graded by education, and further graded by literacy; but never graded by “health literacy” because health was not the kind of thing that proper Yorkshiremen were permitted to worry about. I think this composite term is useful for allowing us to address the fact that a third of the population lacks the ability to understand basic written health information. That does not mean that they are beyond the reach of explanation, or cannot share in the making of decisions about their care: it just means that it needs to be done in different ways, both directly and with the use of video. And low health literacy is of course associated with lower levels of health and poorer health outcomes.

Migraine with visual and sensory aura is a peculiar phenomenon, which I have had a lot of chances to observe lately, but cluster headache belongs to a different league of pain and autonomic dysfunction. Before the arrival of triptans and the discovery of high-dose oxygen as a treatment, I remember having to pretty well flatten patients with opioids to combat the intense pain and distress. Billed as the first review of the condition in the BMJ for fifty years, this one could hardly be bettered, and ends with a brief narrative from a patient who sought to beat her head with a telephone handpiece to relieve the pain, while trying to stop her children from noticing.

Arch Int Med  9 Apr 2012  Vol 172
555   Scraping the barrel of things to watch on Netflix the other night, we ended up sitting through a suitably interminable account of the 4,300 mile journey of exploration by Lewis and Clark in 1804-6, of the Louisiana Territories purchased by Thomas Jefferson. As they moved upstream, the diet of their men changed from ordinary beef to bison, then horse, then elk, and antelope: when they reached the Western side of the Rockies, the river beneath them was thick with huge salmon, but such was their yearning for red meat that they preferred to barter with the local tribes for fattened dogs. Oh dearie me, how very unhealthy! Amazingly, none of them died on these epic travels through often hostile territory, and one or two made it beyond the age of 90. But we should not draw the wrong conclusions from this, because red meat consumption is once again shown in this study to be associated with an increase in total mortality and mortality from cardiovascular disease and cancer. There are many reasons why one should perhaps consider giving up red meat; personally I would not rank longevity as high as the feeling inspired by our next Netflix offering, Buster Keaton’s Go West (1925), in which he is movingly befriended by a young cow called Brown Eyes.

Plant of the Week: Linnaea borealis

It is a nice touch that Carl Linnaeus, who was extravagantly vain in so many ways, chose this humble mountain alpine plant as the bearer of his name. It is a small ground-hugging relative of the honeysuckles, with lovely little elongated bell-flowers of white streaked with purple, said to be fragrant if you care to bend to within a few inches of the ground.

We went searching for spring wild flowers in the mountains of upstate Connecticut, and the Linnaea was all we found: the trilliums were not yet out. It a lovely little thing which I assume does well in colder gardens on acid soil. The plant we found used to be called Linnaea americana, but botanists have changed their mind and declared that just as there was only one Linnaeus, so there shall be only one Linnaea.

Sumerian Proverbs for Medical Editors

There will be a prominent place for a capable scribe

A good word is a friend to numerous men

Good fortune [calls for] organisation and wisdom

Accept your lot and make your mother happy

Ignoramuses are numerous in the palace

From many oxen, is there no dung?

clay tablets from c 2000 BC