Richard Lehman’s journal reviews—30 October 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 26 Oct 2017 Vol 377

Naughty eosinophils in COPD

Eosin is a stain that dyes cells pink, like rosy-fingered dawn in Homer’s famous epithet, eos rhododactylos. The original meaning of “eosinophilic” would therefore be something like “loving that which pertains to the dawn”, or even “in love with Eos, the goddess of dawn.” But three millennia after Homer, eosinophilia leads us to the miserable exacerbations of chronic obstructive pulmonary disease. Or at least it leads some people there. The presence of extra eosinophils in peripheral blood or sputum is generally taken to indicate a non-infective inflammatory process, often due to hypersensitivity. About 40% of people with COPD show eosinophilia during exacerbations. Enter mepolizumab, which disrupts the work of eosinophils by targeting interleukin-5, at a basic cost of £840 for 100mg per month.

In two recent trials in people with eosinophilic COPD, there were 0.3 fewer exacerbations per year on this dose than on placebo. Now let me see: there are 1.2 million people with diagnosed COPD in the UK. Which means 480K with eosinophilia. Giving them all mepolizumab would cost £48 billion, and they might benefit by one exacerbation less over 3-4 years. I fear I am falling out of love with this goddess of dawn.

Surgery for kids with resistant epilepsy

Chopping bits out of children’s brains sounds like the work of villains in a Philip Pullman book (by the way, the latest is a good read). But it has its place, according to a trial in India:

“In this single-centre trial, children and adolescents with drug-resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behaviour and quality of life than did those who continued medical therapy alone at 12 months.” Just so long as they still have their daemons with them afterwards.

As for the bits removed, they show 36 different kinds of histopathology in kids and adults, hippocampal sclerosis being the commonest.

A CRISPR Way to diagnose infectious diseases

“There remains an important gap in our diagnostic armamentarium: rapid, reliable, easy-to-use, inexpensive diagnostic tests that can be conducted at the point of care.” I particularly like the “inexpensive”: less than the cost of a course of amoxicillin, and you’re home. “To this end, Gootenberg et al. have reprogrammed an endonuclease that associates with CRISPR (clustered regularly interspaced short palindromic repeat) sequences in the DNA of prokaryotes (these sequences are part of prokaryotes’ adaptive immune system) to achieve single-molecule analytical sensitivity for rapid nucleic acid detection.” This gets better and better. If you can get access to this piece, you must read it. An alternative title would be “SHERLOCK and the Case of the Promiscuous RNAase Activity.”

JAMA 24/31 Oct 2017 Vol 318

Weedkillers and the liver

“Where Man is not, Nature is barren” said William Blake, and I agree. But I’m not sure Blake would have approved of fields being made barren by Man using glyphosate as a herbicide before using them to grow high-yield wheat. This ubiquitous practice has led to more and more glyphosate appearing in the urine of humans, at least in Southern California where it rose 13-fold in two decades from 1993. At the same time we are seeing an epidemic of fatty livers in richer countries, attributed to obesity and/or alcohol. Now it so happens that glyphosate in very low concentrations causes liver steatosis and fibrosis in mammal models. More epidemiology here please, and hurry up.

No robots thanks

It would be interesting to study the kind of comics that surgeons read when they were boys. I say boys, because in my day it was understood that girls all read Bunty, whereas Dan Dare already featured robots and death rays. Nowadays no private surgical hospital brochure fails to mention robotic assistance and lasers, perhaps with proton beams thrown in. I blame Dan Dare. Two JAMA papers look at the benefits of robotic assistance: the first is in laparoscopic resection of rectal cancer where it did not help a bit. In the laparoscopic resection of kidney tumours, it also made no difference to patient outcomes, but led to longer operations and higher costs. This is not what we were led to believe when we read those key papers by D. Dare in 1957.

JAMA Intern Med Oct 2017

Wealth and health in the UK and US

Every true Briton knows that people live longer here than in America, and we tend to put this down to our universal health coverage. But here is a neat study comparing two cohorts, one in the US (HRS: the Health & Retirement Study) and the other in the UK (ELSA: the English Longitudinal Study of Ageing) which shows close similarities in the effect of the most important health factor: wealth. The cohorts aren’t directly comparable, but the differences between top and bottom quintiles of income are very similar. In people between age 54-64 in England, those in the highest wealth quintile had a 4% mortality and 17% disability risk over 10 years, compared with 16% and 42% respectively in the lowest quintile. It’s enough to make a Marmot want to dig a burrow.

The Lancet 28 Oct 2017 Vol 390

High blood pressure in China

First, a couple of interests to declare: I am a friend and admirer of one author of these two papers on blood pressure in China, and I have a new job that gives me a special interest in Chinese health. Now I’d urge you to share this interest with me for the next two minutes, because these studies raise all the important issues about elevated BP and its treatment. First of all, should we be calling it “hypertension”? I hope the Chinese have come up with a more helpful word. Secondly, what are its main population determinants—genetics, food, lifestyle, salt, aldosterone? Is it just another cardiovascular risk factor, or something more? If we don’t understand it very well ourselves, can we expect other people to? How can patients self-manage? How can they select treatments for themselves? Which health professionals should be helping? When and where? What outcomes should we measure, apart from just BP reduction? How much of the evidence base, derived almost exclusively from Western populations, applies to the fourteen hundred million people living in China?

A sample of 1.7 million shows that “Among Chinese adults aged 35–75 years, nearly half have hypertension, fewer than a third are being treated, and fewer than one in twelve are in control of their blood pressure.” Something needs doing, and the temptation will be to do the wrong things fast instead of the right things slowly. But making the right drugs available looks like a good place to start: a second study of 3362 primary health-care sites and around 1 million people shows that “China has marked deficiencies in the availability, cost, and prescription of antihypertensive medications. High-value medications are not preferentially used.”

The BMJ 28 Oct 2017 Vol 359

Is pharma paying your editor?

If you want to get rich from pharma payments, don’t edit a high-impact general medical journal (median pharma income $0). In the USA, go for endocrinology ($7207, $0-85 816), cardiology ($2664, $0-12 912), gastroenterology ($696, $0-20 002), rheumatology ($515, $0-14 280), or urology ($480, $90-669). This is disappointing. If I was an editor who wanted to sell my soul to pharma, I would be asking for a whole heap more.


There’s no innovation like exnovation. This word has been specially coined to become the twin of “deadoption” or, as in Vinay Prasad and Adam Cifu’s must-read book, “Medical Reversal”. It’s a major focus of the various “Choosing Wisely” campaigns across the world, which began in the USA, and this article focuses on the decline (exnovation) in carotid endarterectomy or carotid artery stenting within fee-for-service Medicare claims between 1 January 2006 and 31 December 2013. Now I know that The BMJ would like to build its American readership, but can I suggest that whenever it publishes an observational study like this from the US, it also publishes a similar study from the UK? Even better, it could compare figures from within the NHS to those in the UK private sector (which I’ve seldom seen done), since one moral here is that “The lowest rates of decline occurred in physicians specializing in vascular or thoracic surgery, for whom the procedures accounted for a large share of revenue.”

Plant of the Week: Salvia greggii “Creme Caramel”

Most salvias we have coveted over the years have had fabulously clear blue flowers, but I’ve generally failed to buy them because they rarely last more than one year. But we now have a favourite with lovely cream flowers on a base of brown, which is still flowering its heart out as November approaches. It goes wonderfully well with a pale blue form of Campanula posharskyana which is also in full flower. Neither is a big plant, so they are ideal for putting together at the edge of a sunny border.

This advice from Ashwood Nurseries is worth following: “Many salvias are reasonably hardy if planted in a sheltered sunny position. The soil should not be over rich, and winter drainage must be good. It is advisable to take a few cuttings in late summer as insurance.” One of ours has survived three years.