Richard Lehman’s journal review—21 November 2016

richard_lehmanNEJM  17 Nov 2016  Vol 375
Diabetes kills in Mexico City
“Overall, between 35 and 74 years of age, the excess risk of death associated with diabetes accounted for approximately one third of all deaths from vascular causes and one third of all other deaths.” That is a shocking statistic and it applies to the largest conurbation in the northern half of the Americas. People in Mexico City have high rates of diabetes and a third of people with it run glycated haemoglobin levels above 10. That is too high, even in my belief system. I also believe that duration and rate of progression are the most important factors in type 2 diabetes, both for individuals and society. Obese youngsters without hope of work and with a diet of cheap carbohydrates will get diabetes early and die early as a result. So what will help these people most? Building a wall and keeping them poor, obviously.

Passive HIV protection
Human immunodeficiency virus is famously able to avoid destruction by the immune system and then to destroy the system from within. But it has now become possible to engineer potent and broadly neutralising antibodies (bNAbs) against HIV, which makes passive immunisation a potential strategy for prevention and treatment. A study in this week’s NEJM suggests that this will not be very straightforward. In an open label trial, the antibody was tested on 24 people who were taking a break from antiretroviral therapy. It slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week eight. The potential uses of bNAbs are discussed in an editorial, which adopts a generally cautious tone.

Ticagrelor for PVD
For me, the name ticagrelor always carries associations with Excelsior, a poem of Longfellow’s which was much recited in parlour rooms from 1841 onwards. The victim of the story was a young man who bore a banner with a strange device up through the Alpine forests and cried “Excelsior”—ever higher. And so it is with ticagrelor, a banner product of AstraZeneca that was supposed to climb higher than clopidogrel. But alas, it never arrives. In this latest trial in patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. How like the tragic ballad:

At break of day, as heavenward
The pious monks of Saint Bernard
Uttered the oft-repeated prayer,
A voice cried through the startled air,

A traveller, by the faithful hound,
Half-buried in the snow was found,
Still grasping in his hand of ice
That banner with the strange device,

There in the twilight cold and gray,
Lifeless, but beautiful, he lay,
And from the sky, serene and far,
A voice fell like a falling star,

Celecoxib, ibuprofen, or naproxen?
When I was still a working GP, I used to prescribe celecoxib quite a lot, until I ran into trouble with the local prescribing watchdogs. I knew there was some controversy about its alleged superiority to other NSAIDs in relation to gastrointestinal safety, but even 10 years ago there seemed to be sufficient evidence to say that it carried no more risk for cardiovascular events than the rest. The real reason they didn’t like it was cost. Here’s a large randomised trial comparing celecoxib, ibuprofen, and naproxen in 24 081 people taking regular NSAIDs who were at elevated cardiovascular risk. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up, so interpret with care. But the intention to treat figures and the actually treated figures tell the same story. At moderate doses, these three drugs show no differences in cardiovascular risk, but the risk of gastrointestinal events was lower with celecoxib. Full circle then. Be guided by patient preference—and cost.

Lancet  19 Nov 2016  Vol 388
Self-absorbed stent degrades itself
Self-absorption can be a bad thing. It can put you out of touch with reality and make you a danger to others. It is degrading and could be lethal in an American President, for example. Or a stent. Let’s stick with the stent: it’s less scary. The ABSORB II trial pitted an everolimus eluting bioresorbable vascular scaffold against an everolimus eluting metallic stent in 501 people (usual question: how many of these stable patients really needed a stent in the first place?). At three years, the lumen of the target coronary arteries was smaller in the bioabsorbable group, but more importantly, they had more myocardial infarcts (6% v 1%, p=0.1). The conclusion of the abstract is a long bleat for more research, different antiplatelet strategies etc, but I think this idea has now biodegraded itself sufficiently.

World BP trends
I seldom mind when the Lancet goes looking at The World. Its contributors are generally very good at this, and glancing at their pieces makes one wonder whether if all these clever people joined up the dots we could make a better world. Then somebody decides to switch on the television news. Never do this: it just adds to the global burden of high blood pressure, which is the topic of a massive survey based on data from 19.1 million participants between 1975 and 2015. “During the past four decades, the highest worldwide blood pressure levels have shifted from high income countries to low income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.”

The BMJ  19 Nov 2016  Vol 355
PPIs and pneumonia
An enormous number of people take drugs to stop cells in the stomach lining doing what they were put there to do: pumping hydrogen ions into the lumen to produce hydrochloric acid. It’s not natural, that’s for sure. But is it harmful? A careful analysis of 23 years’ worth of data from the Clinical Practice Research Datalink shows that the alleged association between the use of proton pump inhibitors and risk of community acquired pneumonia is likely to be due entirely to confounding factors. In fact, there is a signal that they might be protective.

Ankle sprains don’t need physio
An Australian trial has me wondering if kangaroos sometimes need physiotherapy. They must put a lot more mechanical strain on their ankles than we slouchy mammalian bipeds ever do. Humans have been spraining their ankles ever since they came down from the trees. Hobbled hunter gathering men must have found great comfort from women who rubbed mammoth fat into their swollen ankles and bound them with auroch hide. Each day they would have their arm held and be helped through their pain barrier as they practised walking along the bumpy cave floor. Many experts aver that certain stick figures in early cave paintings represent the first physiotherapists. They may be the world’s oldest profession. On the other hand, it is possible that other cave women just said, “Oh just get on with it yourself, you giant sloth. You were a fat lot of help when I did my ankle in gathering sticks for your fire.” And, according to a well powered trial comparing usual (self) care with physio for simple grade 1 or 2 ankle sprains, that would have been equally effective.

Fungus of the Week: Hydnum repandum
I am just off to collect some hedgehog fungi. From Croatia.

It is very good of Tesco to stock these in a year when I haven’t had time to find them in my usual haunts. They keep well and they are distinctive and delicious. I shall be using them in a wine and cream sauce to go with butter roasted partridge.