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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—23 January 2017

23 Jan, 17 | by BMJ

richard_lehmanNEJM  19 Jan 2017  Vol 376
Transmission of drug resistant TB
Tuberculosis in Europe used to be known as the White Death, and that is the title of the best book about its history. But in parts of South Africa extensively drug resistant (XDR) tuberculosis might be called the New Black Death, because there it kills an increasing number of people who are almost invariably poor and black. It’s unusual to see a paper like this one in the NEJM, dealing with a disease (I almost wrote “health issue”; bah) among disadvantaged people in a remote country. Three quarters of the 404 patients from KwaZulu-Natal Province had HIV and over half of them carried the same strain of XDR-TB. The rest mostly fell into small clusters of 30 other different TB genotypes, and complex evidence points to person to person transmission as the most important factor. more…

Richard Lehman’s journal review—16 January 2017

16 Jan, 17 | by BMJ

richard_lehmanNEJM  12 Jan 2017  Vol 376

PROMS and PROs
I first went to the Proms in 1966. I enjoyed the queuing, the atmosphere, and the music: young Barenboim playing Beethoven with Boulez, Kertesz conducting Dvorak, Heather Harper singing something English and so forth. So long ago. Now the word prom seems to mean a passing-out ritual (in both senses of the word) by school-leaving teenagers, or Patient Reported Outcome Measures. The Americans prefer PRO for the latter, but that is equally confusing. PROMS/PROs have become something of an industry over the last ten years or so. The title of this Viewpoint says it all—”Patient-Reported Outcomes—Harnessing Patients’ Voices to Improve Clinical Care.” They are a way of harnessing patient voices. Once harnessed, these can be converted into metrics and tick-boxes and studied quantitatively at a distance. All this is well-described in this article, which ends by saying that “There is sufficient scientific rationale and understanding of implementation methods to expand collection of PRO data in clinical care. Doing so could turn the rhetoric regarding ‘patient-centered care’ into a reality.” But there is a much better, quicker way of doing that. It consists of  unharnessing patients’ voices and actually listening to them. This is called Experience-Based Co-Design and it works in real-time cycles where patients have the power to change things. No wonder it hasn’t caught on. more…

Richard Lehman’s journal review—9 January 2017

9 Jan, 17 | by BMJ

richard_lehmanNEJM 5 Jan 2017 Vol 376
The trials of big pharma
As a fan of Ben Goldacre’s Bad Pharma and Peter Gøtzsche’s Deadly Medicines and Organised Crime, I was not expecting to think highly of a piece called “The Large Pharmaceutical Company Perspective” in the NEJM series called “The Changing Face of Clinical Trials.” It is written by Mike Rosenblatt, for many years the chief medical officer at Merck. It is a very compelling account of the difficulties and risks of developing two preventive drugs: a rotavirus vaccine and a bisphosphonate to treat osteoporosis. Large trials, he says, can now cost up to a billion dollars without any certainty of return. He identifies the chief enemy as complexity and lists a large number of factors.

He is certainly a very able Mephistopheles, but he hasn’t completely persuaded me to feel sorry for the fallen angels lurking in the shadows behind him. Why are they still wearing those tails and horns? For sure, I think pharmaceutical companies do have to invest a lot in the development and initial testing of their compounds. But what is the real level of financial risk for them in relation to their total profitability? more…

Richard Lehman’s journal review—3 January 2017

3 Jan, 17 | by BMJ

richard_lehmanNEJM  22-29 Dec 2016  Vol 375

Co-amoxiclav for OM in under-twos

This trial firmly establishes the superiority of a ten day over a five day course of co-amoxiclav for babies and toddlers with acute otitis media. The figures are clear: with only five days treatment, failure of resolution at ten days is 34%, whereas if ten days of treatment are given, it is 16%, and the babies suffer fewer symptoms. So here we have a nice simple trial to inform practice in a very common and distressing clinical situation. More is sometimes more. more…

Richard Lehman’s journal review—19 December 2016

19 Dec, 16 | by BMJ

richard_lehmanNEJM  8-15 Dec 2016  Vol 375

Geographical variation in trials

This review article on geographical subgroup variation is a master class in how to think about and analyze randomised controlled trials. Salim Yusuf and Janet Wittes have been leading figures in the design and interpretation of RCTs for the last thirty years, and that shines through their paper. But I do find it a little too polite. It begins from the premise that all trials are done to determine the objective truth and equally well conducted across all geographical locations. But most of the RCTs I come across are funded by the manufacturers of the intervention and spread across many more centres than are required to recruit a sufficient number of participants. Then again, a basic principle of science is that all results should be replicated, but the literature is full of trials prematurely ended and never replicated, on the basis that it would be unethical to repeat a single experiment that appears to demonstrate benefit or harm. In this Panglossian world, nobody anywhere ever cheats, though billions of dollars are at stake. I hope this is true. Whether it is or not is something you won’t find hinted at in this paper, though I’d still recommend that you read it. more…

Richard Lehman’s journal review—5 December 2016

5 Dec, 16 | by BMJ

richard_lehmanNEJM  1 Dec 2016  Vol 375
Can genes prove how drugs work?
Medicine is the application of neat science to a messy world. We love it when it works simply: for example, when a single gene controls a single biochemical process, which we can then block with a single chemical. Statins are often cited as an example: they block 3-hydroxy-3-methylglutaryl–coenzyme A reductase, an enzyme that is governed by the HMGCR gene. By doing so, they reduce circulating levels of low density lipoprotein cholesterol (LDL-C) and, bingo, down goes your cardiovascular risk. But for less obvious reasons, they also raise blood glucose slightly and cause muscle symptoms in many people. If your glucose is highish to start with, they may cause you to “get diabetes,” i.e. cross an artificial threshold and bundle you together with millions of different people with this scary label. But can all this really be put down to the HMGCR gene? Here’s a population study, which concludes that it can, provided you throw in a second gene locus governing LDL-C levels. more…

Richard Lehman’s journal review—28 November 2016

28 Nov, 16 | by BMJ

richard_lehmanNEJM  24 Nov 2016  Vol 375

AAA in UK & USA

It grieves me to say it, but there are certain things that American medicine does better than British medicine. Repairing abdominal aortic aneurysms seems to be one of them. It’s not that men on the whole live longer over there, but only a third as many die from a ruptured AAA in the USA as in England, according to a study using linked databases on both sides of the ocean. In America they tend to go in and repair at 58mm whereas we tend to wait until 64mm, and they do twice as many repairs, suggesting a screening effect. Perhaps as our screening programmes gather momentum, we will see a gradual levelling of difference; but for the time being, America definitely trumps England. Damn, I must learn to stop using that expression. more…

Richard Lehman’s journal review—21 November 2016

21 Nov, 16 | by BMJ

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. more…

Richard Lehman’s journal review—14 November 2016

14 Nov, 16 | by BMJ

richard_lehmanNEJM  10 Nov 2016  Vol 375

Reinventing connected medicine

A 1300 word Viewpoint article can hardly do justice to a theme as grand as “Meaning and the Nature of Physicians’ Work”, and a lot of this piece is taken up with describing the current realities of American hospital medicine for those at its coalface. But here’s a proposal we can all identify with:”Perhaps the greatest opportunity for improving our professional satisfaction in the short term lies in restoring our connections with one another. We could work on rebuilding our practices and physical spaces to promote the sorts of human connections that can sustain us—between physicians and patients, physicians and physicians, and physicians and nurses. We could get back to the bedside with patients, families, and nurses. We could get to know our colleagues from other specialties in shared lunchrooms or meeting spaces.” It’s not rocket science. But it’s certainly how the greatest rocket scientist operated. He was Sergey Pavlovich Korolev (1907-1966), who lived and worked with his teams day and night, and put the Soviet space programme way ahead of any other while he lived. more…

Richard Lehman’s journal review—7 November 2016

7 Nov, 16 | by BMJ

richard_lehmanNEJM  3 Nov 2016  Vol 375
Tolerating uncertainty
“At once it struck me what quality went to form a Man of Achievement . . . when a man is capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason.” John Keats, December 1817

This quotation heads a wonderful short essay by Arabella Simpkin and Richard Schwartzstein about uncertainty in medicine. The year 1817 marked the point at which the young John Keats decided to leave medicine and take up poetry, and the “Man of Achievement” he was thinking of was almost certainly Shakespeare. The defining characteristic of Shakespeare (and of Keats in his finest works) is of being taken beyond the circumference of the individual mind to a place where feelings and words have no outer bound. Then Keats coughed up blood, and he knew he was going to die. A few years later, his illimitable gift was destroyed. But over the next 140 years, “irritable reaching after fact and reason” would result in a cure for tuberculosis. more…

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