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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—3 May 2016

3 May, 16 | by BMJ

richard_lehmanNEJM 28 April 2016 Vol 374
Colon cheer
1605 As we get more affluent, we drink more alcohol, grill more meat, grab bacon or salami sandwiches for lunch. Up in heaven, a wrathful god looks on and smites us with bowel cancer. Oh wait, no, he seems to be easing off: for all our sins, the incidence of bowel cancer has dropped by 45% from its peak in the mid-1980s. This is not due to screening, as Gil Welch and Doug Robertson explain in the most interesting article in this week’s NEJM. I don’t see how it can be diet either. We don’t know why colorectal cancer is getting rarer: it’s another of those happy conundrums in the history of cancer epidemiology. more…

Richard Lehman’s journal review—25 April 2016

25 Apr, 16 | by BMJ

richard_lehmanNEJM 21 April 2016 Vol 374

Aliskiren in Cardioland

1521 What does the R in the RAA pathway stand for? I used to pose this question in lectures several times a year, believing all that I had been told about the importance of the renin-angiotensin-aldosterone pathway in heart failure. I’d explain that we had drugs which blocked the AA but not the R. Then, a few years ago, along came aliskiren, a direct renin inhibitor. But early trials raised fears that poor Alice had come too late to the party. And this trial in people with chronic heart failure and reduced ejection fraction really pushes her down the rabbit hole. “In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril. (Funded by Novartis; ATMOSPHERE)” shouted the Queen of Hearts. “Not non-inferior, not non-inferior” squawked the Mad Hatter. Alice went to look for her friend the Walrus, because she couldn’t stand the atmosphere any longer. more…

Richard Lehman’s journal review—18 April 2016

18 Apr, 16 | by BMJ

richard_lehmanNEJM 14 April 2016 Vol 374

Fixing spinal stenosis
1413 Magnetic resonance imaging was like magic when it first appeared. Suddenly structures in the back that could only be guessed at on x-rays or even CT scans could be seen in lavish detail. It became clear that there was no such thing as a normal back: discs bulged here and degenerated there, narrowed nerve foramina abounded, and vertebrae showed slippage in many wanton and disturbing ways. For millions of patients with back pain, plausible explanations could be demonstrated on the screen and treated with expensive new operations and devices. Just to give a keynote lecture about one of these could earn an orthopaedic surgeon $1 million from a manufacturer less than 20 years ago. For lumbar spinal stenosis, simple decompression operations were rapidly overtaken in the US by combined procedures of decompression and fusion, which increased by a factor of 15 between 2002 and 2007. Two publicly funded trials in this week’s NEJM may mark the end of the party, surely one of the most extravagant even in the history of American medicine. From cool Sweden comes a trial in 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels. They were randomized to undergo either decompression surgery plus fusion surgery, or decompression surgery alone. The combined procedure cost more but did not result in better outcomes at two or five years’ follow-up. more…

Richard Lehman’s journal review—11 April 2016

11 Apr, 16 | by BMJ

richard_lehmanNEJM 7 April 2016 Vol 374
Prebirth steroids and baby lungs
1311 Most of you will be familiar with the logo of the Cochrane Collaboration, consisting of a blue circle with a vertical line crossed by some bars with a diamond shape at the bottom. This is the forest plot of Iain Chalmers et al’s meta-analysis of the trials of prenatal corticosteroids to improve outcomes in very premature infants. All of it was groundbreaking at the time: the idea of meta-analysis, this way of visualising its results, and the fact that giving steroids to mothers could save thousands of tiny babies. These methods are still basic to evidence based medicine, but so is the principle that a single well conducted and adequately powered randomised trial can give you a reliable answer in one go. Here is one such, and again it’s giving mothers a corticosteroid to prevent respiratory distress in premature babies. But this time the babies were further on in gestation: 34-37 weeks, and the steroid given was parenteral betamethasone. The effect was modest—a 2.8% absolute reduction in the composite outcome of severe events. But a definite benefit from a cheap and harm free intervention. more…

Richard Lehman’s journal review—4 April 2016

4 Apr, 16 | by BMJ

richard_lehmanNEJM 31 Mar 2016 Vol 374
Going Dutch with Lyme
1209 When you open a journal with New England in its name and read about Lyme disease, you somehow don’t expect the study to have been carried out in the Netherlands. But never mind: it’s a good study and the investigators managed to collect enough cases of genuine Lyme disease from those densely inhabited flatlands. They gave a couple of weeks of intravenous ceftriaxone to 281 patients with persistent symptoms attributed to Lyme disease: musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, dysaesthaesia, neuropsychological disorders, or cognitive disorders, with or without persistent fatigue. They were then allocated randomly to receive 12 weeks of doxycycline, or a combination of clarithromycin and hydroxychloroquine, or placebo. There was no difference between the three groups in terms of symptom resolution. Whatever causes this disabling syndrome, it doesn’t seem amenable to longer antibiotic treatment. more…

Richard Lehman’s journal review—29 March 2016

29 Mar, 16 | by BMJ

richard_lehmanNEJM 24 Mar 2016 Vol 374
Flinty problem, leaden response
1101 John Snow, the arch-hero of epidemiology, died in 1858 a disappointed man. It was only after he had died that there was a proper inquiry into the cholera outbreaks that he had mapped, and during the interval the water company denied all possibility of contamination. This was in high Dickensian London, 160 years ago. Never again? The mass poisoning of an entire city of over 100 000 people (Flint, Michigan) by lead in the water supply is still happening in 2016. It is hard to believe. “We have the knowledge required to redress this social crime. We know where the lead is, how people are exposed, and how it damages health. What we lack is the political will to do what should be done.”

Incretin drugs & heart failure
1145 So called type 2 diabetes is a vascular risk state signalled by elevated levels of blood glucose. Everybody rushes in to fix the elevated blood glucose but this is not the key to reducing vascular risk. more…

Richard Lehman’s journal review—21 March 2016

21 Mar, 16 | by BMJ

richard_lehmanNEJM 17 Mar 2016 Vol 374
Unnecessary pessary
1044 “This randomized trial showed that placement of a pessary in girls and women who were pregnant with singletons and who had a short cervix at 20 to 24 weeks of gestation did not result in a lower rate of preterm delivery before 34 weeks of gestation than the rate with expectant management.” The last sentence of this paper tells you all you need to know, leaving me free to muse on the rhyming possibilities of the word “pessary”. I think I have already exhausted them in the title. But this does remind me of the quatrain written by a nineteenth century bishop when challenged to come up with rhymes for “cassowary” and “Timbuctoo”:
If I were a cassowary
On the plains of Timbuctoo
I would eat a missionary,
Cassock, bands, and hymn-book too.
This has been variously misquoted and misattributed, but it was most likely written by Samuel Wilberforce, Bishop of Oxford from 1845 to 1869, who became famous for mocking Darwin’s new Theory of Evolution at a public meeting and being coolly demolished by Thomas Huxley. He was known as “Soapy Sam” and he once led a procession of 100 vested clergy through the streets of my local town, Banbury, in the hope of attracting them to the Church of England. It is nice to have this further proof of his sense of humour. more…

Richard Lehman’s journal review—14 March 2016

14 Mar, 16 | by BMJ

richard_lehmanNEJM 10 Mar 2016 Vol 374
Treating malaria in pregnancy
913 Here’s a tonic for those of us who lie abed with thoughts about the stupidity of the world and the pointlessness of medical research. The PREGACT trial was supported by the European and Developing Countries Clinical Trials Partnership and it tells doctors in Africa exactly what they need to know: which is the best treatment out of four commonly used combinations to treat malaria in pregnancy? There’s no point in my listing the alternatives, because anyone who treats malaria can just look up the paper. The bottom line is that currently the best choice in Africa seems to be dihydroartemisinin–piperaquine. The manufacturers of the various drugs donated them to the project, and without commercial support the trialists used simple, robust randomisation methods and good ascertainment. It can be done like this. It should be done like this. more…

Richard Lehman’s journal review—7 March 2016

7 Mar, 16 | by BMJ

richard_lehmanNEJM  3 Mar 2016  Vol 374

Inducing for better outcomes?
813 This useful British trial was done with the ultimate aim of reducing stillbirth, which tends to happen more in women who give birth for the first time at the age of 35 or older. The presumption is that induction at term will reduce the stillbirth rate, but critics have said it would increase the rate of caesarean delivery. This trial did not use stillbirth as an end-point: there are 3,600 stillbirths per year in the UK, which is a lot, but still means that you would have to randomise half the country to get a definitive result. So 619 nulliparous women aged 35 and over were randomly assigned to labour induction in the last week of gestation, or to expectant management, and the primary outcome was caesarean section. In fact there was no difference in the CS rate between the groups, so in theory a very large trial of induction to prevent stillbirth could go ahead. more…

Richard Lehman’s journal review—29 February 2016

29 Feb, 16 | by BMJ

richard_lehmanNEJM 25 Feb 2016 Vol 374

Aspirin with your cabbage?

728   Most people who undergo coronary artery surgery take aspirin. Nobody knew whether they should carry on or stop when they had their CABG. Now we have the results of a big multinational trial: “Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo.” But I’m puzzled to note that the patients were only “eligible for the trial if they had not been taking aspirin regularly before the trial or had stopped taking aspirin at least four days before CABG surgery.” So why is the article title “Stopping vs. Continuing Aspirin before Coronary Artery Surgery“? I checked with the authors and was told that the trial was designed this way to allay fears that aspirin continued right up to surgery might pose a bleeding risk. Most of the patients were indeed on long-term aspirin which was stopped just for the four days before surgery. I think I understand this, but it still makes the title a poor match for what actually happened in the trial. more…

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