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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—30 August 2016

30 Aug, 16 | by BMJ

richard_lehmanAfter a month’s break, I’m catching up with articles of interest in the main non-BMJ journals throughout August. Normal service will be resumed next week. 

NEJM  Aug 2016  Vol 375

No parasites for five years

405   Following its famous “data parasites” editorial last January, the NEJM has struggled to find a comfortable position on the issue of opening up trial datasets for independent analysis. In its first print issue for August it hosted four Viewpoint articles offering a range of options, mainly for the sharing of trials conducted by academic centres. Completely open sharing does not get a mention—the idea that researchers should make their de-identified data available without restriction. The NEJM spectrum instead begins with the Yale Open Data Access project, of which I’m a proud founder member. We pioneered the “academic intermediary” model and still run one for those who wish to use it. If researchers want to use more direct methods of sharing data, we’re hardly going to stop them. But alas, the very opposite tends to be true. A piece from a hitherto unknown body called The International Consortium of Investigators for Fairness in Trial Data Sharing argues that researchers should retain sole use of their databases for up to five years. I’m genuinely sad and baffled that people with prosperous careers supported by public funding can argue that the research they have performed through the altruism of unpaid people taking voluntary risks is somehow their private property. more…

Richard Lehman’s journal review—25 July 2016

25 Jul, 16 | by BMJ

richard_lehmanNEJM  21 July 2016  Vol 375

MenB vaccination for students
220    We’ve been waiting for decades to get a vaccine against Neisseria meningitidis serogroup B. But now that it’s arrived, it’s hardly the kind of thing that gets people looking for champagne bottles in the fridge. It’s an expensive way to prevent a rare disease, and it’s actually quite hard to prove that it has saved any lives so far. This report from its use during an outbreak at “University A in New Jersey” illustrates the problem. Although this paper (and another in Pediatrics) has input from Princeton University, neither actually mentions this august institution by name. I guess this coyness is because it would prefer to be linked in the public mind with Albert Einstein rather than the outbreak of meningococcal disease that began there in December 2013. Nine students were affected and one died. Nearly 6000 were then given meningitis B vaccination and none of the vaccinated students got the disease. more…

Richard Lehman’s journal review—18 July 2016

18 Jul, 16 | by BMJ

richard_lehmanNEJM 14 July 2016 Vol 375
Olanzapine stops chemo vomiting
134 For about five thousand years, doctors sought out plants that would make their patients vomit, believing that this would expel noxious humours. In this week’s NEJM there’s a good example of this in an interesting short piece about early clinical trials featuring Adrien Helvétius (1662–1727) who introduced ground ipecacuanha root (ipecac) from Brazil. It was still given to children who had taken accidental overdoses when I was a junior doctor. But the true benefactors of mankind today are those who discover powerful anti-emetics to help people taking cancer chemotherapy. Many anti-emetics have been discovered by chance, and the latest of them is olanzapine. We’re used to seeing it used as an antipsychotic which causes somnolence, weight gain, and type 2 diabetes. But over the last two or three years it’s been increasingly used short-term as an anti-emetic for cancer patients. This trial shows that it is highly effective even at the extreme end of the vomiting spectrum. It was compared with placebo in combination with dexamethasone, aprepitant, or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. I think I shall start taking olanzapine half an hour before switching on the news. It might prevent that strange feeling of nausea and being about to go mad.

Richard Lehman’s journal review—11 July 2016

11 Jul, 16 | by BMJ

richard_lehmanNEJM  7 July 2016  Vol 375

Bayesian cancer trials

I’m glad I haven’t got any cancer that I know of. I’m not unique in that, but I’m of an age when friends start getting cancer, and when they ask for advice it really brings home the current realities of oncology. This is the Wild West, with everything from futile treatments offered purely for the sake of doing something to expensive genomic buccaneering based on the belief that a new treatment might offer some sudden cure. There may be one best option for each individual, but for the time being there is no short cut to finding out what it is. In twenty years we might have cracked it, but what is going to happen to my friends (or perhaps me) in the interval? I guess one option is to get recruited into a trial using adaptive randomization. It may not cure you but it might give you a clue about what to try next and it might help similar patients in the future. That’s the sell. Now what of the reality? more…

Richard Lehman’s journal review—4 July 2016

4 Jul, 16 | by BMJ

richard_lehmanNEJM  30 Jun 2016  Vol 374

Cervical sense

2509   This week’s NEJM is an odd mix of the down-to-earth and the arcane. The down-to-earth comes first, ahead of midostaurin for advanced systemic mastocytosis, PD-1 blockade in Merkel-cell carcinoma and deficiency of sFRP4 as the cause of Pyle’s disease. If these conditions did not exist, it would be necessary for the New England Journal to invent them. Meanwhile, in the great world outside the Massachusetts General Hospital, hundreds of thousands of women die avoidably each year from cancer of the uterine cervix. Here’s a really clear short open-access piece describing why and what we could and should do about it instead of destabilising the world in a series of fantasy games. more…

Richard Lehman’s journal reviews—27 June 2016

27 Jun, 16 | by BMJ

richard_lehmanNEJM  23 Jun 2016  Vol 374

Adolescent BMI: big data, little meaning
2430  “How might adolescent BMI affect adult cardiovascular mortality? In our study, we could not control for important risk factors (e.g., smoking, exercise, and physical fitness) or for adult BMI.” Ah, a slight problem then. This study tells you the exact correlation between adolescent body mass index in 2.3 million Israeli Jewish males and cardiovascular mortality up to 40 years later. Overall, less than a tenth of deaths in these men were cardiovascular. They were more likely to die this way if their BMI was over the 50th centile when they were about 17 years old. However, when you can’t even adjust for obvious confounders, what does this actually mean? more…

Richard Lehman’s journal reviews—20 June 2016

20 Jun, 16 | by BMJ

richard_lehmanNEJM  16 Jun 2016  Vol 374
Data about parasites
2335   I love it when it’s parasite time in the NEJM. Tenaciously clinging to the wall of the large bowel, tapeworms suck up the digested food that North Peruvians have carefully gathered and prepared, just like people who reanalyse or meta-analyse data that others have gone to the trouble of producing. Such tapeworms—I mean the Peruvian kind—can be eliminated by a number of strategies. The ones considered here involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. A scaled up strategy of mass antiparasitic drugs for humans and Taenia solium vaccination for pigs eventually did the trick. At the end of the exercise hardly any village pigs were found to contain meta-analysts. I mean T solium cysts. more…

Richard Lehman’s journal reviews—13 June 2016

13 Jun, 16 | by BMJ

richard_lehmanNEJM 9 Jun 2016 Vol 374
All sorts of AML
2209 Ernest Rutherford (1871-1937), New Zealand’s greatest son, said that physics is the only science, and the rest is just stamp collecting. Nowadays physics seems largely about making stuff up, so I feel safer with the stamp collectors. And what wonderful stamps they are finding every day! When you were a student with your medical school stamp album, there was just one Penny Black, called Acute Myeloid Leukaemia (AML). Now they’ve looked at the watermarks and all that sort of thing and it turns out that there are 76 types of Penny Black or AML. And this, of course, matters a great deal if you happen to have one of them. more…

Richard Lehman’s journal reviews—6 June 2016

6 Jun, 16 | by BMJ

richard_lehmanNEJM 2 Jun 2016 Vol 374
Germs, catheters and hospitals
2111 Anyone who has an indwelling urinary catheter will get bacteriuria, sooner or later. I was taught this as a medical student, as a medical HO and urology SHO, and observed it through 35 years as a GP. This article begins by stating that up to 69% of catheter-associated UTIs are considered to be avoidable, provided that recommended infection-prevention practices are implemented. It’s the kind of claim that begs questions: is asymptomatic colonisation the same as “UTI”? Is this a statement about hospitals, or the community, or nursing homes, or all three? Still, it’s hard to argue against taking precautions against introducing organisms into the urinary tract, especially in already sick patients in hospital. And a prevention package may work, according to this carefully reported before-and-after study. Data were obtained from 926 units in 603 American hospitals as they introduced a program designed to reduce catheter infection. Infections went down on the wards but not on intensive care units. more…

Richard Lehman’s journal review—31 May 2016

31 May, 16 | by BMJ

richard_lehmanNEJM 26 May 2016 Vol 374
An end to oncology drug madness?
2001 “Seamless Oncology-Drug Development” is a viewpoint piece about the research and regulatory changes that have allegedly been driven by a desire for “early access to transformative new anticancer drugs.” To my simple way of thinking, this would mean first showing that the new drug was transformative, through large double-blinded randomised controlled trials demonstrating a sizeable survival benefit. Secondly, in order to achieve “early access,” the drug would then be immediately available to all patients, and charged at production cost to the health provider. Thirdly, further trials would be conducted using it earlier in the disease process, compared to existing standard treatment. more…

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