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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—23 November 2015

23 Nov, 15 | by BMJ

richard_lehmanNEJM 19 Nov 2015 Vol 373
Spooky RSV trial
2048 There’s a hint of Porton Down about this phase 1 study of an oral treatment for respiratory syncytial virus (RSV). The 62 volunteers trooped in and the steel doors shut behind them. Two days later, masked personnel in white coats proceeded to inoculate them intranasally with four log10 plaque-forming-units of the RSV-A Memphis 37b challenge virus. They spent another two days in quarantine and were then monitored twice daily for signs of incipient RSV infection. As soon as these appeared, nasal samples were sent off for a polymerase chain reaction test to confirm that it was indeed RSV, and they were then given the mystery agent ALS-008176, or a placebo. At this point Sherlock broke in to the secret chamber, the lights went out, klaxons sounded, and the experiment had to be aborted. Ah no, that was just for the television: in real life the subjects continued to languish in durance vile until two weeks had elapsed. more…

Richard Lehman’s journal review—16 November 2015

16 Nov, 15 | by BMJ

richard_lehmanNEJM 12 Nov 2015 Vol 373
SPRINTing to conclusions
OL There’s no denying that the research event of the week has been the online publication of the SPRINT hypertension trial. So here I am departing from the usual pattern of these reviews, because it would seem odd not to begin with it. I’m going to be very brief. The trial shows that in people of mean age 68 years with elevated cardiovascular risk, but not diabetes, aiming for a systolic blood pressure target of 120 rather than 140 mmHg produced a significant reduction in death and cardiovascular events over a median period of three years and three months. The patient characteristics, benefits, and harms in this trial are very well described. If you are consulted by an individual who fits its criteria, you could have an informed conversation about their risk lowering options, of which tighter BP control might be one.


Richard Lehman’s journal review—9 November 2015

9 Nov, 15 | by BMJ

richard_lehmanNEJM  5 Nov 2015  Vol 373

Now for the good news

1824   In the middle of the joy and uncertainty of pregnancy, you are told you have cancer. It happens to a few women every week across Europe. Thanks to a collaboration between national referral centres in Belgium, the Netherlands, Italy, and the Czech Republic we can find out what happens to children born to mothers who were treated for cancer while pregnant. Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. I love reading this kind of study from bodies like the International Network on Cancer, Infertility, and Pregnancy: medicine as a collaborative endeavour for people facing distress. This will come as immensely welcome news for women in one of the worst situations that life could throw at them. Let’s hope longer term data are equally reassuring. more…

Richard Lehman’s journal review—2 November 2015

2 Nov, 15 | by BMJ

richard_lehmanNEJM 29 Oct 2015 Vol 373
Noddy meets oncology
1679 PARP stands for poly(adenosine diphosphate [ADP]–ribose) polymerase. For every child who grew up in England since the 1950s, it is also the noise that Noddy’s car makes. Now there is a PARP inhibitor called olaparib which costs about £900 a week for treating metastatic cancers of the ovary and prostate. more…

Richard Lehman’s journal review—26 October 2015

26 Oct, 15 | by BMJ

richard_lehmanNEJM 22 October 2015 Vol 373
Neatest knee trial
1597 “Whatever next. A patient centred, surgical RCT on a common operation with a thoughtful, patient centred editorial in the NEJM,” wrote a friend on the day this paper appeared. Like minded messages and tweets poured in from both sides of the Atlantic. This randomised trial of total knee replacement is exactly the kind of trial that the US Patient Centered Outcomes Research Institute was set up to encourage. It’s exactly the sort of common and important question that the UK National Institute of Health Research tries to prioritise. But this trial was not funded by PCORI or NIHR. It was designed by orthopaedic surgeons in Aalborg University Hospital, Denmark, and it was funded by the Obel Family Foundation and a group of other public donors. more…

Richard Lehman on prescribing spironolactone

23 Oct, 15 | by BMJ

richard_lehmanThe liveliest e-mail streams I have ever encountered are the ones which are currently coming out of the Overdiagnosis Group, set up by Margaret McCartney last year. The group is now a standing body within the Royal College of General Practitioners and most of its members are working GPs. But there are participants from all over the world too, and from other medical or non-medical disciplines.

A lot of recent discussion has centred on how we actually share decisions with patients. Since I retired from full time general practice five years ago, it’s something I have thought a lot about. It is far more complex than just using evidence synthesis and decision aids, though these can be valuable in their context. Andrew Spooner, an experienced GP and RCGP Council member, suggested that we use the example of spironolactone as add-on treatment for heart failure to debate the key issues. This pressed several buttons for me and I found myself writing a rather long case example: more…

Richard Lehman’s journal review—19 October 2015

19 Oct, 15 | by BMJ

richard_lehmanNEJM 15 Oct 2015 Vol 373
NEUROSIS about tiny babies
1497 The first paper in the NEJM this week has me flummoxed. Its acronym is NEUROSIS—who thought that was a good idea for a trial of inhaled budesonide in very premature infants? The European Union funded the trial which took place in 40 centres around the EU, and it recruited 863 infants of gestational age below 28 weeks to receive budenoside or placebo through a metered face mask. The idea was to prevent bronchopulmonary dysplasia, which affects about half of premature babies of this age. But in the end fewer than half the participants had adequate data for outcome analysis. Comparing 40% of the active group with 46% of the placebo group, there was a statistically significant reduction of bronchopulmonary dysplasia in those given budesonide, but a nonsignificant increase in mortality. Cut it as you may, I can’t see how evidence like this can reliably inform clinical practice. more…

Richard Lehman’s journal review—12 October 2015

12 Oct, 15 | by BMJ

richard_lehmanNEJM 8 October 2015 Vol 373
1397 Famous as a pioneer of hypertension studies, Sir George Pickering (1904-1980) was a man of forceful opinions, and used to command the attention of his hearers by gripping their arms tightly for the duration of the encounter. As I was a medical student and he was Master of my college, I endured this treatment quite frequently while others around me would unaccountably disappear. I now realise that he was probably testing an early form of ischaemic preconditioning. Limbs deprived of oxygen this way generate a magical neurohumoral response that protects all the other organs from ischaemic damage. Pickering’s views on his colleagues or life in general could easily have provoked a stroke or heart attack, but he provided complete protection through his vice like grip. But two studies in this week’s NEJM show that this protection does not extend to invasive cardiac surgery. The first trial, funded by the German Research Foundation, randomised 1403 adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anaesthesia with intravenous propofol to undergo real or sham ischaemic preconditioning. The real or sham procedure was performed after induction of anaesthesia, and the blinding protocol is an amazing demonstration of German thoroughness. But by any criterion, clinical or biochemical, there was absolutely no difference in outcomes between the groups. more…

Richard Lehman’s journal review—5 October 2015

5 Oct, 15 | by BMJ

richard_lehmanNEJM 1 Oct 2015 Vol 373
1307 What will happen to all the overweight children and young adults we see around us? The honest answer is that nobody knows. There has never been such a generation before in human history, and it is entirely possible that during the next decade or two they will all be rendered thin by some miraculous new intervention. Measuring their “cardiometabolic risk factors” doesn’t really get us much further. Here is a cross-sectional analysis of data from overweight or obese children and young adults 3 to 19 years of age who were included in the US National Health and Nutrition Examination Survey from 1999 through 2012. Although there is a general association between the degree of obesity the risks of a low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated haemoglobin levels, it doesn’t get very strong except among the most severely obese, especially males.


Richard Lehman’s journal review—28 September 2015

28 Sep, 15 | by BMJ

richard_lehmanNEJM 24 Sep 2015 Vol 373
1220 I suspect that good randomized trials of common procedures are difficult to do. Each French doctor probably has a favourite way of gaining central venous access, probably dependent on how they were first taught. But in this trial they were commanded to use the femoral, jugular, or subclavian route according to permuted-block randomization with varying block sizes. Who would dare to do otherwise when supported by funds from the French Ministry of Health Programme Hospitalier de Recherche Clinique National to the Délégation de la Recherche Clinique et de l’Innovation of the Caen University Hospital? Eh bien, it was a win for the subclavian. This route was associated with the fewest bloodstream infections and episodes of thrombosis, though it led to pneumothorax in 1.5% of patients.


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