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Richard Lehman’s weekly review of medical journals

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.


Richard Lehman’s journal review—21 September 2015

21 Sep, 15 | by BMJ

richard_lehmanNEJM 17 Sep 2015 Vol 373
1095 Well, here’s a paper that nearly caused me to stop breathing. It was certainly followed by a sharp intake of breath. Cheyne-Stokes breathing is common in advanced heart failure, and so is central sleep apnoea, which causes frequent periods of nocturnal hypoxia in these patients. Thus continuous positive airways pressure should help them feel better and live longer. This trial shows that it actually causes them to die faster. And, unlike in a similar trial which was reported recently, it did not make them feel better. This is important, because most people with heart failure would prefer feeling better to living longer. So we now know that for men aged around 70 with marked reductions in ejection fraction, CPAP is effective in reducing sleep-disordered breathing, but is unlikely to have any symptomatic benefit and increases the risk of cardiovascular death. This should not preclude further trials in different people with other types of heart failure, but it probably will. more…

Richard Lehman’s journal review—14 September 2015

14 Sep, 15 | by BMJ

richard_lehmanNEJM 10 Sep 2015 Vol 373
997 Are any readers looking for a nice short term research project in evidence based medicine? Here you have it. On 1 September, the MATRIX triallists reported the results of a trial which randomised 7213 participants with an acute coronary syndrome to receive either bivalirudin or unfractionated heparin prior to percutaneous coronary intervention. Bivalirudin costs over £300 per vial while unfractionated heparin costs £2-£5. The two groups had the same outcome, both in terms of cardiovascular events and adverse events. So what someone now needs to do is map the de-adoption of bivalirudin. How soon will the NHS, for example, start saving £300+ per patient undergoing emergency PCI? How will this play out in the US within Medicare and the large insurers? How many cardiologists will still be using bivalirudin for ACS in a year’s time? Those who do want to carry on will find some comfort from the editorial on this trial, though I didn’t. The author declares 12 possible conflicts of interest, including a grant from the makers of bivalirudin.


Richard Lehman’s journal review—7 September 2015

7 Sep, 15 | by BMJ

richard_lehmanNEJM  3 Sep 2015  Vol 373

895   The cool new look is beige and fat. Understanding beige fat may be the beginning of the end of obesity in humans. Or it may disappear and be forgotten as soon as the next panacea offers itself on the pharma catwalk. The NEJM clearly thinks it is important, since it has made the full text of the study free and more importantly the editorial, which explains the basic genomics and how changes in fat type might govern metabolism. It’s not an especially easy read, but now that the nights are drawing in I commend it to your attention. In large genomewide association studies, the strongest genetic signal related to body weight has been in the FTO locus. more…

Richard Lehman’s journal review—1 September 2015

1 Sep, 15 | by BMJ

richard_lehmanNEJM  20-27 Aug 2015  Vol 373

726   We start with a basket trial. Say you are in a supermarket and put lots of brown things in your basket—bread, a joint of lamb, a tin of brown beans, some kiwi fruit, and a shirt. Now, out of scientific curiosity, you decide to dip the contents of your basket in anti-brown, a corrosive substance that binds to anything that’s brown. You find that the bread dissolves completely, the lamb turns blue, the kiwi fruit explodes, the shirt shrinks and the beans remain unaffected. The actual basket trial described here was only slightly more sophisticated. It gathered together 120 patients with various forms of non-melanoma cancers, all of which expressed the oncogene BRAF V600. They were all given a selective oral inhibitor of the BRAF V600 kinase, vemurafenib. The short-term responses were then observed. “Preliminary vemurafenib activity was observed in non–small-cell lung cancer and in Erdheim–Chester disease and Langerhans’-cell histiocytosis… There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab.” more…

Richard Lehman’s journal review—27 August 2015

27 Aug, 15 | by BMJ

richard_lehmanNEJM 6-13 Aug 2015 Vol 373

503 Outcomes in early breast cancer surgery just keep on getting better. But between 20-40% of patients who have a partial mastectomy need to undergo further surgery soon afterwards because the excision margin shows possible tumour involvement. A team at Yale decided to see if this could be averted by routinely performing a further shave of the cavity margins after all grossly visible tumour had been completely removed. Randomization—either to close the wound or to perform extra shaves—occurred at the moment of decision during the operation. And sure enough, those who had the extra shave were half as likely to need re-excision surgery, and had no increase in complications.


Richard Lehman’s journal review—3 August 2015

3 Aug, 15 | by BMJ

richard_lehmanNEJM 30 July 2015 Vol 373
405 This week’s first paper has an interesting title: Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function. It’s the first time I’ve seen the word “therapeutic” used to describe something done to a person who is already dead. The hypothermia they refer to here occurs in a newly deceased cadaver. The currently recommended alternative is to maintain heat in the cadaver until the kidneys are harvested. This is what it means when it says “after declaration of death according to neurologic criteria, donors were assigned by means of computer-generated block randomization to mild hypothermia (34 to 35°C) or normothermia (36.5 to 37.5°C).” So it’s the whole body and not just the kidneys: I’m labouring the point because it took me a few minutes reading the paper to work it out myself. The result of the trial shows that cooler is better. It was stopped early at the point when delayed graft function had developed in 79 recipients of kidneys from donors in the hypothermia group (28%) and in 112 recipients of kidneys from donors in the normothermia group (39%) (odds ratio, 0.62; 95% confidence interval, 0.43 to 0.92; P=0.02). more…

Richard Lehman’s journal review – 27 July 2015

27 Jul, 15 | by BMJ Group

richard_lehmanNEJM  23 Jul 2015  Vol 373

307   Four summers ago I found myself dabbling in the early history of outcomes research. I was astonished to find that surgeons over a century ago were reflecting on much the same issues as they do today. In cancer, for example, there was lively debate about the place and timing of radiotherapy in relation to surgical procedures. Here’s a study of regional node irradiation in early-stage breast cancer, which recruited between the years 2000 and 2007. Ionizing radiation was first used to treat cancer in 1896 and this trial shows that we are still learning how to use it. The median follow-up here is 9.5 years, and irradiating the regional lymph nodes as well as the breast made no difference to the primary outcome, which was overall survival. It did, however, reduce the recurrence rate of breast cancer by an absolute margin of 5%, at the cost of a small difference in the occurrence of lymphoedema (absolute increase 3.9%) and pneumonitis (1%). more…

Richard Lehman’s journal review—20 July 2015

20 Jul, 15 | by BMJ

richard_lehmanNEJM 16 July 2015 Vol 373
209 I’ll say it again: “Cancer boasts the worst trials in medicine. Also the worst drug regulation. Also the worst cost/benefit ratio for new treatments. And also the worst drug toxicities. Plus the highest levels of public and charitable funding. My forehead hits the desk when I read about this stuff.” I’m developing quite a lump. Here’s a Pfizer funded trial of palbociclib, a new add-on last ditch treatment for breast cancer, which has become resistant to anti-hormone treatment. Don’t bother with the abstract which just obscures the findings. The editorial gives the results in a nutshell: “The rate of objective response with palbociclib–fulvestrant (10%) was not much higher than the rate with placebo–fulvestrant (6%), but the rate of clinical benefit (response or prolonged stable disease) at 6 months was significantly higher with palbociclib–fulvestrant (34%, vs. 19% with placebo–fulvestrant). There was no significant between-group difference in overall survival, but it is too early to expect such a difference.” But the “clinical benefit” referred to is just a temporary halt in the growth of the cancer, while “palbociclib adds considerable cost and toxic effects, including mechanism-based myelosuppression, some fatigue, nausea, and an increased risk of infection.” So what is the place of this drug in clinical management, and how does this trial help us make decisions with women who are dying of end stage breast cancer? No idea. Expect much more of this kind of thing now that the 21st Century Cures Act has been passed in the US and the Saatchi Bill is being relaunched in the UK. Palbociclib is not a cure. It isn’t low hanging fruit. It is unripe fruit. And if you eat unripe fruit, you get stomach pains and diarrhoea. If you use unripe drugs, you harm people and give yourself brain pains and logorrhoea. more…

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