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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—18 May 2015

18 May, 15 | by BMJ

richard_lehmanNEJM 14 May 2015 Vol 372
1887 Something strange seems to be going on in the New England Journal of Medicine. This week it publishes two trials of gene therapy for Leber’s congenital amaurosis, one at the start and the other at the end of its research section. Neither of them achieved more than fleeting benefit in one genetic variety of an uncommon form of blindness, which can be caused by mutations of at least 19 different genes. It takes a long editorial to explain to generalist readers what this is all about and why it may never work. I am all for publishing negative results, but I’m not sure most of us really needed to know this right now. more…

Richard Lehman’s journal review—11 May 2015

11 May, 15 | by BMJ

richard_lehmanNEJM 7 May 2015 Vol 372
1860 This week the NEJM is offering everyone a free lunch, in the form of an open access article and editorial on the theme of “Re-interpreting Industry-Physician Relationships.” But as everyone knows, there is no such thing as a free lunch, especially when it comes to relationships between doctors and the pharmaceutical industry. So what is going on? The key lies in the word “re-interpreting.” Using two straw-man examples and one real one (Vioxx), Lisa Rosenbaum, a national correspondent for the journal, seeks to show that too many people are cognitively biased towards an “Ugly House” interpretation of the pharmaceutical industry. She intends to develop this theme in two further essays, warmly commended to our attention by her editor Jeff Drazen. The only conflicts of interest they declare are their ties to the NEJM. But that is a pretty massive conflict, isn’t it? How much of the NEJM‘s income comes from reprint sales to the pharmaceutical industry? Sorry, I didn’t catch that… commercial confidentiality?—ah, I see. more…

Richard Lehman’s weekly journal review—5 May 2015

5 May, 15 | by BMJ

richard_lehmanNEJM 30 April 2015 Vol 372
1684 “Virtual Visits—Confronting the Challenges of Telemedicine” is a Perspective piece which starts full of optimism about the potential of telemedicine and then switches tack half way through. “For providers, using telemedicine may be more efficient than seeing patients in brick-and-mortar offices, since it reduces the time and space needed to run a medical practice. For patients, telemedicine can reduce travel expenses and the opportunity costs associated with obtaining care, such as missed hours or days of work.” Actually, that sounds unlikely on first principles. Could telemedicine really save on time and office space? Won’t the great majority of medicine always have to be a direct human interaction? What proportion of illnesses actually lend themselves to remote consultations and how many ill people would rather use a device than see a doctor face to face? Sure enough, when trials have been done—even in convenient chronic conditions with e-savvy populations—they have failed to show any improvements in outcomes and have usually increased service use and costs. Telemedicine may seem like the shiny future, but in reality it is a return to the Middle Ages. Those who could afford a physician would get examined by his clerk, who would take the history, measure the pulse, examine the urine, and report to his gowned master. The physician himself was far too important to actually touch a patient. more…

Richard Lehman’s weekly journal review—27 April 2015

27 Apr, 15 | by BMJ

richard_lehmanNEJM 23 Apr 2015 Vol 372
Last week, dear friends, we kicked off with alirocumab and evolocumab. This week it’s the turn of nivolumab, ipilimumab, and pembrolizumab. It’s driving me mab. Whoumab canumab possiblyumab remememberumab whatumab theseumab drugumabs actuallyumab doumab? When monoclonal antibodies started to be marketed as therapeutic agents, wise and distinguished men (with no doubt a few women in their midst) decided to impose a system of nomenclature on the new drugs.


Richard Lehman’s journal review—20 April 2015

20 Apr, 15 | by BMJ

richard_lehmanNEJM 16 April 2015 Vol 372
1489 Your learning task this week is to memorise “proprotein convertase subtilisin–kexin type 9 (PCSK9).” The next big lipid lowering debate will be all about inhibitors of PCSK9, and somebody should urgently invent a popular name for them. I suggest fatins (fat lowering injections), to rhyme with statins. There are two of them at the moment: alirocumab and evolocumab. In this trial, alirocumab was given as an injection every two weeks to two thirds of 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 1.8 mmol per litre or more and were receiving treatment with statins at the maximum tolerated dose. The rest had a placebo injection. “At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was −62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks.” The trial was not powered to detect a fall in actual cardiovascular events over this period, but as its name ODYSSEY LONG TERM implies, it means to go on:
To strive, to seek, to find, and not to yield. (Last line of Ulysses by Tennyson) more…

Richard Lehman’s journal review—13 April 2015

13 Apr, 15 | by BMJ

richard_lehmanNEJM 9 Apr 2015 Vol 372
1389 The major trials of coronary artery thrombus aspiration for myocardial infarction are TAPAS, TASTE, and TOTAL. Think of a bar crawl in Seville. The TAPAS and TASTE are obvious, and TOTAL could refer to the bill, which is sometimes just chalked on the surface you’re leaning on, or to your state of inebriation after eight glasses of fino sherry. Either way, these bars are more interesting than this procedure, which is now ready for burial as a routine intervention for MI. Both TASTE and TOTAL find that it does not improve cardiac outcomes and TOTAL finds an increase in stroke. The accompanying editorial thinks it may yet prove of benefit to high-risk patients, citing observational follow-up and post-hoc subgroup analysis. Maybe one further trial needed in such patients before saying ADIOS to the bartender. But why does cardiology come up with so many failed hopes? It seems so obvious that sucking out a clot as soon as it has blocked a coronary artery will be of benefit, but it just isn’t. Even procedures we believe in, like timely percutaneous intervention for MI, aren’t having the impact we hoped for. The editorial also points out that, “Although door-to-balloon times have improved significantly over the past 10 years, in-hospital mortality for STEMI has remained virtually unchanged.” more…

Richard Lehman’s journal review—7 April 2015

7 Apr, 15 | by BMJ

richard_lehmanNEJM 2 April 2015 Vol 372

372 In English nursery rhyme, it is traditional for a Duke to have 10 000 men. Here is a trial from Duke University that recruited 10 000 men and women, and allowed in a further three for extra measure. These 10 003 recruits were those “whose physicians believed that nonurgent, noninvasive cardiovascular testing was necessary for the evaluation of suspected coronary artery disease.” That is a fate which befalls a staggering four million Americans every year. These people were randomised to be investigated either by coronary computed tomographic angiography or functional testing, which in almost every case meant exercise ECG. I struggled a little with some of the figures, but I broadly agree with the conclusion: “In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of two years.” But I do just wonder how many of these people really “required” testing in the first place. more…

Richard Lehman’s journal review—30 March 2015

30 Mar, 15 | by BMJ

richard_lehmanNEJM 26 Mar 2015 Vol 372
1193 Is the NEJM preaching Socialism? “We believe that all financial incentives and logistic barriers to providing the least expensive drug, among drugs equivalent in safety and efficacy, should be eliminated so that patients may benefit fully from the results of this Diabetic Retinopathy Clinical Research Network trial as well as those from other comparative trials.” more…

Richard Lehman’s journal review—23 March 2015

23 Mar, 15 | by BMJ

richard_lehmanNEJM 19 Mar 2015 Vol 372
1093 “All bacteria will be susceptible to common cheap antibiotics by 2050″ is not a headline you will see in any newspaper. But I’d like you to think seriously whether this is not more likely than the widely-touted doomsday scenario of a post-antibiotic era in which we are all endangered by untreatable bacterial infections. Very few bacteria are pathogenic to humans, and those which are simply adapt to the environments we create for them. Staphylococcus aureus quickly became resistant to penicillin after it was widely introduced into hospitals and the community in the 1950s. Then in 1959 Beecham marketed meticillin as a beta-lactam antibiotic to deal with penicillinase-producing strains of S aureus. Its replacement, flucloxacillin, remains active against most staphylococcal infections in the UK, but not in the USA, where skin and tissue infections are now most commonly caused by meticillin-resistant staphylococci (MRSA). But this study shows that these infections respond well to treatment with either clindamycin or trimethoprim-sulfamethoxazole (co-trimoxazole) and that there is nothing to choose between these two cheap old antibiotics in terms of efficacy or safety.


Richard Lehman’s journal review—16 March 2015

16 Mar, 15 | by BMJ

richard_lehmanNEJM 12 March 2015 Vol 372
1009 Stroke is a wonderfully straightforward word. When used in a medical context, everybody thinks of a sudden blow. It is something that needs swift action. But actually “stroke” isn’t a straightforward word: ask the cat that has just jumped on to my lap. Now it means a slow and pleasurable process in which she purrs while I pass my hand along her back. That’s the problem with words with deep Indo-European roots: the *streig root is well preserved in several languages, but over thousands of years it has come to mean almost opposite things. And brain strokes can vary between anything from a hammer stroke, which obliterates life, to a brush stroke, which causes some local weakness for a few days. The problem lies between the two ends, and in the need for investigations and treatment to be done at great speed. Two trials of endovascular therapy for ischaemic stroke with perfusion imaging selection in this week’s NEJM present a major advance in stroke treatment, but also illustrate these difficulties. The interventions compared in the first trial (mainly Australian and publicly funded) were intravenous alteplase within 4.5 hours with or without endovascular thrombectomy using the Solitaire FR (Flow Restoration) stent retriever. The patient groups had a mean age of 68 and 70 (the groups were not perfectly matched), and had occlusion of the internal carotid or middle cerebral artery, and evidence of salvageable brain tissue and ischaemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The trial was stopped prematurely because the thrombectomy group showed markedly better neurological improvement at three days and 90 days. more…

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