Richard Lehman’s journal review—4 March 2013

Richard LehmanJAMA  27 Feb 2013  Vol 781
781    Heart failure divides into two broad classes: the first is caused by damage to the myocardium and is associated with reduction in the left ventricular ejection fraction, and we know pretty well how to treat it; the second is associated with stiffening of the ventricles and the main capacitance vessels, and we don’t know how to treat it, or even what to call it. It is often called “diastolic HF” but this term should really be reserved for the subset who have demonstrable reduction in diastolic filling. And as we fuss over these imaging-based definitions we lose sight of the patient as a whole, who is typically elderly and hypertensive with other comorbidities and taking a variety of pre-existing medication. That’s not to say we shouldn’t try to apply some science to improving their treatment, and this German-Austrian trial was inspired by the theoretical possibility that aldosterone blockade would reverse some of the effects of diastolic dysfunction. And it did. But unfortunately the patients could not notice any difference between spironolactone 25mg and placebo, because what little benefit the former had was purely on LV remodelling and BNP levels. Their diastolic filling indices actually dropped and so (non-significantly) did their walking distance.

792    We tolerate a lot of rubbish in medicine, and it is time that patients took over running the show. The hierarchy of medicine is based on distance from the patient, in the same way that 5,000 years ago, the high priest at the top of the ziggurat was more important than the low priest who helped people at the bottom. About twenty years ago, today’s top ziggurats started calling themselves “centres of excellence,” and we duly bowed and worshipped and made pilgrimages. In the USA, Medicare decided to restrict payment for certain procedures to these centres of excellence, including bariatric surgery. But this outcomes study shows that it makes not a bit of difference whether you have your obesity surgery at an “excellent” ziggurat or an ordinary one. Volume and status do not equate to quality.

814    Busy clinicians take all sorts of short cuts that we don’t really like talking about. We console ourselves that somewhere beavering in the background are academics who generate new evidence and sift the existing evidence and turn it into something called evidence-based medicine. We think  we can learn about this from reading the odd article and following the latest guideline, but the awful truth is that EBM is full of short cuts and biases too. Interventional trials are generally only done to sell things, whether they be drugs, devices, or concepts: and systematic reviews just top-slice the most methodologically rigorous of these trials and perform a statistical analysis of the results. All this can be a far cry from helping patients make choices at the times when it really matters. So when you see an article called “Reporting of Patient-Reported Outcomes in Randomized Trials: The CONSORT PRO Extension” don’t flick quickly by and leave it all to the dweebs: this is an important step forward from evidence-based medicine to patient-based medicine.

NEJM  28 Feb 2013  Vol 368
785    The most interesting content in this week’s New England Journal consists of four Perspective articles about Open Access publishing, and you can read them all for free. But is it worth your time and bother? On the whole, yes. Ann Wolpert begins by listing the five stakeholder communities which have dominated medical publishing over the past 60 years: “In the simplest terms: funding agencies and foundations provide funds to conduct research; universities and other research organisations host the intellects who conduct the research, maintain the research facilities, and educate and train future researchers; authors, with no expectation of monetary compensation, write research articles describing their research findings; publishers accept contributed research papers on condition of copyright transfer, facilitate the editorial process, and manage the production and distribution processes needed for disseminating the articles; and libraries use institutional funds to purchase, organise, and preserve this publisher output and make it available for current and future research and teaching. In a system this interdependent, destabilisation at any one point perturbs critically important relationships.” But where is elephant number six—Big Pharma, the bull who dominates the herd? Shush. This is the NEJM, which gets a large amount of its revenue from the sale of advertising space and reprints to Big Pharma. If you mention his name out loud he can get very angry and stamp on the ground before charging at you, tusks first.

787   So, argues the next author, let’s keep to the status quo and avoid mention of the moody elephant whose name cannot be mentioned. Martin Frank PhD points out that the so-called “open access” journals base their business model on payment by authors, or rather by their institutions or grant-awarding bodies in most cases, typically to the tune of £2-3000 per research article. He does not specify the business model of existing journals, but leaves the reader to assume that subscribers pay most of it. In a nicely disingenuous last paragraph he states: “Open-access publishing has evolved over the past dozen years. Although publishers and authors are increasingly embracing the model, there remains concern about efforts by funding agencies and institutions to mandate use of gold open access. At a time of limited resources, should we be diverting funds from research in order to fund open-access publishing? Personally, I think not.”

789   Now if you are consulting with a patient and want to look something up, where do you go? Do you look it up on PubMed under “reviews” and “human?” Or do you make your excuses and go to a library and pull out a big textbook and consult the index? No, dear readers, you Google up Wikipedia and share the article with the patient in real time. Wikipedia works by a system of Creative Commons licensing and is populated by voluntary contributors and editors. It lacks a watertight system of quality control but in real life it is the most important source of medical knowledge. So we must help it to become the best. This article is a helpful guide to the issue of Creative Commons for those who want to know more.

791   And now finally an article which mentions Big Pharma, but only as an elephant which poos on the territory of a competitor: “Many observers were … disturbed when the journal publisher Elsevier admitted in 2009 that it had published six ‘fake journals’ funded by pharmaceutical companies—in Elsevier’s own words, ‘sponsored article compilation publications . . . that were made to look like journals and lacked the proper disclosures.’ The company had intentionally exploited the word ‘journal’ to give the impression that these publications were honest and reliable.” Gosh, how very very stinky. Not like basing what you publish on the amount of reprint money it might bring in from Big Pharma. Shush! I think I can hear a big elephant stamping in the distance. This article does all it can to discredit the idea of open access publishing, as a form of corrupt vanity publication. The take home message? Let’s stick with subscriber based paper publications and their higher moral standards.

Lancet  2 Mar 2013  Vol 381
727   Nice observational science to inform policy: a registry based cohort study to compare outcomes from donor kidneys explanted from brain dead donors or from donors who died from circulatory failure. “Kidneys from older circulatory death donors have equivalent graft survival to kidneys from brain death donors in the same age group, and are acceptable for transplantation. However, circulatory death donor kidneys tolerate cold storage less well than do brain death donor kidneys and this finding should be considered when developing organ allocation policy.”

735    But Elsevier journals like to publish a different kind of study too, and here is the conclusion of this pharma-funded trial of a new first-line treatment for HIV: “The non-inferior efficacy and similar safety profile of dolutegravir compared with raltegravir means that if approved, combination treatment with once daily dolutegravir and fixed dose nucleoside reverse transcriptase inhibitors would be an effective new option for treatment of HIV-1 in treatment-naive patients.” Ooh, you wouldn’t want to deny patients the benefit of this me-too drug, would you dear approval agencies, seeing as how The Lancet is begging you to?

752   I approached this review of frailty in older people with a certain amount of foreboding, since the term is vague and authors in The Lancet tend to prefer the ivory tower to the unfragrant passageways of sheltered accommodation and nursing homes. But this outstanding summary is very useful reading for both clinicians and researchers. Many old people do not become frail, but an awful lot do, and they now crowd our hospitals to the extent that “general (or internal) medicine” and “geriatrics” have come to mean much the same thing. “Frailty is a state of increased vulnerability to poor resolution of homoeostasis after a stressor event, which increases the risk of adverse outcomes, including falls, delirium, and disability.” This article ties up cognitive decline with a general decline in neuroendocrine control via the hippocampus, and a tendency to negative energy balance. There are many frailty scores which are little used in clinical practice, but whether by scoring or by instinct, frailty in an important thing to recognise. “Distinction of frail elderly people from those who are not frail should therefore be an essential part of assessment in any healthcare encounter that might result in an invasive procedure or potentially harmful medication. It allows practitioners to weigh up benefits and risks, and for patients to make properly informed choices.”

BMJ  2 Mar 2013  Vol 346
First there was television, then there was telemedicine, and now there is telehealth. The first of these has a distinct meaning, but the other two don’t, and they deserve to return to the linguistic rubbish heap from which they came. “Telehealth” is a Greek-Germanic coinage which can mean anything that involves remote monitoring and advice to patients. The Whole System Demonstrator was designed as a great advertisement for cutting edge British technology in telehealth, ushering in a new era of care for patients with diabetes, COPD, and heart failure. Its success was assumed and proclaimed in ministerial speeches.  It is central to the remit of the new Academic Health Sciences Networks, which divide England into 13 regions competing to bring the latest technology to bear on patient care in the NHS. Telehealth will be a launch pad for selling great British products for the good of UK plc. Actually this is rubbish. This paper shows that the Whole System Demonstrator form of telehealth does not provide better outcomes than usual care. I guess it will take some time for the ministers and the industries that they backed to change their rhetoric, still longer for them to realise that there is no simple, labour-saving answer to the care of long-term chronic conditions.

I don’t think the balance sheet of the great H1N1 influenza pandemic has yet been drawn up, but compared with normal seasonal influenza there seems to have been a massive reduction in deaths in the older population to set against a distressing number of deaths among children and pregnant women. In developed countries, billions of dollars were spent on antiviral drugs and on immunisation programmes, though we are still uncertain whether the drugs had any benefits at all and we are beginning to recognise the possible harms of immunisation. This British study is the latest to show an association between vaccination in childhood or adolescence with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine (Pandemrix) and the subsequent development of narcolepsy. The odds ratio of 10 strongly suggests causality.

JAMA Intern Med  25 Feb 2013  Vol 173
258   Few drugs have been in longer use than aspirin, yet we are still finding out what it does to us. To be fair, the widespread use of long-term, low-dose aspirin is a relatively recent phenomenon, so some of this ignorance is understandable; but it still makes one wonder what we have yet to discover about other agents which we now hand out for years to millions of people. This study brings unwelcome confirmation that regular use of aspirin really does more than double the rate of macular degeneration, even controlling for smoking and vascular disease.

Plant of the Week: Prunus subhirtella “Autumnalis”

Cherry blossom means spring. Birds chirp and bulbs flower, shoots burst forth on shrubs and trees, and the soil heaves with hidden glories to come. Not that this has really yet happened in England, but there are foretastes of it, and this small tree offers the best and the earliest.

It is a simple sort of cherry, which just happens to produce its abundant small pink or white flowers a good time before all the others. In a forward year (not this one) the sight of it helps to get one through the dismal, unwanted four weeks of February. March is also a bit pointless, but at least it marks the end of true seasonal affective misery.

We’ve had two tries at growing this excellent plant, both ending in death from bacterial canker. Not our fault, but if you live near dying cherry trees, yours is likely to go the same way. There is no treating or preventing it: you just have to go off elsewhere and admire other people’s trees.