Richard Lehman’s journal review—17 December 2012

Richard LehmanJAMA   12 Dec 2012  Vol 308
2349   The run-up to Christmas never finds me in the best of moods, and now it seems that the editor of JAMA is trying to wind me up by showcasing all my pet hates. Well, some of them anyway: to showcase them all would require a space the size of the South Kensington Natural History Museum. “Chronic kidney disease” as a prognostic marker—again—would you believe it! And in this study the comparator is an estimated glomerular filtration rate of 80—would you believe it? They factor in albuminuria too, and conclude that “both low eGFR and high albuminuria were independently associated with mortality and end stage renal disease regardless of age across a wide range of populations.” Well I never: bad kidneys get worse more often than good kidneys, CKD is a weak surrogate for poor vascular health, and eGFR and albuminuria are weak prognostic markers among hundreds of others: how fascinating. Let’s go measuring them in everybody and then treat the surrogate markers. Bah, humbug!

2369   How is the mighty sea-god insulted! POSEIDON stands for A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction. If I were Poseidon, I would rise up from the ocean and impale the authors of this study with my trident for their acronym alone. I would mount upon my hippocampus (meaning a horse with a finny tail) and cause sea-monsters to devour them because they don’t describe any patient-important end-points in their study. I would raise storms to destroy their ships because they use the silly term “ischaemic cardiomyopathy” to describe local damage and fibrosis caused by myocardial infarction. And I would send serpents to bite the editors of JAMA for publishing yet another study of stem cell treatment for heart failure that is of minor technical interest only: autologous cells gave slightly better physiological outcomes and graft success than allogeneic cells, but the patients involved cannot have noticed any difference. Wake me up when there is a stem cell treatment that helps people with heart failure in real life: I have read enough of these little short-term studies over the last ten years. Know that I am Poseidon and I shall smite you.

2380   And here’s another trial of bone marrow mononuclear cells to repair myocardium: this time they were autologous cells given either 3 or 7 days after acute myocardial infarction via coronary arteries. Again, no patient-detectable end points were measured: the primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging. “Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo.” So away with you! Know that I am Poseidon and I shall smite you!

NEJM  13 Dec 2012  Vol 367
2275   People with heart failure can die in three ways: (1) suddenly without warning, (2) by slow drowning, or (3) from something else. If I had heart failure, I would particularly want to avoid the second option, but implantable cardioverter defibrillators are specifically designed to move you from option one to option two. Whether to have an ICD is a very difficult decision to share with patients, because it means taking them to horrible places they can scarcely imagine. As doctors we have seen lots of people die from pulmonary oedema: would you want to show a patient a video of that? Or of someone undergoing repeated electric shocks from an implantable device? I know there are several centres developing shared decision aids for ICD placement, and I’ll be interested to see what they come up with. There is a glimmer of reassurance from the trial described here, which shows a better way to programme these devices: “Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up.”

2284   We are being encouraged to cherish our British pharmaceutical companies and see them as the wealth producers of the future for UK plc. And personally I would rejoice if GlaxoSmithKline were to produce an effective malaria vaccine and price it in such a way that malaria could quickly become a disease of history. If some of that money flowed back into Britain and paid for the NHS, so much the better. I would also rejoice if GSK were to identify the personnel responsible for the criminal fraud it has admitted to in the recent $3bn+ US settlement, and ensure they are brought to justice: and also if it were to deliver substantively on its promises to release full data from all its human trials. But none of this seems likely to happen any time soon. The GSK malaria vaccine described here only succeeded in preventing 26% of severe malaria in African children, despite being highly effective at producing anti-circumsporozoite antibodies. This particular route seems to miss the destination by 74%—and what’s worse, it seems unlikely to take us any further.

2296   The other big idea of Mr Cameron and his advisers is that the NHS can be used to create wealth through the early adoption of new, British-made innovations. I don’t know if any British firms are involved in the ultrafiltration business, but perhaps they should get in there while device regulation remains nearly non-existent. In the USA, Gambro sell something called Aquadex System 100 (CHF Solutions) specifically for use in fluid overload, which is supposed to be the answer when diuretic therapy appears to fail. The National Heart, Lung, and Blood Institute in the USA tested this claim in a trial involving 188 patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion who were randomised to ultrafiltration or stepped pharmacologic treatment (i.e. more diuretics). The diuretics worked better and had fewer adverse effects. So will all the hospitals that bought these devices now throw them away? It would be interesting to find out in a year’s time. And do the sales that Gambro achieved in the USA count as national wealth creation?

Lancet  15 Dec 2012  Vol 380
It is the season of goodwill, so I shall praise the Lancet and quote Richard Horton at length. “Publication of the Global Burden of Disease Study 2010 (GBD 2010) is a landmark event for this journal and, we hope, for health. The collaboration of 486 scientists from 302 institutions in 50 countries has produced an important contribution to our understanding of present and future health priorities for countries and the global community.” I agree. Might Elsevier do their little bit though, and remove the paywall in time for Christmas?

“What are the headline findings? First, although 52•8 million deaths occurred in 2010 (in 1990, the figure was 46•5 million deaths), great progress is being made in population health. Life expectancies for men and women are increasing. A greater proportion of deaths are taking place among people older than 70 years. The burdens of HIV and malaria are falling. Far fewer children younger than 5 years are dying. Infectious diseases are increasingly being controlled. In some parts of the world, there has been substantial progress in preventing premature deaths from heart disease and cancer.
But this hopeful picture is being challenged by old and new threats. Huge gaps remain in progress for some regions of the world. Tuberculosis and malaria are estimated to have killed around 1•2 million people each in 2010. 8 million people died from cancer in 2010, over a third more deaths than 20 years ago. One in four deaths was from heart disease or stroke. 1•3 million deaths were due to diabetes. Deaths from road traffic injuries increased by almost half. Blood pressure is the biggest global risk factor for disease, followed by tobacco, alcohol, and poor diet. And young adults are emerging as a new and neglected priority in global health: GBD 2010 finds that young adults, especially men, are dying in far higher numbers than previously appreciated. But the most afflicted continent remains Africa. Here, maternal, newborn, and child mortality, along with a broad array of vaccine-preventable and other communicable diseases, remain urgent concerns.”

All great stuff. Though I don’t understand the bit about alcohol, a potent protector against cardiac disease. So pull open that bottle of malt whisky, give the fire a prod, and slump back and pore over the charts and tables in this fascinating issue of the Lancet. Assuming, of course, that you are a subscriber as well as an imbiber.

BMJ   15 Dec 2012  Vol 345
The BMJ kicks off rather oddly with a Danish editorial on allergic reactions caused by methylisothiazolinone. This is a preservative widely used in paint and cosmetics and it causes allergic skin reactions which look like photosensitivity because they occur only on exposed parts of the body such as the neck, arms and face. I saw a woman with just such a rash a week ago and I hadn’t a clue what was going on. I think everyone needs to be aware of this potential problem – and may wish to see this chemical banned from all consumer and occupational products, as the editorialists do.

It’s odd how long it has taken our profession to realize that if you need a vaginal swab, it is perfectly OK to give the patient the means to do it and let her hand it back to you. The interesting thing about the two studies here—one on chlamydia and the other on gonorrhoea—is that self-taken swabs actually have a higher diagnostic yield than endocervical swabs taken by a health professional.

“Magic bullets with a hefty price tag” is an article mainly about monoclonal antibodies and why they are so phenomenally expensive. The author is from Tufts University, Boston, Mass. and he predicts that by 2014 these “biologicals” will account for 30% of the branded prescription market in the USA, at $166bn. The cost of a year’s monoclonal antibody treatment for paroxysmal nocturnal haemoglobinuria is currently over $400,000 per year. He is keen to protect the manufacturers from any accusations of profiteering and never drops any hint that there could possibly be a different business model for developing and marketing these drugs. I think it’s time that healthcare payers in all developed countries got real about the future, and joined together to set up a different way of doing things. To my mind, it can only lie in collaborative global not-for-profit development of targeted treatments: otherwise all medical innovation is going to become unaffordable, and absolutely unavailable to those who most need it.

Speaking of being unavailable to those who most need it, I am going to have another nag about the BMJ’s Clinical Review series. My complaint is that it has become the best and most practical guide to clinical practice regularly featured by any medical journal; it’s ideal for an international readership and exactly the kind of learning and teaching material required in the developing world. This week’s diagnosis and management of supraventricular tachycardia is an excellent example. But in countries where the HINARI agreement doesn’t hold, few practitioners will be able to benefit from it, and where HINARI does apply, they will need to go through a cumbersome procedure via an academic centre. Open access must come, even if not in time for Christmas.

Arch Intern Med  10 Dec 2012  Vol 172
1707   If eating before having a blood test for lipid levels made much difference, you would expect there to be an overall increase in levels according to the time of the last meal. This cross-sectional study from Canada could detect no such difference in samples from 200,000 individuals whose samples were taken in the community. One more piece of evidence that we should give up advising patients to fast before measuring their cholesterol, and let them have their blood taken at a time to suit them.

Plant of the Week: Schoenoplectus lacustris

I have been looking around the winter landscape over the last week, trying to spot the plant that looks best in frost and fog. My current favourite is the bulrush, appearing out of misty roadside ditches as one approaches, tall and white with rime, its bulbous frost-covered tips trying to catch a hint of the sun that shines above the morning fog.

The British bulrush is quite a distant relative of the bulrush that features in everybody’s favourite Bible story. Remember those picture books, and the sweet concern in the eyes of the pharaoh’s daughter as she pushes aside the flags to discover Baby Moses, with her maidens in attendance. The kind of bulrush that formed the basket that Moses was floating in was probably Cyperus papyrus, a sedge of the Nile that never sees frost.