Richard Lehman’s journal review—16 July 2012

Richard LehmanArch Intern Med  9 July 2012  Vol 172
988   The moors around Sheffield which I used to frequent in my youth remained much the same as in 1813, when John Farey made his list of the “noxious and useless plants” to be found in the Peak District. “The following are a few Memorandums that I made on the Herbage of these disgusting Moor Lands…  Cranberry (vaccinium oxycoccus) grows and ripens its Berries, which the Poor gather, in some of the moister parts of the Moors.” The Poor of my time would boil the gathered berries with sugar to make a sauce which they bottled up to serve with turkey, hoping that the bitter-sweet paste might enliven the interminable carnivorous monotony of the Christmas Feast. Few in those days considered making a drink out of cranberry juice, though perhaps this was a Derbyshire folk custom I never had the occasion to encounter, being then of sound urinary parts. Here, a largely Korean systematic review claims that cranberry juice has long been used to prevent urinary infection, and the authors find that on the randomized trials on the whole indicate that such claims may be true, especially if you are female and drink a lot of it.

992  Two trials in the last decade have stopped cardiovascular medicine in its tracks: AFFIRM and COURAGE. In both cases, a widespread presumption about the superiority of more invasive treatment was proved wrong in a large randomized trial. AFFIRM in 2002 showed that rhythm control is not superior to rate control in atrial fibrillation, and this was later confirmed in the heart failure population (AF-CHF). But some cardiologists have been reluctant to abandon their gut feeling that rhythm control must be intrinsically superior; and this Canadian population study will give them a glimmer of support. There is a tiny difference in favour of rhythm control in observed survival at 9 years; nothing significant at 4 years. Informed patient choice should guide treatment here, as in all areas where there is virtual equipoise.

1005   Most oral drugs for type 2 diabetes lower sugar by about the same amount: so does that mean they all have similar effects on end-points? Oddly enough, even very intelligent diabetologists often act on the assumption that they do. Trying to explain choices to patients, they rely on aggregated data showing that for such and such a lowering of HbA1c you will get such and such a lowering of, say, heart attacks or blindness. But convenient though this approach may be, it simply won’t do: everything depends on the agents you use to lower sugar, and we know far too little about them. GlaxoSmithKline has just been fined a billion dollars for concealing data about the cardiovascular risks of its thiazolidinedione drug rosiglitazone (Avandia), and another billion apiece for two unrelated drugs. But you could still argue—from very unconvincing aggregated data—that for patients wishing to avoid eye damage, there might still be a case for using any drug which lowers glucose. This study shows that is not true: both thiazolidinediones (pioglitazone as well as rosiglitazone) are associated with an increased risk of macular oedema in this study using the British primary care THIN database. Both harms and benefits in the treatment of type 2 diabetes are class and agent-specific.

1014   So what’s to be done if your diabetic patient does get macular oedema? The standard approach is to use laser photocoagulation around the macula, but this is not uniformly successful, so it’s good news that evidence has begun to accumulate demonstrating the effectiveness of injectable intravitreal drugs that inhibit vascular endothelial growth factor (VEGF). None of these has yet been licensed for this indication by the FDA, but there have been 15 randomized trials showing that they are uniformly more effective than conventional laser treatment, with little evidence of local or systemic harm. Bevacizumab is the one that can be used much more cheaply than the rest ($50 rather than $1-2K per dose) so it’s high time that it became part of the standard treatment schedule.

JAMA  11 July 2012  Vol 308
Last week, I expressed the hope that JAMA Boring might progress to JAMA Slightly Interesting, but this has not happened. Instead, it has turned into JAMA Negative, no doubt for the worthiest of reasons:

147   Effect of Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid or Gemcitabine vs Observation on Survival in Patients With Resected Periampullary Adenocarcinoma: The ESPAC-3 Periampullary Cancer Randomized Trial. Result: no meaningful effect on this uncommon kind of pancreatic cancer.

157   Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting: The RED-CABG Randomized Controlled Trial. Red Cabbage! That is so funny. Result: acadesine had no effect.

165   Risk of Adverse Fetal Outcomes Following Administration of a Pandemic Influenza A(H1N1) Vaccine During Pregnancy. Result: in a Danish cohort, this vaccine did not increase adverse fetal outcomes.

175   Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec. Result: The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

NEJM  12 July 2012  Vol 367
97   To assist a dying patient to die at a time and place of their choosing could be considered a natural part of the role of a doctor. But in most parts of the USA, as in the UK, it is illegal, and many doctors would like it to remain that way. In this open-access Perspective piece, the authors consider the evidence and point out that the legislation enacted in Oregon has not led to a flood of requests or any hint of coercion of the vulnerable. If doctors don’t want to provide dying patients with the means to kill themselves painlessly, others could, with the same rigorous safeguards. Readers who are interested in this issue should also read Sam Ahmedzai’s letter in the current BMJ, and a paper examining the experience of the Netherlands which has just appeared on the Lancet website. The refreshing thing about reading contributions from abroad is that they assume that their legislatures are competent to protect the vulnerable, unlike the dames and bishops who issue solemn warnings here in Britain.

107    The research section of the NEJM offers thin pickings this week. GlaxoSmithKline has produced a new orally available treatment called trametinib for advanced melanoma, which works by a novel pathway and extends survival by about 3 months compared with conventional chemotherapy in this open-label phase 3 trial in BRAF mutation carriers. I guess that this is newsworthy because it proves that inhibition of the MEK proteins can cause tumour regression in this and other BRAF-mutation carrying cancers. But like other drugs which modify the BRAF pathway, it can cause a range of cutaneous and other serious adverse effects; so it is not at all clear whether it will ever move to the forefront of treatment rather than remaining an experimental or last-ditch drug. If a GSK rep offers you a reprint, I would decline politely.

115    The search for a magic bullet in multiple sclerosis goes on. “We screened serum IgG from persons with multiple sclerosis to identify antibodies that are capable of binding to brain tissue and observed specific binding of IgG to glial cells in a subgroup of patients. Using a proteomic approach focusing on membrane proteins, we identified the ATP-sensitive inward rectifying potassium channel KIR4.1 as the target of the IgG antibodies. We used a multifaceted validation strategy to confirm KIR4.1 as a target of the autoantibody response in multiple sclerosis and to show its potential pathogenicity in vivo.” A nice example of focussed science, without immediate clinical implications. Don’t expect to be offered a reprint unless you have a friend in the German Ministry for Education and Research and Deutsche Forschungsgemeinschaft, who funded this study.

135   Graft-versus-host disease (GVD) is a common sequel of allogeneic haematopoietic stem-cell transplantation, so a very important problem for thousands of unlucky people facing treatment for cancers of the blood and marrow. Existing immune suppressant treatment can have severe long term effects and limited success. So full marks to Pfizer for spotting that the mode of action of its anti-HIV drug maraviroc makes it a candidate for preventing GVD. Maraviroc inhibits chemokine (C-C motif) receptor 5 (CCR5) and so prevents the migration of lymphocytes into tissues considered as “foreign”. This paper explains the science and describes its effect in a small number of patients at high risk of GVD. If you are a haematologist who treats such patients, and the Pfizer rep offers you a reprint, accept it with good grace; but don’t be tempted to use maraviroc off-label until some bigger, longer-term studies have been done.

Lancet  14 July 2012  Vol 380
While the New England Journal this week concentrates on the preliminary and the abstruse, The Lancet indulges in one of its pomp-and-glory issues about contraception and its global effects. In its sweetly anachronistic way, The Lancet refers to contraception as “Family Planning.” But the great social advance that came with universally available, reliable contraception was the dissociation of the enjoyment of sex from any thought of having a family. Of the two great therapeutic revolutions of the twentieth century, the antibiotic revolution may be seen as of less importance to the future of the planet than the contraceptive revolution. The next century will have to see the human population stabilise or risk mass extinction. But there: I am beginning to sound like something out of this week’s Lancet. If this sort of thing turns you on, there are enough editorials, modelling studies and special topic reviews for several rainy afternoons, provided you (and your dearest one, perhaps) have nothing better to do.

BMJ  14 July 2012  Vol 345
The UK Department of Health is charged with providing a National Health Service for the amount of money allocated to it by the Chancellor of the Exchequer. Earlier this year, a minister from the DoH announced that a study had shown that telemedicine could save the NHS £1.2 billion per annum. This is because patients would avoid the two highest-cost items in the NHS budget—doctors and hospitals. Ideally, the DoH would like to eliminate these altogether, but this may take time. Now telemedicine—or telehealth in the verbiage of this paper—can mean all kinds of things, and two recent US studies of using it intensively—in complex comorbid elderly patients and in COPD—showed no drop in hospital admissions and large increases in mortality. This DoH-funded Whole System Demonstrator study shows a small reduction in admissions and mortality in heart failure, diabetes and COPD. The Department got the positive answer it wanted; except that far from producing a saving of £1.2 billion, it is not at all clear that this kind of “telehealth” would yield any savings. There is only one way to save costs in these elderly comorbid populations: he comes not with a telemonitor, but dressed in a hood and carrying a sickle.

For those who like to compile a list of the benefits and harms of regular alcohol consumption, here’s an observational study from the Swedish Mammography cohort showing a halving in the observed rate of rheumatoid arthritis in women reporting drinking more than 3 glasses a week.

The diagnosis and management of tinea: here is a cracker of a clinical review, to delight someone like me whose idea of a good time is to pore endlessly over pictures of fungi. I have come to be regarded as a mushroom expert, but all that is required is a few books, a lot of time, a warped mind, and preferably a microscope. I probably should have become a dermatologist.

Fungus of the Week: Lepiota procera

The true parasol mushroom is unmistakable, with a flat expanded cap up to 25 cm across, buff-cream and covered in pale brown flecks, slightly lifted at the centre. It has a perfectly straight thin, elegant stem of darker brown, featuring a ring which can easily be freed to move up and down the stem. The only genus with this characteristic is Lepiota, and while some lepiotas with caps of 5cm and less are poisonous, they never approach the size or appearance of this handsome whopper. The only fungus it can be mistaken for is its cousin the shaggy parasol, which is a little darker and shaggier and also edible in principle, though it quite commonly causes mild diarrhoea. To be certain, simply pull the stem from the cap: if the exposed circle becomes orange, then you have a shaggy parasol, and you may want to take Imodium if you decide to eat it. With the true parasol, prophylaxis is never required.

The taste of the parasol is mild and somewhat nutty. It isn’t often that you stumble on these gentle giants, so I was highly delighted to bag a kilo somewhere near London a few weeks ago. I guess this is a bumper year for them, and that they are to be found all over the fields of England this July, provided you have the appropriate boots, woollies and rainwear.