Journal Watch - October 2011

JAMA 12 Oct 2011 Vol 306

1549 It has been a bad week for vitamin supplements. Worst hit, as usual, has been vitamin E. The SELECT trial began collecting 35 000+ healthy men with normal-feeling prostates back in 2001 and randomized them to get a selenium supplement, a vitamin E supplement, both, or placebo. Those given vitamin E had a "significantly increased" risk of prostate cancer - by a factor of 1.6 per thousand person-years. Even selenium seems to do a tiny bit more harm than good in this respect. Once again a properly conducted large RCT puts to bed a mass of anecdote, observational "evidence", bad little studies, and health supplement advertising.

1566 I've never quite understood how α-tocopherol managed to get the status of a vitamin with its own capital letter, whereas the truly vital amine folic acid is plonked somewhere with the other B vitamins and often forgotten about. Since the 1970s, we have become keenly aware of its role in early fetal neurodevelopment, especially the prevention of neural tube defects. This prospective observational study from Norway looks at nearly 40,000 children born to mothers who did or did not take folic acid supplements from 4 weeks before conception to 8 weeks after. Severe language delay at 3 years was twice as common in those who did not. The case for folic acid fortification of bread flour grows ever stronger.

1582 But that would be of little use to the one in a hundred mothers who has coeliac disease. I don't know if anyone has studied neurodevelopmental outcomes in children born to mothers who have subsequently been diagnosed with this common and variable condition. In this clinical review and case discussion, it is claimed that its prevalence has been steadily rising over the last 50 years. This is anything but the case: its estimated prevalence used to be one in 2-10,000; then along came serological testing in the 1990s, and it shot up to 1 in 100 and has stayed there since. It is also described as a disease which shortens life and causes osteoporosis: but again, this only applies to classical grossly symptomatic CD. Taking in the whole spectrum of antibody-positive disease, there is little evidence of harm to asymptomatic individuals. But it is still worth testing for in everyone with recurrent anaemia and/or tiredness-all-the-time: some people's lives are changed by treatment. Others just find it a bore and revert to eating gluten.

1593 Most pharmaceutical and medical device companies conduct human experiments (clinical trials) and then fail to publish the results of some of them at all, or publish them selectively. Through widespread ignorance, and occasional collusion, we have put up with this ethically outrageous situation for decades. "Evidence-based medicine" is often missing half the evidence; patients who gave consent to risk harm so that others might benefit are cheated. There have been occasional calls for open access to all trial data from industry but legislators and regulatory bodies have paid little attention, and until now nobody has come up with a working model for individual patient data to be analysed in a way that guarantees integrity and independence. But in the last 4 months, Harlan Krumholz at Yale has not only come up with the model but has also persuaded the largest medical device company, Medtronic, to support and fund two totally independent analyses of its data relating to a controversial bone product. I can't believe my luck in being involved with this benchmark project, which is outlined here by its originator and a close colleague. If any company present knoweth of any just cause or impediment why its human trial data should not be disclosed in this way, let it speak now, or forever hold its peace and deliver them up.

NEJM 13 Oct 2011 Vol 365

1376 Barrett's oesophagus is a classic example of a condition which has been talked up out of all proportion to its significance. It provides a comfortable living for an army of endoscopists and needless anxiety to countless thousands of individuals who live in daily fear of developing a nasty and usually lethal kind of cancer. In fact just 5,000 people a year die of oesophageal cancer in the USA, and the great majority of these have never had Barrett's oesophagus. It is true that this is six times the figure in 1975, but it is still a tiny risk. Multiply it by 11 and it is still small, and this is the figure arrived at for the added risk from having a diagnosis of Barrett's in this Danish whole-population database study. It agrees reasonably well with a previous Northern Ireland whole-population study. There is absolutely no evidence that regular upper GI endoscopy makes any difference. The all-cause mortality of people with and without Barrett's is identical. As I've said before, I do wish he had never invented his oesophagus.

1406 Influenza is a diagnosis we seldom make with confidence in children between six months and six years of age. It is usually a mild febrile illness which rarely needs specific treatment. This Finnish trial shows that by giving two shots of an influenza vaccine with oil-and-water adjuvant, you can effectively protect children from a selected range of influenza viruses, as shown by PCR testing. Following each dose, there is a 60+% chance of a mild febrile illness and a local reaction. So you would have to be jolly worried about your child getting flu to want them to have this vaccine.

1417 In this article about adult primary care following childhood acute lymphoblastic leukaemia, there are two striking figures. One displays survival improvement from 1975 (40ish %) to 2003 (90+%): it's a great teaching slide to illustrate incremental progress in therapeutics. The red line wiggles slowly upwards as treatment regimens are gradually refined. The other picture is of identical twins, one of who had treatment for ALL as a child. She is unrecognizable as a sister, let alone a twin: several inches shorter, with a moon face and obesity, as lasting legacies of prolonged steroid treatment and an irradiated pituitary. If you have such a survivor in your practice, it's worth having a look at this piece: though if you carried out every bit of "primary care" that it advises, you might have to cancel the rest of your appointments for a couple of days.

Lancet 15 Oct 2011 Vol 378

1388 Here is a fine example of a genre of Outcomes Research first suggested by Francis Clifton in 1732: the surgical case-series. Two neurosurgeons from Queen Square report on the outcomes of 649 consecutive operations performed for adult epilepsy since 1990. They managed to cure half their patients completely, and most of the rest appear to have benefited. Nice when you can flourish personal results like these in The Lancet, while seeking generalizable lessons on case-selection and surgical technique in adult epilepsy.

1396 As I try to put together a book on Outcomes Research in one of the world's leading centres of outcomes research, I am naturally keen to learn a bit about the subject. So far I have picked up some of the basics. You need data that are reliable. You need outcomes measures that are well defined and well documented. To link the two you need statisticians who understand the material. If you tried to use the software on your own you would go mad and produce garbage. You might anyway. Often you have to work with data that happen to be there, rather than the data you would like to have. These data are usually complex and so you have to think very hard about what variables matter, how they inter-relate, and what adjustments need to be made. Now this study of preoperative anaemia related to postoperative mortality and morbidity is fairly straightforward. The data come from American College of Surgeons' National Surgical Quality Improvement Program database, a prospective validated outcomes registry from 211 hospitals worldwide in 2008. Anaemia is defined by haematocrit, which is confusing to UK readers, but is perfectly logical. The post-op outcomes seem reasonably well ascertained. So we can be pretty sure about the bottom line: if you come to non-cardiac surgery with a low haematocrit, you tend to have worse 30-day outcomes. Even mild anaemia is important. But the key clinical questions that arise are not answered in this study: we don't have any information about the causes or duration of anaemia in this heterogeneous population, nor any information about any therapy given pre-operatively. Like all outcomes research, it suggests that a lot more outcomes research is needed.

BMJ 15 Oct 2011 Vol 343

The BMJ shows admirable impartiality in publishing this study comparing the speeds with which various medical updating sites actually update their material. The BMJ's own product, Clinical Evidence, is the slowest by a good margin. The paper is written in a translated-from-the-Italian style which is hard to follow; it acknowledges that its methods were essentially bibliometric and did not examine content in detail. So it is quite possible that Dynamed, which dashes to cite everything the moment it appears, may suffer by tending towards the opposite extreme. Given the quality of much of what we call evidence, sometimes slow adoption is a good thing.

Looking at the contributors to diabetes and lipid guidelines in the USA and Canada, the authors of this study find that half of them have conflicts of interest. This is amazing. Where did they find the half without conflicts of interest? This murky topic draws a superb editorial from Edwin Gale and commentary from Fiona Godlee. Something must be done about this: and slowly, I think, there are signs that it is going to be done. But even without conflicts of interest, guidelines will always err towards over-investigation and overtreatment. Try not to use them.

Arch Intern Med 10 Oct 2011 Vol 171

1625 In an already famous contribution to the Less Is More series, a miscellaneous group of authors analyse data from the Iowa Women's Health Study. In 1986, two-thirds of the cohort (mean age 62) were taking vitamin and/or mineral supplements; by 2004 (mean age 82) this had increased to 85%. There are striking differences between those who did and didn't in these ill-balanced groups: for example, those not taking supplements did twice as much exercise. So in interpreting the mortality differences cited in this study, bear in mind how much depends on the accuracy of its multivariable adjusted proportional hazards regression models. Still, I am quite content to believe that all this stuff does no properly nourished person any good, and unnecessary iron supplementation almost certainly does harm.

1655 "Two major factors associated with skeletal fracture in older persons are intrinsic bone strength and risk of falling." Hard to disagree with that. Now there are lots of risk-of-falling scores which we can look up but seldom use. This one requires just a stopwatch and a chair and it is called TUG, which stands for Timed Up and Go. Place your postmenopausal lady of advanced years in a chair and command her to get up and walk 3m and sit down again. This should take less than 10.2 seconds. Measure her hip bone density. Put the TUG score and the BMD together and you have a measure of non-vertebral fracture risk.

Fungus of the Week: Craterellus cornucopioides

Walking up Mount Tom in Rhode Island with my son Tom a week ago, I stopped to tie my bootlace, and he drew my attention to a little cluster of grey tubes emerging from the ground nearby. They were all but hidden in the leaf litter, and only by careful searching did we find a few more of these fabled trompettes des morts scattered in the vicinity. I could have stayed there all day, grubbing about like a hedgehog, but I sensed that this was not the young man's idea of a good time. We strode to the summit and admired the vistas of New England fall colors. The next day we did Mount Tom in neighbouring Massachussets: a formidable forest climb, but no more trompettes to be found. The next day it was the turn of Mount Tom in Connecticut: fabulous views, but again no trompettes.

Alas, there are only two ways to find this fungus: by happy accident, or by knowing where it grows. To some extent this applies to all fungi, but Craterellus is so well-camouflaged that you have almost to be on all fours to spot it. So far as I know, dogs and pigs have never been trained for this purpose, though these little grey funnels are the nearest thing in taste to an above-ground truffle.

If you have the good fortune to come across some, bake a sea-bass or grill a Dover sole in their honour. Tear the trompettes into small pieces and cook them briefly in melted butter with pieces of shallot. If flavour means more to you than appearance, now add some white wine and reduce briskly: then add thick cream and boil briefly. Pour this sauce on the white fish and sprinkle with finely chopped parsley and a little chive. If appearance is important, you could do the wine and cream reduction separately and add the black trompettes after pouring this white sauce over the fish. But you will pay for your black-on-white showmanship by losing some of the magical intensity of flavour they can impart to the cream: a poor exchange.

JAMA 5 Oct 2011 Vol 306

1461 American medicine is a mass of quirks and contradictions: like medicine anywhere else, but magnified by huge financial forces pulling in different directions. There is a big financial incentive for cardiologists to do percutaneous interventions in elderly patients with stable coronary disease, for example, though the evidence suggests that few of them need it. I don't know how Medicare handles that dilemma, but it willingly pays for these patients to spend a night in hospital following PCI. And I guess because the hospitals and the cardiologists get paid, nobody complains. But the fact is that most of these patients could perfectly well go home the same day, as confirmed by the small subgroup of patients who actually did in this Medicare patient study. Yet the incentives are all weighted towards them staying in unnecessarily, including the fear of litigation when something goes wrong, as always will happen. So American PCI patients are stuck with a night in hospital, whether they need it or not, and ours are stuck with going home the same day, whether they are fit to or not. I would love to see the day when health services really begin to learn from each other, but until that happens there is only one safe rule: never copy the USA.

1483 Now I shall immediately appear to break that rule by praising this Commentary piece which explains the idea of time-limited trials near the end of life. This has nothing to do with research trials, but rather practical trials of treatment to see if they make dying patients better. The key point is to have an explicit plan for stopping them if they don't. We all automatically do such trials of treatment in the hope of helping the dying in real life, I hope: the difference here is the clarity with the process is made explicit, and that is something America tends do better than Britain.

NEJM 6 Oct 2011 Vol 365

1273 The main papers in this week's NEJM give me déjà-vu like I can't remember. Will there ever be an end to trials of new chemo combinations for breast cancer and new drugs for relapsing multiple sclerosis with tantalizingly small benefits? I suspect that as long as I go on reviewing, I shall have to keep telling you about such things. Incremental advances in combination treatment have led to complete cures for certain types of cancer, but this trial does not get us any nearer to that in HER-2 positive early breast cancer. The title of the editorial, "Steady progress in HER-2 positive breast cancer" belies its message which is that trastuzumab-containing regimens do not improve on existing anthracycline-containing regimens. Anthracyclines can induce irreversible heart failure and some leukemias, while trastuzumab does not: but the final balance sheet of mortality is the same.

1293 What is the current best treatment for relapsing multiple sclerosis? If it is not placebo, then this trial was arguably unethical. Although I've read all the main MS trials over the last 13 years, I wouldn't be sure what to opt for if I had MS. I don't think I'd bother with teriflunomide on the basis of this pharma-funded trial. Hair loss: that I can live with (or I would be dead by now); diarrhoea and nausea: OK, I've lived with those from time to time, but I don't want to more than I have to. A 6% absolute reduction in disability over two years might result, which is a benefit I would never be aware of. Personally, I would say no.

This is a great teaching paper, to be used in conjunction with Know Your Chances by Woloshin, Schwarz and Welch. I've put myself in the position of the patient here and said no thanks. But real patients might want to make a variety of decisions, assuming that NICE approves the drug and your local consortium decides it can be afforded. The manufacturers, of course, herald this as a 30% reduction, whereas from the patient's point of view it is a reduction from a one quarter chance of progression to a one fifth chance in two years. The patient needs to know the detail and have time to mull it over. Discuss how the content of this paper would need to be processed to enable this decision. Would a trial to assess tolerability be a good first step?

Lancet 8 Oct 2011 Vol 378

Once again there are no clinical trials in this week's printed Lancet, and such studies as there are I have already told you about from the website. As some readers predicted, that makes it difficult for me to know when to talk about what. I could talk about the general decline of The Lancet,and Richard Horton's Offline page, which now exerts a horrible fascination, like the poetry in JAMA, or watching Fox News. But I do not want to advertise these deplorable aberrations. Let's turn to the one trial of interest to general practice on The Lancet 's website:

Nobody could describe The Lancet as the friend of British general practice, but when studies from UK primary care do make it into these supposedly august pages, they tend to be very good. This one is outstanding, and should inform daily practice. Patients with low back pain were assessed and randomized as they presented to ten GP surgeries. The physiotherapist assessors divided them into three groups: low, medium or high risk for lasting disability. They were then allocated to further care at the discretion of the physio, or tiered care according to their risk of chronic incapacity. Tiered care proved better. The notable features of this trial were (a) that the comparator was better-than-usual care (i.e. immediate triage and physio) and (b) that it stratified patients logically and avoided the one-size-fits-all approach that discredits most research in the eyes of the jobbing practitioner. As for the scoring instrument, economic assessments etc, I have no doubt that criticism is possible, but it will not come from me. General practice needs many more trials for like this, generating questions from the point of view of the patient, using interventions that are cheap and practical, and providing answers in terms of the outcomes that matter.

BMJ 8 Oct 2011 Vol 343

On my first clinical "firm" as a medical student, the consultant asked the student next to me to describe arcus senilis. He looked the ageing consultant in the eye and described it perfectly. It seems that we must call it arcus corneae these days, and it predicts nothing, according to the Copenhagen City Heart Study. By contrast, xanthelasmata are a marker for accelerated atheroma, independently of other risk factors. This is not significantly mediated by total cholesterol. The take-home message therefore is not "well, we all knew that already" but that we can measure cholesterol in people with xanthelasmata out of curiosity, but prescribe statins irrespective of what it turns out to be. And above all offer them help to stop smoking, if (as is likely) they are smokers.

Always approach modelling studies with scepticism, and that includes the "standard error" figures they give. You and I have to take these things on faith, and faith is not a virtue when reading the medical literature. I only draw your attention to this modelling paper on smoking and tuberculosis to emphasize that these are two evils which combine to kill millions in the resource-poor world, despite the fact that the first is totally avoidable and the second is largely treatable. If the toll goes up in the next 40 years, as this paper predicts, then the world will have messed up big-time.

Ann Intern Med 4 Oct 2011 Vol 155

Clinical decision rules abound, and to me they are rather like most works of classical music written after about 1920: I know I should try to understand and like them, but all they do is fill me with a vague sense of unease. They seem to work against intuition, rather than with it: they mess with the smooth inner workings of the mind. The classic playground for decision rule-makers is venous thromboembolism, and pulmonary embolism in particular, where Wells has gifted us a Schoenberg-like series of scores. I exaggerate: Wells is more like common sense slowed down. So what if you just take out the score, speed up common sense, and then do a D-dimer? According to this meta-analysis comparing clinical decision rules with what the Americans call gestalt, the results are just the same.

Plant of the Week: Colchicum autumnale

I was reminded of this plant by a report in this week's Annals of a randomized trial of colchicine as prophylaxis for recurrent pericarditis:

It reduces recurrences by about a third.

I first came across colchicine in the school biology lab, where it was used to arrest mitosis, so we could pretend to see and admire the spindles of a dividing nucleus under a high-power microscope.

It is still a great treatment for gout in people who can tolerate it, and is the only safe agent in the gout we induce in heart failure patients by giving them loop diuretics. But hey, I am supposed to be talking about the beauties of the autumn crocus (or "naked ladies" as they are sometimes called).

All colchicum flowers are purple in various states of paleness: they rise and then sag in various poignant poses among the bare ground and the leaves of autumn. They are plants for the larger garden, to be wandered among as the mists rise and the sun gives a watery glow. Stuck in a small flowerbed, they just look out of place, and sad in all the wrong ways.

You can buy bags of the corms for planting earlier in the year, usually giving the name of a variety and a misleading description and picture. To me they all look much the same when they come up. Do not eat any part of this plant: Wikipedia informs us curtly that "Murderess Catherine Wilson is thought to have used it to poison a number of victims in the 19th century."

JAMA 28 Sep 2011 Vol 306

1329 Intra-aortic balloon counterpulsation reduces left ventricular load and improves outcomes in animal models of myocardial infarction. But in previous small human studies of MI without shock, it hasn't been shown to do anything much, and this trial confirms that it does not reduce infarct size significantly.But such is the success of primary PCI for MI these days that it would need something bigger than this 337-patient, nine-country trial to settle the issue with hard end-points: here there were just 3 deaths at six months in the PCI-plus-IABC group versus 9 deaths in the PCI-alone group.

1338 Reading surgical case-series reports from more than a hundred years ago, I'm struck by how many of the themes of modern outcomes research are already present - adjustment of case-mix, the need for proper follow-up, individual operator versus institutional outcomes, the relationship between operator volume and outcomes, and the learning curve effect. Here Brahmajee Nallamothu and colleagues take a look at the results of carotid stenting according to the annual volume and experience at the time of the procedure among new operators who first performed carotid stenting. It's a nice study design, and confirms the intuitive expectation that the more of these procedures you do, the better your outcomes tend to be. It raises important issues about how we can best protect patients while taking new operators through their inevitable learning curves. And also what we do with those operators whose learning curves aren't climbing enough. As for the more general issue of whether anybody should do carotid stenting in the first place, I will leave that for more learned persons to decide. Medicare decided to give it the go-ahead, but that does not make it a good procedure.

1344 Saw palmetto extract achieved fame about fifteen years ago when the balance of evidence at the time seemed to show that it was a safe, cheap and effective remedy for the symptoms of benign prostatic hypertrophy. Kind Nature was thought to have placed relief for nocturic old males in the berries of Seroana repens, and even sceptical doctors like me would scrawl the annoying common name of this plant on a scrap of paper for patients to take down to the local alternative remedy shop. Hokum, according to this double-blinded RCT, using increasing doses of saw palmetto extract versus placebo. The stuff makes no difference at all.

N.B. Could any kind reader point me to the origin of the saying "Use new remedies early, before their effect wears off." ?

NEJM 29 Sep 2011 Vol 365

1173 Could it be that the gene gnomes have pulled it off at last? A discovery that will genuinely to guide treatment in a common condition - as common as inhaled glucocorticoid treatment in asthma? Well, there is much rejoicing in their ranks over the discovery that people with a certain GLCCI1 variant show only one third of the response to inhaled steroids as other asthmatics. For the second week running, the NEJM runs an editorial with "Personalized Treatment" in its title, this time by the great editor himself, Jeffrey Drazen. But without wishing to dampen the celebrations, I would point out the last phrase in the Results: "with genotype accounting for about 6.6% of overall inhaled glucocorticoid response variability." So more than nine times out of ten, genome profiling would not help you in this aspect of clinical management. Even if you could ever access it and afford it.

1184 Many of you will know the famous Fletcher-Peto curve of the progression of chronic obstructive pulmonary disease with and without smoking cessation - it dates back to 1976 and is a classic for several reasons, one being that it nicely illustrates the use of a graph to represent the natural history of a condition. I am surprised that this kind of depiction has never caught on as a teaching aid for other conditions: still more surprised that there is no similar graph in this paper on the variation in trajectories of COPD as measured by FEV1 after a bronchodilator in 2163 people over 3 years. Not surprisingly, the course of decline varies a lot between individuals and is normally distributed. For a longer term delineation of the natural history of COPD, nicely illustrated, you need to look elsewhere (see link below).

1193 Nicotineis one of many neurotoxic substances that plants have evolved to poison insect predators: the one in laburnum plants (Cytisus spp.) is called cytisine. It actually hits the same α4β2 nicotinic acetylcholine human brain receptors as nicotine, and laburnum extracts have been used as a smoking cessation aid since the 1930s, when Hitler encouraged the use of herbal remedies against the filthy habit of smoking which was sapping the fighting power of the German People. The Soviet People followed suit, and cytisine still remains available for next to no roubles in Russian pharmacies. In the capitalist West, we buy it chemically modified at great expense in the form of varenicline. Why not instead spend thruppence and use cytisine? This study shows that it definitely helps - 8.4% abstinence at 12 months after a 25-day course compared with 2.4% on placebo. A shame this wasn't a head-on trial with Champix/Chantix/varenicline.

Lancet 1 Oct 2011 Vol 378

If there are important, believable randomized controlled trials out there waiting to be published, once again The Lancet has decided against letting us have them. The original papers this week have all been on the website for weeks, and I let you have a couple during the lean weeks of August and September. Here is one I didn't:

1219 The circulation is circular, and so is a lot of the thinking that goes on around it. I read this modelling paper about the cost-effectiveness of options for the diagnosis of high blood pressure in primary care with particular care because the topic is important and I've been interested in it ever since I became involved in the first primary care ambulatory blood pressure studies which were done in Oxford 20 years ago. Another couple of Oxford colleagues are involved in this paper: but I am afraid I can't agree with some of their modelling assumptions and hence their conclusion. The data to compare home monitoring with ABPM in relation to hard outcomes are simply lacking, as they say; Framingham is a less accurate predictive tool than QRISK for the UK population; a practice can buy 22 home monitors for the price of one ABPM machine, and patients much prefer these and often buy their own. The jury remains out and a wholesale (or even retail) move to ABPM is premature.

BMJ 1 Oct 2011 Vol 343

There are very few journals where a jobbing general practitioner could find a chance to publish these days, and the BMJ is not one of them. I got my chance back in 2000, when they still did Brief Reports, but these have now disappeared from the main journals. General practice is the most fertile of all research settings, potentially, and very much the best generator of patient-important questions; but funding arrangements are such that it is virtually impossible to realize these advantages, and even academic departments of primary care usually offer little help. Perhaps this may be about to change, according to this editorial on a new European strategic report. But some of us remember the UK Mant report from the 1990s, and will not be holding our breath.

I usually read editorials with personalised medicine in the title expecting to find a lot of genome-babble to disbelieve, but this strange piece is from a renin enthusiast hoping to reform the treatment of hypertension. Those with exceptionally long memories will remember the vogue for renin-based classifications in hypertension in the 1960s, but Morris Brown argues from first principles that now we could apply better assays more logically to the individualized treatment of blood pressure using specific drug classes which did not exist then. Perhaps: but some evidence would be nice.

Medical papers in praise of chocolate are rather common these days. They used to guarantee media attention, but on that I cannot possibly comment as I live a hermetic existence 3,000 miles from all British organs of public intelligence. I am also on a chocolate-free diet since I need to lose weight. Nevertheless the ideas of chocolate-driven cardioprevention set forth in this systematic review of observational evidence are very attractive: all we need is some way of making cacao palatable without the addition of sugar.

Arch Intern Med 26 Sep 2011 Vol 171

1542 Here is a paper which shows that patients who visit their doctor more frequently get more treatment. And if the condition is diabetes and the treatment is to the wrong targets, then that is not a good thing. The targets here were HbA1c below 7; BP below 130/85; LDL-cholesterol below 100mg/dl. The evidence? Harm to most patients in the first case; no benefit in the second; and no evidence in the third. And how often should one monitor each? Six monthly seems logical for HbA1c which is a reflection of glycaemic control over 3 months. Monthly seems the maximum for BP if seriously out of control, to allow for multiple measurements and regression to the mean. And LDL-C? Why measure it at all when we know that all these people will benefit from a high-dose statin. But this study conducted in two American primary care facilities linked to a teaching hospital shows that such targets are best reached by seeing diabetic patients every two weeks. So now you know another way to harm people with diabetes and waste health service money: see them too often. But in the USA, Merck is supporting an organization (ACE) which is publicizing this paper under the headline: Frequent Doctor Visits Benefits Patients With Diabetes (sic).

1571 So far the plant neurotoxins we have mentioned are nicotine, cytisine and theobromine (in chocolate): now it's time for caffeine. The stimulant properties of tea and coffee were discovered by Europeans at approximately the same time, and were followed in both cases by ultimately successful attempts to discover and steal the source plants and grow them in European colonies. Anything pleasurable and mildly addictive has always attracted medical censure in certain quarters; but as with chocolate, the evidence of benefit from caffeine outweighs any evidence of harm. Not that this is too wonderful a study: out of 50,000 US women, those who drink caffeinated coffee report less depression than those who don't. Not exactly a randomized trial.

Fungus of the Week: Grifola frondosa

The alleged English name for this fungus is "Hen of the Woods", which seems a bit odd as there is another quite different fungus called "Chicken of the Woods". Why stick to the poultry yard when naming fungi that grow on trees? Why not "Pig of the Woods"? Or "Porpoise of the Forest"? I think I will stick with the Latin.

The Grifola grows at the base of trees, usually oaks. There is a gigantic version (G gigantea) which produces enormous brown fronds and kills its host: this one is sensibly proportioned and grey in colour and lives in a state of mild parasitism. It appears as a little cluster of fronds growing up through the soil, growing steadily larger until it has had enough, usually at about 50-70cm. It is simply there to shed spores, after all.

To harvest this fungus for the table, you have two options. You can pick a biggish specimen and then pull off the fronds when you get home, discarding the woody central mass. Or, if you are lucky, you can pick the whole thing while it is less than 20cm across and cook the lot. But the great challenge is to render it clean enough to be edible. Bear in mind that it has grown through the soil, and if the soil is tenacious, then you must resign yourself to a bit of mild pica.

Unfortunately the soil round the red oak from which I get my supplies is sandy, so the pleasure of eating this fungus is distinctly modified by loud crunching noises as grains of silica encounter dental enamel. The structure of the fronds is actually very beautiful but almost impossible to clean. Look carefully at the underside of many fronds and you will see the Mandelbrot set in all its wonder: a multiplicity of similar shapes at every scale, none predictable. This may give you enough satisfaction, without you feeling the need to proceed to the cooking stage.

However, if you are prepared to brave the grimaces of your loved ones and the inner doubts which I have sown in your mind, proceed as follows:

Recipe A: for fronds. Tear the fronds from a young but well-developed specimen. Under running water, attempt to remove all soil, insects, grit etc using your fingernails, a shaving brush and/or a toothbrush. Do not expect to succeed. Heat olive oil moderately in a frying pan and add the fronds while they are still wet. Reduce the heat so that they stew for 10 minutes. At this point add some scraps of chopped shallot and season with salt and pepper. Simmer further until the mushroom liquor is nearly evaporated, but do not let them brown. Serve with finely chopped parsley, eat jauntily and claim that they have a mild and delicate taste and that everybody should try some.

Recipe B: for a whole infant cluster. Cut the base from your cluster and attempt to remove dirt etc. from under the little fronds under running water. Do not expect to succeed. Cut the cluster into slices about 0.75cm thick. Cut some very fatty bacon or pancetta in cubes or pieces and fry until the fat has been largely melted into the pan. Now add the sliced grifola, followed by a few scraps of shallot. This time you can allow a little browning to occur, but beware of drying out. Serve with or without parsley, and murmur "delicious" as you eat the bacon with as little of the fungus as you can get away with.








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Page last edited: 01 November 2011