So there is a weak argument for giving antibiotics even in the last group, but a much stronger one for waiting and seeing.

Half the cardiovascular research of the last two decades seems to have involved tinkering with some bit of the renin-angiotensin-aldosterone system, though there is a glaring exception right at the beginning, with renin. Apparently it is very difficult to create an orally available renin inhibitor, but soon there will be a whole family of them, the kirens. Aliskiren is the first to arrive, and Alice may shortly be joined by her brothers Enal, Remi and Zan. The problem may be finding a niche for these products, as they will have to prove their superiority to the many well-investigated agents for hypertension and heart failure which block later stages of the system.

Arch Intern Med 9 Oct 2006 Vol 166

The tabloids love a dirty hospital story. Epidemiologists too can relish using the words “nosocomial” and “fomites” (i.e. stuff in hospitals). But do nosocomial fomites really spread killer bug plague shock horrors? Yes, a bit. In Boston, Mass, you stand a slightly higher chance of acquiring meticillin-resistant staphylococci or vancomycin-resistant enterococci if the previous occupant carried them.

This study of over 18,000 US citizens of average age 65 (REGARDS) finds that about 5% have had symptoms which may have been caused by undiagnosed cerebral ischaemia (5.8% for painless hemibody weakness, 4.6% for sudden loss of vision). A slight pause here while my aspirin dissolves. I shall occupy it by telling you that the risk is greater in African Americans.

Breathing in other people’s tobacco smoke is unpleasant and can cause respiratory impairment (see last week’s JAMA) but does lifetime exposure to second-hand smoke really increase one’s risk of myocardial infarction? Not significantly, concludes this case-control study.

Metformin is the one drug for type 2 diabetes that really benefits patients, but did you know that it can induce vitamin B12 deficiency? It certainly seems to in about a third of Chinese diabetics who take the drug (this study is from Hong Kong) but it is not clear how significant this is clinically, partly because we lack a good biochemical test for physiological B12 status.

For a fortnight they have been trooping in endlessly, filling the car park and the waiting room, exchanging brief greetings with the practice nurse before rubbing their arms and departing. Does annual influenza vaccination in community-dwelling elderly individuals really reduce lower respiratory infection and pneumonia? Yes, reader, it does.

“It’s probably a trapped nerve” “Oh good, doctor, I was worried it was my circulation”. GPs have this exchange about once a week, but beware the lower limb. This study of non-diabetic patients with peripheral vascular disease shows that patients with low ankle-brachial indices often also have impaired peroneal nerve function.

Cheer up at once. It is too late once you have had a heart attack. Depressed people who have a myocardial infarction fare badly; people whose depression lifts after the MI also fare badly; and people who get depressed after MI do equally badly. It’s enough to make you lose heart.

Fungus of the Week: Boletus edulis

A long time ago I was waiting to be served in a restaurant in the faded Tuscan town of Poggibonsi, when there came the loud noise of motorcycles outside, and the little eating house was invaded by four large youths in leathers, who sat down and immediately placed their order with a single word—porcini. A few minutes later, each was presented with a plate on which lay a single fried specimen of fungus which bears this name, supposedly because pigs enjoy eating them. The leather clad bikers fell silent as they ate these (rather expensive) woodland delicacies, then wiped their lips happily and roared off into the evening.

A year ago in Warsaw I had a similar experience, give or take motorbike or two. In the October sunshine, everybody seemed to be ordering borowiki, served Polish style in sour cream with onions, and poured into specially constructed loaves of brown bread.

Now in England this mushroom, which we are suppose to know folksily as the “penny bun”, but actually call the cep after its French name, only appears fresh in the poshest restaurants but is quite common in our woods. It is easy to identify but very unpredictable. You either find none or too many. If the latter, it is easy to tire of them because they have a somewhat slimy cooked texture which becomes cloying once the novelty has worn off. On the Continent, they are dried in huge quantities for later use. But supposing you want to show off your cep-hunting success, you could serve them twice with beef in the same meal without exhausting the patience of your guests:

Crudo: Take as many firm, freshly picked young ceps as you need or have, and slice them thinly, including the gills and the stem in single slices. Interleave these slices with bresaola and then dress with lemon juice and the best Italian olive oil you can find. Add shavings of Parmesan and serve.

Cotto: Use your bigger maggotier ceps in a rich beef stew. I shall not presume to tell you how to make the stew. Just fry up the chopped ceps with a bit of shallot and oil, dripping or butter, and put them into the stew for its final half hour. Sprinkle with parsley after serving. Yum.

J A M A 11 Oct 2006 Vol 296

From the US Centers for Disease Control and Prevention, a Journal of the Plague Year: so far, 2006 has yielded 13 cases of human plague, the largest number since 1994. Thanks to early recognition and antibiotic treatment, the death toll was just two. There is a reservoir of Yersinia pestis in various rodents, mostly rabbits, in a wide assortment of American states. Give sick American rabbits a wide berth.

It’s not exactly news that all chronic inflammation increases cardiovascular risk, and we already know that this applies to psoriasis in hospital populations. This new community-based study relies on the UK GP Database, which may, perhaps, record psoriasis fairly accurately, and myocardial infarction more so. There is indeed a bit of extra risk, but for older patients with mild disease, not enough to worry about.

The next study comes from the bars and pubs of Tayside, where workers were assessed for respiratory symptoms and function before and after the smoking ban. Tayside’s most famous poet has risen from the grave to report its findings:

“’Tis the shame of our homeland to find dram-houses and drink-dens in fair Dundee:
And time was, before the current ban came into force, they were as a general rule abominably reeky;
But since the wise law-givers of Edinburgh enacted their anti-smoking legislation
The fair lassies who serve intoxicating liquors by the banks of the silvery Tay have noticed a marked improvement in their respiration.”
William McGonagall (op posth)

N.B. For poetical reasons, McGonagall only refers to the lassies, but this applies to the laddies as well, and especially to those with asthma.

All the major studies which have compared thrombolysis with primary percutaneous intervention for ST-elevation myocardial infarction have come out in favour of PCI. This study looks at the real-life situation from the National Registry of Sweden, a country where rapid access to PCI must be particularly problematic in many locations. If it can be done within 2 hours, the mortality benefit is 30+%, just as in the randomised trials: if the time to intervention is going to be more than 4 hours, however, pre-hospital thrombolysis may be equally effective.

The Rational Clinical Examination series has been running for over a decade now, covering what seems like a random assortment of topics, always valuable but all too sporadic. Here it addresses the old question: Do Opiates (recte opioids) Affect the Clinical Evaluation of Patients with Acute Abdominal Pain? There are some situations, like acute pancreatitis or severe renal colic, where it would seem appalling to withhold immediate opioids, so it is reassuring that there is nothing in the literature to suggest that this has resulted in missed diagnosis or incorrect management decisions.

N E J M 12 Oct 2006 Vol 355

Do you sometimes wonder if the antipsychotics we use for treating agitated or psychotic people with Alzheimer’s disease actually work? If so, you are right. In this trial, olanzapine, quetiapine, risperidone and placebo all got ditched within a median time of less than 9 weeks. The first two showed some benefit, but all three active drugs had a high incidence of side-effects. The incremental-dose study design is commended in an editorial which concludes that olanzapine and quetiapine may be worth trying in some patients.

Ramipril fulfilled every HOPE some years ago: but could the DREAM come true again? Not really. The DREAM trial, you remember, allocated patients with impaired glucose tolerance to ramipril and/or rosiglitazone in a 2x2 factorial design: the primary outcome was newly diagnosed diabetes or death. Ramipril for 3 years didn’t have any effect on either.

People who lose weight generally end up putting it back on. The way to reduce this is to weigh them daily face-to-face. Hmm. Seems weigh over the top to me.

To the horrible unfairness of getting childhood cancer, add the horrible unfairness of what happens in the long term. Compared with a sibling, your risk of having a joint replacement is 54-fold (!), of getting heart failure is 15-fold, and so on down a list of miseries (Table 3).

A discussion of external-beam radiotherapy for localised prostate cancer, based on a clinical vignette. A detailed account of what this treatment entails, well worth reading - especially if you are a male, in which case your chance of undergoing it may be about one in ten.

B M J 14 Oct 2006 Vol 333

It’s been an article of faith for years, nay decades, that children need lots of calcium to make strong bones, and that, as there is a limit to the amount of milk and sardine bones they can be made to eat, calcium supplementation is needed. A meta-analysis of the RCTs of calcium pills for children shows that they don’t work. Kids build bones by other means, especially playing.

The management of colorectal cancer has moved from rough-and-ready surgery to a fine art, combining preoperative imaging, meticulous resection, and targeted radiotherapy and chemotherapy. Colorectal surgeons need to be good thinkers as well as good operators (see the clear but complex editorial on p.766). This study (MERCURY) shows that preoperative MRI can accurately predict who is most likely to get a local recurrence and would therefore benefit from post-op radiotherapy.

In a previous article, Peter Gøtzsche warned us against believing what we read in the Abstracts of papers: here he warns us not to trust the methodology and accuracy of industry-supported meta-analyses. Are there any safe short-cuts left for the jobbing doctor? Cochrane and EBM, I think. I do hope Gøtzsche never gets round to these reviews. He would have a fit.

A few months ago, a paper in the Lancet described how Aberdeen lab doctors set up an interactive advice system to discourage local GPs from ordering unnecessary tests, such as ferritin for anaemia. Moving down the east coast, we now have a couple of lab doctors from Sunderland showing GPs that ferritin is the most useful test in iron-deficiency anaemia, and that they should consider a trial of iron in patients within the “low normal” range (15-40 μg/L). They are right, and also in advising serological tests for gluten allergy.

The ABC of obesity could read: eat more, do less. The ABC of helping people to reduce obesity means drugs, which are usefully discussed here.

Lancet 14 Oct 2006 Vol 368

It may come as a surprise to some readers that migraine has its own specialist journal (Hemicrania) and that migraine also features prominently in the journal Cephalalgia, a pain in the head. Since most of us do not seek out these heady delights, a Lancet editorial points out a small study from the latter, in which migraineurs who did not respond to triptans alone were given the prokinetic drug trimebutine in conjunction with their rizatriptan, and mostly got relief.

A household survey of 11 countries in Asia assesses the effect of payments for health care on poverty. Does paying up-front for medical care impoverish people? Well I never, it does.

The Art of the Medical Journal

A couple of readers took me up on my statement last week that “Alone among the medical journals, JAMA attempts to civilise us with offerings of visual art, poetry and prose.” A distinguished academic from Canada pointed out that CMAJ did at least as well as JAMA. Another from Oxford drew attention to the artistic merits of J Royal Soc Med. My mistake was to omit the word “weekly” before “medical journals.” Among the monthlies, there is also QJM, which features some wonderful photographs on its front cover, and always ends with a wise, elegant, witty Coda by John Launer.

Ann Intern Med 3 Oct 2006 Vol 145

Who deals with most depression? Yes, it’s us - “usual care” as we are sometimes known. We are the bog standard of badness. We need an army of facilitators to help us manage anything, since they know much better what we should do, not having to do it themselves. Here mental health teamsters were randomised to goad American GPs into doing all the textbook things for depression (“decision support”). Did the patients fare any better? No. Did the doctors go bonkers? I think we should be told.

“Usual care” is also sometimes known as an “ambulatory setting”, though personally I prefer to sit down while seeing patients, and often invite them to do the same. But whether sitting or ambulating, we all make mistakes. Fortunately most are not serious, and are easily forgiven: but the more serious missed or delayed diagnoses result in malpractice claims. We usually enjoy reading about these, provided they are not our own, but this paper kills all interest by just listing the sorts of errors which we make, and the mechanisms by which we make them, without the slightest hint of a clinical or human story.

Thinking of going up a mountain soon? Worried about high altitude pulmonary oedema? You could take either dexamethasone or tadalafil. This tiny study does not really tell you which: I guess it depends on who you’ll be sharing your tent with.

We know that cardiovascular risk is better predicted by low density lipoprotein cholesterol level than by total cholesterol, and many learned committees have declared what levels we should seek to achieve. Based on sound evidence? Alas, no, since all the main trials are full of avoidable errors, according to this narrative review.

Electrocution has held interest for Americans since Benjamin Franklin first flew a kite, and this narrative review looks at what actually happens to people who are subjected to electrical discharges, excepting those made to do so by the United States judiciary. Oddly enough, a further shock to those whose hearts have been stopped by a previous one often revives them. But the survivors often have burns which go deep, and if you look after them, you should read this paper.

Fungus of the Week: Langermannia gigantea

The fungus season is good this year: get out in the woods! Though in fact you don’t need to. This season is particularly good for grass-loving species, such as the common mushroom, the fairy-ring champignon, and puffballs of every kind. Today (Sat 14th) I found my first intact example of the giant puffball, previously known as Lycoperdon giganteum. It weighs an exact 500 g, and tomorrow I shall slice it and fry it in butter and bacon fat, perhaps with a dusting of parsley and a few slivers of roast partridge breast and fried pancetta.

This is the largest of ground-growing fungi, a simple white football which converts its centre into a mass of black spores, which can number 10¹³´2. If they all produced puffballs of equal size, they would form a mass 800 times the weight of the Earth. “We are on safe ground in asserting that this does not happen”, says the irreplaceable John Ramsbottom (Toadstools and Fungi, 1953).

J A M A  4 Oct 2006 Vol 296

Among the medical journals, JAMA alone attempts to civilise us with offerings of visual art, poetry and prose. Can an attached CD of musical items be far behind? If so, let the music be chosen by M. Therese Southgate, their veteran ex-editor who does the front covers. If it came from the “poetry” editor, I would run screaming. As for the prose, it appears weekly as “A Piece of my Mind”, and often hovers dangerously close to the level of the verse. This week’s Patagonia Pastorale is different. It tells of a football match with an acromegalic goalkeeper in that benighted region. Read on…

I had always thought that young Italian men had the good sense to confine their dangerous activities to smoking languidly in groups on street corners, shouting to passing girls, or hurtling along cobbled streets using improbable forms of motor transport. But some in Veneto, alas, opt for competitive athletics and pay the price by dropping dead. The cause is usually cardiomyopathy, and the rate fell when screening was introduced.

Some years ago, a review of cerebral palsy (NEJM 2003;349:1765) concluded that the vast majority was due to gestational rather than intrapartum factors, and this big European study using MRI confirms that. Nearly 90% of children with CP have abnormal MRIs, and most of these are not consistent with birth injury.

Whenever I prescribe antidepressant drugs for the first time, I warn that patient that (a) they will take a fortnight at least to work and (b) although there is usually an antidepressant that works best for a person, there is no way of telling which in advance. Now maybe there is in Korea. A study of monoamine transporter gene polymorphisms shows some prediction of response, which if confirmed “would permit refined pharmacogenetic selection of antidepressant treatment.” No time soon, I fear.

Two important systematic reviews about cyclo-oxygenase 2 inhibitors have been sitting on the JAMA website for some weeks, and being interested in this subject I read them a while back, but keep to my usual custom of only reporting what comes out in print. Rofecoxib emerges as the true villain, and if you want a clear blow-by-blow account of how its manufacturers sought to disguise the fact, read the editorial on p. 1653. Alone among the COX-2s, it causes renal damage and arrhythmias.

Nearly all non-steroidal anti-inflammatory drugs, however, do carry cardiovascular risk, as the next review of the RCTs, shows, and one of the worst is diclofenac, with the risk of adverse cardiovascular events (mostly myocardial infarction) increased by about 40% especially in the first month. This is not as bad as rofecoxib, but it is much worse than naproxen (no added risk) and ibuprofen (less than 10% increased risk).

N E J M  5 Oct 2006 Vol 355

Reminded daily of the woes of old age by a stream of patients, the GP soldiers on, hoping that fate will be kind and grant an old age without pain or blindness. Cataracts are now just a ticket for conveyor-belt surgery; glaucoma is just a matter of putting in the drops; but age-related macular degeneration (reviewed here) still triggers the Homeric formula which has killed more hopes than ever died on the plains of Troy: “there isn’t a lot we can do for you, but come back in six months”. Will that soon be replaced by a cheery, “We’ll have you back for the injections every month”? Quite possibly. Ranibizumab seems to be the biz. Big biz, in fact, at $2,000 per vial. But there is another mab which might work equally well, at a small fraction of the cost—bevacizumab. Whether it will see the light of day, or help others to, is another matter. When there is such a lucrative market, expect turf wars, and don’t expect much quarter if you’re just some oldie going blind.

Monthly intravitreal injections sound off-putting to a squeamish wimp like me, but ranibizumab works and is safe, whereas the existing standard treatment for neovascular age-related macular degeneration, intravenous verteporin followed by laser treatment has a higher incidence of adverse effects and is not nearly as successful. This was a double-blind trial with sham IV injections and sham intravitreal injections. Ouch.

Twenty-five years ago, the practice nurse would spend a considerable proportion of the early year giving people injections of grass pollen extract to cure allergic rhinitis. These worked for some, but a few people died every year from anaphylaxis. This study shows that you can get a better result by combining the antigen with phosphorothiate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC). As everyone knows, this acts as a Toll-like receptor 9 agonist. So far, it has only been tried for allergic rhinitis due to Ambrosia artemisiifolia, or ragweed as this ambrosial creature is rudely known. But can grass be far behind? And will such expensive-sounding concoctions triumph over simple sublingual tablets of grass extract (see J Allergy Clin Immunol 2006;118:434)?

I would really like to see my time as a jobbing doctor end with meningococcal disease consigned to history. And it may yet happen, if the right vaccines come on line. Read all about them in this review, and take comfort from the incidence graph for the US Army (figure 2).

B M J  7 Oct 2006 Vol 333

If the Pope decides to abolish limbo, where does that leave academic medicine? It certainly isn’t heaven. All the medical schools I know of seem to operate by random interaction between the whims of educational fashion and the clash of medical egos. This cannot be the best way to educate the doctors of the future. And if I were God, I would know where to consign most of the medical educational literature.

I’ve never seen a case of visceral leishmaniasis but it’s uncommonly difficult to find anything to write about in this week’s BMJ, and this review of dipstick testing for a nasty but treatable endemic disease of poor communities in tropical places seems much the most worthwhile.

Except perhaps for Jeff Aronson’s proposed scale to assess patient consultation exercises, which derives from Paul Glasziou’s observation that most of these consist of: “This is what we intend to do; tell us how much you agree.” The written response form could consist of: “Agree/Agree strongly/ Agree very strongly/ Agree enthusiastically/Couldn’t agree more.” Come to think of it, I’ve just had one of these relating to closures at our local hospital.

Blake for the Week:

God forbid that Truth should be Confined to Mathematical Demonstration!

Annotation to Reynolds’ Discourses

Lancet 7 Oct 2006 Vol 368

Editorials and developing-world topics provide most of the interest in this week’s Lancet too. Richard Horton takes a keen personal interest in what goes on at the World Health Organisation (WHO), and has asked the candidates for the Director-General post to set out their stalls in his journal. He then marks up their strengths in a little table. Two candidates, both with Spanish names, score nothing: Julio Frenk from Mexico gets full points and a billing on the front page of The Lancet. It’s hard to judge from the generalities set out in their interviews, and none of them are household names. Julio WHO?

Fiddling about inside a nearly occluded carotid artery is dangerous work, but leaving the artery to occlude completely or throw off emboli is even more dangerous. So which is the safer technique—endarterectomy or stent-protected angioplasty? In the SPACE trial (n=1183), those randomly assigned to traditional endarterectomy fared slightly better than those who were stented. But the confidence intervals crossed zero and, as the editorial title wittily points out, SPACE is not the final frontier.

Fiddling about inside tiny new babies is also dangerous work, never more so than when they have necrotising enterocolitis. The case-fatality rate for those who come to surgery is between 27% and 50%. Here is a comprehensive seminar on this nasty condition which affects premature babies for poorly understood reasons.

Arch Intern Med 25 Sep 2006 Vol 166

How do statins actually prevent coronary events? Much ink has been spilt on this question, though the jobbing clinician may well say “Who cares? The main thing is that they do, and a lot more besides.” The question arises particularly in the context of acute coronary events: early studies seemed to show mortality benefits from giving statins right away, long before cholesterol-mediated effects have time to kick in. Then some later studies cast doubt on this. But in this meta-analysis, the message is clear: statins save lives when given at high dose immediately after acute coronary syndromes.

Many placebo-controlled trials have shown that there is a rather spooky adherence effect: patients who take placebo religiously often do better than those who take the beneficial active drug less religiously. This study looks at 11,532 diabetic patients in a managed care organization and finds that nonadherent diabetics tended to start healthier, but ended up sooner in hospital or the mortuary. Keep taking the tablets, whatever they are.

Patients who stop taking their tablets following myocardial infarction are at particular risk, as you’d expect.

There are various ways of getting GPs to do what they are told; one is to dangle financial carrots in front of them—see how they jump!—another is to send in an “outreach group” (pharmacists in this case), or to ring them up, or to send them electronic reminders. This trial used everything, except the money, to improve therapeutic monitoring. These interventions all succeeded in getting more liver function tests sent off, but whether any patients benefited is another matter. A lot of this monitoring depends on the whim of manufacturers rather than solid evidence.

Studies from various parts of the world have shown an increased risk of cancer in patients with diabetes. This large Japanese cohort study shows an overall increase of about a quarter, mainly from liver, pancreas and kidney: other places will show different patterns.

Now that we’re all suddenly interested in eGFRs and kidney disease, we’re becoming aware that quite a few of our chronic renal impairment patients are well known to us because of other problems. This Framingham write-up tells us that these are most likely to be hypertension, obesity and diabetes. Yes indeed. For a good general overview of chronic kidney disease and mortality risk, the place to go is J Am Soc Nephrol 2006;17:2034.

Heart failure is an unpredictable condition—or is it? As I’ve said before, levels of B-type natriuretic peptide are highly predictive, but in this study, like so many others, they don’t feature at all. It’s a follow-up study of elderly patients hospitalized for HF: their median survival was 2.5 years—not bad considering their mean age was 79—and quite a few went on for five years or more. They’d be the ones with a low BNP.

NSAIDs are dangerous, co-proxamol has been withdrawn, glucosamine is feeble: so what are we to give our patients with osteoarthritis? Diacerein perhaps. Dia-what? I too had never heard of diacerein before reading this meta-analysis of controlled clinical studies which states that it works as well as NSAID during treatment, with milder adverse effects, and has a carry-over effect too (Cochrane classes the evidence as gold level). It inhibits interleukin-1. Time we got hold of some.

Plant of the Week: Vitis vinifera “Purpurea”

This is the vine we plant for its lovely purple leaves which turn to gorgeous reds at this time of year. There are lovely clusters of small grapes too, which can be used as house ornaments for a few days, but I would not venture to eat them. Perhaps their best use is to make verjuice, one of the condiments used in classical Roman cookery, along with bird droppings and fermented mackerel blood. Apicius recommends verjuice as a dressing for oysters: I might just try it. No doubt it is the ancestor of the red wine vinegar, lemon and shallot dressing which all good oysters deserve.

Or perhaps I shall marinate a few choice dormice in verjuice and garum, before frying them in honey as usual.

J A M A 27 Sep 2006 Vol 296

If you’re a jobbing GP like me, you may not find much to change your practice in this week’s JAMA, especially if you don’t have a patient with Lynch Syndrome (or Lynch’s syndrome, named after the person who wrote up the fullest account of hereditary non-polyposis colorectal cancer). All the same you can take your hat off to these authors who have done an immense amount of hard work matching the known genetics of this syndrome with family histories, and have come up with a (fairly) simple prediction model based on family history. What is more, they have put it on the web for everyone to use.

Meanwhile, another set of researchers from the Colon Cancer Family Registry (do they call themselves “the Lynch mob”?) have come up with a slightly different prediction model, incorporating histopathological features. Applying this complex body of literature to the care of individuals with an inherited predisposition to Lynch Syndrome is the subject of a large systematic review on p.1507.

If you work in a developed country, you might chance to have a patient with Lynch syndrome, but you won’t see a case of trachoma. This study comes from Vietnam, a country which was the beneficiary of billions of dollars of US money, in the form of high explosives, defoliants and napalm. Here they are forty years later, working out how best to spend a few pence to prevent children going blind from recurrent conjunctivitis spread by flies. What a world.

N E J M 28 Sep 2006 Vol 355

If you have a cutaneous melanoma between 1.2mm and 3.5mm in thickness, your chance of being alive five years later is 71% if you are treated conventionally or 78% if you have sentinel node biopsy, followed by immediate lymphadenectomy if micrometastases are detected. Oddly enough, the difference was in non-melanoma deaths.

To be a modern medical hero usually requires endless patience. People have been trying pancreatic cell transplants for diabetes since the 1970s, with little success until Shapiro’s Canadian team in 2000 developed the “Edmonton protocol” which resulted in several patients becoming independent of exogenous insulin (see accompanying editorial). Now, the pancreas contains several thousand islets of Langerhans, each consisting of just a few fragile cells. The Edmonton protocol requires that somebody should sit down and tease out these cells from not just one but two recently deceased pancreases, and then put them into the hepatic circulation of an immunosuppressed recipient. So at best this is a “proof of concept” procedure, rather than a practical cure for diabetes. And alas, most of the initial patients, and most of those in this bigger (n=36) trial, became insulin-dependent again after a year or two. So next the heroes will have to develop a way of culturing islet cells.

Godfrey Fowler, who later became the first professor of General Practice at Oxford, told me that when he initially went to see the (then) Regius Professor of Medicine to suggest teaching our humble art to medical students, he was asked whether he had ever heard of Flexner. This was meant to put him in his place. Flexner, he was told, had put American medical education in order by getting rid of all soft rubbish and insisting on a rigorous scientific approach to medicine. Fortunately Godfrey is a firm believer in non-violence. Moreover, he knew more about Flexner than the Regius Professor, and could point out that within a few years, Flexner had come to regret that American universities were misinterpreting his ideas and producing doctors with too narrow a perspective. Here is a nice overview of Flexner’s ideas and influence on medical education.

The tuberous sclerosis complex: a comprehensive, well-illustrated review to turn to if you have a patient or family with this autosomal dominant disorder.

I suppose it’s a sign of progress that influential US voices can now be heard condemning the management of hunger strikes at Guantanamo Bay. The author of this piece admits that he once defended the practice of force-feeding prisoners, but has changed his position. Yet as you read this, it is going on.

B M J 30 Sep 2006 Vol 333

Anaphylactic reactions to iodinated contrast media are rare, and this systematic review of prevention strategies concludes that they are not worth bothering with: a conclusion reinforced in the accompanying editorial. (N.B. This is an entirely separate issue from contrast nephropathy, which can usefully be prevented by N-acetyl cysteine).

The Danish national birth cohort study finds that babies born following fertility treatment have a somewhat higher risk of congenital abnormalities. The investigators think that some of these—the genital tract malformations—may relate to infertility treatment, but most are in some way related to the cause of the infertility itself.

The last time the issue of bullying in medical schools came up in the BMJ, an Oxford medical student wrote in to say that he hadn’t come across any. This study is from the USA, where it seems rife. The accompanying editorial is by the director of medical education at Cambridge (a university in England), and thinks it may still be going on there as well. I cannot possibly comment.

The last year has seen two major new studies of meningococcal disease in children, both from the same Oxford/London collaboration. One describes a new set of early features, which appear well before the petechial rash; the other, more controversially, casts doubt on the current dogma of giving parenteral antibiotics before admission. Both get short shrift in this Clinical Review, which is a summary of conventional wisdom by an academic microbiologist and an academic paediatrician.

Why, argue some Californians, should we wait for evidence when something is so obviously good as mass circumcision to prevent AIDS, or misoprostol to treat post-partum haemorrhage? There are quite a few reasons, well summarised in the Rapid Response, Has Christmas Come Early. This article is so bad that it may do some good.

The best thing for me in this week’s BMJ—actually, I’ll make that a real compliment, and say in this week’s journals—is Kevin Barraclough’s Soundings piece about Illness Behaviour. If you ever wonder what GPs are for, look no further.

Blake for the Week:
When Nations grow old, The Arts grow Cold
And Commerce settles on every Tree
Annotation to Reynolds’s Discourses

Lancet 30 Sep 2006 Vol 368

This trial of low-dose pravastatin in a predominantly female Japanese cohort with mild hypercholesterolaemia once again illustrates that statins produce a fall in coronary heart disease out of proportion to their cholesterol-lowering effects. Here it was a 30% reduction over 5 years, from an 11.5% drop in total cholesterol, or an18% reduction in LDL cholesterol.

Women gain weight in pregnancy, and a fair few hang on to some of it after the baby has emerged. This study of interpregnancy weight gain in Sweden shows that this is not benign in relation to any subsequent pregnancy: for three extra BMI points, women increase their risk of pre-eclampsia by 78%, stillbirth by 63%, gestational diabetes by 102%, and stillbirth by 63%. That even applies to those who stay within the “healthy” BMI band.

The urinary stones I tend to produce are piddling in size, if that is the right expression, but the pain they produce certainly isn’t. Anything to make them come down the ureter faster has to be a good thing. This meta-analysis of medical therapy to facilitate urinary stone passage comes down in favour of calcium channel blockers and α-adrenergic blockers.

Ann Intern Med 19 Sep 2006 Vol 145

In the age of highly active anti-retroviral therapy, what do most New Yorkers with AIDS die of? The answer is AIDS, of course, but a quarter die of other causes, mainly coronary disease or substance abuse.

Of the various Holy Grails talked of by cardiologists, the True Grail must be a reliable non-invasive method of detecting coronary artery disease. The leading contender used to be cardiac MRI, but this misses quite a lot of significant non-LAD disease; another is multislice computed tomography but this involves iodinated contrast medium and quite a lot of radiation. The gold standard is coronary angiography. In many ways, this German study is a model of how to investigate diagnostic tests: the population was realistic (people with suspected ischaemia from previous testing), it was done in a single institution with blinded assessments, and 108 patients out of 129 were able to have all three tests. So in this population we can actually attach some meaning to those much-misunderstood terms, sensitivity and specificity. CT had a sensitivity of 92%, MRI 74%; CT had a specificity of 90% and MRI 87%. So CT wins, but whether these predictive characteristics are quite good enough for coronary disease is another matter.

In my younger days, it was a liberal article of faith that everybody was basically bisexual. This always rather worried me: it meant that either I had never met the right man, or I was in denial. Later, an older, homosexual friend told me that after the age of 50, these things don’t matter anyway. Phew. But it still behoves the clinician to remember that many men do indeed swing both ways, and may not admit it right away, as this study (again from New York) discovers.

Blunder of the Week: MAGPIE

I am afraid that I am sometimes given to making sweeping statements in these reviews, purely in the hope of getting a rise of out of some reader somewhere. So when I read a paper in last week’s JAMA about PET in Norway, which opened with a reference to the “many advances in its management over the last forty years”, I decided I would claim that there had been none, except to get the baby out earlier. The reader who objected was none other than a certain DS of the Trout Research and Education Centre at Irish Lake, Canada, who expressed considerable surprise that I had not mentioned MAGPIE.

Readers with better memories than mine, and a weaker tendency to make pronouncements about things of which they know little, will remember that MAGPIE was a study of magnesium sulphate to prevent eclampsia, published in The Lancet in 2002. At the time, I reported it tersely as “A study which shows that intravenous magnesium sulphate reduces the risk of eclampsia in all pre-eclamptic situations.” Now MgSO₄ is as cheap and harmless a treatment as you can find, and so well worth using, even though the NNT in developed countries is estimated at 324, with a confidence interval stretching to infinity (BJOG 2006;113:144).

By the way, do not go searching for these papers in Medline using the terms MAGPIE and PET, or you will get a paper about the dangers of catching Cryptococcus neoformans from your pet magpie.

J A M A 20 Sep 2006 Vol 296

Pre-eclampsia is an unsolved mystery of human gestation, without any parallel in the animal world. There has been only one advance in its management over the last forty years, and that is to get the baby out earlier. In Norway since 1967, this has cut the stillbirth rate in PET by two-thirds, but the relative risk of neonatal death following PET remains the same, at double that following normal pregnancy.

Had you ever wondered about the long-term effect of fatty fish consumption on the risk of renal cell carcinoma in Swedish women? Oddly enough, I hadn’t either. I had imagined that everyone in Sweden ate fatty fish—raw, cooked or carefully rotted—at least three times a day. But apparently there are some Swedish ladies who manage to avoid consuming these delicacies for weeks at a time, and they seem a bit People with cardiovascular disease are more likely to have renal disease, and by the time you get heart failure, you’re quite likely to have renal failure too. So it would be nice to know that the trials on which we base our treatment of cardiovascular disease included a representative proportion of people with renal impairment. But only 44% of the main trials actually did—fewer still for heart failure. And those that did hardly ever analysed the subgroup with renal disease.

Almost everyone admires hospital chaplains, even that rare creature, the “hardened atheist”. This article shows why. It’s about spiritual issues in the care of dying patients. Somebody—an editor perhaps—has given it the subtitle “it’s okay between me and my God”, which nearly stopped me reading it. But the chaplain in the text of the paper doesn’t go for God, just for the things all dying people want—the comfort of somebody with them, meaning, affirmation, closure, saying goodbye.

N E J M 21 Sep 2006 Vol 355

This is the kind of old-fashioned schoolboy-adventure medical research you desperately want to work: chap has a heart attack, so clever boffin takes cells from chap’s bone marrow, bungs them into coronary arteries and whizzo!—heart mends itself. If only it were so simple. A formidable team of Norwegians tried to do this and achieved nothing measurable in terms of left ventricular function.

Ah, but perhaps that’s because they didn’t fractionate their bone marrow progenitor cells adequately, or because they were not German. This study (REPAIR-AMI) did much the same thing, but achieved a 2% improvement in left ventricular ejection fraction. Now if they could multiply that by ten, patients might notice the difference.

B M J 23 Sep 2006 Vol 333

This study of a short course of traditional acupuncture for persistent non-specific back pain compares it with “usual care”. I’m surprised that it shows such a weak effect, given how useless usual care is. On the basis of this tiny effect at two years, Chinese acupuncture is hailed as cost-effective in the next paper and in an editorial by a health economist. What we should really be investigating is a long course of sham acupuncture. Administered at random by anyone with a plausible manner and a suitable set of needles, it would probably be hugely cost-effective by keeping people with back pain away from expensive doctors and dangerous non-steroidal analgesics.

Here is a handy guide to halitosis, a source of much misery to its real or imagined sufferers throughout history. Satan, dragons, vampires, the fabled catoblepas of Pliny the Elder, and Grendel from Beowulf all gave out foul and poisonous breath; angels, princesses and panthers on the other hand always had sweet breath. The latter group obviously paid greater attention to their oral hygiene, which is the cure for most kinds of halitosis.

Lancet 23 Sep 2006 Vol 368

The cover of this week’s Lancet refers to MGD-4, which (you will find by looking inside) stands for the fourth Millennium Development Goal—a two-thirds reduction in mortality among children under five, to be reached by 2015. Naughty bad Richard Horton for sticking an abbreviation like that on his front cover. But nice good RH for doing once again what The Lancet does better than any leading medical journal—providing an authoritative and humane perspective on a major global health issue.

One way to reduce child mortality is through GAVI. This is the name of an Italian white wine, with a fresh citrus and vanilla bouquet, plenty of fruit and good length, offering notes of whortleberry and burnished cedar in the finish. Perhaps. Otherwise it’s the acronym of Global Alliance for Vaccines and Immunisation, here hailed as a model public-private partnership. OK, whatever works for the kids.

As the incidence of type 2 diabetes rises inexorably in all developed countries, and quite a few developing ones too, it’s the DREAM of every drug company to come up with something that can prevent diabetes. This trial shows that rosiglitazone 8mg given to people with fasting glucose levels between 6 and 7mmol/L will cut the development of overt diabetes by well over half. On the other hand, 0.5% will develop heart failure, which is a bit of a damper if millions of people might be given the drug. We need a head-to-head comparison with intensive lifestyle management and metformin.

Plant of the Week: Cornus mas “Variegata”

The reason that I pick this dogwood out now is because this is the time that you can sample its fruit. The Romans brought it over partly for this reason—so that they could enjoy the so-called “cornelian cherry”—quite a tart little thing, but a pleasant curiosity. Maybe the main reason the Romans planted it was to make spears from its very hard wood, as alluded to in Ovid. Centuries later, a cornelian cherry tree (no relation to the true cherries) sported a variegated branch, from which all these variegated cornelians derive.

You will notice that cornus takes a female adjective; moreover, she belongs (almost uniquely) to the 4^th declension, so that her plural is also spelt cornus, but pronounced with a long “u”. Among all the Cornus (with a long “u”), there are more handsome variegated ones than this, notably alternifolia and controversa, but the cornelian has sharp-scented little yellow flowers in early spring and nice red autumn colour on the previously green bits of the leaves. It is well worth a place in any garden, growing into a biggish shrub, and ideal when pushing through a low evergreen like Ceanothus thyrsiflora.

Arch Intern Med 18 Sep 2006 Vol 166

Sleep, that knits up the ravell’d sleave of care,
The death of each day’s life, sore labour’s bath,
Balm of hurt minds, great Nature’s second course,
Chief nourisher of life’s feast…

In the Scottish play, Lady Macbeth interrupts her husband’s wonderful hymn to sleep by rudely interjecting “What do you mean?” That’s the question posed by this fortnight’s Archives too, and I don’t think they go very far towards answering it. The summarising editorial points out at great length that people who are ill sleep less well, and people who don’t sleep well feel more ill. All chickens come out of eggs, but not all eggs produce chickens, and not all chickens lay eggs. On the other hand, many chickens do lay eggs, and some of these can produce chickens, which, if… oh dear, I must have dropped off.

If you want to know how long students in 27 countries think they spend asleep, here’s the place to look. Also how this correlates with self-reported health. Shorter sleep is associated with more illness, whereas longer sleep isn’t, in case you wondered.

Great Nature gets up to some interesting tricks while we’re asleep. Our monocytes may need a good kip to promote cellular immunity, according to researchers from Lübeck. On the other hand, poor sleep may encourage inflammation, according to two papers (read here and here).

The rural folk of Keokuk County, Iowa, are among the latest clutch of Americans to have their lives followed in every detail by medical researchers. The investigators have enough data, and enough software, to adjust for sex, age, educational status, physical job demand, household income, depressive symptoms, marital status, alcohol consumption and snoring. This still leaves a substantial correlation between reduced sleep duration and increased body mass index.

As I hinted, it’s quite tricky working out cause and effect in some of these studies. However, here’s a longitudinal study which did sleep studies on an unselected cohort at 4-year intervals. Those with sleep-related breathing disorder had an almost two-fold risk of developing depression.

The nose is of course directly implicated in snoring, but these Frenchmen claim to be the first to confirm a definite relationship between allergic rhinitis and impaired sleep quality. They advise GPs to be particularly attentive, but I for one have been trying out Beconase on snorers for years with very patchy success.

There’s quite an extensive literature about sleep and type 2 diabetes, reviewed at the beginning of this new study, which concludes that sleep duration and quality are significant predictors of HbA_1c. The authors suggest that improving sleep might improve diabetic control. But have they shown which is the chicken and which the egg?

Lots of people who have trouble sleeping use complementary and alternative medicine, and nearly half of them find it helpful. The spectrum of therapies is enormous, but this paper makes no attempt to analyse them individually. I’m not quite sure what light it is supposed to shed on the subject.

Sleep come, sleep come, sleep come to my son, sleep hasten to my son! Put to sleep his open eyes, settle your hand upon his sparkling eyes—as for his murmuring tongue, let the murmuring not spoil his sleep. The first recorded lullaby—Sumer, 3^rd millennium BCE

J A M A 13 Sep 2006 Vol 296

Your humble workplace may not much resemble the Emergency Room at Yale, where this study was carried out, but you probably see just as many children with otitis media. As we all know, there is no evidence that antibiotics alter the course of otitis media; equally, as a professor of evidence-based medicine once said to me, “there is a lot of evidence that writing a prescription for amoxicillin gets the patient out of the door quicker”. The compromise is to write out a prescription, but to advise waiting 48 hours to give analgesia and time a chance to cure the earache. In this study, wait-and-see prescription (WASP) cut down antibiotic use five-fold. Let WASP be your buzz-word.

Left ventricular hypertrophy is a very simple phenomenon whereby individual cardiac myocytes get bigger in response to increase in load. This happens pretty quickly—three weeks is enough—and it disappears within the same period in response to unloading. The only way to measure this accurately is by cardiac MRI and the only way to measure it approximately is by ultrasound. If you use cardiothoracic ratio on X-ray or ECG voltage criteria, you can pick up a random percentage of gross LVH. Unfortunately most longitudinal studies do the last of these, and the one here is no exception. It shows that reducing ECG-LVH in patients with high blood pressure reduces their chance of developing atrial fibrillation. Which is what you’d expect. Stretched hearts go into AF: by the time you get to Grade 4 heart failure, the proportion is 50%.

It is hard to imagine a world without tea. The opening sentence of this paper declares that it “is the most consumed beverage in the world apart from water”. At present, I don’t contribute much to this statistic, but reading this 40,000 strong cohort study, I think I shall have to develop a taste for green tea. Regular consumption is associated with a reduction in stroke, cardiac mortality and all-cause mortality in that order. The authors looked hard for confounding factors, but do not mention the Japanese tea ceremony, which may in itself impart calming and health-giving properties such as “humility, restraint, simplicity, naturalism, profundity, imperfection…” (Introduction: Chanoyu, the Art of Tea).

Yippee: another paper in the always-excellent Rational Clinical Examination series, answering the question Does This Patient With Headache Have a Migraine or Need Neuroimaging? To diagnose migraine, remember the mnemonic POUNDing—Pulsating, duration of 4-72 hOurs, Unilateral, Nausea, Disabling. Go for neuroimaging in all cases of thunderclap headache, cluster headache and whenever you detect any neurological signs.

N E J M 14 Sep 2006 Vol 355

Over the eight years I have been churning out these reviews, I have repeatedly had to comment on various kinds of coronary artery stent. Gradually the Stent Wars have narrowed themselves down to single combat between sirolimus and paclitaxel, two immune suppressant drugs leached out (“eluted”) by the leading brands of stent. The study here shows that sirolimus-eluting stents put in immediately after myocardial infarction block less than bare stents in the first year, whereas the next paper shows that paclitaxel works less well. But—oh horrors!—two meta-analyses of their long term effects, presented in Barcelona last week, have shown that these stents actually produce worse results than bare metal stents in subsequent years. So the Stent Wars may have ended in defeat all round. It only remains to commemorate these fine names in a French Baroque Opera, in which Sirolimus, a Roman navigator, is washed up on the shore of Mexico and meets Paclitaxl, the great Aztec chieftain. The two swear friendship, but then both fall in love with Elutina, exiled daughter of the celebrated English dentist, Charles Stent. The climax comes when Paclitaxl, already mortally wounded, plunges his obsidian knife into the chest of Sirolimus and removes his beating heart, to a grand chorus of raving priests surrounded by massed llamas.

Talking of strange drug names, what are we to make of fingolimod? No doubt it belongs to that ubiquitous class of drugs, the thingummybobs. Actually it derives from the fungus Isaria sinclairii which has long been used in traditional Chinese medicine, and it works on the sphingosine-1-phosphate receptor. A thingummybob, in other words. It’s the latest drug to show promise in treating relapsing-remitting multiple sclerosis. But previous experience shows that it is best not to talk of a “breakthrough” on the basis of one short-term study.

B M J 16 Sep 2006 Vol 333

This editorial on emergency contraception is subtitled “is it worth all the fuss?” The Daily Express thought it was worth all the fuss of a front-page banner headline. For the American religious Right, it is also a major fussing issue. The analysis here shows that the correct answer is that it’s probably useful, but no substitute for regular contraception. Or indeed for chastity, as practised by the Daily Express and all right-thinking Americans.

The evidence is that blood pressure has been falling steadily over the last four decades in the USA, as in the rest of the developed world. Despite frantic efforts to massage the data, no study has ever convincingly demonstrated that salt in food has any effect on health. But this editorial depicts a battle between the dastardly Salt Lobby and the noble American Medical Association which wants to halve salt content in processed and restaurant food. As far as I understand the evidence, the only result is likely to be an increase in food poisoning.

Blue or orange, long or short? This study looks at the effect of needle gauge and length on local reactions and immunogenicity following infant vaccination. Go for a 25mm (long) needle length and the gauge doesn’t matter.

A thoughtful, well-described study of post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens. In the town of Dubbo, somewhere in southeastern Australia, investigators looked hard at what happened to people following significant infective illnesses such as glandular fever, Q fever and Ross Valley fever. The severity and duration of muscle pain, fatigue, and neurocognitive blunting depended on the severity of the presenting illness and not on “premorbid personality”.

Can you feel the head? I remember nodding dishonestly like most medical students in my first antenatal clinic, but after a busy O&G job I became confident enough to diagnose breech presentation and even attempt external cephalic version. But this is still not good enough, according to this Australian study. Only ultrasound will get it right all of the time.

This clinical review of ankylosing spondylitis contains all the right information, but it’s hardly an exciting read. Look out for morning stiffness lasting more than half an hour, waking up in the second part of the night, improvement with exercise, and alternating buttock pain.

It’s worth reading what these lab doctors are saying, though it’s irksome that they follow the usual pattern of talking at rather than with their primary care colleagues. Here they discuss HbA_1c. The main thing to remember is that it’s pointless to recheck it before at least two months.

Plagiarism of a minor sort is rife in medicine, and from time to time even I have had the gentle pleasure of reading a phrase or two of my own devising in other people’s work. Wholesale lifting is another matter. TS Eliot may have said that lesser poets borrow while greater poets steal, but what may be good for The Waste Land is not so good for academic medicine. The commentator says that ethical writing should be taught, but it seems to me all that’s needed is basic honesty.

Lancet 16 Sep 2006 Vol 368

So, do we now have a vaccine against H5N1 influenza A? Yes, several, and this Chinese phase 1 trial shows that one of them (inactivated whole-virion) is safe and immunogenic. If this is still an issue which gives you goose-bumps, other vaccination strategies are described in the accompanying editorial).

Fewer than a quarter of patients with acute myocardial infarction in the UK get immediate revascularisation; the percentage is probably even smaller for those with non-ST elevation MI. Are they missing out on a life-saving intervention? This five-year follow-up study of the Swedish FRISC-II shows that the answer is that any benefit is marginal, and perhaps only for males, non-smokers or those with two or more risk factors.

The Olmsted County Study is one of those big US epidemiological studies which inform our knowledge of cardiovascular natural history—a sort of Framingham Mark II. Valvular heart disease was once commonly rheumatic in origin, but Olmsted shows that it’s now mostly degenerative. And it gets commoner as you get older—11.7% over the age of 74, if you do echocardiography on everybody.

Panic disorder is the term used when panic attacks come on without any specific trigger. This often happens in the middle of the night, which to me casts doubt on the usual cognitive-behavioural explanation. Something sets off bad vibes in the amygdala and all sorts of autonomic and perceptive changes ensue. As this review comes from the USA, benzodiazepines are considered mentionable, even as a long-term treatment. And of course, cognitive behavioural therapy and SSRI antidepressants.

Plant of the Week: Kirengeshoma palmata

This is the handsomest of September perennials with its big palmate leaves and lovely yellow shuttlecock flowers. Plant it near the bright clear blues of Gentiana asclepiadea or the creeping Ceratostigma plumbaginoides. The books are right in saying that it likes decent soil and a bit of shade, but wrong in saying that it won’t tolerate lime. It thrives on ours.

J A M A 6 Sep 2006 Vol 296

When doctors are first let loose on real patients, especially in conditions of sleep deprivation, harm to both parties is not uncommon. This study looked at needlestick injuries to American interns in their first year, and finds that they occur more during night shifts and in the latter part of extended shifts.

Most of us shudder to remember those first years when we sometimes learnt from our mistakes. This Mayo Clinic study into perceived medical errors was as gentle as the investigators could make it, and found that a third of resident doctors felt that they had blundered badly at some time during the three-year study. These doctors had a doubled rate of psychological distress and showed a decline in empathy, as measured by standard questionnaires. The authors wonder if this can lead to a vicious cycle.

Now it could be that all doctors make the same number of mistakes in their resident years, but only the more conscientious and introspective notice and worry about them. This systematic review shows that by and large, physicians are bad judges of their own competence. It is a dangerous world for patients. Doctors can be self-confident but incompetent, or competent but self-doubting. Fortunately most of us manage to keep reasonably sane and reasonably competent for most of the time. I think. But then…

It is not for nothing that the word “doctor” means “teacher”. All doctors are educators to some extent. At the very least we sometimes try to educate our patients about what is wrong with them. Even the irascible surgeon barking at his theatre staff is an educator of sorts, using the oldest educational tool, fear. You will not find many discussions of fear in the literature of medical education, though it can still figure importantly in the lives of medical students and trainees. To help overcome it, the gentle figure of the mentor is supposed to waft in from time to time, befriending and understanding the learner and her/his needs. Does this actually happen and does it do any good? “The evidence to support this perception is not strong”, conclude these reviewers.

Evidence based medicine has been likened to a religion which seeks to make converts of all doctors. There are certainly some keen missionaries in our midst, though I am the more passive sort of believer. However, it is an agreed basic principle of our Faith that we should always seek evidence for what we do, and that includes evaluation of education in evidence-based practice. This review reveals that we need better instruments for extracting confessions. Nobody must escape the Inquisition.

N E J M 7 Sep 2006 Vol 355

Research into pre-eclampsia has been intense for the last thirty years at least, with very little to show for it. Could endoglin be the breakthrough? This study shows that circulating levels of circulating endoglin go up markedly 2-3 months before PET develops. So now we have a promising way of predicting pre-eclampsia, and we only lack a treatment. I’m not sure how we are supposed to pronounce this simple word. Is it endo-glin, a sort of Internal Welshman, or is it end-oglin, like when the time runs out on a peep-show?

A couple of weeks ago, a trial published in JAMA showed that unfractionated heparin could be used as simply and effectively as low molecular weight heparin following venous thromboembolism. This open-label study following elective percutaneous coronary intervention compares the LMWH enoxaparin with unfractionated heparin adjusted for clotting time, and favours the LMW preparation, though not by much.

So what actually happened to those poor guys who took part in the disastrous phase 1 trial of TGN1412? Here is a Brief Report (a mere 10 pages) from the London doctors who looked after them during the cytokine storm. Meddling with T-cell superagonists is perilous but, according to the related article in the same issue, full of potential. Any volunteers out there?

When I grew up, social anxiety was not so much a disorder as a state of mind which teachers and parents sought to instil in every child. It was known as breeding. You wore uncomfortable embarrassing clothes on all social occasions and were constantly frightened that you might be caught using the wrong item of cutlery. Disabling shyness was considered a virtue. But now that we have emerged from this Alan Bennett play into an adult paradise of total freedom, there are still some poor souls who suffer. The remedy? You guessed it—cognitive behavioural therapy. Don’t put your elbows on the table, dear, and tuck away that hankie before auntie comes in.

B M J 9 Sep 2006 Vol 333

This Antipodean study randomised patients to ibuprofen following hip replacement, not for its analgesic properties but because it inhibits ectopic bone formation. In this it succeeded, but that didn’t correlate with any clinical benefit, and the ibuprofen group had more post-operative bleeds. We think of ibuprofen as a friendly sort of NSAID, but it’s not really any friendlier than the rest.

We have entered the age of polypharmacy—well, I have, anyway. Poor compliance is associated with increased mortality. This can be improved by periodic phone calls from Polly in the pharmacy. If you wonder what she looks like, there is a picture on page minus 2.

In a couple of Lancet editorials, Peter Rothwell has urged us to pick the low-hanging fruit of clinical research. In this little study he brings us a basket of data from his own unit to show that the older you are, the less likely you are to be investigated for carotid disease following TIA or stroke.

Acute appendicitis is common and remains primarily a clinical diagnosis, as this review states. The interesting question for primary care is how to avoid missing it. Remember that urinary tract infections and gastroenteritis can coincide with appendicitis, and that if in doubt, there’s nothing so useful as re-examining the patient after a couple or more hours.

Most articles with titles like “Challenges for educationalists” are hot air, but this one from Maastricht isn’t. It is really good. “Finally, we think that medical education and general medical journals have accepted poorly performed and poorly reported research papers too often.” Amen.

I have dabbled in student education, and have even examined a few from time to time. This means I have “done OSCEs”—selected patients for objective structured clinical examinations. What an odd exercise this is. This article describes the selection of OSCE patients with pneumonia. In febrile patients coughing up mucky phlegm, do we base our treatment decisions on aegophony, fremitus and whispered pectoriloquy? No, thank God. We get them better.

Lancet 9 Sep 2006 Vol 368

Working on the topic of palliative care for heart failure (see Advertising Feature below), I came across the excellent narrative work done by Marilyn Kendall and Scott Murray in Edinburgh. This developed from sequential interviews of the dying patients to a 360 degree approach, involving the relatives and professionals as well. Scott now holds the first UK chair in primary palliative care and if that is your interest, or if you are interested in the experience of chronic illness, read this editorial.

The metabolic syndrome describes a cluster of cardiovascular risk factors that a lot of fat middle-aged people get. Obviously they should be on a statin, but which one and a what dose? This trial shows that atorvastatin prevents more events at a dose of 80mg than at 10mg. But I can’t see that persuading me to use that dose or this statin.

A common side-effect of serotonin reuptake inhibitors is ejaculatory delay, and from time to time I have prescribed paroxetine, the “worst offender”, to men with premature ejaculation. Now comes a short-acting SSRI, dapoxetine, specifically designed to prolong intravaginal ejaculatory latency time. The stopwatch in the bedroom reached a dizzying average of 3.3 minutes using the higher dose (60mg). I suspect that when it appears, the cost of this drug will cause a few ejaculations of surprise; and it remains to be seen whether our prescribing will be limited to the BSI (British Standard Intercourse) level of once a week.

A short review of novel strategies for stimulating erythropoiesis which describes several very complex-sounding ideas as “exciting”, only to acknowledge in the conclusion that epoietin (recombinant human erythropoietin) is an excellent safe drug which leaves little to be desired.

For some reason, the editor of The Lancet has given the Minister of Health of Mexico several pages inside and a big plug on the front cover. I have no doubt that his Seguro Popular scheme is a very good thing, but it sounds like creeping socialism to me. With a threat like that it in its own back yard, the USA will have to start spending more than a mere $450 billion a year on its armed services.

Advertising Feature: Heart Failure and Palliative Care: a team approach eds. Miriam Johnson and Richard Lehman. Radcliffe, September 2006

Reading those JAMA papers I was reminded of the awfulness of my own house-job years. One of the worst experiences was watching the death of a “pet” patient, a forty-something man who disguised his terror following a large heart attack by becoming very pally with all the junior doctors. He had been discharged but came back in severe heart failure. I had to sleep on the ward, which doubled as a CCU, and through the night I tried to relieve his distress with ever larger doses of furosemide and morphine in front of his inconsolable wife. The ward sister eventually sent me to bed, as he became ever more frothy and cyanotic. Every few years in general practice, I encountered the same awful scene. Then in 1991 my father died at home from heart failure. It seemed to me that the resources of palliative care needed to be brought to such patients, and this book brings together the thoughts of those who feel likewise. I think it is the first of its kind.

Ann Intern Med 5 Sep 2006 Vol 145

The Shingles Prevention Study showed that a vaccine against varicella-zoster virus can halve the incidence of shingles in immunocompetent people aged 60 or more. This study works that out to be 0.6 day of quality-adjusted survival. I suppose health economists have to write this stuff. What is the cost of a health economist per QALY gained?

The USA has been called an “obesogenic environment”, not least because of meal sizes in public dining places. This study attempts to compare the true calorie size of a meal and the estimate of the eater, and finds that people, both normal and fat, tend to underestimate the calorie content of large helpings but can guess accurately for smaller portions.

Americans spend an estimated $23 billion on vitamins and other health supplements each year, and here the US National Institutes of Health try to assess whether this is having any effect on chronic disease. Possibly: smokers taking carotene in supplements probably increase their risk of lung cancer. No benefit of any kind to anyone is likely.

Plant of the Week: Morus nigra

The black mulberry is a tree which has been cultivated “for ages”, according to Krüssmann, who is usually more precise. It is so widely popular around the Mediterranean and the Near East that nobody is quite sure where it comes from, or indeed when it reached our islands. Every other tree of such ancient cultivation, including the white (silkworm-feeding) mulberry, has sported many varieties, but the black mulberry comes in one form only, wherever it grows. It wears a gnarled, ancient appearance even when quite young, and drops boughs which readily form new trees, as in the Shakespeare Memorial Garden at Stratford, where the mulberries are supposed to be descendants of the bard’s own. Generally you can eat the fruit at will, as most people never bother with it. Ripe mulberries are delicious, but be sure your sin will find you out, as they quickly cover you and your clothes in purple stains. If you go gathering them, eat them the same day, as they will be covered with mould on the morrow. Do not cook them, or they will lose their distinct flavour. They would be heavenly in some French or Belgian concoction, with light almond pastry and crème pâtissière.

N E J M 31 Aug 2006 Vol 355

Primary Care—Will It Survive? is the question that opens this week’s NEJM. The scene is the USA, of course, where primary care physicians earn half as much as most specialists and are becoming less popular with patients, despite having consultation times twice as long as ours. American GPs still feel rushed, and have a sense that “the knowledge and skills they are expected to master exceed the limits of human capability”. At the same time, academic medicine treats them as dimwits and failures. No wonder recruitment is falling to critical levels. Beverly Woo tries to redress the balance with “Primary Care—The Best Job in Medicine?”, in which she describes the intellectual and emotional rewards of general practice, skilfully avoiding any hint of sentimentality or self-congratulation.

Until two years ago, cyclo-oxygenase-2 specific inhibitors were bringing in vast profits from the osteoarthritis market, but the manufacturers of rofecoxib and celecoxib were also eyeing up an even more lucrative market. They hoped to prove that these drugs would prevent bowel cancer. The only way to do this in the patent life of the drug would be to demonstrate that they prevent colorectal adenomas, which are thought to be the main precursors of invasive cancer. And they do prevent them, as demonstrated by this trial and the one on p.885. The details are unimportant because it became clear that patients on rofecoxib and to a lesser extent on celecoxib were experiencing an increase in cardiovascular events, and all the trials were stopped about two years ago. If you ever tried to use these drugs to prevent bowel cancer, you would bump off far more patients than you saved. All this is very well summarised in the editorial on p.950, which also mentions that celecoxib has about the same COX-2 specificity as diclofenac, and carries about the same cardiovascular risk. Now that the dust has settled on this question, the best place to find a summary is probably the BMJ review from May this year (332:895).

Deep brain stimulation for me at the moment consists of reading a book called “Quine: a guide for the perplexed”. Perhaps implanted electrodes would relieve my perplexity more effectively. In this trial, subthalamic nucleus electrode stimulation was used to alleviate Parkinson’s disease, with some success, though it’s hard to see this becoming a common option given the technical challenges and the possible complication of major brain bleeding

Marburg is small German university town, reasonably well-preserved despite having been a “target of opportunity” for bomber aircraft on their way to more important places. In medical circles, it is of course best known as the eponym of a deadly filovirus, carried to Marburg in 1967 by monkeys imported from Uganda. We still don’t know what its main animal vector is. This study shows that it has multiple genetic lineages and that people who venture into central African mines and caves are at particular risk. To do so is a batty idea.

We’re always being told that medical advances are giving diminishing returns and that most of the observed increases in life expectancy and health over the last forty years are due to non-medical factors. But this survey of US medical spending and outcomes from 1960-2000 proves that medical advances account for at least 75% of survival gain.

Do you have a cerebral aneurysm? “Autopsy studies indicate a prevalence in the adult population of between 1 and 5 percent”, which certainly means they are common. Quite how common or how risky is not clear from this otherwise excellent review, which like all medical reviews contains some baffling and contradictory arithmetic. Aneurysms under 7mm across are very unlikely to rupture, and radiologically directed intravascular coiling is the treatment of choice for most aneurysms in most circumstances.

B M J 2 Sep 2006 Vol 333

RLS stands for Robert Louis Stevenson (1850-94), the first great writer of short stories in English, whose popularity has withstood many changes of fashion. Restless Leg Syndrome has purloined his initials, but I suppose it can claim priority, judging from the excellent description by Thomas Willis in 1685. This editorial provides a very useful little summary. Check the ferritin. Prescribe a dopamine agonist for better sleep and fewer kicks.

Two reports from the OCTOPUS trial (are there six more arms to come?) which suggests that the best way to manage children with mild head injuries is to CT scan them rather than admit them for observation—see Harvey Marcovitch’s editorial.

Most GPs in the UK have been running in-house diabetic clinics for over 10 years, stimulated (in part only, of course) by various kinds of financial reward. Now we even get points for tight glycaemic control, though we know from UKPDS that this is much less important than good blood pressure control in reducing the vascular complications of diabetes. This review restates the main lessons. Polypharmacy is good for diabetics: the best drugs are statins and hypotensives, and the worst are the sulfonylureas.

Articles written for “primary care”, like this one about abnormal “liver function tests”, should in principle always have at least a co-author from general practice, but I will waive my objections for this very useful little piece. The quotation marks around “liver function” emphasise the fact that the enzymes we use as “LFTs” are not specific to the liver. For lovers of foie gras, a succulent slice is illustrated. Bring your own black truffles and a bottle of Château Montbazillac.

Over the Blair years, the NHS has gone into a series of jerks from one direction to another - a kind of chorea that even Sydenham would be hard put to describe (see book review). Dementia in the elderly suddenly became important a few years when cholinesterase inhibitors were marketed for their supposed benefits in Alzheimer’s disease. They were prescribed widely until NICE decided they shouldn’t be, no, sorry, that they should be; no sorry, I meant shouldn’t. Memory clinics sprang up everywhere. Now they have little to offer, and the authors of this article plead for a diversion of resources into actually helping the patients and their carers.

Lancet 2 Sep 2006 Vol 368

Poison via the ear may have seen off Hamlet’s dad, but in that case he must have had a perforated ear drum so that it could trickle down the Eustachian tube. The nasolacrimal canal is a much more reliable route for poisoning people. We do this all the time by the use of eye drops, especially those containing β-blockers. This editorial points out that timolol 0.5% is a popular ingredient in combination eye-drops for glaucoma, and is five times stronger than needed to reduce intra-ocular pressure. The timolol misses the liver first time round and builds up to considerable concentrations, with all the usual side-effects, possibly including a higher risk of cardiovascular mortality.

For the last few months, The Lancet has sported an occasional column called Cuttings by Clarice Audrey. I don’t know who she is, and despite the title of her column, you will find no gardening tips. She offers advice in a somewhat regal tone to a variety of medical potentates: this week it’s to the editor of the BMJ, suggesting a return to Richard Smith’s all-about-my-pet-rabbit style, plus political outspokenness about the demise of the NHS. Hmmm. Forget the pet rabbit; and a much quicker way to save the NHS would be to detain Anthony Blair under the Mental Health Act. She should address her advice to the President of the Royal College of Psychiatrists.

Are you up to date with modern immunotherapeutics? Do you know your chaperonins from your heat shock proteins from your Toll-like receptor (TLR) inhibitors? You do? Well, hah, hah, they’re all the same thing. The inflammatory cascade involved in rheumatoid arthritis is truly confusing and there are over one hundred new drugs in various stages of testing. I suppose the simplest way to think about it is that the chaperonins are there to stop the TLRs getting carried away and doing naughty things to the synovium. If you could make artificial chaperonins then you might be able to stop all this undesirable hanky-panky and cure rheumatoid arthritis. This happened to varying degrees in this short-term trial of chaperonin 10.

Penicillin was first tested on Staphylococcus aureus (for the full story, read The Mould on Dr Florey’s Coat by Eric Lax), but retaliation was swift: fifteen years later, most staphylococci had acquired penicillinase and were gobbling up penicillin. Then came meticillin and we got the upper hand again. But not for long, and now, as we know, hospitals and communities are full of meticillin-resistant Staph aureus (MRSA). Whether this a killer plague threat or a mere inconvenience remains to be seen. These bugs are versatile, and so are we: Staph Wars has a few sequels to run yet.

Fungus of the Week: Amanita virosa

This is one of the most beautiful of fungi, a pure white creature of angelic appearance. In fact its common name is the Destroying Angel. It looks so tempting, and so like a very white edible field mushroom with albino gills. It contains a number of lethal toxins. It grows on every continent and is nowhere very common, but there are case reports of fatalities in most European countries, in Iran, China, Australia, the USA and South America. Moral: never eat a white field mushroom unless it has brown gills.

It has even been suggested that A virosa might be used for terrorist or criminal purposes (Vet Hum Toxicol 2003;45:226). The best account of its toxicology, oddly enough, is in Homeopathy 2004;93:216. One very good place to find the fungus is right by our local Postgraduate Medical Centre.

Sumerian Proverb of the Week (ca 3000BCE):

A thing never seen before: a young wife who did not fart in her husband’s bed.

This somewhat surprising item is found in one of the main Sumerian Proverb tablets. The world’s first joke of its kind?

J A M A 23-30 Aug 2006 Vol 296

What we dignify with the name of heparin is a pretty crude sort of liver extract, one step up from Bovril or Liebig’s Meat Tea. So when more highly fractionated, low-molecular weight (LMW) heparins came on the scene, they rapidly replaced the older kind in most clinical situations. This trial compared a fixed subcutaneous dose of LMW heparin with a fixed subcutaneous dose of unfractionated heparin, in people who had acute venous thromboembolism. The trial was called FIDO, perhaps because liver that has had the heparin taken out ends up in delicious blobs of dog food. Cheap crude old heparin performed just as well as its low-weight successor.

It’s only a few weeks ago since a reported outbreak of Fusarium keratitis from Singapore, a destructive fungal infection of the cornea caused there by infrequently cleaned contact lenses. The outbreak described here affected people in 33 US states. Fusaria are ubiquitous and mostly useful fungi which rarely attack the human cornea, so when case reports came flooding in to the US Centers for Disease Control and Prevention in March this year, the hunt was on. The culprit turned out to be a contact lens solution called ReNu with MoistureLoc. No longer a leading brand, I imagine, except as a culture medium for mycologists with an interest in Fusaria.

Herpes simplex viruses are a recurring bane to many people, mostly around the mouth or the genitalia. As a rule, it is type 1 for non-sexual infection and type 2 for sexual infection. But this US epidemiological study shows that type 1 is gradually entering the genital market, so to speak.

Patients, mostly old but some young, still come out of hospital with bedsores, provoking cries of “bring back matron”. Maybe. This systematic review of preventing pressure ulcers is certainly no bag of hi-tech surprises. Even ripply mattresses and turning regimes lack evidence, though there is some support for the idea of moisturising the skin and feeding the patient.

N E J M 24 Aug 2006 Vol 355

Just as we’re abandoning BMI (I hope) in favour of the much more predictive waist-hip ratio, or indeed just the waist circumference, comes this immense analysis of BMI and all-cause mortality in Americans aged between 50 and 71. The crude figures are quite reassuring for a 56 year old male non-smoker with a BMI of 27, who is the person I am most interested in. Do some beastly multivariate analysis, however, and it’s beginning to look a bit worse, but not by much. If you come from Korea, you can look up your odds on p.779.

Most of us will never see a case of Chagas’ disease, a parasitic infection with Trypanosoma cruzi which can kill people in Latin America by cardiac involvement. This study from Brazil comes up with a risk score for death based on measures of cardiac function like ECG, echo, etc etc. But what is the best way to predict cardiac death in any individual? Measure B-type natriuretic peptide. It is as simple as taking blood, and it has already been shown to be the best marker for cardiac involvement in Chagas’ disease (Lancet 2002;360:461), by another group from Brazil. I hope this lot have stored sera from their cohort, and I’ll bet them 1,000 Brazilian reais that a single measurement of BNP outperforms their fiddly scoring system.

Self-importance is a key attribute for neurologists. I say this not to cast any moral slur on this fine body of colleagues, but simply to point out that this is what we use them for. When we send them a patient, we are saying, “Your pattern recognition is better than mine. Please give this patient a label.” When a patient comes along with dystonia, we ask a neurologist, rather than writhe about in ignorance. There are 13 numbered genetic dystonias plus another two with weird names, almost all very rare. This is a comprehensive review containing a number of tic boxes. As for treatment, the bottom line for most of them is botulinum. I’ll try to stop now. Unfortunately I have a rare autosomal recessive bad-punning syndrome.

B M J 26 Aug 2006 Vol 333

Tests for cancer are amongst the most studied of diagnostic tests, but are the studies much good? The way to find out is to do a systematic review; but are the systematic reviews much good? This analysis of them is written by leading experts on the reviewing of diagnostic tests, but is their review much good? The answers are no, no and yes. The accompanying editorial points out that diagnostic research is still a poor relation to interventional research. If you want to look for the evidence, she sets out a useful strategy.

We tend to think of renal physicians as Awfully Clever Doctors who know what to do in situations where we don’t have a clue, like acute renal failure. So: do you give an oliguric patient in ARF furosemide or intravenous fluids? This meta-analysis and the accompanying  editorial show that renal physicians don’t have a clue either.

This is a really good review of obsessive-compulsive disorder for the general clinician. As ever, cognitive behavioural therapy is the best treatment. If you can’t get access to that, at least hoard away several copies of this article, refer to them repeatedly and make sure you wash your hands several times afterwards. Did you switch the iron off?

Lancet 26 Aug 2006 Vol 368

In this editorial, Richard Horton (aka The Lancet) calls for us to “step out of the straightjacket of the seemingly unifying name” of asthma. I think of it less as a straitjacket (correct spelling), i.e. a confining garment, more as a sort of king-size duvet cover inside which a number of children are playing, while we fumble on the outside, trying to guess who is which.

Asthma is of course managed almost entirely in primary care, but as this is The Lancet (aka Richard Horton), this demeaning fact is nowhere apparent, least of all in the authorship of the papers in this asthma special. But let’s not carp: there is lots of interesting stuff here of the sort which The Lancet does well, such as world epidemiology. The acronym is ISAAC (International Study of Asthma and Allergies in Childhood). In places where asthma was less common, it is becoming commoner; in places where it was more common, it is declining. Isaac turns out to be something of a sheep.

Here is another study of an inhaled long-acting β2-agonist plus corticosteroid combination (formoterol/budesonide), looking specifically how best to treat exacerbations of asthma in patients taking this combination. These exacerbations are probably more dangerous in patients taking such a combination than those not (see meta-analysis, Ann Intern Med 2006;144:904), but if this big study is to be believed, the best way to treat an exacerbation is to inhale more of the combination rather than turn to a short acting β2 agonist like salbutamol or terbutaline.

Pre-school wheezing is not necessarily a precursor of chronic asthma in later life, and is increasingly being investigated as a separate entity. Various trials are now being reported about the early use of inhaled steroids in wheezy children. None of them show any benefit in preventing further episodes.

This birth cohort from Germany sheds further light on the natural history of wheezing in pre-school children. It may be quite simple. If a child becomes allergic to a common perennial allergen in the first three years of life and starts wheezing, that child will have atopic asthma later in life, and impaired lung function at school age. By contrast, 90% of children with no atopy who wheeze before school age stop wheezing later and have normal lung function at school entry.

By contrast, looking at β2-adrenoreceptor polymorphisms in a cohort of 8000 people born in 1958 showed little correlation with asthma. Another one for the Journal of Negative Genomics.

The current fashion for genomics means that anything previous called a “group” or “kind” is now called a “phenotype”, so that although we know little useful about the genetics of asthma, this paper identifies various phenotypes and sub-phenotypes of severe asthma in adults, no doubt hoping that genotypes may follow one day. It’s a depressing review, with lots of complicated inflammatory cascades that don’t always respond to steroids, meaning that nasty drugs like methotrexate and TNF blockers may have to be used.

It would be nice to think that we know more about how to treat mild or moderate persistent asthma, and this review is certainly upbeat about the role of long-acting β2-agonist/corticosteroid combinations, which do seem to help a lot of my own patients more than separate use of short acting β2 agonist inhalers and steroids. But I still worry about that meta-analysis in the Annals (see above).

Abraham and Isaac

Mention of the ISAAC trial reminds me of an Emily Dickinson poem about the enigmatic story of Abraham and his son:

J A M A 16 Aug 2006 Vol 296

Like most GPs in the UK, I hope to be able to spot the signs of HIV infection, but leave its management entirely to specialists, so I have don’t usually comment on papers about HIV/AIDS. But for those who do want the latest information, the Lancet a couple of weeks ago and this week’s JAMA provide rich pickings. Knowing more about heart failure than HIV, I am struck by the similarities in interventional trial design for these two life-threatening illnesses where you can’t afford to take risks: both tend to add the latest drug on to standard treatment, with diminishing returns. A trial which added one of the latest anti-retrovirals, abacavir, to a standard regime of lamivudine, zidovudine and efavirenz showed no additional benefit in treatment-naïve patients. But I shall shut up and let those who need to browse the whole issue. For the generalist, the article of greatest interest is likely to be the one about metabolic and skeletal complications of HIV infection.

N E J M 17 Aug 2006 Vol 355

Most early antibiotics were first isolated from fungi, and for a long time any new antibiotic tended to bear the suffix –mycin. There was even a story that drug companies used an early computer to generate words ending in mycin, but stopped when it reached godamycin. Daftomycin would be another poor choice, at least in England (does the word “daft” exist in US or Australian English?), and daptomycin is only slightly better, as a name and as a drug. Used to treat Staphylococcus aureus bacteraemia, with or without endocarditis, it gave equivalent results to standard treatment, but resistance developed in significant proportion of patients despite the novelty of the agent.

Methicillin-resistant Staphylococcus aureus is racing across the USA, to the extent that most staphylococcal infections in American communities are now meticillin (UK spelling) resistant. Fortunately they are sensitive to a lot of other antibiotics, notably timethoprim/sulfamethoxazole, and in any case they usually respond to traditional non-drug treatment. Super-invasive killer strains are a theoretical possibility, as the editorial on p.724 indicates, but by no means a likelihood.

About fifteen years ago, when the bisphosphonates were quite new on the scene, I remember asking a bone expert at a meeting whether we should be using them to prevent steroid-induced osteoporosis. He blustered something about it being illogical to use an anti-resorptive agent for something caused by suppression of bone production. I didn’t follow that at the time, and whatever he supposed to be the logic of the matter, he was wrong. Here is a trial showing that alendronate works and alfacalcidol (a vitamin D₃ analogue) doesn’t.

It must be agony being the parent of a very preterm infant, knowing that despite the endless efforts of the special care baby unit, neurodevelopmental damage is very likely. Can it be predicted by brain MRI at term equivalent? This study shows that it certainly can, though whether I would want to know is another matter.

Goodness me. In the USA, it’s healthier being rich and old than being poor and old.

A couple of London rheumatologists present a case discussion illustrating the use of tumour necrosis factor inhibitors for rheumatoid arthritis. This is a useful article, which runs through the alternatives for severe RA, and summarises the main dangers of TNF blockers—activation of latent TB and susceptibility to serious infection—while putting their other dangers—risk of cancer and heart failure—into perspective. They also comment wryly on the restrictive nature of the NICE guidelines.

B M J 19 Aug 2006 Vol 333

The great worry about the Chinese has always been that there are so many of them. The British in the early nineteenth century decided that the answer was to flood the country with Indian opium and render the population passive and addicted. I guess the word “junkie” dates from this. The Japanese between 1937 and 1945 just killed as many as they could, using whatever came to hand (bullets were considered too good): estimates vary between 20 and 35 million. The Great Helmsman Chairman Mao Zedong proclaimed that the country’s strength lay in its people, and encouraged childbearing, but still managed to starve at least 5 million by his policy of forced agrarianism. Against this backdrop, the 1970s One Child Policy seems positively rational and humane, though it caused anguish to tens of millions. It was a key factor in China’s economic miracle (see accompanying editorial) and now that it has been relaxed, China’s population is increasing again, albeit at the sedate rate of an extra million every five weeks.

Hidden among the chinoiserie this week, here is a really good succinct account of psoriasis and its management. I didn’t know, for example (or have I just forgotten?), that widespread psoriasis is a major risk for cardiovascular disease; or that some centres insist on regular liver biopsies for people taking methotrexate.

The Lesson of the Week is don’t trust vitamin B12 assays. If they are good for anything, it is telling you how much B12 is in the serum, 10% of which is bound to transcobalamin and therefore physiologically active. The rest is junk. What we need is access to assays of the B12-transcobalamin complex (holotranscobalamin), which might start to tell us what is really happening.

An article on research priorities in traditional Chinese medicine. We are told abandon inappropriate Western scientific paradigms. Just so. Let us instead follow Confucius, who when dying was sent medicine by a nobleman:

“When K’ang Tzu sent a gift of medicine, the Master bowed his head to the ground before accepting it. However, he said, “Not knowing its properties, I dare not taste it.” Analects X.16.

Plant of the Week: Ceratostigma willmotianum

Like most of what is best in our gardens, this little shrub comes from China. I have sung its praises before, but will do so again in case there are readers who still haven’t planted this jewel in a sunny spot. There is no excuse for such an omission, unless you live on some cold bleak Northern hillside. Put it in a public place and you will give joy to all who see its abundant sharp blue flowers spread all over the sprawling thin branches. They are produced over many weeks until the leaves turn orange and red, providing a spectacular end to its season. When they have dropped off, cut it back to within a few inches of the ground.

Ann Intern Med 15 Aug 2006 Vol 145

237 British GPs have suddenly become interested in the kidney (or perhaps I should say kidneys, as I discover that there are two of them), ever since we started earning money by keeping registers of those who have estimated glomerular filtration rates of less than 60. Most of us were happily oblivious to our patients’ eGFRs until this year, and perhaps better so: this study proves that cystatin C is a much better marker. This is perfectly straightforward in the elderly (aged over 65 in this study): elevated cystatin C predicts cardiovascular events, death and kidney failure much better than eGFR. The paper claims that it is a dependable measure of kidney function at all ages, but in young people, low cystatin levels are more predictive of trouble. It is tempting to believe that there is an ideal marker which has “a constant production rate regulated by a “housekeeping” gene expressed in all nucleated cells, free filtration at the glomerulus, complete reabsorption and catabolism by the proximal tubules with no reabsorption into the bloodstream, and no renal tubular secretion.” , but alas, it is not quite so simple, though much better than anything else we have had to date.

So perhaps the paper which follows is destined to be come obsolete before it is put into practice. It provides data from the Modification of Diet in Renal Disease study which would result in more accurate estimation of the eGFR based on serum creatinine: the gold standard here was GFR measured by ¹²⁵I-iothalamate.

This paper sums up the disappointment of a huge crowd of investigators at finding no link between common vitamin D receptor gene variations and osteoporosis in a cohort of over 26,000. I feel every sympathy for them, but would not this sort of thing be better placed in a Journal of Negative Genomics?

Lancet 19 Aug 2006 Vol 368

When I was first a GP, the common dogma was that one didn’t try to reduce blood pressure in the elderly too much because they would just fall over more. Now the trend is towards aggressive BP reduction. This is actually quite a complex issue, very clearly discussed in this editorial by two leading investigators from Framingham. Pulse pressure and arterial stiffness become more important as age progresses, and I am not sure that we can do much about them by that stage.

It needs repeating that smoking causes heart attacks. This is an analysis of the 52-nation case-control INTERHEART study. Some of it is to do with tobacco, since those who chew rather than smoke the stuff still get more MIs; some of it is to do with smoke, since those who smoke beedies containing small amounts of tobacco get as many as those who smoke full-tobacco cigarettes. Pipe smokers fare worst.

Last week I mused on the alleged magical advantages of angiotensin-converting enzyme inhibitors over other blood pressure lowering and vasodilating drugs. Here comes a population-based case-control study appearing to show a specific protective effect against ruptured abdominal aortic aneurysm. As some English teenagers have been saying this last week, “A straight three As! ACE!”

Nowadays we shepherd our patients with coronary artery disease once or twice a year into nurse-run clinics where they are weighed and receive dietary advice. I maintain a merciful ignorance of what gets said on these occasions, but this systematic review shows what it should be. If a patient has a BMI of less than 20, they need to put on weight urgently. If it is below 25, they need to put it on less urgently. If it is between 30 and 35, that is just fine. But, unwilling to let the plump get away so lightly, an Italian commentator  suggests that we should still harry them about their waist-hip ratio.

When the Polypill papers first appeared in the BMJ, an ecstatic Richard Smith hailed them modestly as the most important to appear for 50 years. I have been umming and erring every since (erring more than umming, according to Jeff Aronson), and now The Lancet tardily looks at adopting the idea for the developing world. They conclude that “regimens of aspirin, two blood-pressure drugs, and a statin could halve the risk of death from cardiovascular disease in high-risk patients”. Indeed, but the main attraction of the Polypill idea is that it applies to all people at all levels of risk, thus avoiding making them into “patients”.

The cardiac bypass pump has allowed all sorts of surgery that was hailed as miraculous when it first became possible forty years ago, including the commonest operation now performed, which is coronary grafting. But these pumps do tend to throw debris into the brain, and central nervous system injury leading to less-than-subtle cognitive changes is very common. When my time comes, I think I would want a beating heart graft.

Arch Intern Med 14-28 Aug 2006

Laburnum seeds are best known among doctors as a cause of potentially fatal poisoning in children, but this review points out that they have been used as an aid to smoking cessation in Eastern Europe for more than 60 years. Linnaeus called the common laburnum tree Cytisus laburnum, placing it among the brooms, and so the active ingredient of the seeds was christened cytisine, not to be confused with cytosine or cystatin. The botanically correct name of the tree is now Laburnum anagyroides, and calling the stuff laburnine would save a lot of confusion. Anyway, it is a potent insecticide like nicotine, and binds strongly to the α₄β₂ nicotinic receptor. Unfortunately all the studies are of poor quality and none of them is in English, but there are good reasons to believe the stuff works, as its derivative varenicline certainly does.

And here is the evidence. In one study, the groups were randomised to varenicline, bupropion and placebo. The paper reports the one year outcomes. Varenicline won with 14.4% still abstinent, versus 6.3% for bupropion and 4.9% for placebo. In another study the results were considerably better, with 22% one-year success for varenicline 1mg vs 3.9% for placebo.

Since most English GPs don’t have many patients with HIV, and leave most of their management to specialist centres, I tend not to comment on most studies about this important topic. However, I was struck by this study which points out that in the developed world the commonest cause of non-AIDS death in this group is liver failure, mostly due to co-existing infection with hepatitis viruses.

Four hundred years ago, the Dutch were perhaps the most intrepid merchants in history, travelling to unknown parts of the world in search of riches, at huge risk of death from shipwreck, violence or disease. Falciparum malaria was probably the biggest killer then, and it certainly is now: in fact it was the only fatal infection in this series of 1743 tropical fever cases in returning travellers admitted to a Dutch hospital.

This study shows that chronic widespread pain is often associated with chronic fatigue, depression, irritable bowel syndrome and joint pains. If only we knew how to help these people, for their sakes and ours.

A recent review told us not to bother looking for the so-called common thrombophilias, because they make no difference to management. But now, hard on the heels of a paper about thrombin generation, comes another Austrian study identifying what looks like a major risk factor for recurrent venous thromboembolism—a single nucleotide polymorphism in the E-selectin gene. Homozygosity for the Ser128Arg mutation if you must know.

Does your testosterone level really matter? I’m not referring to competitive cyclists, but to ordinary blokes over the age of 40. Actually, not completely ordinary blokes, but US Armed Forces Veterans who had their testosterone levels measured as part of a prospective study mainly to do with prostate cancer. Total testosterone below 8.7 nmol/L is associated with a considerably increased mortality risk, for reasons which are far from clear. Anything above that, and you’re OK.

Blake for the Week

Eternity is in love with the productions of time.

Proverb of Hell from The Marriage of Heaven and Hell 1790

J A M A  9 Aug 2006 Vol 296

The journals are in sleepy holiday mode this week. What they need is a 150 Joule shock to the precordium, delivered by an automated defibrillator. If the machine works, that is. Now and again, they fail in the hour of need, for reasons explained in this survey of reported malfunctions in the USA.

Stuck for anything better to tell you about, let me inform you that a huge group of genomists has found that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease. This paper is strictly for lovers of genomic arcana: it illustrates all sorts of fearfully complex analytical processes, like estimations of the Hardy-Weinberg equilibrium in controls. And the clinical significance? If you could ever measure this variability in real life, you would find that such patients went on to develop Parkinson’s disease a third more often. Personally, I find it more interesting that the multinational investigators call themselves the Genetic Epidemiology of Parkinson’s Disease Consortium, but when they publish in the USA, they are made to drop the genitive “s”. This illustrates Lehman’s law of the eponymous genitive, which states that eponyms are nine times more likely to be given the genitive form in European publications than in American. In fact, in the USA, this would to be known as Lehman law, nine times out of ten.

N E J M 10 Aug 2006 Vol 355

Erratum: In last week’s review of this journal, I stated that a rare subtype of neonatal diabetes responded to metformin. What I should have said is that it responds to sulfonylureas. I went on to say that we needed more drugs with the same action, but we certainly don’t need more drugs like the sulfonylureas, which increase mortality in adult diabetics—see CMAJ 2006;174:169-74.

In another dull issue, this is the only paper to SPARCL. It describes Stroke Prevention by Aggressive Reduction in Cholesterol Levels. Which works more or less as you’d expect. Give patients who’ve had a stroke or TIA 80mg of atorvastatin and they have fewer strokes and cardiovascular events than those given placebo. But they die at exactly the same rate. What is really peculiar is that in this study, more patients on placebo complained of myalgia than those on whopping doses of atorvastatin: this seems to happen in most of the trials but never in real life.

I remember being intrigued when reading about Paget’s disease of bone as a medical student. But I have yet to see a case, and in fact its incidence and severity in the UK are on the wane. This is an interesting review which also describes effective treatments if you do happen to come across it.

Lancet 12 Aug 2006 Vol 368

Angiotensin converting enzyme inhibitors are good drugs with troublesome side-effects, and we don’t fully understand how they work. If you take one, you convert less angiotensin I in to angiotensin II for a few weeks, and then, even at maximum doses, you begin to produce more AII again. At all doses of every ACEi, you lose your ability to clear bradykinins, so if you get a cough, it lasts for ages. There have been three big trials using ACE inhibitors in patients with atherosclerosis but normal left systolic function—HOPE, EUROPA and PEACE. The last used trandolapril and did not significantly reduce cardiovascular effects or all-cause mortality. The other two used ramipril and perindopril respectively and reduced both. So perhaps ACE inhibitors do have benefits above simple vasodilatation and blood pressure reduction, but we don’t really know.

One couple in three hundred will experience three or more consecutive miscarriages by pure chance. But in fact recurrent miscarriage (here defined this way) happens to one couple in a hundred, so there are other factors which come into play in two thirds of such cases. This review describes our current state of knowledge, which does not extend to any useful interventions, though the authors recommend referral to an academic centre so that interventions known to be useless or harmful can be avoided. And so that they can recruit patients to trials.

B M J 12 Aug 2006 Vol 333

We know that acute infective conjunctivitis gets better whether or no you use topical antibiotics, but we still use them all the time. This study suggests a successful half-way strategy, just as for sore throats: delayed prescription. The patient or parent learns that time will do the trick but has the antibiotic to fall back on if needed.

A big German trial of different doses of metoclopramide (or none) given intra-operatively with dexamethasone 8mg to prevent post-operative vomiting. Those given 25mg or 50mg of metoclopramide fared best.

In bygone days, liquorice extracts with aldosterone-like properties used to be used to heal peptic ulcers, so do aldosterone antagonists like spironolactone actually promote ulcers and upper gastrointestinal bleeding? This case-control study finds a 2.7-fold increased risk.

A concise review of ulcerative colitis with few surprises. A quarter of patients still come to colectomy.

If you regularly turn to the BMJ Rapid Responses as a way to avoid doing paperwork or seeing the next patient, you will be familiar with the name of Stephen Black. He is a tireless advocate of Blairite management solutions for the problems of the NHS, who writes a rapid response most weeks and is here given a page of the printed mag. “More and better management is the key to fixing the NHS”, is his title and his claim. Less and better management, more like.

Plant of the Week: Cladastris sinensis

This is a tree of fabulous rarity which produces scented flowers in August. Why it should be so rare is a mystery, since it sets abundant seed. I once nearly bought one from Spinner’s Nursery, but was pipped to it by a man from Düsseldorf who travelled by train to claim his purchase and tenderly accompany it home. I believe you can buy this Chinese Yellow-wood from two or three places now, but we have run out of room for medium-sized trees. In any case, it may not really like the English climate in its traditional guise. There is a specimen in Westonbirt which looked on its last legs about seven years ago—they were trying to propagate it by air-layering. There is one at Batsford which looks fairly healthy, though I have never seen it in leaf, as it has about the shortest growing season of any hardy tree. Still, if you want to impress people in about thirty years’ time, buy one now.

J A M A 2 Aug 2006 Vol 296

US Army personnel who were deployed in Iraq show a tendency to mild impairment of sustained attention, verbal learning and visuo-spatial memory. Among all the dreadful consequences of the invasion of Iraq, place this one where you will.

Violence often begins at home: the commonest form probably used to be the beating of children, as enjoined by Scripture and numerous classical texts. Wife-beating has never enjoyed the same degree of divine or literary sanction, though it has probably gone on in most cultures most of the time. It is now probably the most common form of domestic violence in Western culture, if for wife we substitute “female partner”. You don’t have to be a GP for very long to realise how much of it lies beneath the surface, and also how reluctant some women are to disclose it. So it comes as no surprise that the best screening tool for intimate partner violence is an anonymous written questionnaire rather than verbal questioning by an identifiable health professional. Computer entry scored somewhere between the two.

We now move on to what used to be known in insurance parlance as Acts of God. If the deity is responsible for the movement of undersea tectonic plates, then last year’s tsunami counts as one of His more spectacularly unpleasant Acts. The Thailand Post-Tsunami Mental Health Study Group studied adult and child survivors and found, as one would expect, enormous levels of anxiety and mental trauma which gradually improved over nine months, though not of course to baseline.

In the last century, there was a terrible prolonged war in which millions of young men from two great civilised nations fought to a standstill in a barely moving line of trenches, with one failed offensive after another, while hundreds of thousands died under constant artillery bombardment and attacks using gas. This, you remember, took place between 1980 and1988, while Alan Clark (what a wag!) remarked that he did not lose much sleep over one lot of brown men killing a lot of other brown men. During these 8 years, we in the West made sure that one side—Saddam Hussein’s—got a constant supply of modern weaponry and the raw materials for poison gas. This study looks at the effects twenty years later on Iranian survivors of chemical warfare. They are awful. If you want to understand the situation in Iraq and Iran now, think of Europe in 1936, where nearly every family constantly thought of dead sons and carnage, and harboured a deep sense of grief, injustice, and foreboding about the future.

N E J M 3 Aug 2006 Vol 355

The USA was declared measles-free in 2000, but five years later an unvaccinated girl returned to Indiana from Romania, where measles is still endemic. She was incubating the disease and spread it to 34 unvaccinated family members, mostly children. Can we eliminate measles? Only if we manage to do it everywhere, by universal vaccination, as we did for smallpox.

Here is a form of diabetes mellitus which you are bound not to have heard about and are bound never to encounter. One baby in half a million has neonatal diabetes and 12% of these have a dominant mutation in ABCC8 which causes elevation of the basal magnesium-nucleotide-dependent stimulatory action of SUR1 on the Kir pore. I thought you’d like to know, that’s all. Well, not quite all. The intriguing part of the story (apart from the spectacular scientific effort involved) is that these babes respond to metformin, so this study helps to clarify the action of this drug. We badly need more and better drugs which work on these ATP-sensitive potassium channels, since they are the only ones which do our type 2 patients any good.

Do you remember the basic rules of cardiopulmonary resuscitation? Good. Well here are some rules for when to stop out-of-hospital CPR. They are—hang on, where are they? Hidden in the third paragraph: if you have no specialised equipment, give up if there is no return of circulation before transport arrives, if no shock was given before transport arrived, and if the arrest was not witnessed by a trained observer. These patients never make it.

488 On a dafter-than-usual front cover, this week’s BMJ promises to tell us about Conquering Varicose Veins. That’s like conquering terrorism—it can’t be done, unless you get rid of the underlying problem. In the case of varicose veins, that’s the human combination of upright posture and weak venous valves. The NEJM article here is on chronic venous disease: unambitious and dealing largely with these and other mechanisms. I don’t know what the answer is—support stockings for all?

B M J 5 Aug 2006 Vol 333

I have given up trying to find any logic in this (or any previous) government’s attitude towards harmful and/or addictive drugs. This editorial calls for a complete rethink on their classification and the penalties attached. Why, we could even think in terms of harm reduction all round, including the top killers, tobacco and alcohol.

A systematic review of mostly very old studies of antibiotics for purulent rhinitis. Most green snot goes away on its own: almost all of it does if you give an antibiotic. There are few significant adverse effects. So do as you please: this is not a moral issue.

Oxfordshire hospitals are examined for their (combined) rates of staphylococcal infection including MRSA. An earlier report showed that our beloved little local DGH was much safer than the big academic unit where the investigators work: but here there are no figures, perhaps because they are planning to close down much of our nice clean local hospital.

For obstetricians and midwives, antenatal screening for Down’s syndrome is an important issue, which they explain on a daily basis to often anxious pregnant women. This study looked at how well people understood two ways of explaining the meaning of a positive serum test, in terms of percentages or in terms of frequency. Everyone performed abysmally: midwives scored 0%, the pregnant ladies 9%, and the obstetricians 34%. Even the authors got it wrong, by misprinting the last figure as 43% in their abstract.

Here is a useful and practical guide to varicose veins. Conquest, no: sensible advice and treatment, plenty.

Plant of the Week: Hydrangea seemanii

This is an evergreen climbing hydrangea which has been available in the UK for a decade or more, but I have never seen it flower until this year. It will tolerate a north wall, growing slowly with somewhat lugubrious leaves which are frequently scorched at the tips by frost. Maybe with time and global warming it will be quite an ornamental plant with typical white lacecap flowers.

Ann Intern Med 1 Aug 2006 Vol 145

Tudor Hart’s Rule of Thirds for hypertension may no longer apply in the UK, where the data I have read about seem to suggest a major improvement in BP control; though since QOF introduced payment by results, we may see a new rule of thirds emerging, whereby one third of GPs record BP accurately, one third cheat occasionally, and one third cheat quite a lot. This study shows that if you really want to control BP, it’s important to get the patient on side—interventions that included patient education gave the best (true) results.

This systematic review gives unwelcome confirmation that donating a kidney generally raises blood pressure by 5-10 mm Hg over the following 5-10 years. More prospective studies are needed to stratify risk.

Haemochromatosis is often familial, and the genetic type associated with it is C282Y homozygosity. But clinically significant haemochromatosis is relatively uncommon, and most homozygotes for C282Y never come to any harm. So the US Preventive Task Force comes to the conclusion that it should not be screened for in the general population, though its systematic review finds many gaps in the evidence. And this advice does not apply to the families of those with established haemochromatosis, who definitely should be screened for C282Y.

Lancet 5 Aug 2006 Vol 368

In this issue devoted to HIV/AIDS, there is an enormous amount for anyone who has a special interest in the politics of the condition and its treatment, but the general reader can skip straight to this useful and authoritative review. The proportion of women with HIV is constantly increasing, and so is the number of infected people outside southern Africa. In the developed world, treatment is becoming more effective at reducing viral load but there has been little shift in clinical outcomes. What we all want to hear is that there is an effective vaccine on the way, but the review is very guarded about the prospects.

One of the oddest areas of the HIV debate is the place of circumcision. This centres largely around a single prospective trial in which 3274 South African farm labourers were randomised to be circumcised and then followed up with HIV testing for 21 months. The protective effect was estimated to be 60%—interesting, but hardly the kind of safety net you’re looking for with a potentially lethal infection. I have a lot of sympathy for religious feeling in others, but how religious significance became attached to the removal of the male foreskin is something that baffles me.

Frank Harris and Circumcision

In My Life and Loves (1923), Frank Harris describes how he became the greatest editor London ever saw (true) and England’s greatest lover (possible). He spends a whole chapter describing how he underwent circumcision as a young man purely for the sake of prolonging the pleasure that he was able to give to women (ahem). He was London’s loudest talker. He was a generous and loyal friend to Oscar Wilde, but denied that he had ever had a homosexual encounter, and bellowed that he never would under any circumstances, except possibly if Shakespeare (his idol) had asked him. This provoked a wonderful cartoon from his friend Max Beerbohm, which you can find here

J A M A 26 Jul 2006 Vol 397

So far, the predictive value testing for common “thrombophilias” following a single episode of deep venous thrombosis has been too poor to tell us who might need to take warfarin indefinitely. This Austrian study has come up with a better marker, which is quite simple to measure—thrombin generation. This is a continuous variable, and although the investigators identified a particular value which defines a low (i.e.10% at 5 year) risk of recurrence, we need more studies before we can really tell where this is going to fit in to routine clinical practice. In other words, how much thrombin do you have to generate to require lifelong anticoagulation?

For two decades, cardiologists have sought the Holy Grail of an imaging method which could relieve them of the chore of coronary angiography. Many a hermit have they asked, and many a Castle Perilous attempted, but the Grail eludes them yet. This particular troop of pure-hearted knights marched under the banner of CATSCAN, but their scanning has been vain: 16-row multidetector CT turns up too many false positives. But onward! For lo, what is yonder shrine, begirt with magnets bright?

Few medical problems in the developed world are more pressing than the epidemic of type 2 diabetes, but is ever more careful attention to glycaemic control really the answer? The studies of quality improvement strategies make gloomy reading, according to this meta-regression analysis. Essentially, megatons of blubber must be burnt off or otherwise removed from these patients if we are to have any hope of preventing the long-term cardiac and renal sequelae (see Pima Indian study).

N E J M 27 Jul 2006 Vol 355

Nitrogen and oxygen are close pals, in the air we breathe, in the Periodic Table, and in the ways they find to combine with each other as N₂O, NO and NO₂. The useful properties of nitrous oxide have been known to medicine for 200 years, but the full role of nitric oxide has only been recognised in the last 20 or so. To be sure, nitrates have been used for much longer, but their mode of action in the systemic vasculature is much clearer to us now that we recognise the role of NO in combating the deadly endothelins. Perhaps a whiff of NO is also good for the pulmonary vasculature—an idea explored in two studies in preterm babies. These little 26-weekers, weighing about 760g, were randomised to receive NO, or no NO, through their mechanical ventilators. The NO group developed less bronchopulmonary dysplasia and showed no short-term adverse effects.

The results of another trial, this time on babies of less than 34 weeks’ gestational age who required ventilatory support, were a bit different. Only the older NO-treated subgroup showed any reduction in bronchopulmonary dysplasia, but there was an overall reduction in brain injury. So is the answer NO for premature babies? Yes.

The NEJM takes two looks at our National Health Service, this first being an analysis of pay-for-performance programs in family practices in the UK. That’s QOF points, in case you wondered. Has the programme succeeded? Yes. Have some practices indulged in a bit too much exception reporting? The Abstract comments that “More research is needed to determine whether these practices are excluding patients for sound clinical reasons or in order to increase income.” Indeed.

A useful review of resistant or difficult-to-control hypertension. Check on things like compliance, alcohol and salt intake; but also bear in mind that community studies have consistently estimated the prevalence of hyperaldosteronism in hypertensives at 15% or more, yet we continue to ignore this important subgroup.

Rudolf Klein tries to explain the Troubled Transformation of the NHS to a mainly US audience—an impossible task, since it is a random interplay of contradictory forces, with nobody in charge, least of all the Secretary of State for Health. As Wittgenstein said, Whereof one cannot speak, thereof one must remain silent. Though I find that throwing crockery sometimes helps.

B M J 29 Jul 2006 Vol 333

When I first read about laparoscopic nephrectomy some years ago, I thought “whatever next?” That operation consisted of introducing a kind of liquidising device and then sucking out the resulting kidney gloop; but nowadays it seems one can remove an intact donor kidney—with results that are generally superior (in experienced hands) to mini incision open nephrectomy. Pretty amazing, or what?

A nation-wide survey of patients admitted to hospital in Finland with a diagnosis of schizophrenia finds that clozapine is probably superior to perphenazine depot or olanzapine, though the confidence intervals overlap a great deal: but patients given oral haloperidol are much more likely to discontinue treatment or end up back in hospital.

Are you an abstract skimmer or a paper reader? “Significant results in abstracts are common but should generally be disbelieved.” says Peterl Gøtzsche, after listing significant results in his abstract. This is known as the Cretan conundrum: a Cretan said, all Cretans are liars. Is he telling the truth?

An excellent review of subarachnoid haemorrhage which needs to be read by any doctor who might possibly meet with—and possibly miss—this condition.

I haven’t paid to much attention to the ABC of chronic obstructive pulmonary disease because, after all, what can you do about it once you’ve diagnosed it, other than helping the patient to stop smoking? This final article lists a huge array of coming therapies: there is plenty to hope for.

An independent NHS? Four brief articles take up the idea which Fiona Godlee proposed some months ago, but all of them flounder except the last. Only outsiders like Donald Berwick seem to be able to see clearly the value of what we have and what we might have, but are wantonly destroying.

Plant of the Week: Ligustrum lucidum

No-one who has grown up in the English suburbs can escape nostalgia at the scent of privet. Dusty, sweetish, with distinct overtones of cat’s pee; yet how redolent of homeward walks down hot streets in the summer holidays! Now that you are grown up, you can spurn the common privet of hedges, but you should give serious thought to planting this handsome relative. It has much bigger dark evergreen leaves, rather like a camellia, and is completely tolerant of drought and neglect, growing slowly into a small tree with an attractive grey trunk if you let it, though you can prune it back as hard as you like. In the summer holidays, it breaks into sprays of flower, and you may chance to smell that scent again.

Arch Intern Med 24 Jul 2006 Vol 166

A very thorough and useful systematic review of alternative treatments for menopausal symptoms—most importantly phyto-oestrogens but also other herbs, magnets, and exercises. There is no convincing evidence for any of these, and all the trials vary from poor to fair in quality.

You won’t find me commenting on many studies of dietary modification, but here’s one that might be of interest because it shows that foods with a low glycaemic index may help fat young people lose weight and may even reduce their cardiovascular risk factors. But no dietary study in free-living humans is ever going to tell us anything dependable about hard outcomes.

Testosterone is often added to oestrogen replacement therapy in the USA, presumably to increase libido rather than body hair. This study shows that testosterone alone does not increase breast cancer, but in combination with oestrogen the increased risk is about the same as an oestrogen/progesterone combination.

Some months ago, Rod Jackson attempted in a Lancet editorial to pour cold water on the idea that alcohol protects against cardiovascular disease. I drink for pleasure rather than to prolong my earthly existence, but even so I’m glad to find that all the evidence I know of suggests that he’s wrong. This study in an elderly cohort shows that people who have1-7 drinks a week get less heart disease and live longer. A week? And above that, not. Oh dear.

There is a paradoxical relationship between fatness in old age and survival, which is illustrated in this Chinese cohort study. If you have a chronic disease, then being fat tends to improve survival; but if you start off by being healthy, then being fat tends to make you less so as time passes. This sounds like the sort of thing Confucius might have observed, but I can find no mention of it in the Analects.

Somatisation disorder traps people in a maze of symptoms from which they can find no escape. Unable to help them, we often react by concluding that they don’t want to escape, but this study proves (a) that they do and (b) that cognitive behavioural therapy can help. Oh for those 10,000 extra clinical psychologists.

Some case reports from Greece which lend weight to the idea that statins can unmask latent neuromuscular disease in some patients.

Lancet 29 Jul 2006 Vol 368

An editorial usefully summarising the reversal of risk following stopping smoking. Unfortunately for the deadliest disease, lung cancer, some additional risk persists throughout life: but for COPD the benefit is almost immediate and is sustained.

And here’s a useful summary of the contribution of smoking to social inequalities in male mortality. It is much the largest contributor to the added mortality observed in working class men in England, Wales, Poland and North America.

Gradually we’re accumulating the data we need to predict the risk of recurrent venous thromboembolism in individuals. This meta-analysis confirms that maleness adds 50% to the relative risk of having a second episode of VTE.

I keep reading reviews of Alzheimer’s disease, but find that I quickly forget the detail. This may not be diagnostic; and in any case it’s quite handy since a lot of it seems to change as definitions shift, new bits of the amyloid cascade are added to the hypothetical model, and experts continue to debate the contribution of vascular disease to the clinical picture. And in case you thought that this lucrative market would not be seeing many new drugs after the NICE mess we’ve had with the anticholinesterase inhibitors, turn to Table 2 for another 40 or so candidates.

Antineutrophil cytoplasmic antibodies (ANCA) lie beyond that boundary which separates mere earthly clinicians from Very Clever Doctors and renal physicians. The syndromes which result are satisfyingly rare, devastating and difficult to understand. There is a whole theoretical area—autoantigen complementarity—which you can organise conferences about. You can do epitope mapping studies. You can speculate about the role of caeruloplasmine-induced myeloperoxidase physiological inhibition. And you won’t see all that many patients.

Most of us have one more kidney than we really need, and an increasing number of people are giving one of them away as an act of altruism which does something to restore one’s faith in the general improvement of mankind. Read this paper (plus the accompanying editorial) in favour of domino paired kidney donation, plus the one in the BMJ about laparoscopic donor nephrectomy, if you think you might want to make yourself useful in this way.

Confucius for the Week

Reading about Confucius (551-479 BCE) in reference books, I had the impression that the Master was a rather cold fish, advocating little more than social conformity and moderation. But reading his sayings, it becomes clear that he saw the meaning of life in love, music and kindness:

The Master said: “Will the right; hold to good won; rest in love; move in art.”

The Master said: “Poetry rouses, courtesy upholds us, music is our crown.”

The Master said: “A man without love, what is courtesy to him? A man without love, what is music to him?”

The Master said: “To learn the truth at daybreak and to die at eve were enough.”

The Master said: “Is love so far a thing? I yearn for love, and lo! Love is come.”

J A M A 19 Jul 2006 Vol 296

The Women’s Health Study is one of those great big well-funded prospective cohort studies which, together with Medline and the Hubble telescope, plus the earlier series of the Simpsons, constitute the USA’s contribution to world civilisation. There may be others, but I can’t think of them just now, when there are bombs going off and children being buried. Take 27,840 American female health professionals aged 45 and over and follow them up for ten years: what delights of number-crunching can ensue! Most of it teeters on the brink of post-hoc subgroup analysis, since this was principally an interventional trial to investigate the benefits of aspirin and vitamin E. But never mind: you can excuse this as hypothesis-generating and get funding for you next study. This paper generates the hypothesis that women who have migraine with aura are twice as likely to die from stroke or cardiovascular disease. Women who have migraine without an aura do not have added risk.

If you don’t look forward to going blind in old age, perhaps get your CHF Y402H genotype checked out. Stop smoking, and avoid inflammation, since anything that elevates your ESR or CRP will enormously increase your risk of macular degeneration if you have this common polymorphism. On second thoughts, don’t bother: there is nothing you can do about your genes or inflammation or preventing macular degeneration. Just don’t smoke.

Ten years ago I was doing a little study on levels of B-type natriuretic peptide in primary care patients with presumed heart failure. Two of the patients with very high BNP levels turned out to have (undiagnosed) pulmonary hypertension. I had recently met a cardiologist who specialises in pulmonary hypertension, and e-mailed him to suggest that BNP might be the best marker for progression in this condition. His reply was along the lines of “very interesting”. Here is a study of people with sickle cell disease, which on a world scale is probably the commonest cause of pulmonary hypertension, since it affects a third of these patients and kills a lot of them. And guess what might be the best marker for pulmonary BP and death? BNP. Maybe in another ten years, the immense potential of this simple marker of ventricular overload will start to be realised.

N E J M 20 Jul 2006 Vol 355

251, 260 Last week, I said I was heartily glad that I had said all I want to about heart failure. But don’t think that will stop me saying it all over again. Cardiac impairment of any kind gives rise to a clinical syndrome which is associated with high mortality. Its final stage can indeed be called “heart failure”, though by this stage it involves every organ in the body. 25 years ago, it was thought that the best way to spot a failing heart was to measure the percentage of blood ejected in each systolic contraction—the ejection fraction. Almost immediately it was realised that a lot of people have symptoms of cardiac impairment with a perfectly normal ejection fraction. This was christened diastolic heart failure in the USA and Europe; but among British cardiologists it was considered bad form even to acknowledge its existence. There is a Bateman cartoon showing an enraged table of old men at dinner—“The Man Who Mentioned Diastolic Heart Failure at a Meeting of British Cardiologists”. I created it from a real Bateman in honour of David Mant, who was The Man, three years ago. Which brings me (finally) to these papers (click here and here). Quite simply, they show—as we already knew—that up to a half of patients with cardiac impairment in the community have a normal systolic ejection fraction, and they die at very nearly the same rate as those with an impaired ejection fraction. We can conclude that to date, evidence-based medicine has managed to avoid telling us how to treat half our patients with heart failure. Moreover, neither of these papers mentions the measurement which really stratifies risk at every level of cardiac impairment—BNP.

The Bateman cartoon about cardiologists reflects another truth about that fine body of men—that they are almost all men. So, in days gone by, were most authors of medical papers. The sex distribution—sorry, gender balance—of US academic institutions is shown in Figure 1 of this paper. The balance in academic medical papers over the last 35 years appears in Figure 2. In about 15 years it will be equal.

A short article on biventricular pacing. This substantially prolongs life in at least a third of heart failure patients, but by capping NHS spending, Gordon Brown has in effect said “let them die”.

B M J 22 Jul 2006 Vol 333

Some bizarre things are getting into the BMJ. After last week’s editorial about female genital mutilation, this week we have a study suggesting that female speculum examinations can be performed without stirrups. Well, who would have thought it? Can we do them without a saddle too?

This study which found that a third of Oxfordshire kids with chronic cough have evidence of recent whooping cough has been in the public domain long enough for people to point out minor shortcomings, some of which are mentioned in the editorial on p.159. But it’s still a major breakthrough in our understanding of this common problem, and anyone who has tried to do a study like this within the constraints of UK primary care research funding will be full of admiration for the authors. Of course we can’t treat it, but at least we can give worried parents an explanation and reassurance. And somebody can invent a better vaccine.

Pyoderma gangrenosum is a diagnosis of pattern recognition. You may never see it in primary care, but look at the pictures here just in case.

Franklin on Vanity

The United States of America got off to a good start with Benjamin Franklin. Here he ends his list of reasons for writing an autobiography (1771):

“And lastly (I may as well confess it, since my denial of it will be believed by nobody), perhaps I shall a good deal gratify my own vanity. Indeed, I scarce ever heard or saw the introductory words, Without vanity I may say, etc., but some vain thing immediately followed. Most people dislike vanity in others, whatever share of it they have themselves; but I give it fair quarter whenever I meet with it, being persuaded that it is often productive of good to the possessor, and to others that are within his sphere of action; and therefore, in many cases, it would not be altogether absurd if a man were to thank God for his vanity among the other comforts of life.”

Lancet 22 July 2006 Vol 368

It’s not so long ago that Peter Rothwell wrote his previous editorial in The Lancet calling for more practice-oriented clinical research. I’m glad to see that the editor has invited him back to write as much more as he likes. It’s the longest Lancet editorial I’ve seen, and it’s excellent stuff. Primary care would be the natural setting for most of this research, but will it ever happen?

Growing up in Sheffield more than forty years ago, we all used to walk to school across the slag heaps in the driving snow and no child was ever fat. Well, not really, but more kids now are fatter than ever before, and the key to changing this is activity. My solution is simple: abolish school sport. Sport is counterproductive as well as deeply boring: as soon as a child is overweight, he or she learns that joining in any competitive physical activity will lead to humiliation. Take them instead on long walks, reciting poetry or botanising as they go.

It’s amazing to me how long it has taken us (or is it just me?) to understand the workings of important childhood pathogens like respiratory syncytial virus (RSV), the main cause of bronchiolitis. This review is state-of-the-art, but all the immunology still leaves me wondering what really happens in those innumerable babies who get RSV and then go on to have recurrent episodes of chest crackles for a year or two. Ribavarin came and went as a treatment, but now there’s a new, effective form of prevention: the monoclonal antibody palivizumab. At about £3,000 per child per season, don’t expect to be using it any time soon.

Rotavirus is another major player in childhood morbidity, and death in developing countries. In fact this review of vaccines states that all infants get rotavirus infection and about 600,000 die worldwide as a result. The problem with the first effective vaccine, you may remember, is that it was linked to intussusception in some American babies. Other vaccines have been developed and sound promising for use in Africa and Asia, where most of the deaths occur.

Ann Intern Med 18 Jul 2006 Vol 145

Assuming that my scheme for long walks and poetry doesn’t succeed, what can you actually do to help adolescents lose weight? “Behavior therapy” was given to both groups in this study, and when given alongside placebo, had little effect except to make kids leave the study; sibutramine on the other hand helped them to lose weight, so fewer left.

Plant of the Month: Tilia “Petiolaris”

Plant taxonomy can be seriously boring. You will note that the specific name of this wonderful lime tree is not in italics, but in quotation marks with an initial capital, meaning it is a variety and not a species in the Linnaean sense. A biography of Linnaeus lies at my bedside. For insomniacs without access to zopiclone or cognitive behavioural therapy, I can earnestly recommend the stupefying saga of this self-satisfied Swede.

As for the lime tree, it is a native of North European forests, and “Petiolaris” is a natural hybrid of uncertain origin. It is unmatched for stateliness of habit, darkness of leaf, and generosity of flower. The erotic scent of the lime tree in summer makes it a central symbol in German Romantic poetry: I expect many readers will be familiar Uwe Hentschel’s key paper in Orbis Litterarum 2005;60:357, Der Lindenbaum in der deutschen Literatur des 18. und 19 Jahrhunderts.

In English poetry it occupies a more ambivalent place, largely due to Coleridge’s early poem This Lime Tree Bower My Prison (1797). Coleridge was stuck at his cottage while his friend Charles Lamb was out walking in the country, having elevated spiritual experiences as a result of his proximity to real trees like oaks and walnuts; while he, Coleridge, had to make do with a mere bower of planted limes. Nonetheless, in the middle of the poem he catches a glimpse of borrowed or recollected delight:

“Nor in this bower,

This little lime-tree bower, have I not mark’d

Much that has soothed me.”

This ungainly double negative must have satisfied Coleridge as much as it perplexes the reader, since it survived intact through each edition of the poem during Coleridge’s lifetime.

Anyway, if you are going on home visits in the stifling heat of late summer, switch off the air conditioning and keep your car windows open. You will be ravished from time to time by sudden gusts of lime tree scent. You can even prime your CD player with Mahler’s gentle love song about it, Ich atmet’ einen linden Duft. But on no account try to drive while listening to the Schubert song from Winterreise about a lime tree. Der Lindenbaum, especially as sung by Peter Anders in 1945 or1948, could cause fatalities.

J A M A 12 Jul 2006 Vol 296

I am afraid that my attitude towards exercise is somewhat similar to Max Beerbohm’s in his celebrated essay, Going Out For A Walk (1918): “Walking for walking’s sake may be as highly laudable and exemplary a thing as it is held to be by those who practise it. My objection to it is that it stops the brain.” He proceeds to expatiate incomparably on his theme. The fact that Max died in his 80s, adored by all, has always been a solace to me, but then I keep reading papers like the one here, which dispel comfort. The abstract concludes with the chilling observation “Simply expending energy through any activity may influence survival in older adults.” Maybe gardening counts. At least it doesn’t stop the brain.

Now here’s a paradox: in a screened population, women seem twice as susceptible to the carcinogenic effects of smoking, but half as likely to die from their lung cancer. It’s a short paper, with an editorial, but having read them both, I’m not much nearer to understanding why.

Ovarian cancer really does deserve the name of “malignancy”—silent in approach and usually deadly, because it is so good at spreading round the peritoneum. Surely, though, if you remove the ovaries and tubes of women at high risk of ovarian cancer through hereditary BRCA mutations, you can eliminate the risk? Alas, no: you merely reduce it. Some still die from peritoneal cancer.

I think everybody in an affluent society puts on weight in middle life, unless they are awful people with will power. For men, weight gain simply occasions the avoidance of full-length mirrors and the more frequent purchase of trousers; but for women, it increases the risk of breast cancer. Conversely, losing weight in or after the menopause reduces breast cancer risk (Nurses’ Health Study—cohort of 87143 “postmenopausal women aged 30 to 55 years”, followed for up to 26 years).

Get a bit of superglue on yourself, and it forms a tenacious film. Ear glue is just the same, though it probably lacks sales potential. It forms a biofilm on the middle ear mucosa, containing bacterial DNA, mostly from Streptococcus pneumoniae in this study, but also from Haemophilus influenzae and Moraxella catarrhalis. Here the bugs live and thrive and cause chronic otitis media, a condition we still don’t understand very well.

N E J M 13 Jul 2006 Vol 355

I don’t know what it is about the selective oestrogen receptor modulator raloxifene that makes one feel sorry for her. A couple of weeks ago, I pictured her as a little orphan girl, though not in the strict Aronsonian sense, as in this week’s BMJ. Now this study depicts her as RUTH, the exiled Moabitess, sick for home, standing in tears amid the alien corn. The eponym stands for Raloxifene Use for The Heart (honestly), and the study randomised 10,000 women to take the stuff or placebo. It reduced breast cancer but increased stroke and thromboembolism, and it was neutral to the heart.

I am heartily glad to have said all I want to say about heart failure, in research proposals, editorials, papers, lectures, educational courses and a book. It is a silly term and the only dependable epidemiological data about it are from the Framingham study, which settled on a robust clinical definition in 1948 and has stuck to it ever since. Here is the latest set of data about the risk of heart failure in offspring of parents who had the condition. They are at higher risk, as you’d expect, and not all of it can be explained by known factors.

The Israel Defense Force pauses from its more destructive efforts to examine tick bites. Tick-borne relapsing fever in Palestine is caused by Borrelia persica. If you think you’ve been bitten, take some oxytetracycline and you’ll probably be all right.

All you need to know about mouth ulcers from the Eastman Dental Institute. Most of them affect younger, richer people; we don’t know why, or what to do about them. Then there’s the long list of rarer causes, which include AIDS, beta-blockers and NSAIDs—worth a glance in case you see a patient with persistent or recurrent ulcers.

For those who remain puzzled why homocysteine-lowering vitamins have failed to deliver any cardiovascular protection, a lengthy correspondence about HOPE-2 and NORVIT.

B M J 15 Jul 2006 Vol 333

There has always been a good market for “cosmetic” vaginoplasty. When I was a medical student (that’s how long ago), one consultant gynaecologist was nicknamed “the man with the golden speculum” for his skill in tightening up the titled. Nowadays, this editorial tells us, lasers are used, “representing the latest chapter in the surgical victimisation of women in our culture”, and making it hypocritical of us to condemn traditional female genital mutilation in African countries. Really? Were these women held down while their external genitalia were removed at their parents’ insistence?

It is a truth universally acknowledged that if you want a local anaesthetic to work, you need to get it under the skin. Simply spraying lidocaine on to the perineum of women in labour is “acceptable to women and midwives”, but blow me down with a feather, it does not reduce perineal pain.

The front page of this week’s BMJ is a large heap of worms, and I can’t say I rate most of this week’s content all that much higher. But if you are running children’s clinics in Uganda, do give pre-school kids albendazole to deworm them and they will gain more weight.

Cataract surgery is something we tend to let cataract surgeons get on with, and very good they are. Compared with a couple of decades ago, they deal with a veritable Nile of cataracts. If you want to know what they actually do, here’s the place for a clear view.

No issue of the BMJ which contains two contributions from Jeff Aronson can be wholly bad, and this piece on communicating information about drug safety, with RE Ferner, is decidedly good. It advocates a clear warning system for important drug interactions. Elsewhere Jeff discusses the origin and medical uses of the word “orphan”. Although I only became an orphan in middle life, I find it a terribly powerful word:

ne delerinquas nos orphanos do not leave us as orphans

sed mitte promissum Patri in nos but send us the promised of the Father

Spiritum veritatis, alleluia the Spirit of truth, Alleluia

Magnificat antiphon, 2^nd Vespers of the Ascension.

Arch Intern Med 10 July 2006 Vol 166

A systematic review of the association between marijuana smoking and lung cancer. The nineteen studies examined permit no conclusion. But since most marijuana is smoked with tobacco, there is bound to be a risk, whatever the contribution of the hemp itself. It is just very hard to find once you have adjusted for tobacco use.

No aspect of primary care has been more thoroughly covered than the prescribing of antibiotics for sore throats. We know that: GPs are incorrigible antibiotic prescribers; that most sore throats are self-limiting; a percentage (17% in this study) are associated with the presence of group B streptococci, but this does not always predict response to treatment. There are various guidelines such as the Centor criteria which are rarely applied to testing or treatment with any consistency in real life or even in a closely observed setting like this study’s. All this has been demonstrated repeatedly over the last forty years. Time to give up, I’d have thought. As I said, GPs are incorrigible.

Our knowledge of acute coronary syndromes (ACS) and their management has improved enormously in the last few years, and our practice may eventually catch up. But there is a particularly baffling group of people who have ACS with troponin elevation but no ST elevation, and are found at angiography to have no critical coronary artery obstruction. In a former age, this was put down to “coronary spasm”, but three of the Thrombolysis in Myocardial Infarction studies (TIMIs) shed more light on this enigmatic group, half of whom had minor atheroma and half squeaky clean coronaries. Within a year, 2% had died or had another myocardial infarct: not a very terrifying statistic, but well above baseline, and these studies allow you to stratify risk.

The kidney has suddenly become important to British GPs, since it now carries points. This study shows that impaired renal function is associated with heart failure risk and that the association is stronger in black than in white Americans. Moreover, it correlates more closely to cystatin C levels than to these beastly new eGFR things they keep sending us.

There are few things I find more terrifying than fit old American ladies. This study shows that they will never get strokes. They will go on for ever. Please let it be in America.

Another under-investigated subgroup of patients with myocardial infarction are those who get one in hospital. Not surprisingly, they are sicker and have a higher mortality. In US Veterans’ hospitals, 11% of inpatients have a heart attack.

Lancet 15 Jul 2006 Vol 368

The autistic disorder spectrum (ASD) is wide and often baffling to non-specialists. At one end are people like Isaac Newton, who almost certainly had Asperger’s syndrome but who functioned with unequalled brilliance on his chosen intellectual territory: at the other extreme there are those who can barely connect with the world at all. Most children in the spectrum are placed on the special needs register of local education authorities, and this study looks at a London register to see how common ASD might be. By the criteria the investigators adopt, about 1% of children are autistic, but only a third meet the ISD-10 criteria.

If a couple have not conceived after a year of frequent unprotected intercourse, is it worth an immediate trial of intrauterine insemination with controlled ovarian hyperstimulation using clomifene? Definitely not. A third of women conceived in the next six months with or without treatment, and slightly more pregnancies in the intervention group failed.

Status epilepticus in children is a rare emergency in primary care, but it is not rare in ambulance and hospital settings, and it is commoner than adult status epilepticus. Fortunately its prognosis is also better. If paediatric neurology is your thing, this excellent prospective study describes the real life situation in London.

By contrast, biliary colic is one of the commonest emergencies we deal with in primary care, and it might get commoner if people continue to get fatter. This is a very readable account of gallstones, from the south of Italy. The Italian word for bile is also bile, and there, as here, it can also refer to anger. But “bile supersaturata” sounds much more fearsome in Italian than “supersaturated bile” in English: it makes you worry about blood-feuds and poison. In England, you only have to worry about surgeons.

Plant of the Week: Hemerocallis “Barbara Mitchell”

The day-lilies can inspire mixed feelings among gardeners. On the plus side, they are pretty indestructible, and when in flower, they are pretty as well as indestructible. But when they are not in flower, one is sometimes tempted to destroy them, because of the space they take up with their floppy leaves, which form a rotting mess after the first frosts.

However, we have a special fondness for day-lilies because of the person we get them from, Gerald Sinclair, the most gently entertaining of nurserymen, at the Nursery Further Afield. He keeps and propagates a National Collection in his further fields. Among these we picked out Barbara Mitchell, a new introduction. If I were Barbara, I would not know what to think. Gerald used words like “blousy” and “striking” and “a bit in your face”, even “twinkly” as he showed us how light is scattered in tiny beads on the petals. Fragrant, curved, waxy and subtle flesh-pink they certainly are. Sexy, in fact, so this is one we decided to have.

J A M A  5 Jul 2006  Vol 296

Most antidepressants probably help people to stop smoking; the best marketed has been bupropion, but the much cheaper nortriptyline (a TCA) is equally effective. Neither drug directly targets the nicotine addiction pathway, which depends (I learn here) on the α4β2 nicotinic acetylcholine receptor.  Varenicline has been developed as a partial agonist of this receptor, and this stage 3 study describes a blinded RCT comparing it with placebo and bupropion. It seems to be about twice as effective, given over 12 weeks and followed up for another 40, as bupropion. So look out for it when it appears, and in the meantime prescribe nortriptyline or try and follow the fiddlesome and irrational NICE guidance about bupropion.

Those who like to sit in judgement on others develop all sorts of instruments to measure performance, usually once they are conveniently out of reach of them. I believe that Sir Donald Irvine is still at it.  I am all for audit and quality improvement as an honest exercise, but most external instruments are much too crude, from the rack to the AMI core process measures. These examine the pathway from diagnosis to treatment to mortality following acute myocardial infarction. They don’t prove very predictive, and the indefatigable Harlan Krumholz calls for more sophisticated instruments and better risk standardisation.

Extreme obesity is a BMI above 40, and it is increasing rapidly in the USA, especially among African-Americans. This study examines the contribution of weight per se to mortality and cardiovascular disease in women. The risk of high blood pressure and diabetes is directly related to weight and is steeper in those categorised as black. Once you have adjusted for this, mortality shows a slight inverse relation to weight. But seeing that real life doesn’t allow these adjustments, don’t get fat.

 Acetaminophen was first synthesised in 1878 and its analgesic properties have been known for 100 years. That’s why it is probably the drug you prescribe most, and don’t want anyone to criticise. Perhaps you don’t realise that it is the same drug as paracetamol, in which case you are not alone– there was even a recent systematic review of drug interactions with warfarin that placed “acetaminophen” and “paracetamol” in different risk categories! We all know that it kills in overdosage by destroying the liver; we also know that it can trigger asthma, though we try to forget; but this study also shows that it can cause elevation of liver aminotransferase (ALT) even at normal therapeutic doses (4G/day in healthy adults). Worth remembering if you get a patient with unexplained elevation of ALT.

N E J M  6 July 2006  Vol 355

I am no expert in upper gastrointestinal oncology, so I assume there was some logic in grouping together adenocarcinomas of lower oesophagus and stomach in this trial of surgery with and without perioperative chemotherapy. The trial declares in favour of the latter, but admits that the tumours in that group were significantly smaller and less advanced.

As a child, I used to love standing on the railway bridge at Lincoln station waiting for the engines to pass beneath, billowing smoke and steam. I would come home with soot in my hair and no doubt in my lungs. This study shows that carbon in airway macrophages correlates with reduced lung function in children. Worth it for the joys of train spotting, in my opinion, but not when imposed on children for years by motor traffic.

This is quite a week for discussing the evils of motor traffic (see BMJ ) and also for learning about children’s lungs. In connection with the latter, the most important new study is Anthony Harnden’s whooping cough study on the BMJ website, which I’ll mention further when it is printed, but this study of unrecognised influenza in children from the USA is of comparable significance. It shows once again that doctors cannot diagnose influenza clinically, except perhaps in a major epidemic. It is a very common cause of childhood morbidity, and most of this could be prevented by vaccination.

B M J  8 Jul 2006  Vol 333

In 27 years, I have seen several young people with type 1 diabetes go into denial or overdose repeatedly with insulin. This usually ends in death. Insulin-dependent diabetes must be a difficult condition to come to terms with, and you would think that psychological interventions would be key in achieving glycaemic control in a substantial number of patients. But this systematic review shows little effect.

Patients with rectal bleeding often come in terrified of colorectal cancer, and if the bleeding looks fresh and is on the loo paper, I tend to reassure them, even if they are over 45. By all means carry on reassuring them, but only that the chance of it being cancer is less than one in ten, and that they need further investigation for their own safety. This study was carried out in a single practice, but so well that it should change everyone’s practice. It picked up 15 cancers and 13 adenomas in a 10-year period.

A study showing that drivers of four wheel drive vehicles in London use mobile phones while driving much more than other drivers, and seat belts a bit less. I take it that most of these were SUVs and not 4-wheel drive versions of ordinary cars. People who drive these things in cities rarely need them except when out killing birds and mammals; they are perfectly aware of their visibility hazard and their exhaust emissions; they think nothing of blocking parking spaces: so why should they care about any other risk to others? They are the unspeakable in control of the impregnable.

Road safety has improved hugely since the 1950s, with deaths and injuries falling despite a 10-fold increase in vehicle activity. Let’s not count the environmental cost just now. This paper discusses the discrepancy between English police RTA serious injury figures from 1996-2004 – down 21% - and hospital figures – up by 1%. Who is massaging what?

France is a more hazardous place to drive than England, and this study shows a special hazard from Frenchman who admit they have driven while feeling sleepy. “Tiredness kills: take a break” is a road sign that means more than just a motorway service station two miles distant.  

Sumerian Proverb of the Week (ca. 3,000 BCE):

A city does not talk to a city: a person talks to a person

Though Sumerian cities competed for prestige, war was seen as folly and disaster. People talked to people, and kings maintained the canals. 
 

Ann Intern Med  4 July 2006  Vol 145

The Mediterranean diet is one of the chief glories of human civilisation. Cooking oil came from the native olives, fish from the sea; the Persians brought lemons and new kinds of nut; traders from India brought new spices in Roman times and ever since; North Africa and Anatolia provided grain. Around those shores, people have been eating much the same food for the last two thousand years, though pasta may have come a bit later with the Arabs in Sicily. Against such a mighty and delicious backdrop, this piddling dietary study of three months’ duration scarcely deserves the honour of calling itself “Mediterranean-style”. The intervention was to give advice about a Med diet plus one litre of free olive oil a week, or 30 grams of nuts a day; or to put people on to a conventional low-fat diet. Even in this short period, the “Mediterraneans” showed significant reductions in cardiovascular risk factors - cholesterol, CRP, glucose and blood pressure. And to be fair, the cohort will be followed up for several years yet.

Oh no, not another study of acupuncture for knee osteoarthritis. And oh no, yet more proof that every medical abbreviation can cause confusion. I used “TCA” as a standard abbreviation in this week’s JAMA review, thinking that nobody uses it for anything but “tricyclic antidepressant”. Enter Traditional Chinese Acupuncture. Yet again, it worked twice as well as conventional physiotherapy and NSAIDs – pardon me, non-steroidal anti-inflammatory drugs. And yet again, sham acupuncture worked exactly as well. Doubtless we should call this Non-Specific Acupuncture Imitation Delivery (NSAID), to sow further confusion. Maybe if I get struck off the medical register, I shall set myself up as an evidence-based sham acupuncturist.

Have we got enough cardiovascular risk factors to stratify most people? The answer has to be yes. Does C-reactive protein add much to these? The answer, confirmed in this narrative review, has to be no.
 

Lancet  8 July 2006  Vol 368

The UK is the most productive site of medical research in the world, and it is in everybody’s interest that it stays that way. Research is supported from the public purse via the Medical Research Council and the NHS Research & Development programme. Gordon Brown has set a venture capitalist loose to look at these arrangements. There is even talk of extra money. To understand more, read this thoughtful editorial by Richard Horton.

The really magnificent editorial, though, comes from William Jeffcoate, and it is about to how to turn the “worm-infested sham” which the NHS has become back into a first-rate, centrally-funded body which harnesses the professionalism of its workforce instead of demoralising it. There is no comfort for ideologues of either camp. Private management would be a tragedy, but things cannot go on as they are. “New Labour” has actively encouraged mismanagement in order to destroy real Labour’s finest achievement.

I am not sure that I understand the basic principles of modern penology – nothing to do with writing instruments (or the male member), but with the logic of locking people up. It is certainly an unpleasant experience which probably acts as a deterrent for some and a punishment for most. Thirty years ago there was much talk about the rehabilitation of offenders, but now the talk is of lifelong punishment at the whim of victims and the deportation of foreigners who have served their sentence. No wonder prisoners often commit suicide after release. I’m sure the Daily Mail thinks it serves them right.

Nitazoxanide is quite a little performer, said to be active against several protozoans, one or two bacteria, and even a few viruses. This double-blind RCT from Egypt shows that it can halve the duration of severe rotavirus diarrhoea in children. Not bad, and probably more effective than the first diarrhoea remedy from Egypt: figs, grapes, bread dough, fresh earth, corn and elderberries (Ebers papyrus, c. 1552 BCE).

The British epidemic of gonorrhoea seems to have peaked, at least in heterosexual people. In homosexual men it continues to increase, and this study from London genito-urinary clinics shows that this population carries different strains of gonococci from the heterosexual population.

Plant of the Week: Kniphofia “Timothy”

The merits of the red-hot pokers divide gardening opinion, I am told. On the whole, I tend to be slightly fonder of this South African tribe than my wife is, but we are both fond of Timothy. He thrives on neglect – an essential virtue if he is to survive here – and although he gets dry winters and wet summers in his native land, he tolerates the opposite in England, and builds up a nice clump. So many July-flowering plants seem poor exchange for the beauties of June, but not Timothy, who is a charming lad. He rises a foot or even two before forming the characteristic poker flowers in strong but subtle oranges and pinkish yellows. Definitely a class act, and one which goes on for weeks, nicely matched by the Achillea called “Terracotta”.
 

B M J  1 Jul 2006  Vol 333

The best things for me in this week’s BMJ are not in the main body of the journal, which provides meagre pickings, but at the front and the back. In a week which saw revelations that the government has been advertising overseas for private sharks to swallow up the entire system of Primary Care Trusts, Editor’s Choice by Fiona Godlee sounds a timely battle cry in defence of the basic principles of the NHS. There are the usual murmurings of dissent in the Rapid Responses, though her predecessor has refrained from joining in from the boardroom of United Health. Here in North Oxfordshire, local GPs have been asked to smooth the transition of our local obstetric service, a consultant-led service handling 1,600 deliveries a year, into a “low-risk” midwife “led” unit with cover provided 23 miles away. James Owen Drife, normally the most light-hearted of writers, sounds a grim note of caution about this kind of infanticidal folly in Soundings on p.51.

Whenever the question of adherence to drug therapy is raised, somebody interjects that patients are probably better off forgetting to take half the drugs we foist on them. In fact, that’s not true: in randomised controlled trials which studied adherence, they are markedly better off if they stick religiously to whatever they are prescribed, even if it’s a placebo.

The relentless pursuit of ways to measure quality in primary care shows no sign of an end, but from the very start (see Sir Donald Irvine reviewing his own achievements on p49) I’ve wondered whether we can really make the transition from what is most measurable to what is most important. The editorial on p.1 suggests a move away from generalised patient evaluations to more specific questions such as “Were you given a plan to help you manage your diabetes at home” or “Were you given information about any side effects of your medicine” – both of which I would consider things better done by the practice nurse or an information leaflet, and hence markers for wasted consultation time.
 

N E J M   29 Jun 2006  Vol 354

There is lots of evidence that high levels of homocysteine (HCy) are associated with increased risk of dementia as well as cardiovascular disease. At least four vitamin deficiencies can raise HCy, but interventional trials tend to use either folate or B12. This trial was exemplary in using folic acid, supraphysiological oral cobalamin and pyridoxine, versus placebo. This cocktail was highly effective at lowering HCy, but had no effect on the incidence of dementia. Quite a disappointment. Possible reasons are speculated on in an editorial on p.2817.

There’s been a lot published recently on N-acetylcysteine and the prevention of contrast nephropathy, which I have tended to flip past thinking that most of my readers are not Consultant Radiologists like Alan Statham. But actually quite a few of our patients, and even some of us in person, are likely to be needing intravenous contrast for angiography at some stage of our lives, so it’s important to know if they or we might do better with a bolus dose of N-acetylcysteine before the contrast. It looks like the answer is yes, Alan.

It remains a mystery why we humans have evolved to be dependent on iodine – and hence marine food – to have adequate thyroid function. I rather like the theory that all our ancestors were once littoral scavengers, eating seaweed and molluscs: I think I could get used to that. Nowadays, apart from the delicious samphire and disgusting laver bread, the seaweeds we’re most likely to eat are served fried in Chinese and Malaysian restaurants. Some Chinese people actually end up eating too much iodine; this can cause thyroid disorders, but as a world-wide problem, iodine deficiency remains much more important (see editorial).

If we wanted to get our own back on the Americans, we could call them “Lymies”, because of their anxiety about Lyme disease. There is even a John Updike story about a town emptied by the condition: blasted by Borrelia or transmogrified by a tick. It is not a very good short story, but this is a good short review, and you should memorise the pictures because you may see a case sooner or later, and early treatment counts.
 

J A M A  28 Jun 2006  Vol 295

2851   Here is a fascinating study of treatments for insomnia from Bergen in Norway, of special interest to me as I fulfil the entry criteria this week, being a poor sleeper aged just over 55. You’d have thought there was little to keep people awake in Bergen, a place at some remove from the turmoil of the world and brimming with prosperity, with only the weather to worry about. Late middle-aged insomniacs were randomised to placebo, zopiclone or cognitive behavioural therapy. CBT won hands down, as expected, and by a much larger margin than in the Cochrane review, perhaps because these investigators used a more sophisticated end-point called sleep efficiency. But both zopiclone and CBT for insomnia are banned by our local PCT, so to sleep efficiently I had better buy an overcoat and move to Bergen.

2859   We move sideways to Sweden for a study of patients with a first hospital admission for heart failure. If they are like patients in the UK, over a third of them will be dead 18 months later, so anything that helps us understand (and prevent) their condition is useful, even a seemingly random scrap of information such as their elevated nocturnal blood pressure. Nobody really knows why “non-dipping” might increase the risk of HF. Actually, I have some ideas, but I don’t expect many of you would stay tuned.

2867  This report from Singapore about Fusarium on contact lenses provides me with my Fungus of the Week: Fusarium solanum. Like Pseudomonas spp. among the bacteria, Fusarium spp. are omnivores and opportunists among the fungi. F solanum will eat your corneas if you fail to change your contact lenses at the proper intervals in steamy Singapore. But it is equally happy munching at the gills of crustaceans, or ruining the livelihoods of Australian crocodile farmers; or indeed eating potatoes, as its name implies. On the plus side, however, it is also happy to join forces with Aspergillus terreus to gobble up crude oil spillages in places as far apart as Alaska and Kuwait. Good to have as an eco-friend, then, but bad news on your gills or your contact lenses.

2874   Depression makes you a lot more likely to get cardiovascular disease, and also a lot more likely to die from it once you’ve got it. Nobody discussing this topic can resist puns about the broken-hearted. There’s even an interventional trial of setraline for CHD with the acronym SADHART. Just how sad is that. 
 

Arch Intern Med  26 Jun 2006  Vol 166

It’s a well-kept secret that Archives of Internal Medicine is the general medical journal which contains the largest number of interesting high quality papers. This issue is not one of the best. It has nearly as many misses as an England penalty shoot-out, but it is still well worth a look.

“Original investigation” reveals that some menopausal women have disturbed sleep because of hot flushes.  Gosh. The author then earnestly entreats us to “systematically investigate” post-menopausal women with insomnia for the presence of hot flashes (sic). Does this involve nocturnal thermography? Do we just ask them, or do we need to sleep with them?

The Cochrane Collaboration is usually a guarantee of quality, but I’m not so sure about this review of the trials of aspirin v warfarin for non-rheumatic atrial fibrillation. It concludes that aspirin is not as good at preventing stroke but causes more bleeding. How true.

QT prolongation in methadone users was detected in 16% of those admitted to a Swiss university hospital. It can lead to life-threatening arrhythmias, but there are few clues as to how big a problem this might be amongst the millions of people taking this drug as a heroin substitute.

What happens in the US usually ends up happening in the UK, especially while Tony Blair remains Prime Minister. But even I would not jump to blame him if we experience a rise in gram-negative septicaemia, such as that reported here from a “quarternary-care” hospital which kept an audit of PHA-BSIs. That’s Primary Health care-Associated Bloodstream Infections. For reasons that aren’t entirely obvious, gram-negative bugs, which tend to become drug resistant, are taking over from old favourites like Staph aureus.

If a demented nursing home resident gets aggressive, look out for and treat hallucinations, depression and/or constipation. This may not be a very “original investigation”, but the point is worth restating. As a matter of interest, do nursing home residents in the USA retain their constitutional right to carry firearms?

A worry that is sometimes raised about giving people so many vaccinations is that they might cause Guillain-Barré syndrome. This UK study between 1992 and 2000 shows that they don’t.

Plantar fasciitis is a tiresome chronic condition often treated with foot orthoses. This trial devised a sham foot orthosis as the “placebo”, and found that real orthoses do provide some short-term relief. But neither sham nor real ones provided lasting balm to the sole.

Here’s another big prospective cohort study showing that coffee consumption is associated with a decreased risk of type 2 diabetes. The more evidence in favour of coffee the better, I think, since our health service runs on the stuff.

An outbreak of adult pertussis in Jackson County leads the authors to call for a programme of adult vaccination. Maybe: though lasting immunity to pertussis isn’t easy to achieve, as the recent Lancet review makes clear.

Lancet  1 Jul 2006  Vol 368

In The Lancet this week, as in the BMJ, the richest pickings are not in the research articles.

With such an immense body of interventional research, why do experts continue to change their minds about the best treatment for hypertension? This nicely written editorial doesn’t fully answer this question, but it does present a convincing picture of the development of high blood pressure as a lifelong process. The trouble is, we don’t know a lot of the detail. And if what Bryan Williams says is true, we need a Polypill for a lot of people from the age of 15.

This is a fascinating but infuriatingly incomplete descriptive study of diabetes in a Canadian population of over 9 million people, 379,000 of whom had the condition. What condition? Aye, there’s the rub – the record trawling did not reveal whether it was type 1 or 2, or how long they had had it. Nor did it reveal how much cardioprotective medication they were taking. But the bottom-line message is clear enough: if you have diabetes in middle life, add 15 years to your chronological age.

If mitochondrial disease has a prevalence of 5 in 1000,000, you may never see a case, and you are hardly likely to make the diagnosis yourself. But this article is fascinating to skim through if you retain some affection for your Biology A level days. Mitochondria are essential for cell metabolism in eukaryotes, but they may actually be invaders who colonised cell lines a couple of billion years ago: hence their remnants of personal DNA. This DNA can only be transmitted from your mum; though one study found a bit of daddy-DNA finding its way into a mouse embryo. Just the kind of thing you need to ward off boredom now that the England team have come home.

Even better entertainment can be had from David Grimes’ piece speculating that statins are analogues of vitamin D. People on mountain tops and in sunny places get less heart disease. And so on. Certainly, whatever the truth of this hypothesis, statins do a lot more than lower cholesterol.

Plant of the Week: Magnolia delavayi

Earlier in the year – as early as March if conditions are favourable – the magnolias start to dazzle us with beauty and scent on big trees like campbelli and dawsoniana. Then come denudata, stellata and the ubiquitous soulangeana, followed by the amazingly beautiful sinensis and wilsoniae with dangling pure white scented flowers. Then hypoleuca with great melon-scented goblets, and its stunning hybrid weiseneri with the most scented flowers of all.

But then there’s a bit of a problem for magnoliophiles. From mid-June onwards, you have the choice of liliiflora, which I find a bit gloomy, or grandiflora, which looks even gloomier throughout the year in most places, though on a brilliant day its shiny evergreen leaves set off the big, lemon-scented flowers to perfection. These continue throughout the summer, but they are few, and even with global warming, England is not the best place to grow this plant. Oddly enough, a less gloomy effect is produced by an even bigger evergreen, named delavayi after an intrepid Belgian Jesuit missionary to China, though its leaves are huge and matt olive in colour. The books say that you can grow it free-standing in England, but I have only ever seen it grown against a wall, for the very good reason that its vast dull cream flowers only last 48hr and your best chance to smell them is from an upstairs window. If you have enough space, and can get hold of a plant and nurse it through its first winter, you will grow to love this louche giant.

J A M A 21 Jun 2006 Vol 295

Ever since it first appeared about ten years ago, the selective oestrogen receptor modulator (SERM) raloxifene has seemed a bit of an orphan, sadly seeking a condition to relate herself to. Acting as Dr Barnardo to the poor waif comes the STAR P-2 trial, which tries to prove that raloxifene is better than the first-generation SERM tamoxifen at preventing invasive breast cancer in high-risk women. In fact it isn’t, though it caused fewer cataracts and DVTs. The two drugs also have different side-effect profiles but in the end they are much of a muchness. So poor little raloxifene, with a kerchief on her head and a little bag over her shoulder, continues to wander in search of a good home. I suspect her quest will get even harder once the price of aromatase inhibitors comes down.

What a contrast with the statins, spoilt brats if ever there were, good at everything and constantly welcomed into new mansions of medicine. This cohort study suggests that they prevent cataracts. Such a shame that these Little Lord Fauntleroys make some people ache all over.

Drug companies sponsor trials in the hope that they will increase sales of their products, of course. Some of these trials involve huge numbers of doctors, so even increasing prescribing amongst the participating clinicians can be quite remunerative. This Danish study looks at the whether taking part in such trials really leads to such increases, and finds that it does.

N E J M 22 Jun 2006 Vol 354

In this piece, Susan Okrie discusses how to diagnose Attention Deficit Hyperactivity Disorder in Adults. Meaning American adults. So what is the differential diagnosis?

It is said that Casanova pioneered the use of condoms to spare himself the inconveniences of venereal infection, rather than to prevent impregnation. This study shows that condoms help to reduce human papillomavirus infection in young women, about which Casanova would doubtless have cared little since it causes so few problems for men.

Systemic sclerosis (scleroderma) is a nasty disease for which we have few treatments, despite the pioneering work of Carol Black and others. For instance, we’re still at the stage of finding out if cyclophosphamide is a useful treatment for the lung involvement which kills a substantial proportion of patients. So if the title “Stimulatory Autoantibodies to the PGDF Receptor in Systemic Sclerosis” made you turn the page in haste, turn it back again. This may be a major breakthrough. These antibodies may not just be the definitive diagnostic test, but also a key to understanding why fibroblasts misbehave disastrously in this condition.

Likewise, if your eye falls on the title Somatic Mutations in the Connexin 40 Gene (GJA5) in Atrial Fibrillation, do not mutter darkly about bovine excrement and hurry on. Or rather, do hurry on but only as far as the editorial on p.2712 which explains that this is not just New England academic guff but possibly a clue as to why so many people develop AF in later life.

Omalizumab for Asthma. If, with your unlimited drug budget and keen appetite for the very latest in “biologicals”, you were planning to inject some of your more intractable asthmatics with this IgE blocker, pause to read this article. You may not do them much good, and may increase their risk of cancer.

Lancet 24 Jun 2006 Vol 367

The last decade has seen a revolution in the management of myocardial infarction, with the arrival of a better diagnostic test (troponins) and clear demonstration of the benefits of immediate revascularisation in all circumstances. But troponins only confirm the diagnosis when the “treatment window” is nearly closed, and PCI is a scarce resource in the UK; and also in New Zealand, where this study was done. This is an analysis of HERO-2 showing that a really old-fashioned, barn-door ECG marker predicts patients at highest risk—Q-waves on arrival in hospital.

The first neurologist I ever met was the great Prof W B Matthews, a marvellous writer who affected the dusty air of an academic and was rumoured to be studying what were then known as the “slow virus” brain diseases such as kuru. It is impossible to imagine him in the jungles of Papua New Guinea, like the intrepid investigators here, who studied ex-cannibals living and dead, and conclude that kuru (currently classified as a “human prion disease”) can have an incubation period longer than 50 years. One of the few advantages of being my age is that you can safely eat the brains of your enemies.

A seminar on gastro-oesophageal reflux disease. This used to be known just as “oesophageal reflux”, or indeed heartburn, an almost inevitable part of the human condition, especially for those of us who tend to get fatter and like wine with our evening meal. Now it’s a “disease”, and we can take omeprazole every day or two, or Rennies during the night if we forget.

The Lancet has lagged behind Fiona Godlee in addressing the challenge of climate change to human health. I must declare a conflict of interest here. I like to write about fungi in this column, but these naughty creatures are responsible, on some estimates, for the release of 85 billion tonnes of carbon into the atmosphere every year. Indeed, after the greatest extinction of all, 248 million years ago, they reigned briefly over all other life forms - the “terminal Palaeozoic fungal event”. However, the fungal events I’ll be describing are more along the lines of finding a nice crop of chanterelles.

A Zoroastrian Prayer

Whenever I brood on what I would like to teach medical students as part of an imaginary Medical Humanities degree course, I want a major place for liturgy, the preserved record of feeling in the great religions, and so the central repository of human expression. The oldest living liturgy probably dates from about 1700 BCE on linguistic evidence, and is attributed to Zarathushtra. His religion was possibly the first great monotheism, and its central concept is asha - integrity, honesty, wholeness or rightness. Its basic invocation is:

ashem vohû vahishtem astî Integrity is the best of all good,

ushtâ astî ushtâ ahmâi It is the essence of what is wished for,

hyat ashâi vahishtâi ashem. It is wholeness to the one who is whole.

There are innumerable ways of rendering these lines but if you look at the original you will see that the root “asha” permeates the whole in a completely untranslatable way.

Ann Intern Med 20 Jun Vol 144

There are plenty of inflammatory diseases whose causes we don’t understand—from psoriasis to multiple sclerosis—and for all of them boffins have beavered to produce agents to block particular bits of particular inflammatory pathways. In a hundred years, when we are either extinct or have worked out the aetiology of these diseases, this approach will seem rather quaint. Rheumatoid arthritis has naturally been the focus of much research using mabs (monoclonal antibodies) and cepts (fusion proteins) to block the sorts of inflammation which are associated with the severe disease. Abatacept blocks certain T-cell activation pathways associated with RA, and in this year-long trial it slowed disease compared with placebo, but produced a higher rate of infusion reactions and infections.

As if to mock our ignorance of this wide spectrum of disease thought to be auto-immune, the next paper looks at the associations between asthma and lots of other diseases in nearly half a million Israeli military recruits. Pre-existing asthma in fact seems to be associated with a decreased risk of many conditions such as inflammatory bowel disease and rheumatoid arthritis, particularly in women.

Those who have spent the last few years following the progress of the Stent Wars across the whole of the known Universe can be forgiven a certain ennui. Surely, you say, it’s pretty obvious by now that drug-eluting stents are better than bare metal stents, and that it doesn’t much matter whether they “elute” sirolimus or paclitaxel. Not so fast, say the authors of this review. We are reading too much into the SIRIUS trial, and we need more long-term studies. Indeed. Instead of a trial named after a star only 8.2 light years away, why don’t we have a trial called ANDROMEDA, which will shed light on the issue in 2.9 million years’ time?

B M J 24 Jun 2006 Vol 332

Open carpal tunnel release is the sort of surgery I imagine even I could do, but these days there is no procedure so simple that someone hasn’t invented an endoscope to make it more complicated. Is there any point in endoscopic CTS surgery? Not much, conclude these Swedish trialists.

The place of metformin in the treatment of polycystic ovary syndrome remains uncertain. If a woman with PCOS wants to ovulate, just give her clomifene. This Dutch trial shows that adding metformin makes no difference.

Plant of the Week: Cephalaria gigantea

This huge pale yellow scabious smells of new-mown grass to the human nose, and is a wild-looking joyous plant in borders or on banks. Bees seem to smell something even more alluring and surround it drunkenly, as later they surround the flowers of lime trees. I hope they can find their way back to the hive. Cephalaria honey would be an interesting experience. Watching the bees rolling off our flowers, I think it’s probably hallucinogenic.

 J A M A 14 Jun 2006 Vol 295

There is a lot we still don’t understand about anorexia nervosa, and this is reflected in the crude approaches we still take in treating it. This trial looked simply at how effective fluoxetine is at preventing relapse. It isn’t at all.

The SOFA Study Group lounges in the Dutch town of Wageningen, looking at the effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter-defibrillators. Oily fish are particularly revered by Netherlanders ever since William of Orange lifted the siege of Leiden by flooding the surrounding country, thus drowning the Spanish troops and enabling him to sail in with bread and herrings to feed the starving populace. Unfortunately, like previous studies, this one shows no antiarrhythmic effect and perhaps a tendency to harm. However, for those without ICDs visiting the Netherlands, I would recommend regular consumption of smoked eel.

If you have an out-of-hospital cardiac arrest, you are, of course, overwhelmingly likely to die, however much effort bystanders put into compressing your chest and inflating your lungs. This can be hard work, and is seldom done properly, so would the use of an automated load-distributing band (LDB) chest compression device lead to better outcomes? This study was terminated because of a trend to decreased survival and neurological status at hospital discharge in the LDB-CPR group: whereas in the study on p.2629, there was significantly increased survival to hospital discharge. In absolute terms, these arguments are about a tiny percent, and I think we can conclude that these devices help ambulance crew more than patients. 

N E J M 15 Jun 2006 Vol 354

We know that insulin resistance is a major risk factor for cardiovascular disease, and of course for the development of type 2 diabetes, but so far there has been no easy way to measure it. This may be about to change if this study of serum retinol-binding protein 4 (RBP4) fulfils its promise. This molecule is secreted by adipocytes and is elevated when people (and mice) become insulin resistant: the association may even be causal. It is lowered when insulin resistance is lowered, so it may be a good marker for the success of exercise and weight reduction in lowering the risk of diabetes. I hope more work is done quickly, because this sounds like a very useful clinical tool.

Idiopathic short stature can be “corrected” safely by giving recombinant human growth hormone to “sufferers” in childhood, but I’m not sure by what criteria, and this review doesn’t make me any clearer. Jacob Bronowski was under five feet tall, yet made just about the best television series ever, leaping about in such improbable clothes, and talking so wonderfully, that you didn’t notice whether he was a giant or a dwarf. Or, for one of the most moving experiences imaginable, watch tiny Mieczysław Horszowski play a divine piano recital to a Japanese audience in his 97^th year.

B M J 17 Jun 2006 Vol 322

I was a bit baffled at first by the idea of an alternating pressure overlay to prevent bed sores. Does the patient lie pinned and sprawling under some kind of inflatable duvet, I dimly wondered, until I looked them up on Google and discovered that they overlay mattresses rather than people. Ripply rubber things on top of mattresses versus special ripply mattresses was the subject of this trial. There was no difference in bed sore rates but the all-in-one ripply mattresses are nicer to lie on.

To prevent cardiovascular disease (and dementia), everyone who can should take a statin. However, if you want to target those at highest risk of coronary heart disease, you have to make choices of cut-off, usually based on the Framingham risk score, derived from a few thousand white people in North America. Many national committees have sat for many sessions and come up with many guidelines. Here a Canadian team wonder which of these would be best for Canadians. The New Zealand ones for economy, the US ones for coverage.

An observational study of sentinel node biopsy for malignant melanoma, observational because once you have removed the melanoma and the node, there is nothing much else you can do. However, prognostic data like this may be useful for future interventional studies.

Similarly, you may want to do a urine dipstick for protein in your regular CHD clinic. This study shows that t has some prognostic significance, but nothing that would alter management at present.

“It’s me back again, doctor”. It’s their back and they’re back. I don’t know if these puns work in Holland, where this review was written, but low back pain sounds the same there as anywhere else, judging from the patient quotations and the body of the text. It may be possible to identify the patients who might benefit from manipulation, and those who might benefit from cognitive behavioural therapy. Maybe you can even access these in Holland.

Plant of the Week: Anthriscus cerefolium

This is chervil, one of the few herbs you still have to grow for yourself. Time was—twenty years ago—when if you wished to experience the delights of civilised life, you had also to grow your own basil and tarragon. Bought in tiny pots from gardening suppliers, or grown from seed, plants would rarely yield more than a few leaves for culinary use before falling prey to snails or early frosts. My herbs have always fed more gastropods than gastronomes.

These slimy creatures adore chervil too. It is a hardy annual, so in theory you can sow it successionally all the year round to ensure a constant supply. But I bet the snails will beat you to it. Here is how to have your revenge:

Go out on a warm summer evening armed with a torch. Gather as many snails as possible. For a week, feed some on basil, some on tarragon, and some on chervil. Then feed them on a diet of rainwater until they expire, which can take weeks. After various washings (you can tell I haven’t actually tried this), bake them, season lightly with salt and pepper, and serve with plain butter. See if your guests can tell which snails have fed on which herbs.

Sumerian Proverb of the Week (c 3,000 BCE):

What has submitted will exhibit resistance

It’s reported that US troops in Iraq have destroyed lots of clay tablets. They might do better to read them.

Arch Intern Med 12 Jun 2006 Vol 166

Although UKPDS tells us an awful lot about type 2 diabetes, I’ve always felt that it raises more questions than it answers. It has led us to use exogenous insulin for many more type 2 diabetics, often leading to weight gain. In this study from Taiwan, the insulin group were actually leaner than the rest, but they did show higher blood pressure, which seems to relate to the duration of insulin use. Again we’re left with more questions than answers.

I don’t suppose that anyone is ever going to set up a prospective study randomising subjects to a lifetime of high alcohol consumption with or without coffee, though there might be willing volunteers if the right vintages were offered. So this cohort study is probably as good as we’ll ever get. It followed 125,580 people from 1978 to 2001, by which time 330 had developed liver cirrhosis, which was related to alcohol in 199. From available data on alcohol and coffee consumption, coffee protects against cirrhosis in a dramatic and dose related fashion, with the relative risk falling to 0.2 if you drink 4 or more cups a day.

Another foray into the relationship between race and cardiovascular risk, this time looking at a big Chicago cohort study which began in 1967 and analysed data up to 2002. The conclusion in the abstract says that most traditional risk factors exhibit similar effects in black and white patients, but a look at the tables does not bear this out. Smoking seems to confer no cardiovascular risk to black men, whereas it doubles it in black women and all white people, which is a pretty remarkable difference.

Teriparatide is an active bit of human parathyroid hormone (PTH) which has attempted to break into the highly lucrative osteoporosis treatment market. However, it’s going to be uphill work following this cost-effectiveness analysis which finds that it’s poorer value than alendronate in almost all settings except perhaps in combined treatment for very high risk patients.

Reading Foster’s massive new biography of W B Yeats recently, I was struck by his life-long appetite for mumbo-jumbo of every kind, particularly when offered by Indians of impressive physical presence. It’s the misfortune of transcendental meditation (TM) to be caught up in this sort of thing, unable to content itself with mere reductions in cardiovascular risk factors, but compelled to press on to world peace, levitation and yogic flying. For the people with metabolic syndrome in this study, TM for 16 weeks had a favourable effect on blood pressure and insulin resistance, though their gravitational force remained considerable and the world continues unpeaceful.

I never tire of reading about the association between statins and muscle pain, in the hope of understanding why it failed to show up in the major randomised trials but is so common in real life. Here is some correspondence following a study (Arch Intern Med 2005;165:2671) which reported that statin myopathy in 45 patients resolved within 3 months and that half of them were OK on another statin later. Various objections are raised, and I think the appearance of this debate six months after the paper vindicates a policy of not restricting replies to two weeks, as in certain British journals.

Lancet 17 Jun 2006 Vol 367

Prescribing of serotonin reuptake inhibitors (SRIs) has gone up and up in the UK, while suicide rates have fallen to a historical low. This editorial explores the alleged connection between the two in general. To me, these seem amongst the most useful and consistently effective drugs we have, and again I can’t understand the conflicting evidence of the randomised trials.

Here’s a really important primary care study which should transform the way GPs and laboratory doctors communicate with each other. In Aberdeen, the two parties moved on from periodic moaning about one another and started an exercise in feedback, tracking practices with high test usage and advising clinicians about the limitations of a range of tests commonly mis-ordered for diagnosis (e.g. FSH for menopause, ferritin for iron deficiency, both of which I order all the time) or monitoring (e.g. serum B12). Treating GPs as intelligent beings in need of timely guidance succeeds in most situations, where sticks, carrots, lectures and guidelines usually fail.

There is a thirteenth century religious lyric which lists the woes of old age in gruesome detail, as a spur to timely repentance:

Wanne mine eyhnen misten, (When my eyes mist)

And mine heren sissen, (my ears hiss)

And my nose coldet, (my nose gets cold)

And my rude slaket, (my face slackens)

And mine lippes blaken, (my lips go black)

And my muth grennet, (my mouth grins)

And my spotel rennet, (my spittle runs)

And mine her riset, (my hair falls out)

And mine herte griset, (my heart becomes irregular)

And mine honden bivien, (my hands shake)

And mine fet stivien – (my feet stiffen)

Al to late! Al to late! (it’s too late [to repent] when the hearse

Wanne the bere is ate gate. has arrived at your door)

To this cheerful list, we could now add Wanne mine banen þinnen (when my bone grow thin). Osteoporosis comes to us all with increasing age, just a bit sooner in women. Repent! And if you want an exceptionally clear and comprehensive review of the topic, go for this one.

Fungus of the Week: Marasmius oreades

You aren’t likely to find many edible fungi at this time of the year, but at least GPs on home visits have the opportunity to scan grass verges and lawns for fairy rings. These are characteristic round areas of bare grass surrounded by lusher grass, which, if you are lucky, will hide fairy ring champignons. If you are unlucky, they may hide deadly little white Clitocybe species. So if you can’t tell the two apart, don’t even touch them, since death from muscarinic poisoning is unpleasant. The edible ones have an odour of cyanide when their caps are moist, changing to a lovely mushroom smell when fried in butter. Use a large amount of butter and a shallot; pick out the mushrooms, throw away the shallot, and then cook an omelette in the butter, seasoning and adding the caps (and a little chervil) at the end.

J A M A 7 Jun 2006 Vol 295

Suppose you have several small metastases in your brain—not that I am wishing it on anyone—would you want each one picked off with stereotactic radiosurgery alone, or would you go for the highly unpleasant experience of whole brain radiation as well? In the first instance, the recurrence rate is 76% over a year: in the second, 47%. But the mean survival time was only 8 months in both groups. Whole brain radiotherapy could make you feel awful for half that time, so I think I’d give it a miss.

“Race, Breast Cancer Subtypes, and Survival in the North Carolina Breast Cancer Study”. The meat of the paper is strictly for breast cancer whizzes, but it raises again the issue of how best to characterise “race” in the medical literature. Here, the main term is “African American”, which is reasonably clear. Elsewhere in the American literature we get terms like “Asian” and “Hispanic” which are positively confusing. In the UK, most “Asians” are of Indian subcontinental origin, and “Hispanic” is a word we save for history or geography lessons. But in America, “Asians” are of Chinese or Japanese descent, and “Hispanics” are mostly the descendants of native South Americans who sometimes intermarried with Spanish or Portuguese colonists. We need a standard international nomenclature to be able to discuss these issues scientifically without confusion and without sounding racist.

If I ever go into a nursing home, let it be in Hamilton, Ontario, where this study sent in nurses with portable chest X-ray machines, oxygen monitoring and IV fluids and antibiotics to look after those who got pneumonia. But when that time comes, I hope the home might also give me the choice of an alternative regime, mainly malt whisky and morphine.

We know that, by and large, everybody with a myocardial infarction should be treated with immediate revascularisation: but might some patients be too sick for this to be of benefit? This trial looked at patients in cardiogenic shock following MI, and even in this group there are mortality benefits from early revascularisation, which increase over 6 years.

N E J M 8 Jun 2006 Vol 354

The Lancet and NEJM sometimes compete to see who can spill the most coloured ink illustrating the genomic structure of something-or-other. Here it’s Burkitt’s lymphoma, and so far the main point of the exercise is to be able to distinguish it from diffuse large-B-cell lymphoma, both being rare in Western adults, and hard to tell apart (see p 2431). The incomprehensible but immensely impressive international Lymphoma/Leukaemia Molecular Profiling Project will no doubt come up with more relevant work than this. If you’re interested, a review by John Quackenbush explains the basics.

Beware using ACE inhibitors in women of child-bearing age: first-trimester exposure may cause major congenital abnormalities.

Over thirty years ago, when there was no effective vaccine or antibiotic treatment for cholera, I heard a distinguished expert suggest that health workers going to high risk areas should be given the Vibrio and then intravenous fluid at the same rate that they lost it per orem et anum. Fortunately we are now coming up with better ways to induce immunity, and also to treat the disease—a single oral dose of azithromycin will suffice for most adults (like children), provided they can keep it down.

B M J 10 Jun 2006 Vol 332

1346 “Are older antipsychotic drugs obsolete?” No sums it up nicely: for confirmation go to CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) which found that perphenazine did as well as most modern “atypical” drugs, at a fraction of the cost and with no more extrapyramidal effects (NEJM 2005;353:1209).

A trial which finds equivalence between three days of amoxicillin for mild-to-moderate community acquired pneumonia and eight days. Some Dutch doctors regard every day of unnecessary antibiotic treatment as a day of mortal sin. I don’t, so the main message for me is that patients who are going to get better on amoxicillin will generally do so within three days: if they are still feeling awful at that point, change the antibiotic.

Does personality play a large part in susceptibility to heart attacks and cancer? Hardly any, according to this German study.

How green is your baby’s vomit? This paper contains a handy chart. A lot of doctors and parents apparently thought green vomit wasn’t likely to indicate bile, whereas it does and mandates admission in the newborn.

The invention of the cardiopulmonary bypass pump made possible the modern era of cardiac surgery, but it’s by no means harmless, often throwing off microemboli and causing lasting neurocognitive impairment. So off-pump coronary artery surgery is what to go for if you need it, and if you can find a centre that is good at it.

A review of thyrotoxicosis with nothing to make the pulse race or the eyes bulge, but it’s a useful account of the options, worth turning to if your patient gets into difficulties.

Plant of the Week: Decumaria sinensis

This is a plant which should be found on every sunny wall in Britain, but you hardly ever see it. It is easy, tough, vigorous, evergreen and reliably self-clinging. The glossy oval leaves are a bit ordinary, perhaps, but the frothy heads of creamy flower are beautiful, abundant, and marvellously fragrant. For two weeks at least you will come home through a wall of scent, like inhaling a lemon and honey mousse. If you manage to find a plant and dig it in now, it will reach the eaves of your house in about six years. Then you can trim off the excess and try and root bits on for friends.

Proverb of Ancient Sumer ca. 3,000 BCE:

The journey is bad: the beer is good.

This proverb is found on three early clay tablets of Sumerian proverbs from the third millennium BCE. Most beer-drinking cultures have produced similar proverbs (I’m only here for the beer), but the Sumerians are credited with actually inventing beer. They were fabulously good at plant breeding, and their yields of grain were greater than any up to the 19^th century. Much of the surplus was used to render the waters of the Tigris and Euphrates safe to drink, through the filtration and settlement processes of beer-making as well as the antibacterial action of the alcohol. Brewing was carried out by women, who preserved particular lines of yeast and secrets of flavouring.

Ann Intern Med 6 Jun 2006 Vol 144

Is it time for a nap or is it time for a coffee? Once past a certain age, one’s whole day seems to be spent addressing this question. Here it was the subject of a randomised trial in night-time highway drivers, and both groups showed improved reaction times, without suffering any ill effects on normal sleep.

Remember those awful red-eye shifts preceded and followed by a full day’s work? Thirty hour duty periods are still common in the USA, and this study randomised interns to two weeks on and off a nap schedule, in which they could hand over cover between midnight and 7 a.m. to a colleague and try and get some sleep. Oddly enough, they only managed an average of 41 more minutes’ sleep on these nights. However, this did help them perform better. The lessons of these two studies are pondered on in an editorial, which contains a new collector’s item for lovers of American medicalese—circadian dyschronosis. “Circadian” is an elegant modern coinage from the Latin circa (around) and dies (day); cod-Greek dyschronosis you can work out for yourself. Remember to deploy the term if you want to boast about your jet-lag, or if your teenager won’t get up in the morning.

Designing randomised controlled trials of diagnostic tests is the Killer Sudoku level of clinical research—everything influences everything else and you wonder why you ever started. For those who are contemplating such masochistic pleasures, this review article is essential. But here we are looking at an evaluation of D-dimer in the diagnosis of pulmonary embolism. The first requisite is that your trial should avoid killing patients. This trial looked only at patients with a negative D-dimer, i.e. no serological evidence of recent clotting. Patients from both hospital and community settings were then randomised to no further testing or, for the low clinical risk group, a V/Q scan and leg ultrasonography, repeated at one and two weeks, whereas the moderate-to-high risk group had only the latter. Do you follow? I’m not sure that I do. I’m not sure why an RCT was needed rather than just retrospective analysis, as in other studies. But in any case it proved what we already knew—a negative D-dimer in a low-risk patient excludes PE.

Osteoporosis illustrates another conundrum of diagnostic research: how to define something which is part of a normal distribution curve, but carries additional risk at one end. Here it’s the bottom end of the bone density curve; elsewhere it’s the top end of the BP curve, or cholesterol, or whatever. Now say you have several ways of measuring this risk factor, plus a lot of observational evidence based mainly on one of these methods. Here it’s dual-energy X-ray absorptiometry (DXA), whose correlations with fracture risk we know well. Calcaneal ultrasound is a simpler and cheaper measurement, but his meta-analysis shows that it has a poor correlation with DXA. But how well does it predict fracture risk, or response to treatment? We don’t know.

Over recent years, have you been putting a lot of your patients with chronic asthma on salmeterol or formoterol inhalers? I’m afraid we’ve been doing them no favours, as this meta-analysis of the RCTs shows that these drugs increase their risk of severe asthma or asthma related death, an effect not fully offset by concomitant corticosteroids.

Lancet 10 July 2006 Vol 367

We know which patients with atrial fibrillation are at highest risk of stroke, and we put them all on warfarin. But would they do just as well on double platelet blockade with aspirin plus clopidogrel? This RCT (ACTIVE W) was stopped early when it showed a definite advantage for what the editorial on p.1877 calls “good old warfarin”. Old, yes, but good? The person who comes up with a safe direct thrombin inhibitor will be medicine’s biggest benefactor, saving several million blood tests a day.

Corticosteroids given to the mother immediately before premature birth definitely reduce neonatal respiratory distress syndrome, so should we be giving repeated courses to women at high risk of premature delivery, just in case? The babes may benefit, though we don’t know the long-term effects; but a third of the women will then be given several weeks of unnecessary steroids prior to delivery at 34 weeks or later. As the accompanying editorial, it’s a tough call.

Our practice recently took part in a survey to detect pertussis in children between 6 and 12 with a cough lasting more than four weeks. There were whoops of delight when we identified it in 25%, all of whom had been immunised. Not that you can do much about it, but it proves what a common little rotter Bordetella really is, and it affects plenty of immunised adults too. To understand a bit more about the beastly coccobacillus, read this enjoyably written review.

Blake for the Week: The CLOD & the PEBBLE

Love seeketh not itself to please,

Nor for itself hath any care;

But for another gives its ease,

And builds a Heaven in Hells despair.

So sang a little Clod of Clay,

Trodden with the cattles feet;

But a Pebble of the brook,

Warbled out these measures meet.

Love seeketh only Self to please,

To bind another to Its delight:

Joys in anothers loss of ease,

And builds a Hell in Heavens despite.

Songs of Experience 1793

Unusually, Blake wrote this poem complete in his sketchbook and transferred it unaltered to the engraved page. When I present it to medical students, I’m always disturbed by the number who side with the pebble.

NEJM 1 Jun 2006 Vol 354

The simple paradigm for studying diagnostic tests is to decide on a “gold standard” and use that to compare any other tests that come along, by measurements of sensitivity and specificity in particular populations. Pulmonary embolism seems to have a nice clear definition—a clot in the pulmonary arterial tree—and a nice gold standard test—pulmonary angiography. But clots in the lung come in all shapes and sizes, and the gold standard test was considered to be unethically invasive for most of the patients in this trial. The population is poorly defined. So it’s hard to tell whether a new diagnostic CT modality—multidetector computed tomography—really represents a useful advance or not.

“Even moderate weight gain among persons of normal weight may cause or exacerbate symptoms of reflux.” The persons in this study were female nurses: GORD punished those who got a bit fatter.

A review of panic disorder from a country far away, where “cognitive behavioral therapy is provided in 12 to 16 sessions over a period of three to four months”; yeah, right. There’s even an account of the usefulness of benzodiazepines, the very mention of which usually causes hyperventilation, sweating and palpitations over here.

Thomas Pickering carries on the family interest of his father Sir George, and writes about ambulatory BP monitoring, though in rather more measured tones than when the old knight traded insults with Lord Platt in the 1950s. But he still doesn’t persuade me that our practice should replace its recently defunct ABPM monitor. Sure, it showed a few interesting ups and downs, but I can’t remember it ever beating simple home monitoring as an aid to decision-making.

BMJ 3 Jun 2006 Vol 332

I’ve been mulling over this landmark study of parenteral penicillin prior to admission for meningococcal disease in children for over a year now, since I first heard the data presented at a research meeting. This is a meticulously performed case-control study and the message is very clear: children given penicillin before admission die and suffer brain damage seven times more often. Adjust as far as possible for severity at presentation, and the message is the same. The systematic review of the evidence which follows this paper does not include it, and ends up sitting on the fence. This is not an option available to GPs faced with this terrifying emergency once or twice in a working lifetime: you either give the stuff or you don’t. The only way we shall ever know the answer for certain is by a randomised controlled trial; and this, I hear, is opposed by the Meningitis Research Foundation. Is it perhaps contemplating a change of name?

Here’s the straightforward meta-analysis we’ve all been waiting for, to tell us if COX-2 specific anti-inflammatory drugs really carry greater vascular hazards than non-selective NSAIDs. The answer is no, for most practical purposes. Naproxen alone seems to be safer than the rest. All the others, specific or otherwise, cause about 3 extra cardiovascular events per 1,000 patients per year of use. The huge fuss about the dangers of coxibs has come full circle.

The management of myocardial infarction in the UK remains a lottery, in case you hadn’t noticed. Evidence suggests that the target rate for angiographic intervention should be above 90%, whereas in real life it’s 56% if you are admitted to a hospital with a catheter suite, and 30% if you are one of the other four-fifths of British patients with MI.

Lancet 3 Jun 2006 Vol 367

“There is too much secondary care, too many patients are referred unnecessarily to hospital, too many are unnecessarily admitted, and too many stay too long.” Say these King’s Fund authors, citing a 1994 study. They should come and work where I do.

St Thomas Aquinas, who was generally eating when he was not writing or preaching or praying, speculated on God’s purpose in imbuing pepper with the essence of fire, which he perceived as one of the four elements. A good job that thirteenth-century Dominican refectories did not generally offer vindaloo curries, or we might have had an entire Summa Chilliana. In this amusing little editorial, David Sharp celebrates the discovery of the hottest chilli yet—the Dorset Naga, which scores 900,000 Scoville units—the equivalent of 900,000 angels sticking pinheads of fire in your mouth.

The treatment of opioid dependency in the UK seems stuck halfway between the idiotic American “war on narcotics” model (of criminalisation) and the enlightened Swiss “let them have it safely” model. Rates of heroin use have fallen in Zurich since the introduction of drug injection rooms, needle-exchange programmes and heroin maintenance therapy. If this is what “medicalisation” can achieve, bring it on.

1835 Female genital mutilation is a topic which makes even grown men squirm, if they have any feelings, though the commonest explanation for the practice is that it renders women incapable of orgasm and therefore allays male sexual anxiety. It is practised in some Muslim areas of Africa, though it would have been abhorrent to Muhammad, who, according to many a hadith, was keen on giving his wives pleasure. As well as being cruel and immediately harmful, it also increases the risk of adverse obstetric outcomes.

Arch Intern Med 22 May 2006 Vol 166

As some of you may know, I’ve been beavering away on projects to do with B-type natriuretic peptide (BNP) on and off ever since I first read about it in 1994. A simple blood test to tell us how much strain the heart is under—how marvellous! But we seem to have got bogged down with just two aspects of this important marker—how well it correlates with systolic function as measured by echocardiography, which is what this systematic review is about—and how good it is at discriminating between cardiac and other causes of breathlessness, which is what an accompanying cost-effectiveness paper is about. BNP holds a lot more promise than this, and to find out about it you can look in the latest issue of Heart (June) 2006. For a review of its potential applications in primary care, watch out for a future issue of American Family Physician.

The world of medical research is full of scoring systems which over the years get pared down to a few simple points which often bear a striking resemblance to the questions most doctors were asking in the first place. If you want to know if your patient is anxious, for example, you can ask them if they are anxious; or if they are worried, or if they have trouble relaxing, or if they get restless, or irritable, or afraid. Add a few boxes for how often, and you have the GAD-7 scale. By gad, I‘m now getting anxious that I’ve breached their copyright.

To avoid dementia, keep physically active, because this study shows that low levels of physical performance over the age of 65 correlate with more Alzheimer’s. I’d also recommend keeping mentally active, taking most of the Polypill ingredients, eating lots of fruit and veg and fish, drinking wine, and generally doing all the things you dream of doing in your retirement, except sitting around a lot.

Given that there is some evidence (but not a lot) that influenza vaccine is of benefit to the elderly, we might as well give them an immunogenic dose. This study shows that a higher dose than the usual gives them better protection.

Plant of the Week: Papaver orientalis

For two or three weeks these papery beauties dominate the garden with their huge heads of orange-scarlet, or subtle dull pink with black flashes (“Cedric Morris”), or intriguing washy purple-brown (“Patty’s Plum”), or just “Black and White” (my favourite). If you want a second flowering in September (and who doesn’t?), viciously rip off most of their leaves immediately after flowering, and they will start back into growth. They look fragile and exotic but they are as tough as horseradish, and as ineradicable. So when you plant them, be sure that you want them there for ever. If you ever try to dig one up, you will be rewarded by a mass of growth in the same spot the next year, from roots you have left behind.

Tolstoy for the Week:

Each time of life has its own kind of love.

The Kreutzer Sonata (1890)

J A M A  24 May 2006  Vol 295

Colonoscopy is not as bad as you might think: just like having a long thin eel crawl up inside you. Or maybe that’s just the midazolam talking. And it’s very good at spotting tumours: the protective effect of colonoscopy can be detected for up to ten years. So you can make a case for using the eel to screen for bowel cancer in people aged 50-60; but a study in people aged 80 or over shows that by then, 85% of the mortality benefit is lost.
In studies of cost-effectiveness, the main thing to look for is the spread of estimates of cost per QALY. Most often it’s around tenfold, and at that point you may wish to turn to the next paper. Here it’s fifteenfold. Before turning to the next item, let me tell you that this refers to the added benefit of MRI scanning in addition to mammography for carriers of BRCA mutations.
Time was when the poor were thin; a fact welcomed by the Reverend Thomas Malthus, who took Jesus’ words “The poor will always be with you” to mean “so let’s get rid of them before they can breed”. Nowadays, in the USA, the poor tend to be fat (except poor white women, see Arch Intern Med 2005;165:212); this study looks at trends among poor adolescents, and finds that “Non-Hispanic black” teenagers are the fattest. Am I the only one to find the racial categories used in the US literature confusing and mildly offensive?
 

N E J M  25 May 2006  Vol 354

It takes special qualities to be a neonatologist, surrounded by tiny sick babies and sleep-deprived anxious parents, and ever on the lookout for horrible conditions like necrotising enterocolitis. Moreover it’s difficult to carry out randomised trials in these babes, but a US group managed to get 117 into a trial of peritoneal drainage versus laparotomy. 76 were alive three months later, with no difference between the groups.

This paper describes two American clusters of lymphocytic choriomeningitis virus transmission by organ transplantation. Maybe not the most pressing clinical dilemma you face in morning surgery, but a reminder that putting one person’s organs into another, immune-suppressed person is always going to carry risks.

Bone structure is a nice old-fashioned term now mainly used by horse-breeders - and gardeners, who use it to describe the garden features which give architectural interest through the seasons. Doctors tend to regard bones as mere scaffolding, and those with an interest in them, like anatomists and orthopaedic surgeons, are often asked to use the tradesman’s entrance. This interesting review of how bone is shaped and reshaped discounts such silliness; but I do wish it wouldn’t go on about how bones, like everything else, decay with age. 

Lancet  27 May 2006  Vol 367

Two studies (see also here) demonstrate that, unlike the Gulf War of 1991, the Iraq war of 2003 has not had any measurable effect on health outcomes in UK military personnel. I remember those early TV bulletins, as we anxiously watched them edge towards Basra, and worried about the effect on water supplies, electricity and hospitals there. Now that we have had three years to fulfil our commitments under the United Nations Charter to the civilian population, I wonder what the measurable effect on health has been in Basra.

Whatever one may think of the failings and vanities of The Lancet, which sometimes displays a Lord Moran-like contempt for the 50% of UK doctors who have “fallen off the ladder” and become GPs, nobody can accuse it of ignoring the wider world. This week sees the start of a series on “indigenous peoples”, and here is another huge overview of the global and regional burden of disease and risk factors. Things are not all for the best in this best of all possible worlds, but overall they are getting better. Except for sub-Saharan Africa and the former Soviet bloc. Now I know that AIDS has played its part, but could that also be something to do with the collapse of publicly funded health care and particularly primary care in those regions?

Only a week or two ago, the NEJM featured a review of scabies, prompting me to ask if that wasn’t a mite too common for such an august journal. But it seems that The Lancet was itching to follow, so Sarcoptes scabiei has definitely burrowed its way to prestige.
 

 B M J  27 May 2006  Vol 332

I know the BMJ is widely read in German-speaking countries, where the acronym MIST (= dung) for this trial may cause some amusement, or concern. Some acronyms simply don’t make a very good Fahrt between one language and another. It stands for miscarriage treatment, which can be expectant, medical, or surgical. It’s taken the thirty years since I was an Obs&Gyn SHO to work out that miscarriages are not best called abortions and that leaving them alone is most often enough, and does not increase the risk of infection, though a few may need to come in for an ERPC. Why, we could even offer a choice to the women concerned (see editorial).

I don’t know if this a commonly known fact, but many doctors of both sexes have an alcoholic drink when they get home, unless they have some frightfully demanding paperwork to get on with, in which case they may have one later. For men wishing to avoid myocardial infarction, this looks like a good idea: here’s more evidence from Denmark that for males at least, alcohol is the best cardioprotective drug we know of.

Hypertrophic cardiomyopathy: “because a timely diagnosis may help to prevent sudden death, it is important for internists and general practitioners to be aware of the clinical features of the disease”. Sudden death in the absence of preceding symptoms is one such feature, making this a bit of a challenge, since fit asymptomatic young men do not feature greatly in our front-of-brain alarm systems. In fact HCM is pretty rare and not very deadly to most of those who have it: sudden young deaths are the exception, and this review is worth reading mainly to guide management of patients with a family history.
 

Plant of the Week: Rosa “Souvenir du Docteur Jamain”

The season of the rose is now upon us, with all its attendant joys of black-spot and dead-heading. For the most part we ignore such blights, growing climbers to make use of the vertical aspects of our small garden, but this treasure has no climbing form and has to be grown as a bush, which is as ugly as most rose bushes. Ah, but the colour and scent of the flowers! They are deepest dark red, darker even than Guinée, and even more scented. Plant where the midday sun will not spoil them. I have no idea who the worthy Dr Jamain was, but if this rose is a true souvenir, he was no boring provincial Bovary.

Rapid Responses:

Read all Rapid Responses

Richard Lehman is worth more than his weight in gold ...

Caroline [no middle initial] Richmond
bmj.com, 23 Jun 2006 [Full text]

A pleasure to read

veronica m wilkie
bmj.com, 3 Jul 2006 [Full text]

Dr. Richard Lehman is great!

Gauranga C. Dhar
bmj.com, 16 Aug 2006 [Full text]