J A M A  6 Sep 2006  Vol 296

1055   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.

1071   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.

1094   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…

1103   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.

1116   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

992   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?

1006   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.

1018   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 article on p.973, full of potential. Any volunteers out there?

1029   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

519   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.

522    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.

525    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.

530   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.

544   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.

546   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

901   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.

919   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.

929   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.

947   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.

954   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

317   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?

326   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.

364   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.

J A M A  13 Sep 2006  Vol 296

1235    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 48hr 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.

1242    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%.

1255    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).

1274   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

1093    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 (p.1105) 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.

1124   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 (see p.1089). 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

560   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.

561   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.

571   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.

575   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 southwestern 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”.

578   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.

581  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.

586   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.

594   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 (p.596) 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

991   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 editorial on p.965).

998   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.

1005    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.

1023   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   20 Sep 2006  Vol 296

1357   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.

1371   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 more likely to get kidney cancer.

1377   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.

1385   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

1199   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.

1210   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

623    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 (p.626) and in an editorial by a health economist (p.611). 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.

632   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

1067   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. 

1088   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.

1096   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. 

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…

1686   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.

1689   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.

1695   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 papers on pp.1725 and 1756.

1701   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.

1709   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.

1744   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.

1768   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?

1775   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

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.

J A M A  27 Sep 2006  Vol 296

1469    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.

1479   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.

1488   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

1307   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.

1318   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 editorial, p.1372). 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.

1339   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.

1345  The tuberous sclerosis complex: a comprehensive, well-illustrated review to turn to if you have a patient or family with this autosomal dominant  disorder.

1377   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

675  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 (p.663). (N.B. This is an entirely separate issue from contrast nephropathy, which can usefully be prevented by N-acetyl cysteine).

679   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.

682   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 editorial (p.664) 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.

685   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.

701   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.

709   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

1155   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.

1164   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.

1171   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

397   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.

407   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.

416   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 (p.1357) 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.