Journal Watch - March 2010

JAMA 17 Mar 2010 Vol 303

1046 A pleasure that many of us ageing men can look forward to is lying on a table like James Bond while somebody aims a narrow beam of deadly rays at our private parts. It will be no use saying "You're forgetting one thing, Goldfinger" - you will have mounted the table voluntarily to have high-energy photons and/or protons aimed at your early prostate cancer. Nearly ten years later, somebody may come along with a questionnaire for you to complete about changes in your sexual function, together with urinary or bowel problems. By this time you'll be in your mid-70s and not likely to be able to compete with the young Sean Connery for the attentions of leading ladies - in fact your "masculine esteem" will have plummeted (79% of those questioned following either treatment regime). You're likely to be enjoying some form of sexual intimacy but perhaps not the full monty. On the other hand, your bowels and bladder will probably be working OK. Ah well.
http://jama.ama-assn.org/cgi/content/abstract/303/11/1046

1070 This issue of JAMA is dedicated to oncology (from Gk. ogkos/onkos, meaning a mass or lump), a discipline where slow incremental progress is commoner than dramatic Daily Mail- style breakthroughs. Take the fairly uncommon situation of a stage 1 or 2 non-small cell lung tumour in a patient unfit for surgery. At present, 3-year survival would be 20-35%. This study looked at the results of stereotactic body radiation as opposed to conventional radiotherapy: it wasn't randomised or blinded and this is a preliminary communication. Quite promising, though: 55.8% survival at 3 years.
http://jama.ama-assn.org/cgi/content/abstract/303/11/1070

1077 Pyridoxine is one of those methylating B vitamins (no.6) which we know we need but don't fully understand. It's reasonably easy to measure its active metabolite, pyridoxal 5'-phosphate (PLP) in blood so in prospective studies you don't have to depend entirely on subject-reported dietary intake. This meta-analysis of such studies of vitamin B6 and risk of colorectal cancer suggests that the risk of colon cancer may be reduced by a half for every 100 p-mol/ml increase in blood PLP. Provided you adjust for the right confounders and ignore one Dutch study. Eat meat, fish, starchy vegetables, bananas and avocado.
http://jama.ama-assn.org/cgi/content/abstract/303/11/1077

NEJM 18 Mar 2010 Vol 362

975 All my professional life I have been waiting for order to emerge from the chaos of childhood asthma. When I began, GPs were encouraged to stick this label on every child who wheezed, or coughed for more than a week or two. I get the impression that millions of parents worldwide are still panicked by this nonsense and encouraged to give their children continuous inhaled corticosteroids for no reason whatever. The only group who may benefit are children with real asthma triggered by allergy and/or exertion. These kids do benefit from low-dose inhaled corticosteroids but often remain poorly controlled, and we don't have any clear idea of what to use as step-up therapy. We can step up the inhaled steroid (fluticasone, up from 100mcg to 250), add a long-acting beta-agonist (salmeterol) or add an orally active leukotreine-receptor antagonist (montelukast). So which is it to be? This small but excellent trial assigned 182 children to receive all of these therapies, blinded and in random order, over 16 weeks. And really it proves that this is the only way to find out which therapy is going to suit each child best. Not easy to do, but worth a try. Incidentally, the trial had the child-friendly acronym BADGER, but the NEJM seems to have decided to hide this embarrassing fact in the text.
http://content.nejm.org/cgi/content/abstract/362/11/975

986 Performance of common genetic variants in breast-cancer risk models. The paper begins with the words PERSONALIZED MEDICINE and ends by confessing that adding 10 common single-nucleotide polymorphisms to standard risk assessment for breast cancer is largely a waste of time. A lot of time, in France, Poland and America. But not my time: on to the next paper.
http://content.nejm.org/cgi/content/abstract/362/11/986

994 Well, some would say that out-of-hospital defibrillation is also largely a waste of time, but not the 8.9% of Japanese who survived with minimal neurological impairment following bystander defibrillation in public places. It has become public policy throughout Japan to increase the availability of automated external defibrillators (AEDs) and to encourage citizens to use them without legal jeopardy. From the beginning of 2005 to the end of 2007, these devices were used for ventricular fibrillation on 12,631occasions. Most of the recipients were men in their mid-60s, of whom 3011 were alive at one month, 1815 neurologically intact.
http://content.nejm.org/cgi/content/abstract/362/11/994

1014 By now, every British GP must have a cost profile score, which in our case would be a simple aggregate of what we each cost by income, total prescribing, and total costs for investigation and hospital treatment. In the USA, it's a bit harder to keep track of all this and various kinds of physicians and surgeons are allocated scores by other criteria, as examined in this paper. 59% of these had reliabilities of less than 0.7. I won't pause to explain, but the word crap suggests itself, as so often when looking at health management tools.
http://content.nejm.org/cgi/content/abstract/362/11/1014

1022 Vertebral osteomyelitis is a never-miss-this condition. In the days before MRI I remember one teenager presenting with localised back pain and raised ESR and white count, and then 18 months later with an abdominal mass which turned out to be a 5L retroperitoneal collection of staphylococcal pus. More difficult than the young patient with localised pain with or without fever (but always with a high CRP) is the older person with an exacerbation of degenerative back pain. Vertebral osteomyelitis is much commoner in the over-70s (though still only 6.5 per 100,000 annually) and is associated with bacterial endocarditis in a third of cases. Be aware.
http://content.nejm.org/cgi/content/extract/362/11/1022

Lancet 20 Mar 2010 Vol 375

985 If you had a TIA and a narrowed carotid artery, would you agree to have a carotid stent? I suspect that for any health professional who had read this study and the accompanying editorial by Peter Rothwell, the answer would be no. In fact the editorial points out that the main studies of endarterectomy predate modern medical management, so we don't even have a clear idea of the extent to which surgery improves outcomes. On the evidence of this trial (ICSS) it's safer than stenting, at least in the short and medium term; but doubts are now being raised about how often we should be tinkering with the carotid artery at all.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60239-5/abstract

1007 An interesting bit of cross-European epidemiology looks at the recorded prevalence of cystic fibrosis. We know that the genetic characteristics of European populations inside and outside the European Union are practically identical, and that therefore the epidemiology of this genetic condition should also be the same. But in fact there are marked disparities, all of which are compatible with better diagnosis and survival in EU countries than in non-EU countries.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62161-9/abstract

1030 An authoritative update on colorectal cancer goes through a grindingly boring three pages of molecular discourse before getting down to a very useful summary of screening and even more useful sections on surgery and adjuvant treatments, and the increasingly effective treatment of metastatic disease. As ever, the gene gnomes get first say, while the real progress lies with doctors interested in making poorly people better.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60353-4/abstract

BMJ 20 Mar 2010 Vol 340

633 In the Million Women Study, the rate of liver cirrhosis was 0.237 per thousand women per year (deaths and first hospital admissions). About 17% of this risk came with increasing BMI and about 42% came from alcohol. Beware, O fat women who drink! You stand a tiny risk of liver failure.
http://www.bmj.com/cgi/content/full/340/mar11_1/c912

634 And what about fat men who drink alcohol? Where better to look than Scotland - among two population cohorts totalling 9559 men followed up for just over 29 years, 80 had liver failure as the main cause of death (0.8%). Here there seems to be a definite synergy between obesity and alcohol consumption: but again, the absolute risks are small. It would be nice to identify early progression to cirrhosis, but as the editorial (p.606) points out, we can't. "The liver is a stupid organ: it can only grunt", as a hepatologist memorably put it a couple of years ago. So population measures are needed. Good luck to anyone persuading all overweight Scottish men to drink less than 15 units a week. Aye, a week.
http://www.bmj.com/cgi/content/full/340/mar11_1/c1240

637 Let post-modernists say what they will, medicine is a truth-seeking activity. We need clear streams of accurate information if we are to start on the complex business of making people better. The Cochrane Collaboration does this on an industrial scale, and is justly regarded as a Very Good Thing: but quite how good are the systematic reviews that go into it? Do the reviewed randomised trials actually report on the outcomes that they promise to? The Great Policeman, Doug Altman, sets his constabulary the task of finding out, and oh deary me, sir, there do appear to be a few missing items that our inspectors would like you to account for. If you don't mind stepping this way, perhaps you could tell us why more than half of your reviews don't include full data about the primary outcome, why 26% exaggerate the treatment effect, and why 19% report a significance which isn't there in the data? Take your time sir, and make a telephone call if you wish.
http://www.bmj.com/cgi/content/abstract/340/feb15_1/c365

641 Clostridium difficile is a tricky subject to discuss aloud, as people have strong views about how to pronounce it. It is a Latin neuter adjective by the way, not a modern French one. Idiot. It is also difficult to write about, because its basic management is simple, whereas its clinical course is unpredictable and often complicated. Four authors have a decent bash at it here. Difficile. Diffikilay, ner, yeah, wanna fight?
http://www.bmj.com/cgi/content/extract/340/mar12_1/c1296

Ann Intern Med 16 Mar 2010 Vol 152

337 Last year, we got worried about the effect of co-prescribing proton pump inhibitors and clopidogrel, with pharmacological evidence to support the idea that PPIs cancel out clopidogrel's transformation to an active drug, and two papers suggesting that this is clinically significant. Now comes a cohort study of 20,596 patients suggesting that it doesn't matter after all. The PPIs definitely reduce GI bleeding but don't seem to affect cardiovascular events in patients at high risk.
http://www.annals.org/content/152/6/337.abstract

346 I have spent an unnecessarily large amount of time this year pointing out that glycated haemoglobin is not a sufficient surrogate for assessing the benefit of drugs for diabetes. Nor, for that matter, is microalbuminuria a sufficient surrogate for renal outcomes. The only way to find out what happens is to wait for it to happen. Salsalate is an anti-inflammatory precursor of salicylate which has glucose lowering properties. This small study in type 2 diabetes confirmed that salsalate added to any oral regime lowers gHb by about 0.5% and is well tolerated. However, it increases urinary albumin excretion. It would be good to believe that we now have another cheap safe drug to add to metformin, but it's much too soon to tell. It may improve cardiovascular outcomes but mess up the kidneys. Or the other way round. Or neither. Wait many years and see.
http://www.annals.org/content/152/6/346.abstract

370 This week's exemplary and painstaking study to include the familiar name of Harlan Krumholz concerns the all-important question of percutaneous coronary intervention versus medical therapy for angina relief. It was the COURAGE study which stopped us in our tracks on this subject a couple of years ago; but this intelligently stratified meta-analysis shows that the gap between the results of PCI and conservative management was narrowing all the time as evidence-based drug treatment for angina increased from 40% in the older trials to 75% in the later. As this happened, so the symptomatic advantage of PCI melted away, as did any prognostic advantage.
http://www.annals.org/content/152/6/370.abstract

Plant of the Week: Lonicera strophiophora

I have written before about this lovely late winter-flowering honeysuckle, which remains unaccountably rare. Like its near relative purpusii, it's a straggly shrub which can take any amount of shade and neglect. During the growing months, it sports leaves of an interesting plum colour, held quite elegantly. From November it becomes an unlovely collection of sticks until February, or in this year March, when all of a sudden these become covered in pretty little bells of cream and pink with an intense fragrance that carries in the cold air. Plant it where you will pass it and enjoy it every day it flowers.

JAMA 10 Mar 2010 Vol 303

943 Herd immunity is important but difficult to study, as humans generally don't stay in herds for very long. Unless commanded to do so by the Lord himself, as Jakob Hutter felt when reading Acts 2:44 in the newly circulating translation by Martin Luther: Alle aber die gleubig waren worden/ waren bey einander / vnd hielten alle ding gemein. [And all that beleved kept them selves to gedder and had all thinges comen: Tyndale 1526]. Hutter preached the renunciation of private property and the commonality of true believers until apprehended, tortured and burnt alive in 1536. The last Hutterites to die as martyrs were conscientious objectors in an American military prison, just after Armistice Day in 1918. Due to four centuries of persecution, most Hutterites are now to be found in the remoter parts of Canada, where they stay together in colonies and breed almost as avidly as the Amish people, with whom they share many beliefs and customs. A great gift to the interventional epidemiologist, then, especially as they are very happy to take part in medical research of common benefit. In this instance, some Hutterite colonies allowed their children and adolescents to be cluster randomised to receive influenza vaccination or hepatitis A vaccine as controls (by colony: the design is a bit complex). Cases of influenza were ascertained by PCR and by serology, and the basic message is that influenza vaccine works and provides about 60% herd immunity when uptake levels are high. Gott sey gepreiset/ vnd benedeyet.
http://jama.ama-assn.org/cgi/content/abstract/303/10/943

951 I am an ardent believer in the principle of evidence-based medicine, but like socialism (Hutterite or Marxist) it's great in theory, but forever thwarted by the capitalist world. Most evidence about medications is generated by drug manufacturers; studies of comparative effectiveness in the main medical journals, by contrast, are 87% funded from other sources. This paper found 1,500 such studies in the top 6 general journals and thought 326 worth examining in detail. One could argue forever about the selection criteria and the detail of these papers, but a dismal conclusion emerges with some strength: "The fact that only 32% of the studies in these journals evaluating medications met our criteria for CE research supports previous concerns that only limited clinical research is currently devoted to helping physicians use existing therapies more effectively."
http://jama.ama-assn.org/cgi/content/abstract/303/10/951

959 Live kidney donation is a fairly spectacular example of altruism (in most cases, anyway), but the altruists can rest assured that their mortality in the first 6.3 years is no different from that of matched non-donors.
http://jama.ama-assn.org/cgi/content/abstract/303/10/959

NEJM 11 Mar 2010 Vol 362

886 This study looked at nearly 400,000 elective coronary angiographies performed in US hospitals over 4 years. Although preliminary investigations had been done in 84% of cases, the pick-up rate for significant coronary stenosis on angiography was 37.6%. Even these patients may have had little benefit, since COURAGE tells us that in stable angina, people do as well with optimal medical treatment as with percutaneous intervention. So 250,000 of these angiographies were definitely of no value to the patients, and that probably applies to most of the rest too. We need much better case selection for the catheter lab, with all its attendant risks of radiation and bleeding, not to mention cost in money and cardiologist time.
http://content.nejm.org/cgi/content/abstract/362/10/886

896 A recent review of scabies treatment in this journal came out in favour of oral ivermectin but I didn't report it as this drug isn't available in my part of the world. But it jolly well should be if it's as safe and effective as this trial suggests. French children with difficult-to-treat head lice were randomised to ivermectin by mouth (two doses, a week apart) or malathion scalp lotion. It was as if Moses stretched forth his hand over the land of Egypt: the lice perished. What nits we are not to have this treatment available to us in our lousy NHS formulary.
http://content.nejm.org/cgi/content/abstract/362/10/896

906 Thyroxine lowers cholesterol, as most of you will know from treating hypothyroid patients. Statins also lower cholesterol, as most of you will also know: but not always enough for the liking of lipidologists. They and the drug companies are forever in search of the next lipid lowering drug, an easy and potentially lucrative quest based on serum fat measurements of various kinds, as in this study of eprotirome, a thyromimetic compound. My word, it lowers LDL-cholesterol in statin-treated patients without harmful effects over a period of 12 weeks. What a breakthrough. Why, in another five years we might know if it benefits patients, or kills them.
http://content.nejm.org/cgi/content/abstract/362/10/906

917 Commotio cordis is a rather wonderful term, presumably from late Roman medicine, used to describe the heart-stopping effect of a sudden blow on the chest. The result is sudden death, usually seen in young men who indulge in contact sports. Desist, foolish youth, and seek instead the company of books and maidens.
http://content.nejm.org/cgi/content/extract/362/10/917

Lancet 13 Mar 2010 Vol 375

This issue is dominated by the question of blood pressure variability and stroke, and by the intellectual presence of Peter Rothwell, in both the papers (pp.895, 906) and in a long review on p.938. This is impressive, and a Good Thing. I dabbled in hypertension ten years ago, when my main interest was in the relation between pulse pressure and heart failure - a gradual process. Rothwell is a neurologist and is most interested in what happens to link blood pressure with stroke - a sudden process. Not surprisingly, strokes are linked with labile visit-to-visit SBP, indicating a tendency to sudden surges. At the moment in clinical practice we throw these babies away as bathwater. We disregard both pulse pressure and variation, and relax the moment we can enter a BP of less than 150/90 on the patient record. This needs to change following these papers. The evidence (though I would like to see more of it) is that the best drugs to reduce BP variability are calcium channel blockers and thiazide diuretic, whereas most other drug classes actually increase BP variability. So I can see bendroflumethiazide going back in the Polypill, because we know that most people over 65 need a BP reducing agent and that BFZ reduces both stroke and heart failure - albeit at the expense of harmless induced hyperglycaemia which we are inclined to mislabel as diabetes.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60308-X/abstract
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60235-8/abstract
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60309-1/abstract

916 Group cognitive behavioural treatment for low back pain in primary care: a paper that illustrates not only that the intervention works, but that now and again The Lancet will publish papers about important primary care topics. That's despite the "pragmatic" nature of this trial, with 46% of patients lost in the year after allocation to the intervention. The "CBT" these patients received was in fact highly directional and aimed at breaking down pain avoidance behaviours, and delivered on a group basis it proved useful and cost effective.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62164-4/abstract

924 The porphyrias have long been a favourite with medical examiners, illustrating various modes of genetic transmission and penetrance and all the steps of haem synthesis. In other words, all the things that ordinary doctors can get by nicely without. And in fact I have never seen anybody with any of the porphyrias (this exhaustive review doesn't stoop to tell us how rare they are), except possibly in the film The Madness of King George.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61925-5/abstract

BMJ 13 Mar 2010 Vol 340

579 I think that when I enter a nursing home I shall wait impatiently for pneumonia to carry me off - that's if I can think at all, and if anyone allows the old man's friend to do its work unhindered. But one must not assume that everyone shares these gloomy predilections. In fact everyone assumes that nobody shares them, and that we must do everything in our power to prevent pneumonia in the institutionalised elderly, by giving 23-valent pneumococcal vaccine. This placebo-controlled Japanese study shows that it works, a bit. Give me the placebo, please.
http://www.bmj.com/cgi/content/full/340/mar08_1/c1004

580 "I used to be able to give my wife pleasure all night, but now I can only manage three times", complained an elderly Iranian peasant to an Irish doctor in a supposedly factual memoir whose name I now forget. Ageing Americans don't quite come up to this level of sexual activity, but there's a lot of it about, and it correlates with self-reported good health. The paper goes on to construct a "sexually active life expectancy score" out of two separate cross-sectional studies: a feat which, if true, trumps that of the Iranian peasant. This is hailed as an altogether wonderful study by Patricia Goodson, Professor in the Dept of Health and Kinesiology, Texas A&M University, in her editorial (p.544): "To unearth positive news amid the rubble of a trouble focussed literature [on sex in old age] is just as refreshing, stimulating, and invigorating as good healthy sex." Holy baloney! Well, maybe Texans just ain't what they used to be.
http://www.bmj.com/cgi/content/full/340/mar09_2/c810

581 A retrospective cohort study of 18,000 older women who had radiotherapy following breast conserving surgery for cancer between 1991 and 2002 shows that the interval between the two probably shouldn't exceed six weeks if you want to avoid local recurrence.
http://www.bmj.com/cgi/content/full/340/mar02_2/c845

587 Treating articular cartilage injuries of the knee in young people has to be important work. The summary of this review states that "early appropriate treatment of symptomatic lesions may prevent the onset of osteoarthritis and is cost effective." But reading the paper I'm not convinced that there is evidence for anything in this sentence except the word "may". There are nice pictures of mosaic bone grafts and disturbing accounts of drilling or microfracture with the use of a sharp awl deployed through the arthroscope. What we don't seem to have are adequately powered long-term outcome studies.
http://www.bmj.com/cgi/content/extract/340/mar05_1/c998

Arch Intern Med 8 Mar 2010 Vol 170

403 "Patient-centered comparative effectiveness research: essential for high-quality care" is the title of this short but trenchant commentary piece - a nice complement to the JAMA study(p.951) I mentioned above. "Health information technology offers the potential of linking practice and research in unprecedented ways, the foundation of what has been referred to as a learning health care system, one in which care delivery offers both a platform for discovery and a rapid, effective translation of new findings to patient care." In my remaining years, this is exactly what I want to promote. If it were to happen, it would be just about the most rewarding thing the world has to offer.
http://archinte.ama-assn.org/cgi/content/extract/170/5/403

433 Meanwhile the meticulous work of outcomes assessment in real life situations continues, and nobody does it better than Harlan Krumholz and his team at Yale. This week they turn their attention to differences in patient survival after myocardial infarction by hospital capability to perform percutaneous coronary intervention. In the USA, as here in the UK, there is a big debate about how best to regionalise services to ensure that as many people as possible can get timely PCI following MI. The real life situation proves to be far from simple: some regions might get better outcomes from centralisation, but others not.
http://archinte.ama-assn.org/cgi/content/abstract/170/5/433

478 The metabolic syndrome (MetS) was a fashionable concept ten years ago but sceptics have always claimed that it is no more than the sum of its parts. And so it turns out to be, yet again, this time in a systematic review of 3459 patients who took part in 7 clinical trials that monitored coronary atheroma progression with intravascular ultrasonography.
http://archinte.ama-assn.org/cgi/content/abstract/170/5/478

Plant of the Week: Helleborus x sternii "Boughton Beauty"

Once the hellebores are flowering, the gardening season has begun. If you are lucky enough to be able to keep Helleborus niger alive for more than a season, then you may have had hellebores since Christmas; but I rather doubt it, this year. The native stinking hellebore, H foetidus,is usually our first, and its cut leaves and green flowers are very welcome (it only stinks if you handle the leaves, which are highly toxic, like most parts of most hellebores). The oriental hybrids appear at about the same time. These are invariably beautiful in their speckled whites and pinks and various shapes of petal, but they go off with time, unless you take the trouble to split the clumps and replant their outer, more vigorous parts. This applies especially to the rarer blacks, yellows and doubles that you may have been tempted to pay large sums for in the past. But on limy soil, these plants seed generously, and lacking time we just make do with the children.

The hybrids called "x sternii" are mostly grown for their leaves, though the flowers of "Boughton Beauty" are attractive enough, coloured a strange pale yellow-purple. The leaves form rounded marbled lobes of real loveliness, and I have seen other sternii hybrids with even more wonderful leaves, but never on sale. At least this one is easy to find in nurseries. Plant it in a prominent sunny spot.

JAMA 3 Mar 2010 Vol 303

841 O willow, willow, willow. Willows weep, and grow by water. Willow bark is bitter and acrid with an acid which, when acetylated, yields us aspirin. Despite its melancholy associations, aspirin is generally thought of as a very good thing. Everybody who has had a stroke or coronary event gets to take it, and its effectiveness in those contexts has led us, by extrapolation, to offer it to other people at increased risk, for example because of diabetes, hypertension and/or peripheral artery disease. But it seems peculiarly reluctant to yield its benefits until after something nasty has happened. In this randomised controlled trial carried out by a horde of international salicylophiles, 29,000 people with a reduced ankle/brachial pressure index were randomised to 100mg aspirin or placebo and all that happened is that they had more bleeds. O willow, willow, willow.
http://jama.ama-assn.org/cgi/content/abstract/303/9/841

849 Last week, JAMA informed us that elderly people who get admitted to hospital, especially to intensive care, show greater cognitive decline than those who don't. Now it brings us news that elderly people who have been admitted to ICU die more quickly in subsequent years than those who haven't. Especially in the first few months after mechanical ventilation. Ah well. I suppose it's a basic tenet of science that you must never assume that something is obvious until you have proved it.
http://jama.ama-assn.org/cgi/content/abstract/303/9/849

857 Erythropoietin treatment for the anaemia of chronic renal failure is one demonstration of how you can't assume that anything is simple in science - medical science, anyway. CRF depletes erythropoietin and causes anaemia: give them an erythropoietin analogue, and a healthy ruddiness returns to their cheeks. Then people started noticing that the more you gave them, the faster they died. This study takes a look at what really happens in all the haemodialysis centres covered by Medicare in the USA. If the haematocrit is 33% or less, mortality is high and is reduced by giving good doses of epo and iron. Above that, you do more harm than good. Give it to the pale and weary but stop before their cheeks glow.
http://jama.ama-assn.org/cgi/content/abstract/303/9/857

NEJM 4 Mar 2010 Vol 362

779 I hadn't seen a patient in shock for many years until one turned up during an out-of-hours session a couple of weeks ago. I bundled her off rapidly to the arms of doctors who know what to do in such circumstances, and I don't know if she got dopamine or noradrenaline (norepinephrine) or neither. In the casual talk I overhear from these blood-covered hero-doctors who use vasopressor agents, I catch the word "dopamine" most often. But the word I should be catching is "norepinephrine", which is equally effective with fewer adverse effects, according to this European trial. It's called SOAP-II. The daftest acronym of the year competition is hotting up already, and it's only March.
http://content.nejm.org/cgi/content/abstract/362/9/779

790 The last time I read the name ethosuximide, a drug which came out in the 1950s, I was swotting for Finals in 1975. Now it reappears with honour in a study of childhood absence epilepsy, for which it seems the most specific and harm-free treatment when compared with lamotrigine and valproate. Lamotrigine is not very effective, and valproate blunts attention during the learning years, which is no petit mal in itself.
http://content.nejm.org/cgi/content/abstract/362/9/790

800 The majority of cardiovascular events take place against a background of impaired glucose metabolism, usually below the standard threshold for diabetes. You can measure this by fasting glucose or by glycated haemoglobin (gHB, preferred to HbA1c which involves finding subscripts on your computer). The risk curve for coronary heart disease and stroke climbs fairly evenly from any level of gHb over 5%. The authors of this study based on ARIC suggest that we may need to redefine the term "diabetes" using gHb. No! no! Bin the term diabetes until patients become symptomatic. Consider gHb as just another cardiovascular risk factor and treat the total risk; and never use any antiglycaemic drug except metformin unless you really have to.
http://content.nejm.org/cgi/content/abstract/362/9/800

Lancet 6 Mar 2010 Vol 375

807 The Stent Wars have become terminally boring, but the Clot Wars are hotting up and becoming cosmic. The current heroes in the Battle of the Clot are the orally available direct thrombin antagonists and the factor Xa inhibitors. It's a great feature of these wars that the heroes fight each other as well as the Clot, and to excite spectators they are given names like warriors from AstÃƒÆ’©rix or Assyrian battle lists. Apibaxan versus enoxaparin. Well, you know enoxaparin isn't going to win because he's an old injectable and this is a drug company funded study in The Lancet. Bring on dagibatran. We want dagibatran v apibaxan! We want to see a real fight with some blood in it! But no clots, please.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/abstract

834 I'm not going to be put off praising this systematic review of clinical features which identify serious infection in children merely because I know some of the authors. It is exactly what we need. I had it on my desk to read last night but I was interrupted by a constant flow of febrile children in the out of hours centre. "Parental concern" and "clinician instinct" were there by the bucket load, and these are important discriminators in this analysis. I ended up sending one child to the paediatricians (albeit less experienced than myself) and a dozen others home to their parents with advice and safety netting. I hope the nets held. This is not relaxing work, we do not do it sufficiently thoroughly, it still scares me at times after 30 years, and this paper is just a beginning towards better triage of sick children.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62000-6/abstract

846 Bacterial septic arthritis in adults. That's scary too, but pretty rare in Britain - much commoner on the eastern fringes of Europe and further afield. It's a "never miss this" condition, like Kawasaki's disease (which is similarly rare) or subarachnoid haemorrhage (which isn't rare at all). Perhaps I'll retire altogether from clinical medicine after all. It's just too dangerous.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61595-6/abstract

856 I seem to remember mocking The Lancet more than ten years ago for publishing a review of sun exposure in November. Now, amid the March frost of the longest English winter for decades, comes this review of the health effects of hot weather. How we look forward to them. O take me out of the baking heat into some dark room where warm breezes blow through open, curtained windows, where I must rest and drink litres of iced fluids. Kennst du das Land, wo die Zitronen blÃƒÆ’¼hn? ...O Vater, lasst uns ziehn!
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61711-6/abstract

BMJ 6 Mar 2010 Vol 340

518 One of the key issues in the Lancet review on triaging febrile children was how we might safely devolve responsibility on the parents. For a long time, we have been giving adult asthmatics supplies of prednisolone for emergency self-administration. In children of school age, there might be concern that parents would overuse the steroids, but that is something we could easily monitor. No schoolchild is going to come to harm from having a couple of 30mg doses of prednisolone as soon as their asthma gets bad and the salbutamol isn't helping. In fact they stand to benefit, as this trial shows: also read the excellent editorial by Duncan Keeley (p.488).
http://www.bmj.com/cgi/content/full/340/mar01_1/c843

520 For a couple of days last week, I shared the experience of CSF/ME. If I lay down, I felt vaguely awful but my mind seemed normally active; as soon as I got up, my legs felt weak and achy; as soon as I set down any of my thoughts in e-mails, they began to break up and developed an introverted, whingeing tone; and after about half an hour my brain gave out and I had to lie down again. In the wake of this study and the related personal article by Cathie Sudlow on p.510, there was a river of Rapid Responses from ME/CSF sufferers all reporting and exhibiting the same features as I had in the wake of two trivial viruses. Except that for them it had lasted for years. Clearly this is a neurocerebral problem involving reinforcement effects in something the brain usually overcomes rapidly by internal negative feedback. It is neither conscious (and so amenable to cognitive therapy) nor somatic (and so amenable to exercise). Some day we may find the right cerebrally active drug for it. Finding a purported viral cause is never likely to help anyone, except in their desperate quest to be believed. In case you're interested, xenotropic murine leukaemia virus-related virus is unlikely to play a part.
http://www.bmj.com/cgi/content/full/340/feb25_1/c1018

521 Haven't we had enough meta-analyses? The answer, sadly, is no. The Cochrane Collaboration has so far only covered 10% of the medical literature. This is drudgery, but useful drudgery, and it needs to be done well if it is to inform clinical practice accurately. Samuel Johnson in his Dictionary defined a lexicographer as "a harmless drudge", but a bad meta-analyst is a harmful drudge. The most accurate and informative meta-analyses are of individual participant data, and if you are going to become an effective, helpful drudge, you need to read this paper. As for me, my drudging days are done.
http://www.bmj.com/cgi/content/short/340/feb05_1/c221

526 The high quality and practical focus of the BMJ's recent Clinical Reviews is maintained in this one on age related macular degeneration. Particularly good on the merits and pitfalls of intra-ocular vascular endothelial growth factor inhibitors.
http://www.bmj.com/cgi/content/extract/340/feb26_1/c981

Ann Intern Med 1 Mar 2010 Vol 152

287 When did you last measure a leg? Not that easy, is it? In this study they didn't use orthopaedic surgeons fumbling about with tape measures but radiologists with sophisticated and reproducible measuring devices. The aim was to determine whether something as simple as leg length discrepancy could lead to osteoarthritis of the knee. Above a centimetre, it does.
http://www.annals.org/content/152/5/287.abstract

307 We're running out of vitamins to try out for reducing cardiovascular risk. I've seen them all come and go - anti-oxidants like C&E, homocysteine lowerers like folate and B12 - and now will it be the turn of my new favourite, vitamin D? According to abstract of this systematic review, it's not looking too good: "Conclusion: The association between vitamin D status and cardiometabolic outcomes is uncertain. Trials showed no clinically significant effect of vitamin D supplementation at the dosages given." But the last sentence of the actual paper is more upbeat: "Vitamin D remains a promising, although unproven, new element in the prevention and management of cardiometabolic disease."
http://www.annals.org/content/152/5/307.abstract

315 And in fact the next paper is another systematic review showing some evidence of cardiovascular benefit at the top end of the vitamin D dose range, i.e. at least 1000iu/day. I went into a health product shop to buy mine this afternoon. All the vitamins and minerals of proven cardiovascular uselessness are there, still promoted for the purpose, whereas vitamin D, which might be useful, is not trumpeted at all.
http://www.annals.org/content/152/5/315.abstract

Plant of the Week: Daphne kamtschatica

This is the northernmost daphne out of a little group with fragrant yellow flowers in late winter: the others are jezoensis and koreana. Few people have seen one, because they are amongst the most miffy members of this very miffy genus. Miffy was a favourite word of Reginald Farrer, and although I don't know for certain what it means, from the contexts he uses it in I think it's "easily miffed". A plant that is miffed, or miffy, tends to die, or if it stays alive, it is in a resentful sort of way. At work, I collect miffy patients, and at home, I collect miffy plants, so that when the opportunity came to lay out £25 on Daphne kamtschatica, sure to miff and/or die within a season, I seized it with both hands.

I hardly thought that four months would go by without a single day fit to plant it, so I left it in its pot all winter, with its roots frosted on most nights. It seems to have loved it. It is covered with yellow flower buds and one has even opened. Its leaves are presently a healthy green, and abundant. But as summer approaches, they will all fall off. This is not miffiness: it's how this plant likes to organise its photosynthesis. They will come back in the autumn.

This is a plant from the furthest reaches of north-west Russia, where once prisoners would die in the gold mines of Dalstroi and Magadan. These were the worst places in the entire Gulag, where millions of tons of rock would have gold crushed out of them, and hundreds of thousands of prisoners would have hope and life crushed out of them. Perhaps, as they stumbled over the bleak slag heaps in late winter, they would catch a gleam of another gold - the flowers of Daphne kamtschatica, and pause for some brief moment of comfort and delight.

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Page last edited: 26 April 2010