NEJM  1 May 2008  Vol 358

1887    Should we treat high blood pressure in people over 80? Unless the person is seriously tired of life, I think the answer has to be yes. My guess is that most of us, witnessing every day the intractable miseries of old age, hope to die suddenly at some time in our 80s, but I don’t know of anybody who would want to have a stroke that is less than fatal. Nor do I know of anybody who could face the prospect of worsening heart failure with equanimity. A big randomised placebo-controlled trial shows that 80+ year-olds treated to reduce BP to 150/80 or below have a 63% reduction in heart failure and a 30% reduction in stroke: total mortality is reduced by 21%. And the rate of adverse reactions was actually higher in the placebo group than in those treated with indapamide, perindopril or both. http://content.nejm.org/cgi/content/abstract/358/18/1887

1899   Despite knowing quite a lot about its prevention and treatment, we do not seem to be making much headway in dealing with the latest super-bug. I refer of course to Genotypium difficile, which was until recently a rare opportunist pathogen of obscure medical journals, but now threatens to debilitate - or perhaps even kill – some of those that doctors actually read. New strains of G difficile have unfortunately developed the ability to bind with the prestige receptors of their hosts, and as a result Genotypium has become the commonest type of infection in several medical journals, as shown by this week’s NEJM and Lancet. Readers of affected journals typically develop lateral nystagmus (known as flick-past syndrome) as soon as they encounter affected articles, and in some this progresses to total alexia. Editors should use well-established hygienic measures: they should isolate infected articles in remote journals which are only handled by the already-infected, and they should wash their hands of any that may still present themselves. In cases of established infection they should use topical deletomycin to render the Genotypium relatively harmless.

The infected article here is about a gene which may link some types of cardiac hypertrophy in children and adults. For lovers of even more sophisticated genomics, there are papers about the genetic profile of malignant cells in acute myeloid leukaemia (pp.1909, 1919) and how this may affect response to treatment including bone marrow transplantation.

http://content.nejm.org/cgi/content/abstract/358/18/1899

http://content.nejm.org/cgi/content/abstract/358/18/1909

http://content.nejm.org/cgi/content/abstract/358/18/1919

Lancet  3 May 2008  Vol 371

1505   Help – it’s Genotypium difficile again! Before the nystagmus and alexia set in, let me tell you that they’ve found the osteoporosis gene. Or two possible osteoporosis genes. As usual it was by exploring lots of candidate single-nucleotide polymorphisms (SNPs) and coming up a statistical association with reduced bone density which was then tested as an association with osteoporotic fracture in a different population. Tedious to read about and no doubt tedious to do: but perhaps if this type of study didn’t bind to the prestige receptors of host journals it wouldn’t get done at all. As it is, we may be a little nearer to understanding the genetic basis of 30% of osteoporotic fractures. http://www.thelancet.com/journals/lancet/article/PIIS0140673608605991/abstract

1527   Well, G difficile hasn’t completely debilitated The Lancet, which includes an unusually quirky set of topics this week, including this seminar on adolescent idiopathic scoliosis. Now there is a small pocket of genomics at the beginning, but readers can skim past that and learn that, as they thought, nobody knows why the paravertebral muscles in some teenagers decide to misbehave and twist their growing spine. This can have unpleasant consequences, such as progressive curvature, back pain and cardiopulmonary compromise, but the course is highly variable. Prediction is getting better, as is surgical technique, though it’s hard to collect the most important evidence in a condition where the outcomes that really matter happen over a lifetime. It’s particularly hard to know how much bracing and physiotherapy can modify the natural history of the condition. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606583/abstract

1538    Food allergies are common in children, but peanut allergy has a particularly bad reputation and is getting commoner for reasons we don’t understand. In the UK it may affect 3% of pre-school children. It persists into adulthood and according to this seminar by an American professor, it’s a reasonable reason to carry adrenaline (epinephrine) for injection as well as antihistamines. For these unfortunate people, who are currently denied the culinary pleasures of the peanut, the genetic modification of peanuts may one day offer an answer. In the meantime, I think crisps and olives provide a perfectly satisfactory alternative. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606595/abstract

BMJ   3 May 2008  Vol 336

995    If these reviews seem readable rather than rigorous, that shouldn’t blind you to the possibility that I may sometimes know what I’m talking about. This must be the result of many weeks – or was it days? – years perhaps – of attending courses about systematic reviewing and even about medical statistics. It was all so long ago. The world was young, the possibilities seemed endless. I woke occasionally and found that people were looking at me. Anyway, here is a nice crisp paper about how today’s EBM buffs grade quality of evidence. They use GRADE. I too must get round to it some time. http://www.bmj.com/cgi/content/extract/336/7651/995

999    This well thought-out American study of the placebo effect is the most interesting paper the BMJ has published for some years. They begin by identifying three elements to the placebo response – the effect of observation and assessment (Hawthorne effect), the effect due to administration of a therapeutic ritual (the traditional “placebo effect”) and the effect caused by the patient-practitioner interaction (what we could call the “Balint effect”). They then randomise patients with irritable bowel syndrome to observation alone, sham acupuncture without interaction, or sham acupuncture with a doctor attempting to exude warmth, attention, and confidence. The result: resounding affirmation of Balint’s claim that the doctor is the most powerful drug in this kind of situation. http://www.bmj.com/cgi/content/abstract/336/7651/999

1010   Primary care is that awful jungle of sloppy medicine into which specialists are sometimes obliged to make missionary forays armed with picture rolls of Bible stories and beads for the natives. It’s amazing how for decades we have allowed such a travesty to go unchallenged. I think we encourage it by loyally snoozing through slide presentations by “experts” and reading articles like this one, entitled “management of bloody diarrhoea in children in primary care”. Has the author ever seen a case of bloody diarrhoea in primary care? I should stop swearing. Almost certainly not, since he now works in a teaching hospital, and writes a serviceable textbook article on the causes, investigation and treatment of this uncommon presentation which is perfectly designed for anyone taking the MRCPCH. Had he teamed up with an interested GP, he might have written one designed for primary care. http://www.bmj.com/cgi/content/extract/336/7651/1010 

Arch Intern Med  28 Apr 2008  Vol 168

820    Thrillingly tongue-tripping thiazolidinediones have had a troubled time of it from the start. The first marketed agent, troglitazone, had to be withdrawn due to liver toxicity, and when rosiglitazone appeared as a “safe” replacement it was accused last year of killing patients by myocardial infarction. So far I remain loyal to pioglitazone, but here is a paper which tars the entire drug class with the accusation of increased fracture risk. This is a nested case-control study using the UK General Practice Research Database – yes guys, these are your very own patients. After only 12-18 months of use, their risk of hip or wrist fracture may be increased by about two-and-a-half times. The association seems robust for rosiglitazone but uncertain for pio. http://archinte.ama-assn.org/cgi/content/abstract/168/8/820

826    An American database (Group Health from Washington State) provides much weaker evidence of another unwelcome possibility – that alendronate may encourage atrial fibrillation in the millions of women who take it with a glass of water every Sunday morning. But the numbers here are very small and the 95% confidence interval begins perilously close to 1. No doubt somebody is already knocking at the gates of the UKGPR Database. http://archinte.ama-assn.org/cgi/content/abstract/168/8/826

840    We have gotten (sic) used to the fact that in the long run, American English is bound to defeat English English. But what have we here? A paper from San Francisco entitled “Persistent Hot Flushes in Older Postmenopausal Women”. Are “hot flashes” then no longer to be found in California? Oh, they are to be found a-plenty, but here renamed as flushes, persisting or even occurring de novo in women right into their seventh and eighth decades. It’s something we come across in England too all the time, and cannot explain, merely shrugging and agreeing that it’s highly unfair. Or a real bummer. http://archinte.ama-assn.org/cgi/content/abstract/168/8/840

847    Hospital admission for heart failure usually involves the patient in near death from drowning in pulmonary fluid, a terrifying experience that is emphatically well worth averting, not merely because it costs money to the health service. For trying to prevent these horrible emergencies, I’m willing to forgive the OPTIMIZE-HF project its cumbrous acronym. This US-wide study identifies causes of HF admission that are often avoidable or amenable to rapid treatment: arrhythmias, nonadherence to medication, uncontrolled hypertension, chest infections, new ischaemic events and deteriorating renal function. http://archinte.ama-assn.org/cgi/content/abstract/168/8/861

867   The title of this survey – Mort-à-l’Hôpital – will remind readers of Axel Munthe of his description (in that now-forgotten classic, The Story of San Michele) of the Salpiètre in Paris in the 1880s, where death rates approached 100% but the attending nuns remained calm, kind, and sometimes even playful. The nurses in this study are not nuns and they are deeply unhappy about the quality of dying in the patients they look after in 294 French hospitals. Only 35% of deaths are judged to be acceptable to themselves. Since the majority of people still end their lives in hospital, this paper deserves to be thought about by everyone involved in looking after them – and by GPs who are interested in providing something better at home. http://archinte.ama-assn.org/cgi/content/abstract/168/8/867

884   More news from the Women’s Health Study, and by and large quite good for women who are a little on the heavy side. Coronary heart disease risk is associated with high body mass index and low physical activity; but if your BMI is high, you can still reduce your risk substantially by keeping physically active. http://archinte.ama-assn.org/cgi/content/abstract/168/8/884

Plant of the Week: Distylium racemosum

In this section I have tried to tell you about many excellent hardy shrubs which languish in undeserved obscurity. This is not one of them. Its obscurity is totally justified and almost palpable, a design feature in this most mournful and undecorative of plants. Do not buy it, even if – as is most unlikely – you get the chance. It will do nothing for the first three years, and then it will do even less. It has smallish dull green leaves of the usual leaf-shape which refuse to fall off. Its flowers form lifeless dark red clusters which you have great trouble to pick out in early May, when the rest of the garden is becoming a picture of colour and beauty. It boasts a straggly growth in two dimensions – up and across, at about 2cm a year.

It is one of those pathetic plants one keeps in the ground hoping that some day it might become rather special. Every year we hope and are disappointed. It has become almost an enjoyment. Given such reward, what heartless wretch would ever think of digging it up?

JAMA  7 May 2008  Vol 299

2027    It was simple, cheap, and seemed bound to do good. Giving people folic acid, pyridoxine (B6) and cyanocobalamin (B12) lowers homocysteine (HCy); and since cardiovascular disease shows a strong association with homocysteine, these B vitamins were almost certain to lower rates of cardiovascular disease if taken for long enough. But trial after trial has failed to show any benefit, despite a reduction in HCy. This one selected 5442 female health professionals in the USA at high risk of cardiovascular events and randomised them to receive really substantial doses of the three vitamins over 7 years, thus lowering their HCy by nearly 20% compared with the placebo group. But the rated of CV events did not differ between the groups. Not much good to the women then, but a scientific triumph: a plausible hypothesis thoroughly tested and thoroughly falsified. http://jama.ama-assn.org/cgi/content/abstract/299/17/2027

2037    And now for an observational study in another group of US female health professionals: over 100 000 nurses followed up from 1980 to 2004. In 1980, fewer than half had never smoked, and 28% were still smoking. Over the period of the study, smokers were more than two and a half times more likely to die. The added cardiovascular risk dropped very quickly after cessation but for lung diseases the full effect took 20 years. Interestingly the later you take up smoking, the less likely you are to get lung disease or smoking-related cancer. But why we continue to tolerate the universal availability of this lethal addictive drug while insisting on being able to lock people up for 5 years for mere possession of cannabis is a complete mystery to me. http://jama.ama-assn.org/cgi/content/abstract/299/17/2037

2056   The smell of the streptococcus takes us back to the bacteriology classroom, with red agar plates going clear around furry patches of haemolytic bacteria. The lecturer told us that streptococci behave mostly as harmless commensals or occasionally as lethal pathogens, but didn’t seem very clear how or why. Between 1999 and 2005, group B streps invaded 14 573 citizens of 10 US states and killed 1348 of them. The trend was downwards in the first 6 days of life – following a prevention programme – and upwards in adults. The smelly little beasts continue to behave as they will, though we retain the ability to kill them with penicillin (all 4882 isolates in this study). http://jama.ama-assn.org/cgi/content/abstract/299/17/2056

NEJM  8 May 2008  Vol 358

1991   In middle-aged adults, we are coming round to the idea that fasting glucose is a continuously variable risk factor irrespective of what threshold we set to define diabetes. The multinational HAPO study shows the same for glucose levels in pregnancy, as measured by glucose tolerance test between 24 and 32 weeks of gestation. The outcomes were increased birth weight and cord-blood C-peptide levels (a measure of fetal hyperinsulinaemia), and they showed a continuous relation to sugar levels throughout the “normal” range. Not earth-shattering, but another reminder that there is nothing magical about cut-off levels for blood sugar. http://content.nejm.org/cgi/content/abstract/358/19/1991

2003   The standard treatment for gestational diabetes has traditionally been insulin, but this important Antipodean study shows that metformin is safe and effective and preferred by mothers, though it needed to be supplemented by insulin in nearly a half of the pregnancies. There was no increase in perinatal complications. It will be interesting to see how quickly this study changes practice. http://content.nejm.org/cgi/content/abstract/358/19/2003

2016   Idiopathic ventricular fibrillation is mercifully rare. This, combined with the fact that most people who get it die at once, makes it difficult to study. But by trawling across 22 centres around the world, the investigators here managed to collect 206 people who had survived such an event, and found that 31% of them had early repolarisation abnormalities on their ECG. Such abnormalities are found in 1-5% of the population; and whereas we used to be able to tell people that they did not matter, now we can tell them that they probably don’t matter, but then again they may drop dead. http://content.nejm.org/cgi/content/abstract/358/19/2024

Lancet  10 May 2008  Vol 371

1587    A popular and well-validated measure of cardiovascular risk is the carotid intima-media thickness, measured by ultrasound. I would love to think that in time to come, all doctors will have mini-ultrasound machines dangling around their necks or tucked in their white-coat pockets, as suggested in this week’s BMJ (p.1041). By comparison, using a stethoscope to listen for a whoosh in the carotid arteries is a crude and random affair. Of course, if you look at studies of carotid bruit in relation to cardiovascular death and myocardial infarction, you’ll find a strong association; but that’s hardly news worthy of the cover page of The Lancet. Bring on the future, not the past. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606911/abstract 

1595   As we saw from the Nurses’ Health Study, the earlier you take up smoking, the more damage it does, yet more than 17% of children aged 13-15 years already smoke regularly. If we were serious about tackling the biggest cause of avoidable ill-health and death in our society, we would restrict the availability of tobacco to those already addicted, and gradually phase it out altogether in favour of harmless nicotine-releasing products for those who continued to need them. Instead, we search for new marginal strategies like the one in this trial, where peer supporters in their early teens acted as missionaries among their mates, encouraging them not to smoke. Well meant, partially successful, but how hopelessly feeble in relation to the scale and seriousness of the problem. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606923/abstract

1612   A good clear update about stroke is always worth reading. Despite improvements in management, especially tissue plasminogen activator given within 3 hrs, strokes continue to kill half of those who suffer them within one year. Treating TIAs as serious emergencies may help, but we have a long way yet to go in finding treatments which will reduce death and incapacity once an event has occurred. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606947/abstract

BMJ Journals  May 2008 

ACD  364   There has been a recent upsurge of interest in pituitary dysfunction as a long term sequel of serious brain injury in adults. In children, it could have serious consequences not just for overall growth but also for neurocognitive development, yet we know even less about it and it is probably widely under-recognised. This editorial explores the problem and calls for more rigorous assessment in kids who have suffer major head trauma. http://adc.bmj.com/cgi/content/extract/93/5/364

Gut  561   A fascinating editorial explores the role of Helicobacter pylori in protecting children from asthma and allergy. Yes, H pylori can be a friend as well as a foe; it has co-existed with all humans since we first existed and is ubiquitous in all mammals, each of which carries it own pet Helicobacter. Only since we started ingesting antibiotics did H pylori cease to inhabit every human stomach. Could this be why childhood atopic illness has increased so markedly in the last 50 years? Perhaps. Certainly eliminating Helicobacter in adults stops ulcer disease and reduces stomach cancer, but the downside in our age group is an increase in oesophagitis. H pylori is what they call an amphibiont: a microbe that can be a pathogen or a symbiont, depending on context. http://gut.bmj.com/cgi/content/extract/57/5/561

Heart   585   I once wrote a chapter on prognosis in advanced heart failure in which I pointed out that the strongest indicators of impending death are high BNP and a high index of depression. These truths are reaffirmed in a study from Athens. It isn’t just that depression makes you give up and die: it’s also that worsening heart failure depletes brain serotonin and fills you up with feel-bad chemicals. http://heart.bmj.com/cgi/content/abstract/94/5/585

Thorax  388  Every now and again we turn up a case of tuberculosis in primary care and send it off to the chest physicians to be treated with an invariably effective cocktail of antimicrobials. It was of course not always so (see any textbook of medicine from before 1947; half of it will be about TB), nor is it very often so in the countries where TB is still endemic. This editorial on the evidence based treatment of TB explores the rationale of the current standard therapy, designated 2RHZE/4HR, for reasons you will understand if you read it. http://thorax.bmj.com/cgi/content/extract/63/5/388

Ann Intern Med  6 May 2008  Vol 148

637    In the UK, weekly alendronate has become the standard treatment for osteoporosis, while in the USA the market remains more open. Which drug is actually the most effective at preventing non-vertebral fracture? This study looks at 43 135 new recipients of oral bisphoshonates, nasal calcitonin, and raloxifene in New England over the first 12 months of treatment. It detected no significant difference between bisphosphonates and a possible advantage for alendronate over nasal calcitonin. Keep taking the Sunday tablets. http://www.annals.org/cgi/content/abstract/148/9/637656

656   One of the more idiotic aspects of the UK primary care Quality and Outcomes Framework has been the yearly measurement of cholesterol in patients taking statins following a diagnosis of coronary disease or stroke. This study looks at the natural random variability of cholesterol levels (average 7%) and concludes that “in annual rechecks in adherent patients, many apparent increases in cholesterol level may be false positive”. And what does a “real positive” mean in this context anyway? It’s time we dropped this unscientific waste of our time and the lab’s budget.

http://www.annals.org/cgi/content/abstract/148/9/656

662    The treatment of opioid dependency in the USA is even more backward than our own, with methadone only available from designated treatment centres and diamorphine not available at all. So sublingual  buprenorphine has become a popular option, especially in a fixed dose combination with naloxone. Buprenorphine is both an agonist and an antagonist at the μ opioid receptor, while naloxone is a complete antagonist, but is not very well absorbed sublingually. The idea is to stop opioid craving while rendering pointless the use of additional opioids. This article tells how it is done: the main point to remember is that you need to use doses of buprenorphine which may seem enormous (2-32 mg).

http://www.annals.org/cgi/content/abstract/148/9/662

671   Screening for breast cancer in women at high risk is even more fraught with problems than screening the general female population. You don’t want to miss any, but you don’t want to cause terror by detecting harmless lesions in already anxious women. A systematic review of MRI in this context suggests that a combination of this modality with conventional mammography might be the best strategy.

http://www.annals.org/cgi/content/abstract/148/9/671

680   Which men should we be screening for osteoporosis? This guideline from the American College of Physicians reaches cautious conclusions because the right studies appear not to have been done. There are too many which measure bone density and too few that count fractures. But the chaps at risk are the ones you might expect: old men, thin men and inactive men. There is less hard evidence about men who have taken steroids, smokers and men with low vitamin D levels.

http://www.annals.org/cgi/content/abstract/148/9/685

Plant of the Week: Wisteria sinensis

If, like me, you have a surname that is liable to be mis-spelt in a number of ways, spare a thought for poor Dr Caspar Wistar (1761-1816), a once-famous Philadelphian physician who wrote America’s first textbook of anatomy. The discoverer of a fine American climbing plant decided to honour him by calling it Wisteria frutescens (sic): and no amount of subsequent correction to “Wistaria” can alter that, since once a plant has been given a Linnaean name in print, it cannot be changed for other than strictly botanical reasons. As some the most beautiful of all plants, Wisterias will henceforth be cultivated for as long as the Earth survives, and Dr Wistar is doomed to look down wistfully from Heaven to see his distorted name on billions of plant labels for eternity. At least he will never be forgotten.

The American wisterias have short racemes of fragrant blue flowers, borne more abundantly in late summer than in late spring. With the Chinese wisteria, it is the other way round, and the racemes of lavender flowers are wonderfully abundant in spring as well as longer and more elegant. But both species are worth growing if you have the room and the time to train them. If you haven’t, but have a big apple tree or similar, then use that for your wisteria instead: once it has reached the main boughs, it will largely look after itself. Grown against a wall, or as a tree on a single stem, it needs endless attention to stay tidy and free-flowering. Wisterias need a massive root-run, and watering in the first years: but after a few decades (or nearly two centuries, in the case of Banbury’s oldest) they will need nothing and will thrive under stone, tarmac or anything else.

There is simply no finer sight among plants in the temperate world than Wisteria sinensis in full flower. In Rome they sprawl magnificently over the ruins of the Forum in late March or early April. Others no doubt decorate Stockholm and Warsaw two months later. Ours is still not quite out, being a tardy white form. It used to grow up a pole carrying the village’s electricity supply, but we decided that we might become unpopular if it reached the cables. So I led a couple of long growths underground for 2 metres and trained them up the house wall. They duly formed their own roots and have never looked back. Meanwhile, the rootstock of original plant continues to sprout up by the electricity pole and bears flowers of blue, not white. You can’t keep a good wisteria down.

JAMA  14 May 2008  Vol 299

2151   There are three ways to screen for breast cancer – X-ray mammography, magnetic resonance imaging, and ultrasound. Recently we saw that MRI in addition to mammography has a small added detection rate in high risk women at the cost of many false positives, and now here’s a study which shows the same for physician-performed ultrasonography. Fewer than one in ten of lesions biopsied after an abnormal ultrasound (following normal mammography) were cancerous, and the overall added pick-up rate was between 1 and 7 per thousand women. So this illustrates the usual trade-off problem in screening between sensitivity and specificity. http://jama.ama-assn.org/cgi/content/abstract/299/18/2151

2172    How fine does particulate matter in air (mostly carbon) have to be in order to cause an increase in cardiovascular and respiratory disease? The earliest studies lumped together every particle under 10μm but this study attempts to sift them into those above and below 2.5 μm. In many population centres in the USA, there are daily counts of particulate air pollution and hospital admissions. The number of admissions for CV and respiratory disease here was very large (5.1 million) and the effect size of pollution was very small (0.36%): take away the particles under 2.5 μm and you abolish any significant effect at all. In other words, the coarser the bits, the less acute harm they seem to do. http://jama.ama-assn.org/cgi/content/abstract/299/18/2172

NEJM  15 May 2008  Vol 358

2107   ULSAM stands for the Uppsala Longitudinal Study of Adult Men; these adults being of a mean age of 71 and therefore usefully likely to die within the career-span of the investigators. Actually only 315 of 1135 subjects died within a median of 10 years, and thus furnished material for this study of various biomarkers in relation to survival. Not long ago in these columns I told you that anyone could predict their likelihood of dying by measuring their B-type natriuretic peptide and cystatin-C, and this study added in troponin-1 and C-reactive protein. Was I right? Probably, though I can’t quite do the maths. Certainly BNP was the strongest predictor of death and if you add up all the biomarkers then you get an even better predictive value. But why you should want to is another matter. http://content.nejm.org/cgi/content/abstract/358/20/2107

2117   Roughly speaking, BNP measures how much strain there is on cardiac myocytes, and troponin T measures how many of them are bursting open and therefore (for the most part) dying. During myocardial infarction, troponin levels of course go up, and so does BNP because of inflammation and strain. This study shows that during acute heart failure (always associated with a high BNP) there is also often an increase in troponin levels – indicating muscle injury and death, and that this increase is associated with higher in-hospital mortality, as you would expect. http://content.nejm.org/cgi/content/abstract/358/20/2117

2127    The correct management of acute stroke is now a blue-light ambulance and immediate investigation with a view to giving thrombolysis to limit ischaemic damage within a 3-hour window. But what if the stroke turns out to be haemorrhagic? Do we just have to wait and watch the patient die within the first weeks, or survive with gross disability? I’m afraid the answer is yes, we still do. This trial attempted to reduce the cerebral haematoma size in acute haemorrhagic stroke by recombinant factor VII, and so improve outcomes. Depressingly, it achieved the first but not the second. http://content.nejm.org/cgi/content/abstract/358/20/2127

2138   The shoulder is a subtle piece of work, bound together by the rotator cuff which allows it a marvellous range of motion while keeping it stable. But alas, like all other bits of us, the rotator cuff is liable to failure, especially in old age. In fact rotator cuff failure is very common in the elderly and often asymptomatic. We’ve begun to realise this since ultrasonography of the shoulder became a very common investigation. Can anything be done about a completely torn rotator cuff? Not a lot, if it has been there for a long time: something, perhaps, for an acute one where there is still some tendon and muscle to sew back together. http://content.nejm.org/cgi/content/extract/358/20/2138

2148   I once took a keen interest in biomarkers in heart failure, hoping to bypass echocardiography altogether and introduce a workable means of monitoring heart failure treatment in primary care. But an MRC pilot project made us realise that BNP is useless because of excessive random and diurnal variation. Here is a comprehensive overview of the area, covering and classifying more than 30 markers, though only three of them measure the most important thing – the degree of myocyte stretch. I’ve put heart failure research out of mind for now, but maybe when I get a bit of time in the future I’ll read the literature on midregional proadrenomedullin and ST-2. It would be wonderful if we could actually measure how much good we’re doing when we fill up heart failure patients with their cocktail of drugs. http://content.nejm.org/cgi/content/extract/358/20/2148 

Lancet  17 May 2008  Vol 371

1665   Psoriasis is a common ill-understood disease which many people regard with dismay or even revulsion. In the inflammatory pathway which leads to plaque formation, interleukins 12 and 23 are known to play a central part. So the monoclonal antibody manufacturers got to work on producing a human monoclonal antibody against these interleukins and it has now been tried out in two trials called PHOENIX. It works: most patients with moderate-to-severe psoriasis will remain relatively clear if they have an injection every 12 weeks, but those who relapse may need to have a higher dose (see p.1675). And the name of this marvellous substance: ustekinumab. Ustekinumab! Oh, how absolutely fab! Verging on eltrombopag! Put it in your doctor’s bag.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608607254/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608607266/abstract

1685    Mesothelioma is a death sentence, and nothing has happened to alter that. In fact this trial of two kinds of chemotherapy in 76 centres in the UK and Australia merely confirms this dismal truth. Hopes of some prolongation of life rest with vinolrebine, but of a breakthrough there are none. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607278/abstract

1710    Prostate cancer on the other hand is the kind that some of us are most likely to get, being male non-smokers who have avoided asbestos. Its reported incidence is going up while its mortality is going down, at least in the UK, USA and Australia. The old truths are still true: it’s a disease you’re more likely to die with than die from, PSA is a stupid marker, and nobody knows the best approach to localised disease. This review is most notable for a picture labelled “Finger used as a prognostic guide for prostate biopsies” (Figure 3). If your index finger suddenly grows long and blue at the end and sprouts a needle where the nail should be, your prognosis must be very grave. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607291/abstract

BMJ  17 May 2008  Vol 336

1114    Adherence to treatment in hypertension: a study of the studies which monitored it electronically. “Experts” from Belgium, Switzerland and the USA discover that in such studies, the main problem is that patients simply stop taking their pills as time goes by, not that they forget to take a dose now and again (thought they do that too). Now in the UK, every GP has over the last four years either become an expert on the successful management of high blood pressure or an expert on massaging the figures for Quality and Outcomes payment. I get the impression that we are actually quite good at being honest and achieving QOF payments at the same time, and that our patients do keep taking their tablets for the most part. But in the light of this paper we probably ought to do an audit of repeat prescribing. I don’t think we’ll go as far as electronic tagging just yet. http://www.bmj.com/cgi/content/abstract/336/7653/1114

1121   The point of lowering blood pressure is of course to prevent major cardiovascular events; and the only studies that matter are those that have these as their primary end-point. Fortunately we now have lots of these for every major class of hypertensive drug and moreover we have international collaborative groups of academics willing to meta-analyse all the data. The message: just get on with lowering BP using anything that works. There are no significant differences in outcomes when you compare different drug classes, even in different age groups. http://www.bmj.com/cgi/content/abstract/336/7653/1121

1124   I always read pieces on the assessment and management of medically unexplained symptoms. When you have done 30 years of general practice in the same place, most of your regular patients have symptoms you have failed to explain over part or all of that period. They come in every week or fortnight simply to remind you of them. I didn’t really learn a great deal from this piece, thoughtful, clear and well-written though it is. For me the best temporary cure is sabbatical leave, which gives my partners a chance to see them for three months every six years. The permanent cure is, of course, retirement. http://www.bmj.com/cgi/content/extract/336/7653/1124

Arch Intern Med  12 May 2008  Vol 168 

920    As we saw from this week’s JAMA, the effect of particulate air pollution on respiratory and arterial disease seems to be mediated almost entirely by particles of 2.5μm or less, while most studies lump together everything under 10μm. That’s the case with this study from the northern Italian province of Lombardy, which looks at the long-term effects of the motor exhausts of Milan on deep vein thrombosis among the Lombardians. The more they breathe in, the higher their chances of DVT, the largest risk increase being 70% in men who breathe lots of car fumes. The name “Lombardian” was in fact purely male to begin with: it means “long beard” and refers to the Germanic warriors who took a liking to this part of the country in the sixth century. http://archinte.ama-assn.org/cgi/content/abstract/168/9/920

943    The article about medically unexplained symptoms in this week’s BMJ contains the usual warning about the mind/body divide and this is borne out by a study of fatigue in relation to cardiac output in ostensibly healthy individuals. Neither fatigue nor cardiac output are very easy to measure: fatigue here was scored using the POMS scale (no doubt developed in Australia to measure whingeing), and cardiac output was calculated from the stroke volume measured by impedance cardiography multiplied by the pulse rate. Individuals complaining of fatigue had significantly lower cardiac output. Moreover when they were stressed by a public speaking test, they showed less ability to increase their cardiac output. http://archinte.ama-assn.org/cgi/content/abstract/168/9/943

969    For more than a decade, doctors have bickered over the usefulness of the term metabolic syndrome (MetS) to describe individuals who have abdominal obesity, a bad lipid profile, high systolic BP and abnormal glucose metabolism. The Cardiovascular Health Study now has data on 5888 men and women enrolled at age 65 or older and now followed up for 15 years, during which time 2116 have died. In terms of predicting total or cardiovascular mortality, there is little difference between those defined as having MetS and those whose risk is measured in terms of BP and fasting glucose alone. http://archinte.ama-assn.org/cgi/content/abstract/168/9/969

1003    Cancer epidemiology throws up some unwelcome facts, for example that individuals with urological cancer are more likely to get colorectal cancer, and vice versa. A powerful tool for mapping such associations in the USA is called SEER, a database recording all cancers in approximately 14% of the American population. In absolute terms the added risk is not huge, between 1.8 for having a colorectal cancer after a ureteric cancer, and 1.24 for having a urological cancer after a colorectal cancer. But this does raise questions about common pathogenetic mechanisms and the need for screening. http://archinte.ama-assn.org/cgi/content/abstract/168/9/1003

Plant of the Week: Aesculus pavia  Rosea Nana

This plant used to be known as “Induta”, which is Latin for “dressed up”, whereas its present name merely means pink dwarf, which is untrue on both counts. It may be a dwarf by comparison with the towering horse-chestnuts which glorify the English countryside in mid-May, but it gets to be quite a substantial shrub, requiring about 4m of garden space in due course. Moreover its erect spikes of flower are a lovely apricot mixture of yellow and red and not what most of us would class as “rosy”.

This really beautiful shrub should be seen much more widely. True, its flowers have no scent, and when their three-week show is over, you are left with just a green-leaved horse-chestnut. But I would still rate it above the flowering cherries, which are planted in such profusion everywhere and often blight the scene by dying from bacterial canker. And if you want extra ornamental value later in the season, you can always pull the usual trick – hide a viticella clematis beneath and behind it, to cover the plant with blue or red flowers in August.

JAMA  21 May 2008  Vol 299

2279    Have you ever fainted? I did once, following an injection when I was about 13. Up to that point, I found injections fascinating and didn’t mind the sharp sensation of the needle going through my skin. But when on this occasion I keeled over at the bus-stop afterwards I was left with feelings of unbearable embarrassment and became needle-phobic thereafter. Teenagers who give blood in the USA fare likewise: of those who donate at age 16, more than one in ten will faint afterwards, and this only falls a little at 17; but by age 18 the problem has fallen to a rate of 2.8%. And those who have fainted are markedly less likely to donate again, irrespective of whether they have seen Tony Hancock’s famous television sketch. http://jama.ama-assn.org/cgi/content/abstract/299/19/2279

2287    When the Framingham Study was set up shortly after the end of the second world war, it was a visionary idea and its results have informed our understanding, especially of cardiovascular risk, ever since. For better or worse its success has led to the establishment of many similar cohort studies throughout and beyond the USA, with diminishing returns. One of these is CARDIA, which should really be CARDYA as it stands for Coronary Artery Risk Development in Young Adults, surveying the progress of 1889 participants recruited between the ages of 18 and 30 years in four metropolitan areas of the US. The trouble with these admirable studies is that hard end-points are a very long time coming in statistically significant quantities: the investigators are likely to die before the subjects. So here the investigators go for an extremely soft end point: abdominal flab. This marks the so called metabolic syndrome (MetS), denoting those who get fat in middle age and have high blood pressure, bad lipids and poor glucose metabolism. Apparently you are more likely to go that way if you start off with higher levels of oxidised low-density lipoprotein. But as we saw last week from another cohort study (the Cardiovascular Health Study), MetS is not itself a predictive concept: the added risk is associated with BP and fasting glucose alone. http://jama.ama-assn.org/cgi/content/abstract/299/19/2287

2304    Stored blood goes off quite quickly and becomes more dangerous the longer you keep it; it also needs very careful refrigeration, screening for transmissible agents and cross-matching. Fake blood has none of these disadvantages, but unfortunately this meta-analysis shows that it is dangerous from the start. You are more likely to suffer myocardial infarction or death if you receive a cell-free haemoglobin-based blood substitute than if you get some other kind of fluid during your haemorrhagic emergency: a tricky area to study but one in which these investigators identified 16 decently conducted RCTs. http://jama.ama-assn.org/cgi/content/abstract/299/19/2304

NEJM   22 May 2008  Vol 358

2205    Were I to suffer sudden crushing central chest pain, sweating and a feeling of impending death, I would want to be rushed into a large teaching hospital, but I am not sure that I would want to lie there listening to an explanation of the theoretical issues around percutaneous coronary intervention preceded by early treatment with abciximab plus half-dose alteplase versus abciximab alone versus abciximab given at the time of the PCI and then sign a consent form. In fact it’s only by having to type out those options, relaxed on a fine spring morning, that I begin to conceptualise what they might mean. And yet we must believe that 2452 acutely ill patients with ST elevation myocardial infarction were sufficiently tutored on the principles of immediate versus delayed glycoprotein IIb/IIIa inhibition to give their informed consent to be randomised (very rapidly) into one of these three groups. Fortunately, it didn’t matter as they all had the same outcome. http://content.nejm.org/cgi/content/abstract/358/21/2205

2218   There again, as I’m sure you well know, you could just give the direct thrombin inhibitor bivalirudin during PCI for myocardial infarction instead of a combination of heparin and a glycoprotein IIa/IIIb inhibitor. Again, these sophisticated issues surrounding blockade of the clotting system were explained to 3602 critically ill patients with high-risk MI and they duly consented to receive the blinded treatment. In this case, those randomised to bivalirudin alone fared better than those who received the combination, with fewer major bleeds and a reduction in all adverse events. http://content.nejm.org/cgi/content/abstract/358/21/2218

2249    For myocardial infarction as for many even worse modes of death the biggest avoidable risk factor is smoking. Governments the world over love to rake in their tobacco tax receipts while piously encouraging their medical establishments to help people stop smoking. A hundred years hence, I hope people will look back at this situation with disgusted disbelief, but for now, stopping smoking is a matter of individual effort in breaking free of a strong and lethal addiction. We saw from a recent study in young teenagers that peer behaviour can be channelled into the encouragement of smoking cessation. This sociological study comes from Framingham and observes similar network behaviour in interconnected groups of adults. http://content.nejm.org/cgi/content/abstract/358/21/2249

2259   In the late Old Testament book of Daniel, written in Aramaic and Hebrew centuries after the Babylonian Exile, the name of the penultimate king of Babylon is spelt Nebuchadnezzar (it was in fact Nebuchadrezzar) and he is described as being driven from the haunts of men and eating grass for seven years, during which his hair grows into eagles’ feathers and his nails into birds claws. Maybe this was a desperate attempt to cure himself of Mesopotamian grass pollen allergy. The modern equivalent, described in this review, is sublingual grass (pollen extract, “Grazex”). The period of browsing has been shortened by divine edict to three years, during which it would obviously be prudent to keep a close watch for feather and talon development. http://content.nejm.org/cgi/content/extract/358/21/2259

Lancet  24 May 2008  Vol 371

1753    Something in our genes determines that if we eat too much and exercise too little, and therefore go through periods when our blood sugar rises unduly, our insulin-producing cells begin to give up and die. This is manifestly unfair but a fact of life especially in Asian populations such as the Chinese (see p.1783 below) as well as among Indo-Europeans. Since glucose itself seems to poison our β-cells, might very tight sugar control with insulin at the onset of type 2 diabetes halt or reverse this? Several studies suggest so, including this latest one from China. A very clear editorial on p.1725 explains how this fits in with what we already know and may one day be translated into clinical practice. http://www.thelancet.com/journals/lancet/article/PIIS014067360860762X/abstract

1761    Once we expected a lot of antioxidants, because oxidised LDL-cholesterol is abundant in arterial plaque, and diets rich in antioxidant vitamins are associated with decreased cardiovascular risk. But all the prospective antioxidant vitamin trials were flops, and so was this trial of the antioxidant succinobucol, which actually increased LDL cholesterol and increased blood pressure, while having no effect on cardiovascular end-points. But an intriguing and unexpected finding was a marked decrease in type 2 diabetes incidence, which now needs testing as a hypothesis in its own right. Incidentally, this study had the acronym ARISE, for “Aggressive Reduction of Inflammation Stops Events”. Neville Goodman, who hates chirpy acronyms even more than I do, would no doubt wish that the Inflammation had been omitted. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607631/abstract

1777    We can explain the rise in type 2 diabetes on the basis of lifestyle changes, but the ever-increasing rise in type 1 diabetes in children is an enigma and a considerable worry. Especially so in Finland where the incidence under 14 is set to double and occur mostly in kids under 4 years old. The unlabelled picture on p.1730 may contain a clue. Close inspection reveals this not to be the famed white truffle of Alba, but a scabby potato. One theory has it that the incidence of childhood diabetes in Finland is due to the habit of weaning little Finns on mashed potato and other root vegetables. Due to the inclemency of the region, most of these roots are scabby with species of the fungus Streptomyces, which produces toxins that attack the islet cells. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607655/abstract

1783    Twenty years ago or more, 577 adults with impaired glucose tolerance in 33 Chinese centres were randomised to one of three lifestyle intervention groups – exercise, diet, or both - or control. Those in the treated groups had on average 3.6 fewer years with diabetes, but nonetheless the ultimate incidence of diabetes was 80% (versus 93% of the controls) and there was no detectable effect on cardiovascular disease. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607667/abstract 

BMJ  Journals  May 2008

BMJ  1174    The clinic model was widely adopted for diabetes in British general practice about 15 years ago, and although as a practice we were rightly sceptical about other sorts of GP “clinic”, we were quick to see that in a chronic condition needing regular monitoring, this one had merit. The pharmaceutical companies leapt in with educational initiatives promoting self-monitoring of blood glucose but the government of the day was slow to allow the NHS prescribing of the diagnostic testing strips. In retrospect, they were right: changing testing systems with ever more expensive strips are now a serious drain on the NHS drug budget. And we have gradually become aware that far from improving the control of type 2 diabetes, they can generate expensive and self-defeating obsessional behaviour with no clinical benefit.  This is borne out by the ESMON study here and by the DiGEM economic analysis on p.1177.

http://www.bmj.com/cgi/content/abstract/336/7654/1174

http://www.bmj.com/cgi/content/abstract/336/7654/1177

BMJ   1180   Once people have crossed the (admittedly arbitrary) threshold for type 2 diabetes, they rarely return, except by the route of bariatric surgery for the seriously obese. So where should efforts to prevent diabetes be concentrated? Not surprisingly, this cost-effectiveness modelling exercise comes down in favour of screening for impaired glucose tolerance, i.e. pre-diabetes rather than established diabetes. http://www.bmj.com/cgi/content/abstract/336/7654/1180

ACD  419   Can you have chronic fatigue syndrome at the age of 2? According to this case-series article, CFS fulfilling the RCPCH criteria can be found all the way back to toddlerhood and is not rare in the under-12s. The criteria admittedly amount to no more than persisting fatigue which cannot be accounted for by clinical tests. But the burden of disability in these kids is high and they follow just the same course as adults with CFS. http://adc.bmj.com/cgi/content/abstract/93/5/419

Gut  684    Inflammatory bowel disease is associated with osteoporosis though the ranges quoted in this detailed review cross a whole order of magnitude: 3-57.6% for Crohn’s disease and 4-50% for ulcerative colitis, provided you can tell which is which. “Needs more research” is a phrase which suggests itself. Obviously some of this may be due to corticosteroid treatment and the review usefully reminds us that most of the bone loss occurs in the first months of use, so don’t delay giving bisphosphonates in the hope that you will be able to wean the patient off steroids after a few weeks. For the seriously interested, there are diagrams of the various mesenchymal stem cell signalling molecules, with names like “Runx2”, “Osterix” and “Frizzled”. http://gut.bmj.com/cgi/content/abstract/57/5/684

Heart  628   The rapid access chest pain clinic appeared in most NHS hospitals over the last ten years as a way of averting the deaths which had previously occurred between the GP referring them to a cardiologist and the patients actually being seen. As a way of preventing legal action and political embarrassment, these clinics have probably succeeded, but do they actually stratify risk accurately? In Glasgow this seems to be the case: over 4 years, only 3.6% of those categorised as “low-risk” died from coronary disease or had a myocardial infarction, which must be below the Glasgow average. http://heart.bmj.com/cgi/content/abstract/94/5/628

Thorax  415   My usual custom in treating patients with infective exacerbations of chronic obstructive disease is to give them 10-14 days of antibiotics. Wrong, apparently. A meta-analysis of the studies seems to show that a five day course usually does the trick in mild-to-moderate COPD with purulent sputum. http://thorax.bmj.com/cgi/content/abstract/63/5/415

Ann Intern Med  20 May 2008  Vol 148

717    A patient aged 66 with diabetes comes in to have her blood pressure checked. It is 156/88 on your digital office sphyg. She is on the usual cocktail of metformin, gliclazide, ramipril 10mg, simvastatin, and aspirin. Do you:

·          Add another BP lowering drug

·          Find a mercury sphyg so you know what the real BP is

·          Get her to take some home readings

·          Call her back in a couple of months?

I think I’d at least do the last three; it seems a bit precipitate to add yet another drug to her permanent list on the basis of a single reading on an unreliable machine. Though you could argue otherwise – in fact you could argue for lowering the BP of all diabetics until they can no longer tolerate the side-effects. Much better that than lower their blood sugar obsessively. Anyway, here is an article about clinical uncertainty in this area: the net effect is that doctors fudge decisions and diabetic patients go around with high BPs and get myocardial infarcts, strokes, blindness and renal failure. http://www.annals.org/cgi/content/abstract/148/10/717

728    HIV infection in developed countries may not be the death sentence it is for millions of Africans and Indians, but it is still not a pleasant condition to have. The risk of many cancers is increased, according to this surveillance study of nearly 55 000 Americans attending for HIV treatment: 43-fold for anal cancer, 15-fold for Hodgkin’s lymphoma, 2.3-fold for colorectal cancer, to name some examples. Only prostate cancer bucks the trend and shows a lower incidence.

Plant of the Week: Lithodora diffusa  Heavenly Blue

Once a plant gets below about 15cm in height, it disappears into a category that nobody seems to want to write about. Out two greatest garden writers – Graham Stuart Thomas and Christopher Lloyd - died in the last couple of years leaving no systematic guide to the smaller subjects they cultivated all their lives. Sure enough, GST wrote works about plants for ground cover and the rock garden, and CL scatters references to his most and least favourite titchy plants throughout his numerous books. But a great and compendious modern guide on the lines of Reginald Farrer’s English Rock Garden is what we need, and don’t have.

Don’t go for books on “alpines” or you will get stuff about stone troughs and cold glasshouses and little bits of saxifrage that need infinite care to produce the odd tiny flower. The plants we doctors need for our neglected gardens must be of the kind that look after themselves and reliably fill the spaces without becoming too much of a nuisance. Into this category Lithodora falls with almost excessive perfection. A successful plant will form a mound of pure blue of a brightness and clarity that shames any neighbouring ceanothus or lilac.

Unfortunately this particular Lithodora does not like lime in any quantity, and such books as there are tend to extend this calcifugic propensity to the whole species or indeed the whole genus. Not so Reginald Farrer, who saw Lithospermum prostratum, as it was then known, in its native habitat:

“The plant occupies Northern, Central, and South-eastern Spain, indifferent, it would seem, to lime or granite, but in the garden occasionally giving trouble in the matter, though while its best masses are usually associated with sandy or non-calcareous beds and gardens, some others, not inferior, have their soil so filled with chalk that its chunks have to picked off the mats so as not to damage their effect. And yet other prolific patches are growing in pure leaf-mould and mortar rubble, even as the wild types, so it is said, grow with the passionately lime-loving Daphne Cneorum among the limestone blocks around Biarritz… There are varying forms of L. prostratum, such as the glorious Heavenly Blue, which gives a just, if minimised, foretaste or sample of L. japonicum; and there either is, or soon will be, a white, for which we shall all tumble over each other to pay vast sums, but which will inevitably prove inferior to the coerulean loveliness of the type.”

(The English Rock Garden 1918)

Farrer raves about Lithospermum japonicum in a separate section, but I can’t find any trace of this plant in the modern literature: nor of L hancockianum of which he gives the following account:

“L. Hancockianum is talked of with bated breath as being about to come out of China and make the dawn ashamed with the magnitude of its pure celestial blossoms. I know no more of L.Hancockianum.”

JAMA  28 May 2008  Vol 299

2391    Following a stroke, about half of survivors develop depression; most of this happens in the immediate aftermath but a third of it happens later. This study compared escitalopram, problem-solving therapy and placebo given to patients who were judged free of depression at three months after a stroke and who were then assessed at 12 months. Escitalopram definitely prevented some depression, whereas problem-solving therapy didn’t, possibly because a lot of patients gave up on it. But I can’t see this as an argument to give SSRIs to everyone after a stroke, along with their aspirin and simvastatin. Why not just look out for depression and treat it as it occurs? The opening of this paper grandly states: “Prevention is a goal to which every field of medicine aspires, because it reduces morbidity, may alleviate suffering, and reduces the cost of health care.” The last bit should read “almost always increases the cost of health care, by the intervention used, and by enabling people to live longer.” For example, smoking cessation not only cuts off tobacco taxes to governments but also means that on average the state has to pay out another ten years of pension and health care. http://jama.ama-assn.org/cgi/content/abstract/299/20/2391

2401    When is a centile not a centile? I should really be using the word percentile, which is more accurate and is the American usage in this paper about body mass index in US children and adolescents. An impossible 11.3% of these were at or above the 97^th percentile for BMI. This paradox arises from the fact that the pundits of the Centers for Disease Control and Prevention decided to fix the “normal” levels for childhood BMI at the 1980 level: this, and the dubious usefulness of BMI across different racial populations, is discussed in the editorial on p.2442. By whatever measure you use, the epidemic of obesity in American kids is certainly serious and not about to go away: but this study shows that at least it did not worsen between 2003 and 2006. http://jama.ama-assn.org/cgi/content/abstract/299/20/2401

NEJM  29 May 2008  Vol 358

2332    The four therapeutic pillars of palliative care are opioids, aperients, anti-emetics and anxiolytics. Using opioids in advanced illness generally means also using aperients, but constipation can remain a serious and distressing problem for many patients, who often endure their pain without opioids rather than endure the indignity of enemas. Methylnaltrexone is an opioid antagonist, but doesn’t cross the blood-brain barrier: so it antagonises the effect of opioids on the bowel without blocking their central analgesic effects. So you can give subcutaneous methylnaltrexone to patients with refractory opioid-induced constipation and most of them will reach what this study calls the “coprimary outcomes” within 4 hours. Sadly this is not an elegant new coinage from the Greek “kopros” meaning poo, just a spelling of “co-primary”. http://content.nejm.org/cgi/content/abstract/358/22/2332

2344    More good news about hard kopros. Ten years ago, Johnson & Johnson produced a new laxative from their promisingly located base in Movetis, Turnhout, Belgium (I’ m not making this up). One of their investigators is called Vanderplassche. Prucalopride is a 5-hydroxytryptamine₄ receptor antagonist and worked well in nearly half of 620 Americans with severe chronic constipation. A pan-der-splasher for Vanderplassche! If you’ve lots of poo inside, try new prucalopride. http://content.nejm.org/cgi/content/abstract/358/22/2344

2366   Precocious puberty occurs mostly in girls and in the USA is defined as pubertal change seen before the age of 6 in black girls or before 7 in white; in Europe, the threshold age is 8. For boys it is set at 9 and a half, and puberty before this age is often associated with pituitary abnormalities - in boys but not in girls. In fact female precocious puberty often stops mid-way, and the decision to use GnRH agonists is based on an appraisal over many months. Although this review was written in France, Figure 1, with its circumcised male genitalia, was clearly aimed at the US readership. http://content.nejm.org/cgi/content/extract/358/22/2366

Lancet  31 May 2008  Vol 371

1839   Over the last decade, perioperative beta-blockers have been used, in and out of randomised trials, with the intention of reducing cardiovascular events in patients with known atherosclerotic risk. About one patient in twenty who falls in this category will suffer a stroke or heart attack in the month following surgery: an alarming statistic. Giving such patients metoprolol reduced the heart attacks but increased the strokes and the total mortality. This was a big multinational trial called POISE (for Perioperative Ischaemic Evaluation – I make that PIE) which recruited 8351 patients, and I don’t think there are likely to be many more. http://www.thelancet.com/journals/lancet/article/PIIS0140673608606017/abstract

1848    Doing careful bacteriological studies on unexpectedly dead babies is difficult work but vitally important if we are to understand sudden unexpected death in infancy (SUDI, of which sudden infant death syndrome, SIDS, is the subset who died in their sleep). This retrospective case review of 546 infants suggests that Staphylococcus aureus and Escherichia coli, independently or synergistically, may be responsible for some of these deaths. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607989/abstract

1854    A fairly straightforward trial from Dutch primary care compares naproxen and prednisolone for four days in the treatment of acute gout. They were equivalent. I’ve been using steroids for gout for decades and wasn’t surprised. We still need new drugs for gout, though, because it is so common in patients taking high-dose diuretics for heart failure, who are dubious candidates for high-dose prednisolone and must never be given NSAIDs. Colchicine is not a nice drug to have to resort to. http://www.thelancet.com/journals/lancet/article/PIIS0140673608607990/abstract

1861   Ticks of the genus Ixodes are everywhere across the wild places of the Northern hemisphere, and where conditions are suitable, they can carry the flavavirus that causes tick-borne encephalitis. Fortunately, the right conditions for transmission to humans are uncommon, and in the whole of Europe (excluding Russia) there are about 3000 cases a year. Should you need to know more, this review article will fill you in. http://www.thelancet.com/journals/lancet/article/PIIS0140673608608004/abstract

1883    “I realised from the first that he was important, as well as likeable, but I doubted whether I could keep him as an epidemiologist” wrote Archie Cochrane of his meeting with Julian Tudor Hart in 1958. Not long after, JTH said to Cochrane, “Archie, you’re OK. You are doing good, but you are not doing it very fast. I think that by changing to primary care I can have a much quicker effect.” I guess he must be in his mid-to-late 70s by now, but in this essay about the NHS, JTH writes with an incisiveness and breadth of vision that most of us could only dream of. I don’t normally comment on political pieces, but this is one you must read. http://www.thelancet.com/journals/lancet/article/PIIS0140673608608028/fulltext

BMJ Journals May 2008

BMJ  1223    The least used smoking cessation treatment is nortriptyline, while the most widely used is nicotine replacement. Neither is all that effective, so it was logical to try the combination in a randomised trial with NRT chosen by the patient and nortriptyline or placebo added on. In fact there was no significant difference in the cessation rate between NRT plus placebo or NRT with nortriptyline (approx 10%) at one year. http://www.bmj.com/cgi/content/abstract/336/7655/1223

BMJ  1227   Most of the large prospective trials of hormone replacement therapy used a single kind of preparation, while most of the retrospective observational studies lump together many kinds of HRT. If we meta-analyse all these trials by preparation type, differences in risk begin to emerge. Women taking combined oral HRT more than double their risk of venous thromboembolism, in both RCTs in observational studies. There are no RCTs of transdermal HRT, but the observational data are consistent with no increase in VTE risk. This is all nicely summarised on a Forest plot. http://www.bmj.com/cgi/content/abstract/336/7655/1227

Heart  667   Recently one of my patients spent about two and a half hours on the table having a coronary stent fitted, which perforated a coronary artery, which was then fixed by inserting another stent. I wondered silently how much radiation exposure all this invasive cardiology had involved. Reading this German review of the field in some detail, I got lost between my DAPs (mean patient dose area products) and my ALARA (as low as reasonably achievable) and the vast range of doses which separate current practice from what is desirable and potentially achievable using dose-sparing techniques. I suspect that my patient may have had a dose approaching 200Gy x cm² whereas it’s theoretically possible (and highly desirable) to keep it below 10. http://heart.bmj.com/cgi/content/extract/94/5/667

Thorax  387   Two papers, one from Poland (p.402) and one from Tasmania (p.408), occasion this editorial entitled “Provide GPs with spirometry, not spirometers”. In case you hadn’t twigged, the implication is that GPs the world over are crap at spirometry. I have no doubt that I am, but I don’t think the same is true of my practice nurses. The solution of sending in trained respiratory nurses to do all primary care spirometry seems slightly absurd, particularly since the idea is to detect symptomatic COPD in smokers and then tell them there is no effective intervention except stopping smoking. I think I can do that without nurses or spirometry.

http://thorax.bmj.com/cgi/content/abstract/63/5/402

http://thorax.bmj.com/cgi/content/abstract/63/5/408

http://thorax.bmj.com/cgi/content/extract/63/5/387

Arch Intern Med  26 May 2008  Vol 168

1030    The idea of individualised blinded patient trials of therapy gained vogue in the 1990s but never caught on because n-of-1 trials require a great deal of organisation and patience. Or a great deal of patients, if you are talking about research. Most n-of-1 trials would, in an ideal world, not be for research but for individual tailoring of treatment in chronic disease states which cause a fairly static pattern of symptoms. Rheumatoid arthritis is one such, and this modelling study looks at the possibility of using n-of-1 methodology to decide which individuals might benefit from etanercept, an anti-TNF agent which costs about £10k per treatment year. An interesting idea for a primary care based study. http://archinte.ama-assn.org/cgi/content/abstract/168/10/1030

1034    When is it safe to use corticosteroids in infectious diseases? Almost always, is the surprising answer from this very comprehensive trawl through 156 papers on steroids in a wide range of infections. The main exceptions are cerebral malaria and viral hepatitis. For many other infections, steroids are not just safe but beneficial, and short courses are probably justified for such things as persistent symptomatic glue ear and painful shingles. http://archinte.ama-assn.org/cgi/content/abstract/168/10/1034

1055   Coronary calcium scoring is an ingenious way of selling expensive radiation to outwardly healthy Americans, but does it have any useful predictive value e.g. in selecting people who should be taking statins? The Dallas Heart Study tested this hypothesis on 2611 participants who underwent  CT assessment of coronary artery calcification, and found that it shifted the classification of about 8% of the group. The editorial on p.1027 ponders deeply about this before making the obvious point that statins are cheap and beneficial to nearly everyone, whereas CT of the thorax is not.

http://archinte.ama-assn.org/cgi/content/abstract/168/10/1055

http://archinte.ama-assn.org/cgi/content/extract/168/10/1027

1090    I read this paper shortly after giving a demented old lady a small dose of olanzapine in the hope of relieving an incessant flow of anxious muttering. Previously she had been given diazepam 10mg tds on a psychiatric unit, after which she fell and fractured her zygoma. Here is a study of community-dwelling old people with dementia given antipsychotic medication. In the next 30 days, their risk of a serious event increases by a factor of three to four. The risk in nursing home patients is somewhat less. http://archinte.ama-assn.org/cgi/content/abstract/168/10/1090

1104   Older textbooks cite gout as a risk factor for cardiovascular disease but it doesn’t feature much in the modern literature. However, actual gout (as opposed to asymptomatic hyperuricaemia) still remains predictive of CVD mortality in middle-aged men, though only just (HR 95% CI 1.06-1.72). http://archinte.ama-assn.org/cgi/content/abstract/168/10/1090

1111   This study shows that 80% of  patients admitted to nursing homes following fractures in New Jersey are not being given any treatment for osteoporosis. Time you audited your own. http://archinte.ama-assn.org/cgi/content/abstract/168/10/1111

Plant of the Week: Geranium pratense Midnight Reiter

In the weeks to come, the roadsides of England will be decorated with wild meadow geraniums of various shades of blue, or occasionally of washy pink. These are lovely plants, fit for all gardens, though they get a bit gangly and are fond of sex. Somewhere along the line a gene arose that produced purpling of the leaves, and this has been bred into a clone that has clear blue flowers with reddish purple stems and good dark matt purple cut leaves.

Pots of these plants sell by the thousand, and rightly so. The problem is placing a plant with such an assertive and complete character amongst others. The dark leaves disappear altogether against dark soil. They look a bit over the top if placed next to an ordinary green plant of similar size. By a stone wall, perhaps? Again, not quite right. Probably best next to a light green sprawler, like Hypericum olympicum, but I haven’t tried that yet. The main thing is that since this plant is descended from a tough native, it is unlikely to die from being moved a lot while you make up your mind.

But why the odd German/English name “Midnight Reiter”? Surely not a reference to the infamous Nazi human experimenter who somehow got his name attached to a kind of reactive arthritis which had been described 100 years earlier? Or the agonised father “wer reitet so spät durch Nacht und Wind” in Goethe’s terrifying poem? I don’t know. Just silly, if you ask me.