28 May, 12 | by BMJ Group
JAMA 23 May 2012 Vol 307
2161 Daytime sleepiness is one of the main reasons for treating obstructive sleep apnoea, another one being the risk of cardiovascular events and hypertension in untreated OSA. Continuous positive airway pressure is the standard treatment, and observational evidence suggests that as well as keeping people more alert by day, it may also reduce adverse cardiovascular consequences. I hadn’t realized before reading this paper (and the associated editorial) that there is no evidence for this from randomized trials. The Spanish sleep and breathing network considered that it would be unethical to do an RCT in symptomatic OSA: instead they selected people with OSA but without daytime sleepiness and randomised them to a prescription of CPAP versus no prescription. Many of the CPAP group found the fiddle of using it all night long too much, and rarely did, so that on an intention-to-treat basis this trial could prove nothing: in those who were compliant, there was a trend to better outcomes.
2169 Here’s an observational study from some of the same Spanish team showing that OSA is associated with hypertension, and in those who use CPAP it seems to progress less.
I’m afraid that the rest of JAMA this week was well past my threshold for daytime sleepiness.
NEJM 24 May 2012 Vol 366
1949 The opening Perspective pieces in the New England Journal usually deal with specific American issues, and this one by Howard Brody, From an ethics of rationing to an ethics of waste avoidance, is certainly nuanced for a society where the least mention of rationing in healthcare has raised howls about death panels. I have always been highly sceptical about the need for rationing within the NHS, until the arrival of spectacularly costly interventions of little marginal benefit in the last decade. But the need to look at cost effectiveness and savings in the US health system has been blindingly obvious for decades. Brody looks at these issues calmly and subtly from the perspective of a bioethicist who is also an advocate for family practice: the USA could do with many more like him, and this piece is worth reading on both sides of the Atlantic.
1959 Ah, Perugia! Town of my dreams, the very epitome of Italian civilization, cradle of Raphael, home to Perugino and Pinturicchio, a hill covered with miraculous architecture, including an ancient University, from which this paper originates. What a neat little study this is, enrolling just so many subjects as were needed to prove that taking low dose aspirin for two years following unprovoked venous thromboembolism reduces recurrence by nearly a half without an increase in significant episodes of bleeding. And now it is time for lunch—the linguine with black truffle shavings are so good—and a siesta—and then we must visit the astounding Palazzo dei Priori, taking in the annual chocolate festival a little later. One day soon, perhaps.
1968 Doctors are most likely to kill patients when they are desperate to do something. Unfortunately we can do very little for idiopathic pulmonary fibrosis, but one supposition is that it is an auto-immune disease, and so (in the USA at any rate) it is often treated with a combination of prednisone, azathioprine, and N-acetylcysteine. Not for much longer: this trial comparing the combination with placebo was stopped when 8 out of 77 in the active group had died compared with 1 in the placebo group. There were also three times as many hospitalizations in the active group, and triple treatment provided no symptomatic or physiological benefit. So how on earth did it come to be widely adopted? There needs to be some sort of post-mortem among pulmonologists.
1987 If a woman comes to me saying that she wets herself when she coughs or laughs, then I assume she is telling the truth. She has stress incontinence and we get talking about treatment options. For some reason I seldom even trouble her to demonstrate the phenomenon on my couch; though that is what was done in the VALUE study, which compared clinical assessment with urodynamic testing before stress-incontinence surgery. In 630 women with uncomplicated stress incontinence who were randomised to office assessment or full urodynamics, there was no difference in outcomes one year after surgery. Most urodynamic studies are an uncomfortable, expensive waste of time.
1998 In the preamble to this paper, the authors claim primacy for the USA in its rate of unintended pregnancy, and about half of unintended pregnancies are due to contraceptive failure. They set up a programme for providing free contraception in the St Louis region and observed the results in 9256 women over a four-year period. Women using long-acting methods (intra-uterine devices, subdermal implants, long-acting progesterone injections) had twenty times fewer pregnancies than women using pills, patches, or vaginal rings. Now that’s what I call evidence: no matter that it is observational, or that the 95% confidence interval runs from 13.7 to 34.9. The difference between these groups of contraceptive methods is simply huge, and needs to inform practice and policy.
Lancet 26 May 2012 Vol 379
1951 If you can’t cure ’em, give ’em CBT. This central principle of modern medicine seems to get a ringing endorsement in a Dutch study of cognitive behavioural therapy for tinnitus. But is this CBT as we know it in the NHS? Does the therapy consist of waiting to hear from the waiting list office, getting a password, making several phone calls to confirm that you still want an appointment, then getting a letter to say your name has been put forward but unfortunately you will have a wait, and then getting another one saying you can ring in giving your password, and so on until you give up? Ah no, it consists of an intensive programme of multidisciplinary treatment, the like of which I have never seen this side of the North Sea.
1960 Nobody should die from malaria. For a start the disease should have been eradicated 50 years ago, and secondly it is entirely curable using drug regimens based on artemisinins. But in fact around 600,000 people die from malaria every year, and this study indicates that the effectiveness of artemisinins is definitely beginning to wane, though if they will ever become clinically ineffective is still unclear. Everyone who arrived with Plasmodium falciparum at the clinics in this study from northwestern Thailand left alive and cured, using an artesunate-based regimen. But their mean rate of parasite clearance was slower than it had been nine years previously. A brilliantly compressed editorial on p.1928 tells you what this means in the context of malaria in the modern world: there is yet hope that we will defeat this wily old enemy altogether, but the artemisinin story remains nail-biting.
2008 I had hoped to do some revision on primary brain tumours in adults (p.1984), but had to give up when faced with impenetrable jungles of technical detail. Let’s try silicosis instead. In a memorable scene from the 1946 film Brief Encounter, Celia Johnson’s eyes glaze over and her eyelids flutter when Trevor Howard mentions this word amongst a list of occupational lung diseases. “I don’t understand a word you’re saying, but do go on,” she softly begs. But I am afraid that this Chinese review of the topic might prove much of a good thing even for Celia. It is a serviceable and readable account of lung damage caused by silica, which is still an important cause of morbidity, especially in the Republic of China (half a million sufferers). But I think tea at the Khardoma and an afternoon at the cinema are more likely to lead to railway platforms of unconsummated passion.
BMJ 26 May 2012 Vol 344
Is it safe to go on a weight reducing diet during pregnancy? Certainly—the foetus won’t mind in the least and will carry on living like a lord at the end of the cord. Is it beneficial to go on a diet while pregnant? An international jury of meta-analysts looked at the evidence (“without language restrictions,” no doubt because they included Swiss, Dutch, and Polish contributors who between them speak all the principal European languages): there is a tendency to benefit to both mother and baby, but most of the evidence is of low quality.
Drugs which inhibit thrombosis get an airing pretty well every week in these columns, but the pro-thrombotic drug tranexamic acid languishes on the sidelines, despite some startling evidence of benefit in certain situations, such as early use in bleeding trauma patients (CRASH-2). There have been lots of trials in elective surgery too, and this systematic review and cumulative meta-analysis demonstrates that there is a sound body of evidence for a substantial reduction in blood transfusion in a variety of procedures. What is not so certain, unfortunately, is the rate of thrombotic events or the effect on total mortality.
According to the only person in a position to report, I have restless legs during sleep. Does that mean that I have restless legs syndrome? That all depends on how much you want to monger this particular “disease,” and some people want to monger it a lot, as there are big sales to be had—up to 15% of the adult population. This useful clinical review starts with a more conservative definition, closer to Ekbom’s original description—”it is characterised by an urge to move and usually, but not exclusively, affects the legs. This urge to move is typically accompanied by abnormal sensations, variably described as burning, tingling, aching, or ‘insects crawling under the skin.’” Well, I don’t get that. Women get it twice as much as men; and there is sometimes a familial pattern. If simple behavioural methods don’t work, this article recommends treatment with dopamine agonists; but I would beware. The cardiovascular risks of these drugs are just beginning to emerge, and they’re not looking good.
Plant of the Week: Kalmia latifolia
This is a large evergreen shrub with lovely heads of flower in late spring. In Britain I have only seen it rarely, in large gardens on acid soil, planted amongst rhododendrons and pieris. But here in Connecticut it is grown abundantly in large town gardens (or yards, as they are called)—and I have just discovered that it is the state flower. I am not quite sure what privileges that carries: perhaps it can give assent to state bills, appear on stamps and coins, and hold jubilees. A decorative head of state is such a useful thing: a good tub of ericaceous compost is all it requires.
This handsome plant is a relative of the bilberry (or blueberry, as we now call it after the Americans), and so is an extreme hater of lime. It is also a hater of man and large animals, being poisonous in all its parts. If you keep bees, do not grow kalmias. Six hours after eating your toast dripping with kalmia honey, you will, according to Wikipedia, experience “irregular or difficulty breathing, anorexia, repeated swallowing, profuse salivation, watering of the eyes and nose, cardiac distress, incoordination, depression, vomiting, frequent defecation, weakness, convulsions, paralysis, coma, and eventually death. Autopsy will show gastrointestinal irritation and haemorrhage.”
I’m not sure how much of a problem mountain laurel poisoning is around here, where the plant has its origin and grows wild in woods as well as being available in many garden cultivars. These are really beautiful plants with flowers of white, pink or crimson, and many of them were raised by Dr Richard Jaynes at Hamden, a few miles from where I am currently sitting. If I haven’t put you off, and you have the requisite highly acid soil, you can find them in a few specialist British nurseries.