Richard Lehman’s journal review – 6 September 2010

Richard LehmanJAMA 1 Sep 2010  Vol 304
   A couple of weeks ago, the BMJ published a rather strange piece about the terrible psychological effects of chemical castration in men with prostate cancer. But although I’ll no doubt be sorry to part with that aspect of myself if I ever have to, this pales into insignificance compared with the choice that confronts women unlucky enough to have inherited mutations of BRCA1 and BRCA2 genes. If they want to abolish their substantial risk of getting cancer of the ovary and breast, then the best way to do so is prophylactic removal of the organs. In this international prospective cohort study, those who opted for preventive bilateral mastectomy did not get any breast cancer. Those who opted for preventive bilateral oophorectomy reduced their risk of breast cancer mortality and all-cause mortality substantially, and nearly abolished their risk of ovarian cancer; but you have to look hard in the text to find out the mean follow-up period for these various figures. So for these poor women there’s a headline message that sexual mutilation will prevent death, but for each one the exact odds will be different and not very certain.

976    It never ceases to surprise me that by adding nine months and seven days to the first day of a woman’s last period, I can tell her when her baby is going to be born. And although I’m no mathematical genius, I can generally do it in my head while I congratulate her. The human gestational period is meant to be 270 days, and a deviation of just 14 either way carries a more than doubled risk of cerebral palsy, according to this national birth register study from Norway. We share this gestation period approximately with the hippopotamus, the otter and the elk; a properly endowed giraffe requires a variable wombing period of between 420 and 450 days; whereas the infant elephant appears at exactly 616 days following the joyful and weighty congress of its parents.

NEJM  2 Sep 2010  Vol 363
    When the European Medicines Agency withdrew the licence for sibutramine a few weeks ago, The Lancet bemoaned the way that drugs these days get pulled off the market before we can really tell their long term harms and benefits. Bizarre! We should be moaning about the very opposite – the way that drugs can get put on the market because they lower a surrogate outcome – weight in the case of sibutramine, blood glucose in the case of rosiglitazone – when it later turns out that they cause the very harm they are supposed to prevent. Drug companies can make billions of dollars for each year of harm caused, until the evidence becomes too powerful, as it now does for sibutramine in the SCOUT study. “Subjects with pre-existing cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke” – which most of us would consider a poor exchange for 1.7 kg of weight loss. As for swapping a 1% drop in HbA1c for a probable 80% increase in risk of myocardial infarction, as in the case of rosiglitazone, what can one say? Actually one has already said it, as you will find if you go to the BMJ website.

   The sad truth is that medicine is going through a phase of failure. Richard Smith will rejoice about this – see his blog on the BMJ site. He thinks we need the challenge that only failure can provide. Well, here it is: so stop digging the same holes. Stop being led by what will sell more drugs for chronic illness and listen to what is important to patients. If you pile on more antihypertensive drugs for chronic renal failure you are bound to make a lot of people feel terrible and you will not improve outcomes. This is the message of the AASK trial in 1094 “black patients” with hypertensive chronic kidney disease. The same is true of cardiovascular drugs in type 2 diabetes, as two recent studies have shown. When you hit clay or rock, it’s time to get out of the hole.

930   Still, there are plenty of areas where honest endeavour continues to give us valuable information about how to treat patients. Dose-finding studies are amongst the least glamorous and the most worthy, and this one tell us that we are using the right doses of aspirin and clopidogrel in acute coronary syndromes. The CURRENT-OASIS 7 investigators randomised 25,086 patients with ACS to receive standard or double doses of the two drugs using a 2×2 factorial design, and showed that 75-100mg aspirin is enough for loading, as is 300mg clopidogrel.

   Progress in cancer treatment is also achieved mostly in tiny increments rather than sudden breakthroughs. These are holes that are still worth digging. You find out if neoadjuvant chemotherapy for ovarian cancer is best given before or after debulking sugery by doing a big randomised trial, which in this case involved 632 women in about 20 European centres. In fact the two strategies are about equivalent, but preoperative chemo may make surgery a bit easier. Survival depends to a large extent on the completeness of tumour removal at the time of surgery.

    I read every word of this clinical review about calcium kidney stones, being a victim of these little devils every few years. Mine are exquisitely painful for a day or two as they go down the ureter, but as they are always tiny I don’t have to worry about ureteric obstruction, like other members of my family. I haven’t had my parathyroid hormone levels checked as I’ve come to the conclusion that nobody would know what to do with the result. I haven’t altered my diet as I count food one of life’s greatest pleasures; and I haven’t started bendroflumethiazide as I get up to pee quite enough as it is. I just drink plenty.

Lancet  4 Sep 2010  Vol 376
    “He’s got this nasty cold, doctor, and I’m worried he won’t be fit for his op next week, so I wondered if you could give me something.” What you should end up giving, according to this review, is advice that he’d be better to postpone his operation by two weeks. Why two weeks? Because a child who has had an upper respiratory infection 2-4 weeks prior to an operation has a lower risk of perioperative adverse events (RR 0.66) whereas if the URTI happens less than two weeks previously, the risk is increased by more than two-fold (RR 2.4).

784   The palliation of terminal dyspnoea is a subject that used to interest me a lot, mainly in the context of heart failure, where many patients are dyspnoeic without substantial reduction in oxygen saturation. Nevertheless they frequently get symptomatic benefit from inhaled oxygen, some to the point of becoming dependent on an immediate oxygen source. For years I heard some of the authors of this study discuss a blinded randomised trial of room air versus oxygen for such patients, not just with those with cardiac dyspnoea but with a range of terminal conditions. And here at last it is: a landmark in evidence-based palliative care, showing that room air works as well as oxygen over a period of a week. However, I can foresee major problems in real life: “Are you trying to kill him doctor? They’ve delivered a cylinder of compressed air, but Eric needs his oxygen. I told them to take it away.”

803   A nice, sensible, well-written review of asthma in older adults, which deserves all the praise I can heap on it for defining “older” adults as four years older than I am. Also, it points out that the older and the more breathless you get, the less likely you are to use an inhaler properly. And that trying to distinguish between asthma and chronic obstructive pulmonary disease in the over-64s requires expert spirometry but is generally futile, because the treatments are largely the same and should be guided by symptomatic improvement rather than lung function measurements.

814   This next paper, on the management of severe asthma in children, is even better. “We are not aware of any randomised controlled trials in true, therapy-resistant paediatric asthma”, say the two authors from the Royal Brompton Hospital. It’s scarcely believable, but they have been forced to base their “recommendations on personal practice, with cautious extrapolation from published papers adult severe asthma and paediatric mild-to-moderate asthma.” They write from a hospital perspective, but this is an excellent guide for primary care too, especially in its insistence on considering whether the diagnosis really is asthma in the first place, and the analysis of the different kinds of problem asthma given in Panel 2. Life-threatening problems can arise out of nowhere in some children whose daily control is as good as we can currently get it.

BMJ  4 Sep 2010  Vol 341
   A worthy attempt to meta-analyse the data that exist about the outcomes of nurse-led interventions to improve control of blood pressure. Nurses using algorithm-guided protocols show some success in the USA, especially when they are given prescribing powers. But just what are we doing in hypertension? A recent review I read suggested that it really takes 14 office readings to determine whether a change of treatment is needed. Most of what we do to our patients with raised blood pressure is probably futile, and we urgently need better primary care studies to tell us how to do better.

493   The BMJ‘s picture of a migraine aura, caught in the corner of my left eye, sent a shiver of fear through my whole body: I’ve been getting these auras every few days lately, and they are followed by a day or more of non-specific misery. Now I learn from this study of the Icelandic population that migraine with aura is associated with increased cardiovascular risk in both men and women (the previous study, just deals with women). Just another non-modifiable risk factor, like being male and bald and getting kidney stones.

495   The clinical review this week is from the Drug and Therapeutics Bulletin and is therefore drier and less well illustrated than most. However, if you want all the evidence about managing gastro-oesophageal reflux in infants, here is the place to look. You’ll leave more worried than you came. Proton pump inhibitors (unlicensed) and H2 receptor antagonists may or may not improve symptoms (the trials are small and inconclusive), but they can increase the risk of necrotising enterocolitis in very small babies, and gastroenteritis and oral thrush in bigger babies. Evidence about prokinetics is similarly conflicting.

Fungus of the Week: Pluteus cervinus

The August rains have tempted many fungi into early appearance this year, especially the Agaricus species with white caps and brown gills that are mostly familiar and edible, except the one that smells nasty and goes yellow when you cut its base.

These mushrooms named for the field and the horse are actually amongst the best tasting of all fungi, and it they weren’t so abundantly available in commercially grown forms, we would prize them above everything except perhaps Boletus edulis and Cantharellus cibarius. Pluteus cervinus isn’t in this culinary league, but at least it’s fairly handsome and not too rare. In its youth it had a dark brown cap, sometimes nearly black, and white gills. The stipe has distinctive black hairy striations twisting around it. A few days later, the cap will have expanded and become a little paler, the gills will have turned pale brownish pink, and the stipe will have lost some of its black hairy bits, which now look random. Like most edible fungi or the second rank, it turns slimy in the pan and doesn’t really taste of much. You’ll enjoy it because you found it and had a nice early autumn walk in the woods: you shouldn’t expect others to share your enjoyment, but give them some proper mushrooms to eat instead.