Richard Lehman’s journal review—13 May 2013

Richard LehmanJAMA  8 May 2013  Vol 309
1903    When an implanted cardioverter defibrillator goes off inside you, you are sure to feel deeply shocked: whereas, for others, watching you drop dead might be even more shocking. One needs to strike a balance. That was the purpose of the ADVANCE III (Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III) trial. Essentially this was a gamble on how many ventricular tachycardia beats are allowed to happen before the device fired: with current devices it is usually 18-24, whereas in this trial half the patients got a newly programmed device which counts to 30-40. They stayed alive as much, didn’t have more syncopal episodes, and had a third fewer shocks in the first year.

1912   I thought that every human being in the state of nature carried Helicobacter pylori, but I was wrong: about 5-10% of the human race never harbour the bug, no matter how much they are exposed to it. This paper reports on two studies which identify the genotypes of these helicobactrophobic individuals in Pomerania and in Rotterdam. The investigators confess that they cannot think of any use for this knowledge at present; but in the great scheme of things it may come in handy one day; which no doubt is why JAMA decided to share it with us.

NEJM  9 May 2013  Vol 368
1771    Haematological cancer is not my specialty, or yours, in all likelihood. We don’t have to decide when to give platelet transfusions, but those who do have found over the years that they can safely wait until the platelet count has gone down to 10×109 and then give half as many platelets as they used to. The next step would be to give none at all until a bleeding event occurs, and that was the strategy tested in this Australo-British trial. But it was a step too far: the rate of serious bleeding in the no-prophylaxis group was only modestly higher (by 8%) but their bleeds came sooner and lasted longer.

1791   I saw the title and expected a good observational study: Respiratory Syncytial Virus and Recurrent Wheeze in Healthy Preterm Infants. And there is certainly plenty of good observational data in this study; but essentially it is a trial of palivizumab, an anti-RSV agent manufactured by Abbott, in preterm infants, with a primary outcome consisting of the total number of parent-reported wheezing days in the first year of life. So the title should really have been “Palivizumab injections to prevent wheezing in the first year after preterm birth.” I don’t know if reprint-selling disease has spread to the titles of NEJM articles, but it looks that way to me: we’ll never know how many copies of this paper get bought up by Abbott or how they might be used to promote sales of palivizumab, because the NEJM considers that commercially confidential. The economics of palivizumab were discussed in a BMJ piece in 2009: a course of RSV prophylaxis costs between £3-5K in the UK. It’s estimated that at least 60% of babies get RSV in the first year of life. In the great majority it is a mild illness, though some get bronchiolitis and may then wheeze after each subsequent upper respiratory tract infection; by the age of three hardly any do. So it’s hard to put a price on a 60% reduction in first-year wheezing days: a happy outcome, certainly—but worth spending £3-5K on every baby born at 33-35 weeks’ gestation?

1800    They’re at it again! Crunching up thousands of tons of lovely oily fish and turning them into capsules of n-3 fatty acids. These were then fed to Italian “men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n−3 fatty acids (1 g daily) or placebo (olive oil).” Maybe 1G of olive oil is just a placebo: certainly for an Italian. Anyway, there was no difference at 5 years. To derive any protection, you have to eat the fish as well as the oils. Turbot is the best fish for n-3 fatty acids, I’m told: excellent as steaks or fillets fried in butter and served with a sauce of reduced cream, white wine and morels (or since you probably lack morels, some fresh chopped sorrel at the last minute); or just a simple hollandaise. The point of all fish is the butter that goes with them. There are those who assert that the quantity of butter should equal the quantity of fish, but I think that this should be left to the conscience of the individual believer.

1817   Here’s a really comprehensive review of enteropathogens and chronic illness in returning travellers, which makes you wonder what we’re missing in some of these unfortunates. The GeoSentinel Surveillance Network gathered data on 25,867 returned travellers over a 9-year period (from 1996 to 2005). “Of the 2902 clinically significant pathogens that were isolated, approximately 65% were parasitic, 31% bacterial, and 3% viral. Six organisms (giardia, campylobacter, Entamoeba histolytica, shigella, strongyloides, and salmonella species) accounted for 70% of the gastrointestinal burden.” My goodness, that still leaves 2,896 other pathogens in travellers’ diarrhoea, which is more than I thought existed in the Universe. Respect!

Lancet  11 May 2013  Vol 381
1627    Psychiatry is in a permanent mess, alternating between dogma and self-doubt. A century ago, it was the unconscious mind (as expounded by Middle European authority figures) which promised to explain everything: now it is going to be genomics. In the meantime, this is a bad world to be mad in. If you are labelled psychotic, you are required to conform to the latest fashion in treatment: this used to be compulsory admission under Section 17 of the Mental Health Act, but now it is increasingly a compulsory treatment order in the community. The OCTET investigators postulated that patients with a diagnosis of psychosis discharged from hospital on CTOs would have a lower rate of readmission over 12 months than those discharged on the pre-existing Section 17 leave of absence. But that did not happen. “In well coordinated mental health services the imposition of compulsory supervision does not reduce the rate of readmission of psychotic patients. We found no support in terms of any reduction in overall hospital admission to justify the significant curtailment of patients’ personal liberty.”

1634   The next trial reported was an attempt to measure the effect of anticipatory shared decision making by people with serious mental illness. It aimed to compare the effectiveness of Joint Crisis Plans (JCPs) with treatment as usual. “The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency, when he or she might be unable to express clear views.” This sounds like a really good idea, and a strategy that should reduce the need for compulsory admission—but in this trial it didn’t. The investigators seem pretty peeved: so much so that they blame the participating teams. “Our findings are inconsistent with two earlier JCP studies, and show that the JCP is not significantly more effective than treatment as usual. There is evidence to suggest the JCPs were not fully implemented in all study sites, and were combined with routine clinical review meetings which did not actively incorporate patients’ preferences. The study therefore raises important questions about implementing new interventions in routine clinical practice.”

BMJ  11 May 2013  Vol 346
The best news this week comes from Australia, and it is awesome: quadrivalent human papillomavirus vaccination of young women in Victoria caused an 82% drop in genital warts in those offered vaccination, and a similar drop in young men of the same age group (who hadn’t been vaccinated). In the women who were actually vaccinated in 2011, genital warts did not occur at all. As if to drive home the point, no significant decline was observed in older women or men, non-resident young women, or men who have sex with men. As the editorial puts it, “These are exciting times in the science of HPV and the world can confidently look forward to the virtual elimination of genital warts, recurrent laryngeal papilloma, most genital cancers, and some 60% of head and neck cancers.” News doesn’t often come better than that.

Lordy, lordy, how some people never get it about screening. It’s not that I don’t recognize the thoughtfulness and intelligence of the 12 authors who wrote this paper about the Malmö Preventive Project in Sweden, which used data from frozen sera to show that PSA testing at 40-55 can identify a cohort of men at high risk of metastatic prostate cancer several decades later. They build up their argument carefully and acknowledge the problems of harm from overdiagnosis, only to conclude that men with low initial PSAs will need another three tests to be sure they are still at low risk. Ugh. Where is any evidence that this will reduce overdiagnosis and affect all-cause mortality? Until we have a test that tells us reliably if someone has the kind of prostate cancer that might cause death in the next few years, and we have an intervention that prevents this, we should continue to discourage all testing; or else castrate all men at the age of 60.

This reminds me of an anecdote I have just read in Michael O’Donnell’s lovely new book, The Barefaced Doctor. He describes a Dublin surgeon of the 1950s whose idea of patient communication was to walk down the ward calling out the name of the procedure each person should expect: “In those days elderly men with prostatic cancer were offered treatment by physical rather than hormonal castration and one morning the surgeon went on his rounds, declaiming his intentions in his usual way.
‘Laparotomy… castration…appendicectomy…’
‘Hang on a second, sir,’ said patient number two with unforgivable impertinence. ‘This castration business? What exactly would that involve?’
The surgeon, perplexed by the interruption, barked a reply:
‘A simple matter, my man. We’ll just remove your testicles. At your age, they’re no use to you.’
‘Oh, I know that, sir,’ said the man. ‘But they are kind of… dressy.’”

Order your copy now: there is nothing else like it in this dull age.

A very useful follow-up study of 2,411 Danish women following breast cancer treatment in 2005-6 finds that a large number experience pain and that this is least in the group who have mastectomy and lymph node biopsy only (22%), and highest in those who have breast conserving surgery combined with biopsy and chemo and radiotherapy (53%). This would imply that modern treatment modalities are actually increasing the prevalence of long-term pain. The prevalence of pain in the cohort fell between 2008 and 2012, but interestingly the traffic was not all one-way: 36% of those with pain in the earlier survey now had none, but 15% of those who had none earlier now had some.

The high standard of BMJ Clinical Reviews continues with an exceptionally useful account of acne and its treatment. Read and learn: if you prescribe oral antibiotics, always co-prescribe a topical retinoid or benzoyl peroxide. Remember the adverse effects of many treatments and warn your patients: and also tell them to be patient, as nothing works immediately.

Ann Intern Med  7 May 2013  Vol 158
676   Courtesy of the Annals, you can read the whole of a big systematic review of management strategies for asymptomatic carotid stenosis. Golly, what a mess. “Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best available medical therapy… Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy.” Correct me if I’m wrong, but doesn’t that prove that all the 47 studies analysed here were actually unethical, because they tell us nothing about how to manage asymptomatic carotid stenosis and did not give patients an adequate control intervention?

Plant of the Week: Corydalis flexuosa “Père David”

Last week I told you a bit about the work of the French missionary botanist Père Delavay, and this week it is the turn of the arguably even greater Père Armand David, who was ordained in 1862 and shortly afterwards sent to Beijing by the Congregation of the Mission. He set up a Museum of Natural History there, concentrating on zoology rather than botany, and his name is perhaps best remembered for Père David’s Deer, a beautiful ruminant which had nearly died out when he first discovered it in the gardens of the Emperor. He also told the West for the first time about the Giant Panda and 63 other new animal species, and 65 new species of birds: in botany, he introduced 52 new species of rhododendron alone, plus the wonderful dove tree that bears his name, and a host of smaller plants.

The corydalis is a lovely tuft of finely cut brown-purple foliage with an abundance of long tubular flowers of the purest sky blue. Its main flowering season is about now, but it often carries a few a bit later. It has the habit of dying back in the summer, which can be a bit unnerving. It also has the habit of dying for good if allowed to dry out, or if exposed to too much sun. So plant it in a damp shady place and think of Père David, a lanky man with mandarin moustaches, telling his rosary among the beasts and flowers of his new Eden.