JAMA  2 Mar 2011  Vol 305
913   A friend recently began a piece on outcomes research with Bishop Joseph Butler’s maxim, “Every thing is what it is, and not some other thing.” If a trial like SOLVD is designed to measure the effect of a particular ACE inhibitor on survival in people with symptomatic left systolic heart failure, it is not the same thing as a trial designed to measure the effect of a beta-blocker following myocardial infarction. The only thing these trials have in common is that they lower blood pressure in people with established cardiovascular disease. Meta-analysts should remember Butler’s maxim. It is simply not legitimate to combine such dissimilar studies, plus a few from the diabetes literature, and use them to generalise about something called “secondary prevention of cardiovascular disease by antihypertensive treatment in persons without hypertension.” The terms are far too broad, and the analysis also doesn’t adjust for the use of other secondary preventive medication such as aspirin and statins. The effect sizes derived are small but positive – but that means nothing. Nor can I see anything in this misguided lump of disparate studies that can justify an editorial called “antihypertensive therapy for prehypertension”. In the case of the heart failure studies, the patients were more likely to have prehypotension. This is what happens when lumping goes mad: every thing becomes some other thing.

NEJM  3 Mar 2011  Vol 364
797   One of the first things you ever did as a doctor is give intravenous furosemide for acute heart failure. Now it’s an old chestnut of the EBM and heart failure literature that nobody has done a randomised trial of diuretics in acute HF – not strictly true, but there is certainly little evidence to guide dosing or mode of administration. Since decompensated HF is the commonest cause of hospital admission, top billing in this week’s NEJM goes to a straightforward double-blind randomised trial of four strategies for giving IV furosemide: by bolus injection or by constant infusion, at high dose or low. Symptomatic improvement is best with a high dose, and it doesn’t matter whether you give it by bolus or infusion.

806   Most drug names tell you nothing about what they do, but drugs which block factor Xa all end in xaban – get it? Apixaban is a fixed dose oral anticoagulant which in trials so far has shown approximate equivalence to monitored-dose warfarin. In this trial, however, the competing drug is aspirin, given to people with atrial fibrillation who cannot take a vitamin K antagonist. Not surprisingly, apixaban proves more effective at preventing thromboembolic events, and happily is not significantly worse at causing major haemorrhage.

818   Tight glycaemic control in longstanding type 2 diabetes – sorry, I’m on about it again. I promise not to rub it in. I shall not gloat. In the ACCORD trial, over 10,000 people with type 2 diabetes of mean 10 years’ duration were randomised to standard treatment to achieve HbA1c between 7 and 7.9% versus intensive treatment aimed at reducing HbA1c  to 6.0% or less. The trial was stopped early at 3.7 years due to higher mortality in the intensive treatment group. As in previous trials, once the study terminated the two groups gradually shed most of their differences in treatment modalities and glycaemic levels. But as reported here at five years, the mortality difference persists, in favour of less stringent control. Just as when the NEJM published the initial result of this trial in June 2008, there is no accompanying comment from a diabetologist.

829   Now the problem with diabetes is that we want to do better for our patients, and we have confused that with trying to reduce their sugar levels back to normal. But alas, you cannot wind this complex disorder backwards by addressing a single marker. It is the adverse outcomes in diabetes that we need to address, and these are unfortunately abundant, and most of them do not pay much attention to an arbitrary threshold figure for fasting blood sugar. We all know that this is true of death from cardiovascular disease (hazard ratio 2.3), but this big trawl through the observational literature by the Emerging Risk Factors Collaboration also finds additional risks for several cancers (typical HR 1.25) such as pancreas, lung, and breast. Whatever it is that happens in type 2 diabetes, it is general bad news and much more than just a derangement of glucose metabolism.

861   To get an upper limb deep vein thrombosis, you either have to try quite hard, have cancer, or get a doctor to give you one. This is a good review of a problem that most GPs rarely encounter: but doctors who traumatise arm veins with things like pacing wires or indwelling venous catheters, or those who cause or treat upper limb trauma (orthopaedic surgeons) need to be much more alert for it. It is occasionally seen in pregnant women, those taking oral contraceptives, and especially people with cancer. To induce it, any repeated vigorous arm movement will do: it must have been particularly common in galley slaves, but even painting above your head can bring it on, especially if you have an extra rib or something similar. Michelangelo no doubt got it while painting the Sistine Chapel ceiling: this may explain his depiction of the Cumaean Sybil, where venous engorgement can be noted in the highly abnormal dusky left arm (writes a German professor).

Lancet  5 Mar 2011  Vol 377
813   Ever since PLoS Medicine published a couple of pieces on the way medical journals make money from reprints sold to pharmaceutical companies, I’ve been on the lookout for examples in The Lancet, chief among British journals. Not that I know anything about what happens in specific instances, such as this Amgen-funded study conducted in 342 centres around the world in order to collect fewer than 2,000 men with metastatic prostate cancer. I can only surmise that Amgen, who supported the writing of this paper, were highly content with the Abstract conclusion that “Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer.” In fact the study lasted less than a year and the effects of the two agents only diverged significantly at 20 months: those receiving the monoclonal antibody denosumab had about twice as much hypocalcaemia and jaw osteonecrosis as the zoledronic acid group, in exchange for a mean 3.6 month delay to first skeletal event at 2 years. Survival was identical.

823   The winter of my discontent with The Lancet is made still frostier with the conclusion of the next Abstract: “CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.” Now I am not an Aronsonian purist when it comes to medical abbreviations – we all know what CBT is (I think) and in fact we would mostly have recognised CFS had the writer chosen to abbreviate chronic fatigue syndrome. And of course the abbreviations can all be deciphered with reference to the preceding text. The offence is to crowd these unfamiliar initials together in one sentence that is supposed to sum up the meaning of the study – all the worse since this is a useful trial in a common and intractable condition, called PACE for reasons that would only cause further embarrassment. So for your enlightenment, GET is graded exercise therapy, SMC is specialist medical care, and APT is adaptive pacing therapy. If you want to know what these actually mean, you will have to read the paper.

849    Hypsignathus monstrosus, Epomops franqueti, Myonycteris torquata, and Rousettus aegyptiacus – names to make any lover of Linnaean Latin salivate. But beware, for the saliva of these cave-dwelling fruit-bats may contain Ebola virus, and ye shall surely die. On the other hand, there is a certain reassurance in the fact that if you avoid bat-caves and dead primates in remote parts of Africa and the Philippines, you are at no risk at all of getting haemorrhagic shock from a filovirus. Unless, that is, some nasty biological warfare facility develops a way of spraying people with infected fruit-bat saliva.

BMJ  5 Mar 2011  Vol 342
535   It’s odd how personalities can affect your perception of a medical discipline. For a long time I was unfortunate in the haematologists I encountered, and came to regard their subject as boring and disagreeable: but having more recently worked alongside a haematologist who is both interesting and agreeable, I find a new fascination in the science of blood. Which is just as well, since so much of what we do involves tinkering with coagulation, for example following venous thromboembolism. For a long time we followed a one-size-fits-all approach, but this meta-analysis reminds us that there is a big difference between the risk of recurrence in men and women, and between provoked and unprovoked VTE. Most notably the risk of recurrence following a first episode of unprovoked VTE is 2.2 times a high in men as in women, and consideration needs to be given to lifelong anticoagulation in these blokes.

544   Food allergy in children and young people is an important topic, though still, alas, a largely science-free area. The NICE guidelines are a good gauge of this: but to find the level of evidence for their recommendations you need the full website article. Each section is typically accompanied by a comment similar to: All six points in this section are based on very low quality evidence from diagnostic and observational studies and the experience and opinion of the GDG. Where science is absent, quacks abound: we are told to advise worried parents to avoid Vega tests (which measure “energies”), applied kinesiology and hair analysis; but also serum specific IgG measurements, which have never been shown to help diagnosis.

Ann Intern Med  1 Mar 2011  Vol 154
293   A small British trial is hailed as an Advance in the Management of Nasal Polyposis – though to be fair the editorialist puts a question mark after this. The Advance is to use a couple of weeks of oral steroids to shrink the polyps and allow follow-on treatment with a steroid spray. I’ve been doing that for 20 years and I can vouch that it works: I thought everybody did it. This 60-subject RCT comes from Tayside in Scotland, so I’m afraid that a tribute by William McGonagall is compulsory. Look away now if you do not wish to know the score.
It is a sad truth that should never be forgot
That the climate around the silvery Tay favours a build-up of snot,
And folk who have nasal polyps should not leave them alone
But get hold of some Beconase after a course of prednisolone.

Michelangelo on Health & Safety in the Sistine Chapel

I’ve grown a goitre by dwelling in this den–
As cats from stagnant streams in Lombardy,
Or in what other land they hap to be–
Which drives the belly close beneath the chin:
My beard turns up to heaven; my nape falls in,
Fixed on my spine: my breast-bone visibly
Grows like a harp: a rich embroidery
Bedews my face from brush-drops thick and thin.
My loins into my paunch like levers grind:
My buttock like a crupper bears my weight;
My feet unguided wander to and fro;
In front my skin grows loose and long; behind,
By bending it becomes more taut and strait;
Crosswise I strain me like a Syrian bow:
Whence false and quaint, I know,
Must be the fruit of squinting brain and eye;
For ill can aim the gun that bends awry.
Come then, Giovanni, try
To succour my dead pictures and my fame;
Since foul I fare and painting is my shame.

Michelangelo Buonarotti, sonnet-letter to Giovanni da Pistoia, 1509; translated into rhymed English by J.A. Symonds 1876