In his school days, Richard says, he would often walk down Beech Hill Road in Sheffield thinking of chemical explosives, or girls, or Beethoven, but never of age, neuropathology, and dementia. It’s all of those, and much else besides, this week….
JAMA  27 May 2009  Vol 301
Usual care is what you and I provide, and usual care is a bummer. It’s the nickel standard against which the true gold of every new complex health intervention is measured, in this case optimised antidepressant therapy and pain self-management in primary care patients who have chronic pain and depression. With this study, Science has established that putting these patients on a proper dose of antidepressant and giving them 6 sessions of pain self-management advice and taking a proper interest in them for 6 months thereafter provides better outcomes than usual care. Out here, in the world of the usual, our local pain service (35 km away) has just had its sessions cut and its beds taken away. Patients with depression associated with physical pain don’t have enough “caseness” to interest the community mental health team. Cognitive therapy is unavailable. Yes, usual care is a bummer.

Proton pump inhibitors are the nation’s favourite drugs, a cure for every discomfort around the epigastrium or oesophagus. Coleridge – or Hazlitt or Lamb or de Quincey or Leigh Hunt – one of those guys anyway – once speculated that most wars might simply be the result of a bad digestion. PPIs for World Peace! is my slogan. Flood North Korea with omeprazole. Don’t let the Dear Leader struggle on with Gaviscon and Rennies. But wait – here is a paper confirming the dastardly suspicion that PPIs might be associated with an increased risk of hospital-acquired pneumonia. Never mind: nuclear war is more important.

NEJM   28 May 2009  Vol 360
Although we don’t understand the natural history of oesophageal cancer exactly, at least some of it arises in areas of intestinal metaplasia at the lower end of the gullet, called Barrett’s oesophagus. In fact the accompanying editorial claims that all oesophageal adenocarcinoma (5-year survival, 15%) arises from Barrett’s, as metaplasia becomes dysplasia and dysplasia becomes cancer. We also know that these cancers are increasing at an alarming rate – fivefold in the last three decades. So a trial showing that radiofrequency ablation cures Barrett’s in 80% of patients at one year must be good news. It’s also good news that this trial used sham ablation as the control. Bad news, however, that it was relatively underpowered to prove a reduction in cancer, and that radio ablation can cause strictures in 6% of patients. And screening for Barrett’s is definitely not on the agenda – it’s too common and too little of it progresses to cancer.

In my school days, I would often walk down Beech Hill Road in Sheffield thinking of chemical explosives, or girls, or Beethoven, but never of age, neuropathology and dementia. Alas, how things change. Here the pathologists of Beech Hill Rd report on what they found when they sliced through 456 brains from donors aged from 69 to 103 who had taken part in an MRC study of cognitive function. The classic tangles and plaques of Alzheimer’s more frequently accompany dementia in the younger elderly than in the very aged, as you’d expect.

As we gaze in wonder at the fossil of our 47-million-year-old ancestor Ida the early primate, this is a good time to weigh up the pros and cons of human evolution. Big brain: probably good. Upright posture: not so sure. So many of the intractable ills we deal with every day are down to that: postnasal sinuses that drain upwards, a back that’s always giving trouble, hips and knees that degenerate, and varicose leg veins. Our big brains aren’t much help when it comes to dealing with veins with useless valves. But it seems from this very good review that we have been missing something important – iliac vein obstruction. About 60% of non-symptomatic adults have non-thrombotic iliac vein obstruction at the point where it is crossed by the iliac or hypogastric artery. In symptomatic people, the percentage exceeds 90, and the answer may be – you guessed it – the placement of venous stents. Apparently these stay patent for many years and provide symptom relief in the great majority of patients with advanced venous disease.

Over the years I’ve been compiling a list of topics for the Easily Missed series, Addison’s disease has stayed near the top, not surprisingly. We simply don’t know how many people go into septic shock and die of it without the diagnosis ever being made: what is clear from this review is that adrenal insufficiency is difficult to study, particularly in critically ill people. It’s good to see such a first-class single author review appear from Dresden, a city which suffered a brain drain in the days of the GDR because you couldn’t get West German TV reception there, and has fared even worse since due to economic migration and prejudice against “Ossies”. Anyway, read this review; and visit Dresden for its lovely situation on a bend of the Elbe, its marvellously reconstructed buildings, the Zwinger gallery full of great paintings, and the Semper opera full of musical singers who don’t wobble hideously in the modern fashion.

Lancet  30 May 2009  Vol 373
Twenty years ago in Oxford, aspirin was considered a divine substance and I recollect being rebuked sharply by Colin Baigent for suggesting that it might not matter if GPs did not give it immediately to patients with suspected myocardial infarction provided they got it on arrival in hospital. Absence of evidence was no excuse for sloppy practice. In this vast meta-analysis, Colin (now Prof Baigent) finds much absence of evidence, not about this particular issue, but about the net benefit of aspirin for the primary prevention of vascular disease. We all so much want it to be a cheap safe panacea, but it isn’t a panacea and it’s not particularly safe; it may even increase total stroke mortality when used for primary prevention. Cheap it certainly is, but then so are statins nowadays, and they do more good and less harm.

Cystic fibrosis gets a Lancet seminar this week. We all know it’s autosomally recessive, but it is genetically complex, and malfunction of the transmembrane conductance regulator has complex consequences. The basic end result is to produce sticky airways secretions that hold on to germs (especially Pseudomonas aeruginosa) rather than get rid of them, and that block airways rather than clear them. The pancreas gets gummed up too, but that is easier to treat. Until gene therapy becomes a reality, most treatment is aimed at postponing death from pulmonary infection and damage, using antibiotics and nebulised hypertonic saline: this has improved life expectancy from 30 to 37 in the past decade, and today children with CF are expected to live to 50.

BMJ   30 May 2009  Vol 338
Unannounced on its front cover, the BMJ has scooped up a really important study of door-to-balloon time in relation to mortality in ST elevation myocardial infarction. Looking at what happened to 43 801 American patients in hospital, the Yale team comes up with a mortality curve with the tightest of confidence intervals, clearly showing that every minute counts. The authors worked under the supervision of Harlan Krumholz, so everything in this paper is in the right order, clearly stated, closely discussed, and ending with a simple clinical message: there is a benefit from reducing door-to-needle time for all patients undergoing PCI, including those currently treated within 90 minutes of hospital admission.

On a good night, without wine and with an essay by Richard Feynman and a piece of paper to hand, I can persuade myself that I understand the rudiments of quantum physics. On the other hand, the more I read about string theory or prion-related diseases, the more confused I become. I know people have won Nobel prizes for these things, but you can’t help wondering, just a little bit, why they are taking so long to become intelligible to the majority of fairly intelligent people. Here is a study of “disease-related prion protein” in 63,000 British tonsils, using two tests. If one was positive, the other wasn’t, so the end result was: no confirmed CJD prions. Whatever they are. Or do. I am reminded of Hilaire Belloc’s words:
But Scientists, who ought to know,
Assure us that it must be so …
Oh! let us never, never doubt
What nobody is sure about.
From The Microbe, in More Beasts for Bad Children, 1912

Another unannounced scoop for the BMJ is the result of at least ten years’ hard thought by Doug Altman on the subject of prognosis and prognostic research. This may not be your particular cup of tea, but with Doug around, you can be very sure that it is well brewed and contains only the best ingredients. No milk or sugar, thank you. Three more cups to come.

Arch Intern Med  25 May 2009  Vol 169
“From 2001 through 2004, 35.4% of US adults aged 40 years and older (69 million Americans) had vestibular dysfunction.” A truly dizzying statistic. “These data suggest the importance of diagnosing, treating, and potentially screening for vestibular deficits to reduce the burden of injuries and deaths in the United States.” Hmm. They suggest to me that a lot of people get a bit of the wobbles now and then. And just what is this treatment of which they speak? If the US wants to reduce its burden of injuries and deaths, I’d suggest gun control and universal medical coverage.

I rather like some American usages, like “2001 through 2004” which is more precise than our “from 2001 to 2004”. But what about this? “Rapidity and modality of imaging for LBP is associated with patient and physician characteristics but the directionality of associations with desirable care processes is opposite of associations for measures targeting underuse.” No wonder so many Americans get vertigo. This study of imaging for low back pain in a health system which encourages overinvestigation gives rise to a nicely written editorial with the title “Imaging Idolatry”. The word idolatry reminds one of America’s deep roots in the English Bible, which is mostly the work of William Tyndale. Here, just for a treat, is how to write English prose:

“But the serpent was subtler than all the beasts of the field which the Lord God had made, and said unto the woman. Ah sir, that God hath said, ye shall not eat of all manner trees in the garden. And the woman said unto the serpent, of the fruit of the trees in the garden we may eat, but of the fruit of the tree that is in the middes of the garden (said God) see that ye eat not, and see that ye touch it not: lest ye die.
Then said the serpent unto the woman: tush ye shall not die: but God doth know, that whensoever ye shall eat of it, your eyes should be opened and ye should be as God and know both good and evil. And the woman saw that it was a good tree to eat of and lusty unto the eyes and a pleasant tree for to make wise. And took of the fruit of it and ate, and gave unto her husband and also with her, and he ate. And the eyes of both of them were opened, that they understood how they were naked. Then they sewed fig leaves together and made them aprons.”
Genesis the.iii.Chapter. 1530  William Tyndale or Huchyns

Plant of the Week: Geranium renardii

Amongst its other joys, June is the high season for hardy geraniums, those steady fillers of every garden gap. Some of them flower for a long season, but this one bears its flowers for a couple of weeks only, when they are a lovely opal white veined with violet. But this is definitely a plant that every garden needs. It is, as Graham Stuart Thomas wrote,”a first-class foliage plant forming a solid dome of sage-green, prettily lobed, deeply veined, circular leaves.” What more can you ask?