NEJM 21-28 August 2014 Vol 371
711 I have a new little grandson called Timothy. He is lucky being born in August because respiratory syncytial virus generally lies low at this time of the year. Most babies get RSV at some stage of their first year, and the earlier they get it the worse it tends to be, with recurring bronchiolitis every time they get any kind of upper respiratory virus. So I’m hoping Tim won’t get RSV this side of Christmas, and that when he does he will shake it off as a mere cold. There is no effective treatment, although the NEJM seems to believe there may be one in the offing, as they have chosen to give space to a British phase 1 study of GS-5806, a novel oral small molecule that inhibits RSV entry at low nanomolar concentrations by blocking viral-envelope fusion with the host-cell membrane. That sounds like a pretty cunning trick, and in a challenge study in 54 healthy adults, it reduced the viral load and the severity of clinical disease. It also tended to reduce their neutrophil counts and raise their alanine aminotransferase. So not much use for my tiny Tim until it has undergone phase 2 and 3 trials in lots of adults and babies in the community.
744 If you are looking for a good clear summary of aortic valve stenosis, and have access to full text of the NEJM, this is the one to go for. I well remember a patient with aortic valve disease who refused surgery because his symptoms were mild although his pressure gradient was critical. He finally agreed but went into crashing heart failure while waiting for surgery. He didn’t make it. AS gets quite common as we age. Most of it is harmless, but the only way to know is to get an echo.
799 Dear Norway used to export terror to the civilised world for a period of several hundred years. Now they export oil, invest the earnings wisely to the tune of £1m per citizen, and do great whole population epidemiology. By linking the Cancer Registry and the Cause of Death Registry of Norway, investigators estimated colorectal cancer mortality among patients who had undergone removal of colorectal adenomas during the period from 1993 through to 2007. If the adenomas removed were low risk, the bowel cancer risk for the person was lower than the general population, whereas the converse applied to those who had high risk adenomas removed. Kind of what you might expect.
818 More epidemiology, this time a survey of Cardiovascular Risk and Events in 17 Low, Middle, and High Income Countries, good for poring over on a wet afternoon. You need to pore a bit to try and understand the paradox that emerges from this enormous data analysis: “Although the risk factor burden was lowest in low income countries, the rates of major cardiovascular disease and death were substantially higher in low income countries than in high income countries.” The authors put this down to better treatments for risk factors in high income countries, but I am not convinced. In a sense, this is a validation study of the INTERHEART Risk Score, which proves that it is not predictive of real outcomes in whole populations.
836 Next a clinical review of Barrett’s oesophagus. I was going to use just one word, “Run!” But foolishly, I stayed to dabble. Imagine dying from cancer of the oesophagus, which has become seven times commoner in the last few decades. About 6% of the population have the changes of “Barrett’s oesophagus.” Half of it is symptomless, and the other half is associated with heartburn and the usual stuff we all get now and again. It isn’t entirely clear how much additional cancer risk you get from having Barrett’s, but you can be assured of lifelong anxiety and higher insurance payments. So should we screen everybody to reduce the soaring incidence of oesophageal cancer? Oh dear, we’re back in the nightmare world of overdiagnosis and ignorance once again. Run!
JAMA 20-27 August 2014 Vol 312
712 Here is a nice collector’s item of a trial: “The emergency department physicians were not told the primary hypothesis of the study. They were informed that participants had a 50% probability of having their displayed saturations altered by a physiologically small amount and that the true triage saturation was 88% or higher. They were not informed of the magnitude or the direction of oximeter manipulation and were encouraged to continue their usual practice regarding management and disposition. Prior to study commencement, three of the six study oximeters were altered by the manufacturer.” And here is the primary hypothesis: “to determine if increasing the displayed oximetry three percentage points above the true values in infants with acute bronchiolitis in a pediatric emergency department would decrease the probability of hospitalization within 72 hours compared with those for whom the true oxygen saturation value is displayed.” Well, the results did bear out the hypothesis: more kids with falsely raised oximetry readings were spared hospital admission, and the authors conclude that admitting doctors place too much reliance on oximetry as opposed to clinical judgement in kids with bronchiolitis who are not critically hypoxic.
I’m inclined to believe them, and in fact I assessed kids with bronchiolitis for 35 years without any oximetry and with no ill effects, but I’m left with a slightly queasy feeling about the methods of this trial.
789 Twenty years ago, when I was new to the wonderful world of heart failure trials, I can remember arguing with a keen young researcher about hospitalization as an end point. Surely, I said, rates of hospitalization vary hugely between systems and within systems, and are to a major extent driven by the adequacy of support systems within primary care. I’ve been making this point ever since and thought nobody was listening. Those three mighty cardiologists, Javed Butler, Eugene Braunwald, and Mihai Gheorghiade certainly weren’t listening, because I’ve never been near them, but in this piece they make exactly the same point. Make “worsening chronic heart failure” a primary end point for HF trials, not hospitalization.
799 Who is the best person to monitor blood pressure? It’s a no-brainer really. TASMIN-SR was a primary care, unblinded, randomized clinical trial involving 552 patients who were aged at least 35 years with a history of stroke, coronary heart disease, diabetes, or chronic kidney disease, and with baseline blood pressure of at least 130/80 mm Hg being treated at 59 UK primary care practices. And it showed that self-monitoring with self-titration of antihypertensive medication, compared with usual care, resulted in lower systolic blood pressure at 12 months. A great study, but just a start. Now we need to see how people might choose their own treatments based on absolute risk reduction.
JAMA Intern Med August 2014
OL COURAGE, mes amis. People with chronic stable coronary disease do just as well on maximal medical treatment as after revascularization procedures. Putting stents in the pipes does not prevent more infarcts than taking pills. This is what the COURAGE trial taught us in 2007. But seven years later, one third of PCIs in America are still being done for stable CAD. This is the first of three papers exploring the problem. In 40 observed consultations, “Few cardiologists discussed the evidence based benefits of angiogram and PCI for stable CAD, and some implicitly or explicitly overstated the benefits.”
OL So that’s what cardiologists do when qualitative researchers are watching. What do the patients themselves think? The next study examines the effect of “explicit and explanatory information on participants’ beliefs about PCI and their willingness to choose it.” This was a big trial, but the 1257 participants who completed the questionnaire did not have CAD. They were simply asked to think about three scenarios in which they experienced class I angina and were referred to a cardiologist. “In the setting of mild, stable angina, most people assume PCI prevents MI and are likely to choose it. Explicit information can partially overcome that bias and influence decision making.” So the question left hanging in the air is how we can best bring this explicit information to people who are about to make a real life decision, in such a way as to change the practice of cardiologists who often have a financial interest in unnecessary angiography and PCI.
OL Because there’s no doubt that when cardiologists do an angiogram and see a stenosis, they itch to put in a stent. This is called the “oculostenotic reflex,” and its existence is proved by an observational study of 544 US hospitals. “In a national sample of hospitals, performance of coronary angiography in asymptomatic patients was associated with higher rates of inappropriate PCI and lower rates of appropriate PCI.” COURAGE, mes chers amis cardiologiques. Have the boldness to ignore the narrowing and remember the evidence. Even better, have the boldness not to do an angiogram in the first place.
Lancet 23-30 August 2014
691 There are certain things that we rarely notice, such as the fact that we are alive and that our lungs are full of air. But air is full of microbes, which means that we also fail to notice that our lungs are full of germs. Healthy lungs have a seething microbiome, which does us no harm. “The composition of the lung microbiome is determined by microbial immigration, elimination, and relative growth rates of its members. All these factors change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack the features of bacterial infections, including increased bacterial burden and decreased diversity of microbial communities. We propose that exacerbations are occasions of respiratory tract dysbiosis—a disorder of the respiratory tract microbial ecosystem with negative effects on host biology.” Fascinating. And it’s interesting that 40 years ago, when all this was lumped together as “chronic bronchitis,” patients used to be given months of antibiotics to cover the period of highest risk. And now they are again.
703 If this fascinates you, the next review paper discusses the special case of cystic fibrosis, where understanding of the lung microbiota is key to increasing survival. Antibiotics have already made a huge difference to life expectancy, but inevitably they lead to the development of a “resistome” of bacteria within the lungs. And there are lots of other factors at play too, which you can read about if you can access this article and have the time.
747 Several studies over recent years have shown that pulse oximetry in the neonatal period can help to detect congenital heart disease. This one comes from Shanghai and its message to the authorities is clear: “Pulse oximetry plus clinical assessment is feasible and reliable for the detection of major congenital heart disease in newborn babies in China. This simple and accurate combined method should be used in maternity hospitals to screen for congenital heart disease.” Cut to picture of enormous postnatal ward with a hundred cots containing tiny babies with little clips on their fingers.
755 The human herd is getting fatter. And its members have to die of something, which is often cancer. “Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight.” A strange jumble of the rare and the common: “the heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups.” A massive study, worthy of yet another wet afternoon, although this rather plump old granddad would be better burning off some fat in the garden.
The BMJ 23 August 2014 Vol 349
Hurry, hurry: you don’t want to miss “Percutaneous fixation with Kirschner wires versus volar locking plate fixation in adults with dorsally displaced fracture of distal radius: randomised controlled trial.” But actually, you really don’t. Just ten years ago, I would have been amazed to see orthopaedic surgeons doing a trial like this. It shows them putting their latest fashion to the test, and finding it wanting. I have no idea what volar locking plate fixation may be, but it proves to be no better than the cheaper, quicker wire fixation method for this common fracture. At this rate, orthopods will prove better exemplars of evidence based medicine than cardiologists.
One way to combat fatness in the herd is to get the animals to run around. In the centuries of cattle droving, Welsh oxen and sheep must have been pretty lean by the time they reached the butchers of London. Human commuting is similar, as we learn from a population based, cross sectional study in the United Kingdom, brought to us by a professor of population health and a professor of “lifecourse studies” and their research fellow. In our lifecourse, the incorporation of greater levels of physical activity into the daily commute independently predicts lower bodyweight and healthier body composition for both men and women.
One reason you should never prescribe clarithromycin to people at high cardiovascular risk is because such people should all be taking statins, which can cause fatal rhabdomyolysis with clarithromycin. But that applies to all macrolides. Another reason is that clarithromycin itself seems to increase cardiac death even in seven day courses, compared with the closely similar roxithromycin. This emerges from a huge Danish database study, and makes you wonder if clarithromycin should now be withdrawn, given the number of safer alternatives.
Fungus of the Week: Lycoperdon perlatum
The common little puffball is beginning to appear in woods and hedgerows, usually in groups. It has an aromatic scent and is nice to eat when absolutely young and fresh and white throughout. Just slice it in half, to check that it is shining white inside and contains no gills, since very immature amanitas within their volva can sometimes look like puffballs, and fry in butter or oil. Some recommend first dipping the puffballs in batter or egg yolk.
I went off this fungus years ago when I made the mistake of putting it in a chicken pie. This brings out a rather nauseous quality in its flavour, which is hardly present otherwise.
When the puffballs mature they become brown cases for a mass of dark brown spores, known as devil’s snuff boxes. A drop of rain will burst the case and release a slowly rising plume of spores. I look forward to demonstrating this to my little grandson, but only at a safe distance. I don’t want him to get lycoperdonosis, a rare lung disease first described in the New England Journal of Medicine in 1967.
In fact, you have to go to some lengths to acquire this condition, which can do serious damage to your lungs and liver. You have to puff billions of spores up your nose, in the hope of stopping a nosebleed, or just for the fun of breathing them out of your mouth. Fortunately these are rare forms of human behaviour.
(Safety advice: if you must use a puffball to arrest epistaxis, just press a fresh one on the affected side of your nose. Or if it is puffball related fun you are seeking, tread on a devil’s snuff box and see the spores explode out, often with a small bang.)