JAMA 10 Oct 2012 Vol 308
1433 A Viewpoint piece by three Dutch radiologists explores the possible added benefits that could arise if developed countries introduced lung cancer screening using computed tomography (CT) in high risk groups. You will remember that the National Lung Screening Trial (NLST) demonstrated a reduction in lung cancer–specific mortality of more than 20% and overall mortality of 7%. Even hardened sceptics like me can accept the possible benefit of this form of screening. The worry is that you will find stuff you were not looking for, a subject dealt with beautifully in Overdiagnosed by Welch, Schwartz and Woloshin. You go along for your CT and you’re told that the good news is that you don’t have lung cancer. But, sorry, the less good news is that there seems to be a bit of calcium in your coronary arteries, there’s a bit of emphysema in both your lungs, your thoracic aorta is at the upper limit for width and your thoracic spine looks a bit osteopenic. All because you are (or have been) a heavy smoker. So what you now need is a proper coronary calcium score, a further look at your lungs, regular ultrasound of your aorta, and some further bone scanning. You can see how this might have added benefits for radiologists. But for health systems wanting to make the population healthier and save costs there is just one way forward: ban the sale of tobacco and provide free nicotine substitutes for any who need them.
Nice fresh blood. That’s what I’ll be lisping hungrily in a Bela Lugosi accent when I attend a Halloween party in Connecticut, dressed up with plastic fangs, reddened eyes, and an Oxford MA gown. My heavy coffin flies to America next week, so the reviews may come in a little late. Very low birth weight infants, however, don’t mind if the red blood cells they receive have been in the fridge for a week. This Canadian study shows that transfusions of week-old packed blood have the same benefit as the fresh stuff. But we Transylvanians have more particular tastes, my dear.
1460 The first appeal for hospitals to disclose their outcome figures was made, believe it or not, in 1732, by Dr Francis Clifton of London. His canny eighteenth century colleagues shook their wigs, took a good pinch of snuff, and retorted that (a) individuals and institutions would try to cook their figures, and (b) this would act as a disincentive to accept the sickest patients or do risky procedures, even if they were potentially life-saving. Little has changed in nearly 300 years. This study examines percutaneous intervention rates and outcomes in US hospitals. “Among Medicare beneficiaries with acute MI, the use of PCI was lower for patients treated in 3 states with public reporting of PCI outcomes compared with patients treated in 7 regional control states without public reporting. However, there was no difference in overall acute MI mortality between states with and without public reporting.” This actually raises some pretty deep issues. But since most of my readers are not interested in cardiovascular outcomes research with special reference to the USA, I will move on. Those who are need to pore over this paper and also read the editorial.
1469 Another week, another prognostic marker for everything and nothing. “Exclusively in women, proneurotensin was related to incident diabetes (74 events; HR, 1.41; 95% CI, 1.12-1.77; P = .003), cardiovascular disease (224 events; HR, 1.33; 95% CI, 1.17-1.51; P < .001), breast cancer (123 events; HR, 1.44; 95% CI, 1.21-1.71; P < .001), total mortality (285 events; HR, 1.13; 95% CI, 1.01-1.27; P = .03), and cardiovascular mortality (75 events; HR, 1.50; 95% CI, 1.20-1.87; P < .001).” Measure enough weird chemicals in your cohort study, crunch the numbers, and hey presto! You have a paper in JAMA.
NEJM 11 Oct 2012 Vol 367
1387 Dormice fried in honey, lampreys fattened on the blood of slaves, songbirds dressed with their own droppings, testicles seethed with rotted fish blood: the diet of a fading empire should at least display an interesting decadence. Alas, the dying days of imperial America may only be remembered for fizzy drinks sweetened with corn syrup. This NEJM contains five large helpings, which seems about the daily average for an American youth. I find this first draught a bit dilute, gassy, and of indeterminate flavour. People with an aggregate of genetic factors which predispose to adiposity seem to more susceptible to weight gain from sugary drinks. But the cohort here comprised middle-aged female health professionals, who are hardly a typical group of inveterate soda-gluggers. And there is a circularity in the argument too, and confounding. Let’s move straight on to the next inviting cardboard chalice.
1397 This trial involved 641 children of predominantly normal weight, which gives you a clue that it was not conducted in the USA. Moreover, these kids (aged from nearly 5 to nearly 12) were provided with a mere 250ml of canned non-carbonated drink per day, laced either with sugar or a non-calorific sweetener. The Dutch investigators measured weight and adiposity after 18 months and found that there was a significant difference in favour of the non-sugar group. American kids drink an average of three times as much “soda” as this, so this seems like a useful finding.
1407 But now for an intervention to reduce calorific drink intake in overweight and obese American adolescents. Their main strategy was to provide free non-calorific drinks, and they worked hard: retention (of fat teenagers, remember) at two years was a heroic 93%. But alas, although at one year there was a small difference between these kids and the control group, this had disappeared by two years. It doesn’t surprise me. In the USA, everything has corn syrup in it: all bought cooked meats, bacon, bread, crackers; they put it into vegetables and fish if you dine out. And the portions sizes would make any Roman emperor gulp.
Let’s move on to mesothelioma: hardly a comforting subject, but at least here is news of an important diagnostic advance. Fibulin-3, either in blood or in pleural aspirate, can reliably identify mesothelioma and distinguish it from other forms of asbestos-related disease, or other causes of pleural effusion. This is a test which needs to become widely available.
Lancet 13 Oct 2012 Vol 380
1317 Another Lancet issue with thin pickings for the jobbing clinician. Had you ever heard of vorapaxar? Maybe. Or of the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial? Probably, if you are a cardiologist; otherwise, probably not. It was a vast 1,000-centre trial run by Merck to see it their new platelet inhibitor could win a place in the market of secondary prevention in patients with atherothrombosis. To this end, they chose a composite end-point of cardiovascular death, myocardial infarction, or stroke, and recruited nearly 27,000 subjects. They also pre-specified at least 7 subgroups, the largest being those with a myocardial infarction in the previous year—17,779 of the participants. In this group, vorapaxar does prove to have a protective benefit that outweighs the additional risk of bleeding. But the overall trial was stopped for harm, and cash-strapped health systems are unlikely to find the effect size sufficient to rush in and pay for the stuff to be given to every post-MI patient, especially when the field is already so crowded and hard to make sense of. For a valiant mapping attempt, see the editorial.
BMJ 13 Oct 2012 Vol 345
Adolescence is a time of guaranteed misery: a body in disarray, constant exams in subjects of no interest, disgusting skin complaints, unrequitable longings, dependence on stupid adults, loneliness, frustration, beggary and clothes that never fit. Can you stop teenagers getting depressed by giving them cognitive behavioural therapy in the classroom? Like duh, NO. Can you tell which ones will stay depressed? Maybe, but this study doesn’t do that.
Rheumatoid factor is an autoantibody targeting the Fc region of IgG antibodies. There: let that be your learning point from this Danish population study. “Individuals in the general population with elevated rheumatoid factor have up to 26-fold greater long term risk of rheumatoid arthritis, and up to 32% 10 year absolute risk of rheumatoid arthritis.” And actually it’s poorly specific for rheumatoid arthritis: it predicts all auto-immune conditions. So don’t go measuring it unless you know what you are looking for. And if you think your patient has RA, look at the anti-citrullinated protein antibody titre.
Arch Int Med 8 Oct 2012 Vol 172
For more than a decade now, we’ve been putting adults with asthma on long-acting inhaled ß-adrenergic drugs, recently adding inhaled corticosteroid drugs when studies began to show an increased mortality when people take LABAs alone. We can’t help wishing these drugs had never been invented, or at least not licensed before there were proper long-term safety data. So what happens if you try to wean people off them? Alas, this study shows that their symptoms often get worse.
Conversely, we often used to begin treating our hypertensive patients with ß-adrenergic blocking drugs, until long-term studies showed that atenolol actually didn’t seem to do any good and might even cause an increase in cardiovascular events. But can we say the same of metoprolol? Probably, and the way we can do it is by a simple retrospective database study—like this one, which shows no difference in a head on comparison of atenolol or metoprolol for uncomplicated hypertension. Even better, you could examine the issue prospectively by a very simple instant randomised allocation trial in UK primary care: except that nobody would opt to use beta-blockers for hypertension any more.
Plant of the Week: Cyclamen hederifolium
No plants give more delight at this time of the year than these cyclamens with their beautiful leaves and nodding heads of white or pink or soft purple. As your shrubs grow bare, so these lovely Mediterranean flowers reveal themselves, hidden away in every spare spot of the garden. Or that’s the way it should be, if you have given the matter thought over the years. You have to purchase the woody tubers in the spring or summer, when your mind is on other things, and plant them with the fuzzy bit on top, since that represents both the stems and also the roots, which emerge paradoxically from above.
A properly developed garden, therefore, should abound in these cyclamens, and in the closely related C coum, which flowers a bit later and grows its roots from the sides of a much smaller tuber. If your garden fails in this respect, make a note in your diary for next June and buy up a bucketful of dried cyclamen corms to give late autumn joy in the least expected places. You must obey.