Richard Lehman’s journal review – 31 October 2011

Richard LehmanJAMA  26 Oct 2011  Vol 306
1775    There is now pretty clear evidence that CT scanning to detect lung cancer in heavy smokers can save lives. This Dutch study shows that the same scans can also detect chronic obstructive pulmonary disease in about 38% of the smokers they recruited. In this population the sensitivity of CT was 61% as compared with a “gold standard” of pulmonary function testing. This is not very good: but what does it matter? There is no useful intervention for COPD except giving up smoking, which is what all these people either have done already or need to do anyway.

1794    In the USA as in the UK, hospital readmission has come under intense scrutiny as an avoidable burden on the health system. But is it really? It is just what happens when you combine an ageing population with deeply entrenched patterns of care, and to change these would require root and branch reform of the whole system. Certainly all the evidence I have seen suggests that it is a lousy quality marker for hospitals, and that parachuting in complex interventions may achieve some temporary local success, but that these are rarely generalizable across all conditions and all settings. The problems in the USA are magnified by horrific social inequalities, disorganized primary care, and perverse incentives within an endlessly complex payment system. Be sure that in America the insurance companies and provider organizations will be one step ahead of any clumsy attempts by federal government to rein in spending. And be sure that we have the same thing coming to us in the UK if we allow the NHS to disintegrate further into a chaos of competing semi-autonomous purchasers and providers, gaming with government over an endless series of penalties and incentives.

NEJM  27 Oct 2011  Vol 365
1567   Here’s the second study this week to use cancer-screening chest CT to study COPD. But the Canadian-US investigators go a good deal further – in fact all the way down the small airways – to study the pathogenesis of emphysema at each stage of COPD progression. In a few cases they even have lung tissue samples from patients subsequently operated on for cancer. It makes you wonder how smokers manage to breathe at all. Long before the appearance of radiological emphysema, there is almost total destruction of the small airways.

1576   The same human papillomavirus subtypes (mostly 16 and 18) that produce dysplasia and cancer of the cervix are even more strongly associated with similar changes in the anal area of people who have receptive anal sex. This study recruited 602 men who have sex with men to determine whether HPV vaccine can protect against anal HPV infection and anal intraepithelial dysplasia. The study was only just sufficiently powered to detect a protective effect against dysplasia in the intention-to-treat analysis, but in the per-protocol analysis it had a convincing effect, and is likely to be a useful measure against the rising incidence of anal cancer in men and women.

1586   Briakinumab is a monoclonal antibody targeted at the p40 molecule which is overexpressed in psoriasis. Abbott Laboratories ran a year-long trial which proves that this is a very effective treatment for moderate-to-severe psoriasis compared with methotrexate, producing 75% clearance in 80% of patients on weekly briakinumab, compared with 40% taking weekly methotrexate. It could be a great drug, but might also be a dangerous one: there are hints that it might carry a risk of major infection and of cancer, but we won’t know how big the risk is until longer studies have been done.

1597   Life is incredibly unfair to fat people. It seems that evolution has programmed humans to hang on to every scrap of fat they lay down, as insurance against lean times. So if an obese person loses weight, every appetite hormone in the body and brain strives to restore it, and keeps striving for at least a year. This study measured differences from baseline in the mean levels of leptin, peptide YY, cholecystokinin, insulin, ghrelin, gastric inhibitory polypeptide, and pancreatic polypeptide, as well as hunger levels, twelve months after a weight loss programme in adults with diabetes. They were all still significantly different from baseline. And I suspect that the more times people go through the cycle of weight loss and regain, the more the body interprets this in terms of a starvation/plenty cycle, and produces still more of the hormones and hunger signals that drive us lay down fat.

Lancet  29 Oct 2011  Vol 378
1538   Following the example of a friend, I have taken to reading Richard Horton’s weekly Offline column, to find out what he is doing instead of editing The Lancet. It can be quite odd and disturbing at times, but this week he reports an amazing experience: he has become aware of the moral grandeur of British general practice. His first Damascus Road moment came at the Royal College of Physicians, where he fell to the ground blinded by the radiance of Iona Heath’s Harveian Oration. Later in the week he heard Clare Gerada calmly rebutting Andrew Lansley in Liverpool, and his conversion was complete. But I don’t think we should count on him turning from persecutor to missionary for primary care just yet. Just let’s rejoice with him that in the worst crisis to face general practice since the founding of the NHS, our College has the best leadership since it came into being.

1547  Dalcetrapib raises HDL-cholesterol by modulating cholesteryl ester transfer protein (CETP) activity. The last drug to do that, torcetrapib, actually increased cardiovascular harms, and was withdrawn in 2006. And despite more than 200 trials, no non-statin HDL-raising drug has ever been shown to have cardiovascular benefit. Still, Hoffmann-La Roche decided to try and prove that their own CETB-modulating  HDL-lowering drug was less likely to kill people than torcetrapib, so it got a team together to demonstrate this using a specially devised form of arterial wall measurement (dal-PLAQUE). Nobody knows what this novel measurement really predicts, but we are told that because dalcetrapib does not change it in 64 subjects over 12 months, it is likely to be safe. So they are testing a drug which is intended to alter a surrogate marker in millions of people at increased risk of cardiovascular events, and the best evidence they can produce is its lack of effect on another, specially devised, surrogate marker in a tiny sample of subjects. What are we meant to think about a journal that gives space to this stuff?

BMJ  29 Oct 2011  Vol 343
I’ve always felt a bit uneasy about using prothrombotic drugs like tranexamic acid, but it does seem to be useful in some situations of excess bleeding from the uterus or bladder. I’d be particularly uncomfortable about using it in anyone at added risk of thromboembolism, for example due to cancer or major surgery. But a team of Italian investigators went ahead and used low-dose tranexamic acid during radical prostatectomy for cancer, and so reduced bleeding and the need for blood transfusion. Moreover the cheap old drug had no effect on VTE events over the ensuing months.

Now to California, for a large cohort study of women taking antihypertensive drugs during the first trimester of pregnancy. Their overall risk of having a baby with a significant malformation, especially of the cardiovascular system, is increased by about 50%. The study shows that this increase is unlikely to be any different in women taking ACE inhibitors than in women with hypertension in pregnancy generally, whether taking drugs or not.

A little piece called Good news about the ageing brain caught my attention, for some reason. The good news is that oldies can often learn to perform electronic operations, albeit more slowly than the young. I have accordingly signed on to Twittter, as RichardLehman1, though I have no idea what to do next. Somebody please help me while I have a nice mug of cocoa. 

Another advantage of old age is that you can take a synoptic view of human folly while basking in a sense of your own wisdom. The phrase “boring old fart” sums it up perfectly. Nothing in medicine strikes me as more foolish than the amount of money, effort and guile which we allow to be spent on distorting and concealing the evidence base of medicine, while others spend less money but even more effort on trying to assess bias in randomized trials. Here the great notables of the Cochrane Collaboration join to lay out an instrument for getting tough on this form of crime. But what we need is an instrument to get tough on the causes of this crime: and I think we may have just devised one here at Yale. Full disclosure of all human trial data is the only path to a proper science of evidence-based medicine. It is also an ethical imperative.

Fungus of the Week: Lactarius volemus

This is a handsome woodland fungus of stately bearing with a felty cap of a colour between brick and burgundy red. As soon as you pick it, it will start to ooze milky sap from its pale yellow gills. If you put a drop on your tongue, nothing happens: it will not fill your mouth with a burning acrid taste like many other Lactarius species. Later on, the gills will develop a fishy smell. In Roger Phillips’ Mushrooms and Other Fungi of North America he describes it as “Edible – good.” The same description may be found on his website.

His original book of British fungus photographs reached its thirtieth anniversary last week, and the friend who imparted this information also tells me that it has sold a million copies. Like everything he has produced before or since, it is an indispensable guide, giving you everything you need to see and know. Mind you, my own comment on this fungus would read more like “Edible: like cardboard. May be used to absorb bacon fat and should be eaten (if at all) fried with bacon and a scrap of onion.” The same also applies to the ill-named Lactarius deliciosus.

Roger Phillips is a life-enhancing person who has spent his whole life taking photographs of desirable plants and interesting fungi all over the world, and sharing them with us in beautiful, affordable, well-annotated books. I wish him every joy, and I cannot think of any greater than continuing to do the same for as long as possible.