Richard Lehman’s journal review—3 September 2012

Richard LehmanNEJM  30 Aug 2012  Vol 367
787   Most medical research is boring and irrelevant. We take that for granted: most clinicians only read research papers if they urgently need to, and then usually fail to discover what they were looking for. The corollary is that most of the effort of medical academia is futile, and people should be angry about the extent to which their money is being wasted by the research community. I borrow the second half of that sentence from the title of a forthcoming lecture by Iain Chalmers, which I shall sadly have to miss. Patient centred outcomes research is the kind of research which aims to redress the balance, and here is another short piece on what that might mean. But it really needs a whole book to explain it, which does not yet exist. Apologies: I was supposed to have written it by now. Suffice it to say that we need to reverse the power structure of the medical research establishment, so that patients and clinicians together determine the research questions, and judge how well academics have addressed them. We need to hear less about “bench-to-bedside” research and more about addressing the GAP—the Goals And Preferences of people who encounter illness and the health care system.

795   Yet of course a lot of basic science research needs to continue if we are ever to understand the chronic diseases which increasingly provide the main workload of clinicians. Among these, few have less sex appeal than Alzheimer’s disease, and few are more important. Conventional randomized trials run by pharmaceutical companies have resulted in billions of dollars/pounds being spent on drugs which are overwhelmingly ineffective. Our best hope must be to discover the true natural history of the disease and then find an intervention which prevents it, and we might be a step closer thanks to this immensely painstaking study of autosomal dominant Alzheimer’s disease. Mind you, it may not be generalizable to the common sporadic form of AD, and being cross-sectional it can’t really reveal the dynamics of the disease process, though it does give strong indications that brain changes may precede cognitive deficit by as much as two decades.

817   Aspirin is an annoyingly good drug, which may have made Bayer’s fortune over a century ago but makes nobody much money now. Nonetheless, drug companies continue to seek for a marketable antiplatelet drug to replace or complement aspirin, and clopidogrel has been a very nice little earner during the period of its patent. This trial sought to establish whether combining clopidogrel with aspirin would reduce recurrent stroke after recent lacunar stroke. The aspirin dose was set high at 325mg, and adding clopidogrel to this made no difference to stroke recurrence but did cause more intracranial haemorrhage and was associated with higher mortality.

Lancet  1 Sep 2012  Vol 380
807    In my last two weekly reviews, I’ve railed against the use of the expression chronic kidney disease without further explanation of what is actually meant. This paper adds a new twist to the crime: it uses a cut off eGFR of less than 60 in some places, and an eGFR of 45 in others. It refers to 3 grades of proteinuria, and finds that only the top level is predictive; but elsewhere the authors freely use the word “proteinuria,” without specifying its precise meaning or its relationship to eGFR. Most annoyingly of all, the authors talk about CKD in terms of how it compares with type 2 diabetes as a risk for myocardial infarction, usually without adjustment for age. As a result, this analysis of data from the Alberta Kidney Disease Network and the National Health and Nutrition Examination Survey (NHANES) 2003-06 manages to be exceedingly cumbrous while failing to convey any clear clinical message. It will no doubt be used by advocates of universal screening for CKD—ignoring the fact the mean age of the “at-risk” group here was 71, an age at which most people should have been taking statins for 20 years if they wish to reduce their odds of cardiovascular disease—irrespective of their kidney function, or indeed their blood sugar.

815    “Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity.” Hence the arcOGEN genome-wide association study, funded by Arthritis Research UK. Is this a case of the Iain Chalmers principle: should people who give to medical charities be angry about the extent to which their money is being wasted by the research community? Or should they be reassured by the researchers’ assertion that “Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention”? As far as I can judge, if this benefit ever comes at all, it will only come to distant posterity. As with every common degenerative disease, “all risk variants were common in frequency and exerted small effects.”

836   The Lancet seminars this week are about the adult lymphomas. Hodgkin’s lymphoma is now a wonderfully curable disease, and the main refinements described here are more accurate imaging (using 18F-fluorodeoxyglucose PET), finessing of treatment in early disease (meaning fewer toxic effects) and better treatment for disease presenting at an advanced stage.

848    The remaining 90% of lymphomas are classed as non-Hodgkin’s, and here the news is less good. Although treatment of these heterogeneous malignancies is improving, they are also becoming more common. Most of them arise from B-lymphocytes and many have known infective triggers: as a result, immune suppression is a major predisposing factor. You won’t want to read the whole of this article unless you are an oncologist, but it’s clearly written and a good update should you happen to have a patient with one of these conditions—which are by no means rare.

BMJ   1 Sep 2012  Vol 345
Physiotherapy is a generally well-liked form of treatment which managed to become part of orthodox hospital practice separately from the manipulative therapies, which remain beyond the iron curtain of most health systems. Osteopathy, physiotherapy and chiropractic all tend to be highly heterogeneous areas of practice with their own bran-tub evidence bases. The brave authors of this systematic review of physiotherapy for Parkinson’s disease have a good stab at finding the better studies in the tub and trying to make sense of them. Outcomes are mostly judged by improvements in function and balance, which is logical; rigour is judged in terms of blinding and equal allocation, which is also conventional good practice. But I think all these forms of hands-on treatment are primarily forms of social grooming, an insight I owe to Michael Power. Tactile encouragement needs to be personal, and its main outcome is feeling better. I’m not sure this is amenable to meta-analysis, but every cat would understand.

Progestin-only contraception is safe and generally effective, and this study shows that oral preparations and progestin-eluting IUCDs carry no added risk of venous thromboembolism. A question mark, however, hangs over depot injections, which may double the relative risk of VTE. It would be a shame if that were to reduce the use of this method in the population who most prefer this method, who are generally at far higher risk of VTE due to unwanted pregnancy.

Belgium is a civilised sort of place: after a breakfast of excellent coffee and fresh pain au chocolat, you can read a newspaper, check your e-mails, and go for a walk before lunch. After two glasses of monastic beer and several courses of French food served in German quantities, the rest of the day becomes a bit of a blur. Some people caricature this as boring, but it has its attractions. And then there is dinner… However, up to 2006 the Belgian infant would sometimes find its gastronomic education rudely interrupted by violent diarrhoea and vomiting; so the Belgian authorities were swift to adopt rotavirus vaccination in that year, well before the rest of Europe. This excellent study shows that it has an effectiveness of over 90% in preventing hospital admission for rotavirus gastroenteritis in young children.

Coming in a week with a dearth of journals, this issue of the BMJ makes up by having three good research articles and two good clinical reviews, as well as some interesting editorials and various pieces by public health physicians in the grip of an identity crisis. If they all saw patients a couple of days a week, it would do them no end of good. The public health physicians, I mean. The first clinical review deals with the management of renal colic, more properly known as ureteric colic. As a regular stone-former, a wave of dread comes over me when I feel the first twinges of flank pain: fortunately parenteral diclofenac usually curtails the subsequent hours of agony in my case, though not in everyone’s. Next time, in accordance with this article, I might try an alpha-blocker as well, since there is good evidence they speed the passage of the sadistic little beasts as they track down the ureter.

There’s a very good review of primary Sjögren syndrome too, under the guise of a “Practice Pointer.” However, as a Briton I must protest that there should be a genitive S, as it is always known as Sjögren’s syndrome by those who speak the Queen’s English; and as a Pole, I must protest that it should be known as Mikulicz-Radecki’s syndrome, since he first described it. But actually all this is beside the point since Mikulicz-Radecki himself didn’t care a fig about precedence or nationality, and when asked about the latter always gave the answer “surgeon.” Here is a really useful piece for doctors and patients all over the world. I do so wish the illustrations and the box could go straight into Wikipedia to be shared by all. When this finally happens to all good structured medical information, it will be one of the great advances of the twenty-first century, providing a free and accurate resource for shared decision making by patients and health professionals in every part of the world.

Plant of the Week: Anemone hupehensis

The lovely white and pink anemones which make us welcome the end of summer mostly come from Japan. This deeper, tighter-flowered species comes from the Chinese province of Hubei, and only reached Britain about 100 years ago: it is still relatively uncommon. It may in fact be the parent plant of all the “Japanese” anemones.

I do wish we had at least one in our garden, but we haven’t had much opportunity to go out buying plants this season. Also, it’s easy to be put off by the idea of a large boss of yellow stamens in the middle of a deep pink flower, though once this plant has grown to full size ( which is over a metre high and across) its abundant flowers are irresistible, with an exuberance that creates a beauty of its own. A hupehensis comes in a variety of cultivars, such as “Hadspen Abundance” or the German form called “Superbum” – which is to be pronounced as a Latin adjective, and not as a tribute to the Teutonic posterior.