NEJM 25 September 2014 Vol 371
1189 This week we start with mepolizumab. Before we know it, we encounter losmapimod. Enough is enough. I think the World Health Organization should convene an extraordinary meeting of the International Nonproprietary Names Committee with the sole purpose of Stopping Silly Names. Medical practitioners are serious people and they should not be expected to trade in nonsense words. When humanized monoclonal antibodies were new and few, it might have made sense to end all their names in zumab, but now there are so many nobody can remember which is which. Mepolizumab is targeted against interleukin 5. The first of two trials in severe asthma with sputum eosinophilia shows that it allows a useful number of people to avoid the regular use of oral corticosteroids or to reduce their dose. In the 24 weeks of the trial, the rate of adverse effects was the same as placebo.
1198 The second of these trials, designed and analysed by GlaxoSmithKline, compared the effect of intravenous mepolizumab or subcutaneous mepolizumab with placebo. Again, they recruited patients with severe asthma and sputum eosinophilia, who comprise fewer than 10% of the asthma total. Both modes of administration cut exacerbations by half, with a better reduction in severity with sc dosing. This looks like a useful drug for the severest end of the asthma spectrum. I suspect that this humanized monoclonal antibody will also bind strongly to dollars.
1218 Oh joy! A single randomised trial that can be converted instantly into a decision aid for patients! You are a Briton with varicose veins deemed worthy of treatment by the National Health Service. Your options are ultrasound-guided foam sclerotherapy, endovenous laser ablation, or conventional surgery, which here consisted of proximal ligation and stripping of the great saphenous vein only and concurrent phlebectomies. In 11 vascular surgery units around the UK, patients were randomised to receive one of these procedures. Outcomes were assessed at baseline and at six weeks and six months after treatment. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. There you have it: thanks to the willingness of these patients to be randomised, and the initiative of these investigators who set up an excellent practical trial, patients around the world with bumpy calf veins can make an informed choice between these procedures.
JAMA 24 September 2014 Vol 312
1218 A survey of new diagnosis of diabetes in the USA shows a doubling between 1990 and 2008, followed by a plateau, and even, wonder of wonders, a dip thereafter. This is virtually the same plot as obesity over there. And what about over here? I can’t find an up to date plot, although Diabetes UK declares that “Most health experts agree that the UK is facing a huge increase in the number of people with diabetes.” I guess if I looked at the Tesco website a while ago I might have found that “most experts agree that Tesco is facing a huge increase in profits,” but I would have done better to look at the account books.
Lancet 27 September 2014 Vol 384
1187 I’ve already warned you that we would be coming upon losmapimod. It is a p38 mitogen activated protein kinase inhibitor. Understand? It doesn’t matter whether you do or not, because losmapimod did nothing at all in this phase 2 trial, where it was given for 12 weeks after non-ST elevation myocardial infarction. At this rate, it won’t even be around long enough to form a useful rhyme word with god.
1196 But rejoice again—another British trial that can be converted straight into a decision tool for patients! This one aimed to determine whether initial treatment for Parkinson’s disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI). It was non-blinded and doctors were free to add agents and adjust doses as time went on. But this pragmatic approach comparing strategies directly strikes me as more valuable in this situation than any number of separate and more rigorous randomised controlled trials, which would only allow indirect comparisons in more narrowly defined groups. This one tells us all we need to know in a heterogeneous group of people with newly diagnosed Parkinson’s disease. “Very small but persistent benefits are shown for patient rated mobility scores when treatment is initiated with levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists.”
1206 Studying the effect of antipsychotic medications and mood stabilisers is usually a losing battle. People with schizophrenia and bipolar disorder often disappear without trace within medical systems or go for long periods without taking their medication. This Swedish study manages to make a virtue of the latter problem, by comparing the rate of violent crime perpetrated by people while taking their medication with the offending rate of the same people while not taking drugs. “Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics . . . mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder.” There is plenty of room for confounding here, but it is good to see some evidence that these often quite toxic drugs may be having some benefit.
The BMJ 27 September 2014 Vol 349
Here’s a great study in primary care. It couldn’t have started better: before planning their research, the authors carried out a Cochrane review of the evidence on disease specific, health related quality of life and exercise capacity of COPD patients after an integrated disease management programme for at least three months. And wow, they found that it reduced respiratory related hospital admissions and days in hospital, leading to potential savings in healthcare costs. Now we know from the Standard Model of the Universe that Cochrane = Evidence = Guidelines = Service Implementation. So it’s quite likely that integrated disease management programmes for COPD will be introduced all over the place under the banner of patient centredness and cost saving. But hang on, said these intrepid Dutch investigators: does this actually apply to our health system here in the Netherlands? And so they carried out a randomised trial to test the hypothesis that they themselves had promulgated. By so doing they disproved the hypothesis: their cluster randomised trial showed that an integrated disease management approach delivered in Dutch primary care showed no additional benefit compared with usual care, except improved level of integrated care and a self reported higher degree of daily activities. Bravo! And well done Dutch general practice, where usual care for COPD is so good that this specialist package could scarcely better it.
Another outstanding primary care paper on The BMJ website has already provoked some press interest. It deserves much more. In fact, it deserves front page banner headlines, like those given a few months ago to the Chief Medical Officer’s warnings about a coming era of universal antibiotic resistance and a return to the Stone Age of medicine. The new headline should read: “Shock horror: no change in antibiotic failure in British primary care in 21 years.” In 1991, when the General Practice Research Database was just beginning, the percentage of patients returning to their GPs for a second course of antibiotics was 13.9%. In 2012, by which time the database had grown immensely and morphed into the Clinical Practice Research Dataset, the figure was 15.4%. This rise of 1.5% is dwarfed by all the possible confounders within the comparison. And the detailed charts show that the mainstay antibiotics—amoxicillin and flucloxacillin—have remained exactly as effective in the UK community now as they were then. We may be prescribing too many antibiotics when they are not needed, but this study proves that British GPs are not causing an epidemic of resistance.
Ann Intern Med 16 September 2014 Vol 161
392 I have been a bit neglectful towards the Annals of Internal Medicine of late, but a sparse week in the other journals led me to look at it. It’s perhaps worth pointing your attention to a randomised trial, which shows that coronary artery bypass surgery can be beneficial for some high risk patients with ischemic left ventricular dysfunction. That was certainly my experience with two youngish patients who were constantly decompensating before they had surgery, but general practice can provide a very misleading sample, and most of my reading since then has suggested that “hibernating myocardium” generally stays asleep, revascularise it as you may. But this trial, on patients with ejection fraction less than 35%, randomly assigned 602 patients to medical therapy alone and 610 to medical therapy plus CABG. The main sustained improvement in the CABG group was in quality of life—very worthwhile, since it can be pretty awful in this patient group.
Plants of the Week: nearly October
Instead of celebrating a single plant this week, I thought I would take you on a tour of our little back garden, pointing out the plants that still give great pleasure as the season fades.
Perhaps the star of them all is the big clematis which hides our oil tank, called “Kaiu,” after the Estonian locality from which it emerged in 1982. It is spectacularly vigorous and free flowering, even in a mean little dry clay bed at the foot of an east facing wall. It is said to belong to the viticella group and had lovely dangling bluish-pink white bell flowers from late July to the first frosts. It would be wonderful to see it grown up a large tree, or covering an entire red brick house. We keep it under control by cutting it back almost to the ground each winter. At its foot we still enjoy the lavender flowers of Perovskia “Blue Spire” contrasted with the little orange mallow-blooms of a Spheralcea, which has not stopped flowering for three months.
Elsewhere we let nasturtiums abound, and our welcome weeds include Welsh poppies, white mallows, and abundant evening primroses with soft yellow flowers. Other good creamy yellows are provided by a free flowering viola of that colour and the shuttlecocks of Kirengshoma palmata, which defies the textbooks by seeming perfectly happy on limy soil. Near these are the lovely pure blue bells of the ground covering Campanula cochlearifolia “Blue Baby.”
Under the trees everywhere are cyclamens of white and pale purply-pink. There is the odd erodium showing late flowers of veined purple and white, but the hardy geraniums are all over, bar the invaluable Buxton’s Blue. A ground hugging geum whose name was long expunged from memory is offering flowers of sharp red-orange. But to us, the monarchs of the garden will always be the hollyhocks, which for several years resisted our attempts to naturalise them, but which now rise to two metres and more all over the garden. They have mostly finished flowering except for a couple of particularly beautiful ones.
Finally, there are two late flowering roses that particularly gladden the eye and nose. One is the great nineteenth century beauty called “Grüss an Aachen,” with flowers that change through white and cream to peachy loveliness, carrying one of the best of all rose scents. The second is a modern upstart with bright buff yellow flowers which are deeply fragrant with a tinge of liquorice. Its name is “Absolutely Fabulous,” as I have confessed to you before.