Richard Lehman’s journal review—22 June 2015

richard_lehmanNEJM 18 June 2015 Vol 372
2387 For the first time in years, I actually handled a new printed copy of the NEJM last night. What a suave production it is! Flicking though its stylish pages with their subtle sheen, I came across the IMPROVE-IT study once again. It’s a telling reminder of how credulous the medical community can be when faced with a slick presentation of something it wants to believe. No mortality benefit from ezetimibe in over 16 000 very high risk patients over six years. But a borderline significant benefit in a catch-all composite endpoint. Astonishing! Paradigm shift!

2423 Sunt lacrimae rerum et mentem mortalia tangunt, said Aeneas as he looked at a mural of the Trojan war depicting the deaths of his friends and countrymen (Vergil: Aeneid Bk1, 462). Rerum means “of things,” making this famous line quite tricky to translate: “There are tears for [or ‘of’] things and deathly things touch the mind.” I’m reminded of the line by this article showing that ebolavirus can lurk in tears, long after it has departed from the rest of the body. In this case, there are things in tears, and touching them can be mortal, i.e. sunt in lachrimis res quarum tangere mortalis. Enough. Avoid the tears of Ebola survivors. Also my attempts at schoolboy Latin composition. In fact, ignore this entry altogether.

OL One thing that can drive many of us to tears is the genomics of cancer lines. It’s a wonderful new science that can open up new therapeutic pathways, but it’s also fiendishly complicated and has to be taken on trust. On the NEJM website are two state of the art papers, which may—according to the accompanying editorial—improve our understanding of adult diffuse gliomas. If you can access any of these articles, I defy you to read beyond two paragraphs without getting lost. “However, both studies can justifiably claim that molecular classification captures the biologic features of glioma variants better than does histopathological evaluation, even though grade remains an independent prognostic indicator. These new data sets have the potential to inform how we define and treat the range of adult diffuse gliomas at a time when the current edition of the WHO classification of nervous-system tumors is being revised to include, for the first time, molecular information in the classification of disease.” Oh good.

JAMA 16 June 2015 Vol 313
2331 The main reason I mention this next trial is because it is called BiPOP. It is a French trial, so it would always be pronounced as bee-pop—si drôle! In fact the procedure it tests is called BiPAP, which stands for bilevel positive airway pressure, compared here with high-flow nasal oxygen therapy in patients with hypoxemia after cardiothoracic surgery. If you deliver 50L/min of humidified oxygen via nasal cannulae to such patients in intensive care, outcomes are the same as if you give them BiPAP. BiPOP!

2340 A sign of the times—look in this week’s The BMJ and you will find this article described as comparing antibiotic therapy with “appendectomy” for the treatment of uncomplicated acute appendicitis. Can this dereliction of the Queen’s English be viewed with anything but horror and consternation? Surgical removal of the vermiform appendix is known as appendicectomy throughout the British Commonwealth. This trial was conducted by Finns, but that is no excuse. They may call it umpilisäkkeen poisto, but that is their own affair. We are British, and when we lay on a surgical table with right sided pain, we demand an appendicectomy, and sometimes even carry it out for ourselves. But throughout the British navy and merchant fleets, it has been known for a long time that you can often get away with just using antibiotics. The Finns used intravenous ertapenem (1 g/d) for three days followed by seven days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg three times per day). Over 90% of those treated in this way left hospital without an operation and over 70% did not go on to need appendicectomy in the following year.

Lancet 20 June 2015 Vol 385
2465 In a week with very little in the journals, you must forgive me for another foray into the world of interventional cardiology. I have never actually been into a catheter lab so I don’t even have the credentials of a harmless bystander. I’ve seen the various holes they leave in people and read countless accounts of what they have put into coronary arteries, but that’s as far as it goes. I am aware that they usually choose to put their tubes into the femoral artery, but in this article I am told that “It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management.” So in 78 centres in Italy, the Netherlands, Spain, and Sweden, they randomised 8404 patients with acute coronary syndromes to one or other entry site. The radial artery is more superficial and less likely to bleed afterwards, but trickier and more time consuming to get into. But despite the extra time needed, radial access produced slightly better outcomes than femoral, with a just significant benefit in total mortality.

2477 The next paper also involves putting things up cardiac catheters, but this time they are replacement aortic valves. These can only be introduced via the femoral artery or the cardiac apex. This would have seemed like science fiction when I was a medical student. It still does, slightly. The PARTNER 1 trial selected patients who were either considered high risk or unfit for the open operation, and its results are reported in two papers. The first one describes five year outcomes for the high risk patients who were randomly assigned to transcatheter replacement (TAVR) or surgical replacement (SAVR). Mortality was much the same (68% and 62%, respectively) but more of the TAVR valves leaked.

2485 The same centres and the same sponsor (the TAVR device manufacturer) took part in an unblinded comparison in “inoperable” patients (mean age 83) between TAVR and conservative management. This time the five year mortality figures clearly favoured the TAVR—72% versus 94%. But the selection process ruled out eight out of 10 screened candidates and there was a lot of crossover. I guess if I were an 83 year old I might go for the TAVR, not because I would care much whether I lived or died but because it might relieve my symptoms a bit.

The BMJ 20 June 2015 Vol 350
Hurray—here is a British randomised controlled trial published in The BMJ. No matter that most of us have never encountered pyoderma gangrenosum: this is the kind of trial we yearn to see. No pharma funding, using cheap old drugs, answering an important clinical question, designed with patients, pragmatic in that it allowed dose adjustment but valid in that it used blinded assessment. More of these, oh many more please. In fact, this should be done for every situation where there is clinical uncertainty and equipoise. It should be a basic function of the NHS. Ethics committees should ask why it is not being done routinely, rather than putting insuperable obstacles in the way of it being done at all. We should be enraged at the learning opportunities which are missed in every clinic we run. I was a GP for 35 years seeing 30-40 patients every working day, but the consequences of my decisions and those of my patients disappeared into the ether, or latterly into the Clinical Practice Research Dataset. Yet I saw no pyoderma gagrenosum. If you want to use prednisolone or ciclosporin for it, this trial allows you to share the decision. The benefits of the two are about the same but the adverse effects are somewhat different. So we need to give the patient the facts and let them make the decision if they wish, or make it for them if they prefer. No pressure. Let them have a think and send it through by phone or email. Why don’t we do more grown-up medicine in 2015?

Denmark collects data from hospital visits by its entire population to inform clinical decision making. What’s the added risk of infection when tumour necrosis factor α inhibitors are used to treat inflammatory bowel disease? Ah, now let’s see. Click click, “Within the 90 days risk period, 51 cases of infection were observed in users of TNF-α inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1.75).” Well Björn, I think this could make a good paper for The BMJ. Take a look while I go and get some coffee. Why shouldn’t all outcomes research be like this in 2015?

In a single year, an orthopaedic surgeon can do more good for patients than most of us can achieve in a lifetime. At the same time, he (or occasionally she) can do more unnecessary procedures in a year than most of us are guilty of in a lifetime. Irrespective of financial gain, orthopods tend to be enthusiasts. If there’s something that looks like a joint lesion corresponding to a complaint of pain, in they go and attack it. I’m old enough to have witnessed the rise of arthoscopic surgery and the sudden increase in activity that resulted. As MRI then took over from plain radiology, there was a further increase. Degeneration is rife within the ageing body. The answer must be to shave bits off rough surfaces through metal tubes. This Scandinavian systematic review and meta-analysis of arthroscopic surgery for degenerative knee (sic) shows that these procedures are generally useless and sometimes harmful. Why do practices like this continue to be widespread in 2015?

Plant of the Week: Clematis integrifolia

This is the week of the year when gardens cannot help looking beautiful. But within a couple of weeks there will be no more irises, few flowering shrubs, and many plants will one by one start looking a bit rank, or seedy, or out of control. One answer is to cover them with clematis.

There are various “herbaceous” kinds of clematis which can’t attach themselves and just sprawl into neighbouring plants. They die back totally at the first sign of winter. The integrifolias come from south-eastern Europe and grow to about a metre, bearing four-petalled blue flowers over a long period through the summer.

These are welcome wherever you have a small shrub or other plant that has either stopped flowering or has flowers that go well with blue. We have one growing over a little myrtle and another which is accidentally growing with another herbaceous clematis, the purple form of C recta. I say accidentally because we thought the recta had died so we planted this one in its place. In fact, they are completely happy together, the blue flowers of our clone of integrifolia going wonderfully with the dark purple leaves and milky flower sprays of its cousin.

It’s such a shame that these non-climbing varieties of clematis (which also include heracleifolia and x eriostemon) are quite hard to find. Every garden “border,” however humble or makeshift, benefits from their fascinating and beautiful presence.