The medical eponymous genitive is only one of many things on Richard’s mind this week. He makes the distinction between Important Sounding Surrogate End Points (ISSEPs) and Patient Important End Points (PIEPs): hardly new concepts, but possibly new acronyms. These are the fundamental enemies and friends, respectively, of evidence based patient care. Do you think these acronyms work? Or can you think of better ones? Please send in your comments.
JAMA 6 May 2009 Vol 301
Homeless and ill in Chicago, which would you want most – a doctor or a roof over your head? This randomised trial offered chronically ill homeless people 18 months of guaranteed housing after hospital discharge, or usual care. Return visits to hospital were about a quarter fewer in the housed group. Civilisation is the building of cities, the encouragement of arts and learning from the interchange and wealth that they create, and the care of the poor. Not necessarily in that order.
Nobody seems very sure what the human nasal sinuses are there for. From the doctor’s point of view, they exist to cause facial pain, postnasal discharge and the unnecessary prescribing of antibiotics. All this is nicely discussed (with contributions from the patient) in a case-based discussion here, with pictures of what you might find in acute rhinosinusitis if you had a nasendoscope handy. Most acute sinusitis is viral, resolves within 10 days; by this time over 50% of bacterial sinusitis will also have resolved, as far as we can tell. The commonest bacterial pathogens are Streptococcus pneumoniae and Haemophilus influenzae, followed by Moraxella catarrhalis and Staphylococcus aureus. You can only tell which from cultures obtained from endoscopic sampling, and amoxicillin remains a sensible first-line choice of antibiotic. Wait for ten days, if you can persuade the patient to do so.
NEJM 7 May 2009 Vol 360
Coronary stents were quite a new thing when I started writing a few comments on medical journal articles ten years ago. They were all bare metal then, but trials soon appeared comparing radioactive stents (a very bad idea, causing arterial fibrosis) with stents which leach out (elute) immunosuppressant drugs such as sirolimus and paclitaxel. Coinciding with the widespread adoption of immediate percutaneous intervention for myocardial infarction, use of these drug-eluting stents shot up, and bare metal stents soon became yesterday’s technology. But was this just another triumph of marketing over evidence? It seems largely so, judging by this analysis of the Swedish Angiography and Angioplasty Registry which looks at 48,000 Swedes stented from 2003 to 2006. Overall, there was no difference in rates of death or myocardial infarction between those receiving bare metal or drug-eluting stents. Only if you take patients in the highest decile of risk can you find clear justification for using the expensive kind of stent.
OK, I know stents are boring, but bear with me for another sentence or two. The reason everyone started using drug-eluting stents was, once again, that all-pervading enemy of patient-relevant medicine, the important-sounding surrogate end-point (ISSEP). In this latest trial comparing paclitaxel-eluting with bare metal stents following myocardial infarction, the ISSEP is called binary restenosis. Within the first 12 months, patients receiving the two kinds of stent would have noticed no difference at all. Their rates of death and stent thrombosis were identical. But those receiving the drug-eluting stents showed a lower rate of binary restenosis. Aha, that has to be good. Except that the Swedish data suggest it makes no difference to longer term outcomes in most patient groups.
People who have tried to eat the common earth-ball fungus report that it is rather nasty. It is called Scleroderma, meaning hard-skinned. Human scleroderma, or systemic sclerosis, is definitely nasty. This review is big on mechanisms – that is its brief – and light on management. The traditional NEJM colour scheme, based on haematoxylin-eosin staining, is subtly varied with blues and greens in the illustrations. Lots of different cellular mechanisms might lead to the overproduction of collagen and other glycoproteins which characterises this distressing disease, but nobody has yet found a reliable way of switching them off.
Lancet 9 May 2009 Vol 373
Last week I voiced the opinion that few health issues had greater global importance than the prevention of type 2 diabetes. This study of voglibose makes me wish I hadn’t put it that way. It charts the progression of 1780 Japanese “patients” from impaired glucose tolerance to type 2 diabetes. These people were not ill at all: they simply had some evidence of compromise to their beta-cell function, causing some of them to go from one arbitrary threshold up to the next. “Impaired glucose tolerance” and “type 2 diabetes” are not diseases in themselves, they are labels. They are also ISSEPs, important-sounding surrogate end-points for a process we half understand, and which unchecked can lead to patient-important end-points (PIEPs) such as myocardial infarction, visual loss, neuropathy or sepsis. This trial gets several black marks in my book: it compared one ISSEP with another; it compared an expensive new drug with placebo, instead of the best available comparator, which is metformin; it was industry-sponsored, and all the authors had taken fees from Takeda; there was a huge discontinuation rate; it was terminated too early to assess any PIEPs; the reporting of outcomes in the summary is arbitrary and sometimes inaccurate; and so on. Do a-glucosidase inhibitors have an important role to play in the prevention of the risks associated with increasing blood sugar levels? This study doesn’t give me a clue.
While I’m in drum-banging mode, I would say that few interventions are more important than resuscitation at birth, and if babies are to get the best chance of avoiding brain damage, this needs to be done by somebody good at it as quickly as possible, i.e. by a paediatrician, in a hospital. My “conflict of interest” here is that I have fought a long battle to prevent our local obstetric unit from being downgraded to a large midwife-led unit, more than 45 minutes from any paediatric or obstetric help. This study from Bristol shows that babies who require resuscitation have an increased risk of a low IQ score at 8 years of age, regardless of their apparent health in the neonatal period.
Intracerebral haemorrhage is a gloomy topic, and I really admire those who have attempted to do randomised trials in a situation as urgent and hazardous as this. People have tried dissolving the clot with urokinase and aspirating it stereotactically; limiting its spread with activated recombinanat factor VII; or limiting its damage with neuroprotectant drugs: all to no avail in terms of patient outcomes. The aspects of management that still matter most are secondary ones such as stopping gastric bleeding (which is present in 30% of cases) and lowering blood pressure.
BMJ 9 May 2009 Vol 338
I’m all for the BMJ publishing papers that will improve clinical practice in primary care, which is why I’ve put a lot of time and effort into promoting two series in the Practice section and helping to edit one. But I find this research paper from the Netherlands (helped by the Welsh) a bit puzzling. The aim seems to be to reduce antibiotic prescribing for lower respiratory tract infection. Even the full text of the article (on the website) doesn’t contain enough evidence to satisfy me that this is a safe and laudable aim, or that there was a robust case definition for LRTI in this study. The choice of interventions in this cluster randomised trial was normal care, care guided by measurement of C-reactive protein, or care following a focussed communications skill course. The primary outcome was antibiotic prescribing. This was just over 50% in the non-testing, non-trained group and 25-30% in the other groups, including a group that used both CRP and communications skills. A good study to stimulate discussion; less good to change clinical practice, at least for an old lag like me.
The original title for the series that Anthony Harnden and I proposed to the BMJ was Commoner Than You Think? but on the whole the final title Easily Missed? is better. This is well illustrated by Kawasaki disease, and here is a full clinical review written by Anthony as main author, outside our series. Kawasaki disease is not, as far as we know, commoner than most doctors think: in the UK it is so uncommon that most GPs will never see a case. But if they do, then they must try not to miss it. Treatment with immunoglobulin in the first 10 days can reduce life-threatening complications. I know I’m biased, but I can’t think you’re going to find a better guide to it than this: pore over the pictures, look out for the baby or child who is iller than her/his fever warrants; and don’t wait for desquamation of the fingers, because by then the coronary arteritis will already have happened.
P.S. Note that this condition, first described by Kawasaki, is never referred to as Kawasaki’s disease, on either side of the Atlantic. It therefore breaks the usual rules that govern the medical eponymous genitive. Like you care.
Ann Intern Med 5 May 2009 Vol 150
The optimal duration of anticoagulation following deep vein thrombosis depends on the balance between the likelihood of recurrent DVT versus the bleeding risk from continued warfarin. This Italian trial (AESOPUS) went on for 7 years but still doesn’t provide a very clear steer on whether it is useful to perform repeat ultrasonography at 3 months as a guide to continuing anticoagulation at this point. I won’t try and go into detail but there is a suggestion that outcomes may be better if you adopt the strategy of stopping warfarin at 3 months if the USS shows clear veins, but continuing it for 9-21 months if the veins still look blocked; but you will double the rate of major bleeds.
A lot of us wish that prostate specific antigen testing had never been invented, because its value as a prognostic marker in advanced disease is outweighed by its Perfectly Stupid Attributes as a screening test. This study of molecular markers for risk of death from prostate cancer confirms what we were taught as medical students: prostate Ca for most men over 70 is a disease they die with rather than die from – that was true of 78.5% of the men in this study which followed up mainly moderately-differentiated tumours. The Gleason score remains a good basic indicator, but the authors here have come up with three added tissue sample tests which provide some incremental refinement.
Plant of the Week: Paeonia mlokosewitschii
Pardon me, but I can’t help praising this exquisite flower every year at the time of its appearance. Here is Reginald Farrer trying to remember how to spell its name and what it looks like, holed up in remote Western China in 1913 with a case of whisky and his trusty companion Bill Purdom:
“P. Mlokosievitschii. – This pleasant little assortment of syllables should be practised daily, but only before dinner (unless teetotal principles of the strictest are adopted), by all who wish to talk familiarly of a sovereign among Paeonies – a rare plant, and rendered almost impregnable by its unpronounceable name. It has an ample habit and lovely dark foliage, amid and above which are borne huge flowers like strayed water-lilies of delicate saffron or citron yellow. It is in the wilds of the Caucasus that this temptation has its lair.”
The English Rock Garden 1918
In fact its wide-lobed leaves are of a light rather than a dark green, and the flowers can be of light buff mixed with pink, in what some claim to be the species – though never having been tempted as far as its lair in the wilds of the Caucasus, I wouldn’t really know. All I know is that in its commonest and best form, Mollie-the-Witch of gardens, the big papery globe-flowers are of an indescribably soft yet intense pure yellow. For a few days each year they are the most beautiful thing in the garden.
Ludwik Franciszek Mlokosiewicz was a Polish explorer, zoologist and botanist (1831-1909). His name has been mangled by botanists, but he can hold no such grouse against zoologists, who get it right in Tetrao mlokosiewiczi, the Caucasian Black Grouse. Strange how people have such difficulty spelling and pronouncing Polish names: Polish is a euphonious language with simple and consistent rules of spelling in the Roman alphabet. Yet even I couldn’t spell or pronounce my father’s Christian name till I was about 13. Mieczyslaw.