27 Aug, 13 | by BMJ
NEJM 22 Aug 2013 Vol 369
699 Vedolizumab. What a name for an important new drug. Just remember the vedo bit and the fact that it’s a monoclonal antibody, and you might be able to recall the full name. Vedo is the new kid on the block for inflammatory bowel disease. “Hi new kid,” say the lymphocytes in the bowel wall, “what’s your name?” “My name is Vedo, and my aim is to stop you causing mischief. Bow down before me and obey.” “Hah, hah,” say the lymphocytes, and trash Vedo in 53% of cases. But in the other 47% of cases, Vedo wins. This is success in ulcerative colitis, because with placebo, only 25% of patients who relapsed after other treatments go into remission and most don’t maintain it, whereas vedolizumab manages to keep over 40% of the original 47% in remission.
711 But response rates to vedolizumab are much poorer in treatment resistant Crohn’s disease. There’s an editorial to explain what it does and why this might be so. Maybe you need to remember Vedo, maybe you don’t.
722 GlaxoSmithKline pits its new renal cancer drug, pazopanib, against the established Pfizer drug, sunitinib. Pazopanib wins, by causing fewer adverse effects. To confirm this, we need the full clinical study reports, because so far they have only been analysed by the sponsor, GSK. But for its design, this trial deserves congratulations: it was well powered, it measured patient-important end-points including fatigue, and it compared the new drug with the best existing similar treatment. Since GSK has promised to release full data from all its trials, this would be a good one to look at: if its conclusions are confirmed independently, then GSK can market its product with pride.
Ann Intern Med 20 Aug 2013 Vol 159
233 Following Ray Moynihan et al’s measured argument in the BMJ against labelling 11% of adults as having “chronic kidney disease,” there have been lots of responses from single interest people to the effect that this is so that we can target them for special preventive treatment, including tighter control of blood pressure. This study of US Veterans with CKD introduces some observational evidence into the debate. Lowering diastolic BP in these people below 70 is associated with higher mortality, irrespective of the systolic pressure. The best outcomes were seen with diastolics between 70 and 89, and systolics between 130 and 159 Hg. Note that last figure. Male “patients with CKD”—mostly healthy asymptomatic people—are quite OK to run a systolic BP up to 159, and not OK to run a diastolic below 70. These figures bear no relation to any targets set by tunnel-vision committees of specialists and CKD “champions,” and apply equally to those with albuminuria and those without.
JAMA 21 Aug 2013 Vol 310
The order in which I place the journals in these reviews was never meant to be a reflection of merit, but simply reflected the order in which I read them in paper copy back in 1998 (see end section). The reason JAMA has recently appeared lower in the order these days is because I don’t like to start every review with a moan.
699 Moan! A structured hypertension management programme by Kaiser Permanente in the USA achieves better BP control than usual care. Strange indeed had it been otherwise. There’s not much for NHS doctors to learn from here: keep collecting the QOF BP points.
722 A trial to determine whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis. They do not. This is useful knowledge for those who might be tempted down this route. No moan.
731 The ever valuable rational clinical examination series asks “Does This Patient Have Obstructive Sleep Apnoea?” No moan here either, because this patient does indeed have it, and since starting CPAP he finds it much easier to stay awake while writing these reviews. To him, the diagnosis seemed perfectly obvious for years from the excellent descriptions of his nocturnal noise making offered by his spouse, his unfortunate gain in neck circumference, his mildly elevated blood pressure and his inability to stay awake in afternoon meetings. It was merely a matter of getting round to having a sleep study. And like most people with OSA, I wish I’d done it ages ago. An Australian study a couple of years ago dispensed with the sleep studies and just gave out the CPAP machines on the basis of the history, the Epworth score, BMI, neck measurement, and the Mallampati pharyngeal airway score, which is basically how much of the uvula you can see. So you can diagnose yourself in most cases, though this systematic review would have you believe otherwise. That’s the trouble with systematic reviews of the diagnostic literature: they’re hard work, and you end up not believing them, because every study seems to have a different population and a different set of measurement criteria. Forget sleep studies and cut to the CPAP, say I.
BMJ 24 Aug 2013 Vol 347
The management of depressed patients in UK primary care is a mess. It simply cannot be otherwise, given the constraints of the ten minute consultation and the interminable waiting times for psychological therapy. Even the most reluctant GPs feel forced to start patients on SSRI antidepressants, which most people then find difficult to discontinue. The investigators of the CADET trial claim to have found a better way, and suggest that it could be implemented across the UK. They trawled through GP records to find patients coded with depression. They ultimately managed to recruit 11% of those found. The intervention consisted of antidepressants and/or a simplified form of CBT, with adherence supervised by “care managers” in 6-12 contacts per patient. At four months, mean depression score was 11.1 (standard deviation 7.3) for the collaborative care group and 12.7 (6.8) for the usual care group. There is no cost analysis. Ready for roll-out? I don’t think so. Just give us the CBT next week, and we will be able to help our patients.
Here’s a nice big cohort study from Dijon which really cuts the mustard. It looks at the behavioural factors associated with disability in old age. Alcohol? Those who stop drinking fare worst. Encore de bon vin! Smoking? A surprisingly small effect. Pas de cigarettes! Diet? Yes, those who fail to get their fruit and vegetables do quite a lot worse. Encore de salade! Inactivity? Here there’s a really big effect, confounded by reverse causation. Il faut faire la promenade. It’s all there to be mulled over on Table 2.
Anything written by Rudolf Klein is worth reading, and his essay on the NHS in the age of anxiety certainly is. The universally free and comprehensive NHS was set up when Britain was in ruins and bankrupt: food was rationed, but everybody could get free medical care, with specs and teeth thrown in. Now all the political parties collude in the myth that in 2013 we are too poor a country to provide adequate healthcare for everybody. The Lansley “reforms” have lain the whole system open for cherry-picking by the private sector. Why aren’t Her Majesty’s Opposition screaming? Klein’s last paragraph is calmly brilliant:
“The age of austerity is, of course, itself the product of rhetoric. It is the rhetoric of a model that sees salvation in balanced budgets and reduced public borrowing and results in the reality of economic stagnation and cuts in public spending. This hairshirt approach has been challenged by many, Nobel prize winning economists among them. And the best hope for the NHS is that the challenge will succeed before too many irreversible lesser evils have been found acceptable.”
Great clinical pieces abound, as usual in the BMJ these days. Read a good review of Tourette’s, spot imported malaria with the help of Merlin Willcox, and be reminded that type 2 diabetics with totally burnt-out beta-cells can get ketoacidotic.
Lancet 24 Aug 2013 Vol 382
694 The 1665 motto of the Royal Society enjoins us not to take anyone’s word for things but to look at the evidence. The trouble nowadays is that you do have to take people’s word for things, because you can’t possibly do the analyses yourself. Three French authors collect all the limited evidence we have about the transmissibility of the new betacoronavirus, MERS-CoV, and put it through their mathematical software. They arrive at an R0 between 0.6 and 0.65. Aha, I hear you say, is that good or is it bad? Well, let me tell you that this morning I discovered what an R0 is, or at least what it means. If it is less than 1, the world is safe from pandemic spread: it means that the infection will fizzle out, like SARS, which had an R0 of 0.8. If the R0 gets to 1.5 or above, be scared, wear protective clothing, and start producing vaccines as fast as you can.
Fifteen Years of These Reviews
By 1998, I had been at Hightown Surgery in Banbury for 19 years. Our patient list had grown fourfold, and we had become a training practice and had a nice library in our common room. We subscribed to the main generalist medical journals for the sake of ourselves and our trainees, but none of us seemed to read them much. So I suggested that we each took one home each week and wrote down some comments on the papers of general interest.
By the end of August that year it became clear that I would be the only contributor to this process. Either we would drop the idea or I would carry on doing it on my own.
The fifteen year mark has now been reached, and I can look back at some wonderful friendships and opportunities as a result of carrying on. I still enjoy the writing, but above all I am kept going by the feedback I get from time to time.
The down side is that I have not had a free weekend for fifteen years, during which I have managed to keep the process unbroken. Now I feel like a short break, so there will be no reviews for the next fortnight.
After that, another fifteen year cycle begins. Perhaps.