Richard Lehman’s journal review—14 December 2015

richard_lehmanNEJM 10 Dec 2015 Vol 373
Pacific treatments for scabies
2305 Wow. Here is the ultimate cluster randomised trial: an island randomised trial. First find your islands in the vastness of the Pacific Ocean. Make sure they are big enough for your power calculation, and that they have a similar prevalence of your target condition: in this case, endemic scabies and secondary impetigo. The ocean will keep them separate. By now you are itching to go, and you are a mite excited because you will be starting from scratch. So you allocate one island group to standard care involving the administration of permethrin to affected persons and their contacts (standard-care group), the next to mass administration of permethrin (permethrin group), and the third to mass administration of ivermectin (ivermectin group). Your primary outcome is the change in the prevalence of scabies and of impetigo from baseline to 12 months. Burrowing into the data at the end of the trial, both the whole-population treatment strategies proved effective at reducing scabies and impetigo, with ivermectin the overall winner. Maybe there are other conditions endemic on Pacific islands that might get under the skin of researchers and provoke a rash of similar studies.

ISMN a no-no for HFPEF
2314 There are lots of reasons why the clinical syndrome of heart failure can occur without a reduction in systolic ejection fraction, but at present these patients all get lumped together as having HF with preserved EF. Lumpy categories provoke lumpy treatments and lumpy research. A total of 110 patients with this label were enrolled at 20 sites in the United States, with 51 patients assigned to receive isosorbide mononitrate first and placebo second and 59 patients assigned to receive placebo first and isosorbide mononitrate second. Even in these relatively young patients (mean age 69), the nitrate had the effect of reducing rather than enhancing daily activity levels. Try again using something else.

Dangerous valves for emphysema
2325 In this Dutch trial, one-way endobronchial valves were implanted by bronchoscopy to reduce lung volume in 34 patients with severe emphysema. By six months, 23 serious adverse events had been reported in the EBV group, as compared with five in the control group, and there had been one death in the intervention group. To set against this, the intervention group were able to walk on average 74m further in six minutes. If you met the inclusion criteria of this trial, would you want this procedure? Although this was not a commercially-sponsored trial, the conclusion of the abstract seems oddly one-sided: “Endobronchial-valve treatment significantly improved pulmonary function and exercise capacity in patients with severe emphysema characterized by an absence of interlobar collateral ventilation.” No mention of harm at all.

JAMA 8 Dec 2015 Vol 314
Pimping for beginners
2355 I really have no acquaintance with the art of pimping. I just don’t have the right qualities or car for the job. So these papers in JAMA came as quite a revelation. “Pimping has a bad name. In medical education, the term is saddled with negative and malicious connotations, regardless of the intended meaning. Derived from the German Pümpfrage, it has nothing to do with finding customers for prostitutes but instead refers to the practice of a teacher asking a student a series of questions.” Aha. I think I can do that. But it turns out that the questions have to be the kind that cause public humiliation for the student’s “benefit”—an old practice which is apparently still widespread in medical schools. It is a revolting form of bullying and I hoped it had died out 30 years ago. It was supposed to deflate the kind of people we used to call “clever dicks” in those bygone times, but it only seemed to make them into even bigger dicks. I think I had better stop here. This pimp language is getting out of hand.

JAMA Intern Med Dec 2015 Vol 175
The non-science of teaching medicine
There is more about medical education on the JAMA IM website too. I gave my first lecture on the subject of medical education in communist East Germany in 1972, when I was in the middle of my own. I knew nothing about it then and wonder if I know much more now. It is supposed to be about teaching the methods of science and the application of evidence. Amongst the papers here is one called “Promoting Patient-Centered Counseling to Reduce Use of Low-Value Diagnostic Tests: A Randomized Clinical Trial.” That sounds promising, but the trial contained no patients and no tests. It was pure simulation and its result was certain to be null, even before it was found to be null. Nothing will come of nothing.

Curriculum design seems to be driven much more by fashion and internal politics than by any deliberate attempt to match the needs of users—i.e. sick people—with the priorities of learning. An editorial called “Research in Medical Education and Patient-Centered Outcomes: Shall Ever the Twain Meet?
tries to sound hopeful, but after an endless series of sentences ending in question marks, it fades into generalisation: “Acknowledging that these will be complex systems with possibly nonlinear relationships between processes and outcomes, we need to complement our armamentarium of research designs with qualitative methods, mixed methods, and social science methods.” Mmmm.

Lancet 12 Dec 2015 Vol 386
Aripiprazole for codgers
2404 I’m naturally depressive, and as I become less mobile, more forgetful, and closer to death, I’m sure to turn into a horribly morose old codger. They will fill me up with antidepressants, but as I continue to codge morosely, they will give me aripiprazole. That will give me akathisia, but never mind. It is never too late for new experiences. In this American trial, people of about my age who were thought by their psychiatrists to have depression were put on maximal doses of venlafaxine for a month and if that didn’t seem to work, they were randomized to get aripiprazole or placebo. A quarter of those in the aripiprazole group developed akathisia and 17% developed Parkinsonism. A greater proportion of participants in the aripiprazole group achieved remission than did those in the placebo group (40 [44%] vs 26 [29%] participants; odds ratio 2•0 [95% CI 1•1–3•7]. This is described in the editorial as a “major leap forward.” Major leaps forward do not have confidence intervals that begin at 1.1. Also, if a quarter of patients given aripiprazole were asked to leap forward, they would probably fall over.

Cheer up love, it may never happen
OL A major survey funded by the MRC shows that actually life is getting an awful lot better for British codgers. The Cognitive Function and Ageing Studies report that “between 1991 and 2011, gains in life expectancy at age 65 years (4•5 years for men and 3•6 years for women) were accompanied by equivalent gains in years free of any cognitive impairment (4•2 years for men and 4•4 years for women) and decreased years with mild or moderate–severe cognitive impairment. Gains were also identified in years in excellent or good self-perceived health (3•8 years for men and 3•1 years for women).”

BMJ 12 Dec 2015 Vol 351
Depressing comparisons
Forty years ago, psychiatrists distinguished between “reactive” and “endogenous” depression. You used talking therapies for the first, and drugs for the other. I don’t think results were any worse than they are now. The drugs were more toxic, but far fewer people ended up dependent on them, in the way that millions now end up taking their serotonin reuptake inhibitors indefinitely. The talking we did then was based on a lengthy process of history taking, which was probably as therapeutic as cognitive behavioural therapy, and at least meant that you reached a better understanding of the human being in front of you. Modern therapy for “major depressive disorder” is examined in a large systematic review comparing cognitive therapy with second generation antidepressant drugs. “Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences.” This doesn’t mean anything. In real life, offer hope and assurance first, and a commitment to see it through. Use pills if you have to. Bear in mind that online CBT doesn’t work and real CBT is hard to access. And remember that “depression” is a false category: it only exists within individual people who are depressed.

Hypos, sulfonylureas and warfarin
Medicare data from the USA are used to examine the possible risk of hypoglycaemia in people taking gliclazide and glimepiride along with warfarin. In quarter-years when warfarin was taken with these sulfonylureas, admissions for hypoglycaemia were significantly commoner and admissions for fall-related fractures even more so. So there is some presumptive evidence of an important interaction, which could be confirmed by replication studies of other databases like the UK CPRD or the Taiwan whole-population database. Best of all, avoid using sulfonylureas.

Markers, markers everywhere
Here’s a really useful review of all those new tests you keep seeing in letters from the rheumatology clinic. Where there was once a lot of room for diagnostic confusion, there is still a lot of room for diagnostic confusion, but now at least it can be impressively presented as a series of arcane antibody levels. Not for nothing is this called the SLICC classification system. Keep this paper by you if you want to answer back to your local rheumatologist: why have you not checked my patient with systemic sclerosis for anti-PM-Scl and anti-U3-RNP antibodies? A note of warning, however. Like most of the “heavy” papers in this week’s The BMJ, this one comes from the USA. It refers to “titers” instead of “titres”, thus teetering on the verge of Americanism.

Plant of the Week: Solanum tuberosum

Potatoes are irresistible in all forms. As winter draws on, it is impossible not to long for slow-cooked dishes combining layers of potato with fatty meats or cheese. The great treat of Christmas dinner is not the goose itself but the potatoes roasted in goose fat.

At a magnificent feast in Lima arranged by Victor Montori, I sampled about a dozen original diploid potato species from the Peruvian Andes. They are good, but I’m quite happy with their distant tetraploid descendants for everyday eating. King Edwards for mash to accompany sausages, Charlotte for salads and so forth. I tried to do potato snobbery for a while, but it’s pointless. They are all so good.

Born of Polish parents in the potato lands of Lincolnshire, I never stood a chance of avoiding late-life obesity. The wonder is that it took so long. It is potatoes that fuel obesity in America, even more than the corn syrup they add to everything.

Here is how my mother used to make a Polish potato salad. Boil a lot of waxy potatoes to just the right state of firm readiness. Chop them, but leave the chunks fairly large. Add one bunch of spring onions, chopped. Or failing that, any onion. Add a few chopped hard-boiled eggs. A couple of chopped Krakus cucumbers in brine, and a chopped fresh cucumber. A handful of chopped dill and parsley. Last of all, a couple of chopped peeled firm sweet apples, prevented from going brown by the immediate addition of a lot of home-made mayonnaise. Stir it all up, and serve as a meal in itself or with matjes herrings, smoked fish, sliced sausage, ham, or pork loin.

Note: This blog was edited on 15 December to remove a paragraph.