Richard Lehman’s journal review—22 April 2014

richard_lehmanNEJM  17 Apr 2014  Vol 370

1494    Back in the 1970s, people used to say that we had entered an era of safe surgery and dangerous medicine. I find it odd that people are now trying to make surgery safer by using a variety of moderately dangerous drugs on healthy people about to have operations. We now know from other trials that beta-blockers given before non-cardiac surgery may actually do harm. This large 2×2 factorial trial tests the effect of aspirin 200mg given before non-cardiac surgery and continued at 100mg daily for 30 days after. “Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding.”

1504    In case you wondered why they needed a 2×2 factorial trial to test a single intervention, the answer is that Salim Yusuf et al were testing pre-op clonidine at the same time. Clonidine is a drug that reduces central activation of the sympathetic nerves. It is hardly used these days, though in theory it could be beneficial in the post-op period when levels of sympathetic activation are high. Patients in the clonidine group were given 0.2mg before surgery and for three days after. “Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest.” I think bananas should come next: “Administration of bananas in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction. They did, however, increase the risk of clinically insignificant hyperkalaemia, and two banana-skin related injuries were reported.”

1514    Something very good happened to diabetes care in 1995. Up to then, American rates for adverse outcomes in diabetes were on the rise, but since that time there has been a steady fall in rates of myocardial infarction, stroke, amputation, and end stage renal disease. Blindness is not documented in this survey. My hunch is that all of this is due to statins, smoking cessation, and better control of blood pressure; and that feeling is reinforced by seeing similar trends in the general population. Sadly, however, the absolute numbers of diabetic complications are rising, because of a steep increase in the incidence of diabetes.

1532   A single-author review of Acute Infectious Diarrhoea in Immunocompetent Adults is unusually non-abstruse and practical, more like a BMJ clinical review than the old-style NEJM article, which would have an enormous chart of rare diarrhoea-causing microbes with names like Ferocibacter incontinens or Colonococcus fluxigenitus (N.B. I made these up). This review sticks with old favourites, of which noroviruses and Shigella seem the easiest to spread by secondary contact. For Clostridium difficile, the author suggests that antibiotic treatment should last a month, to prevent reinfection from spores; while stool transplantation gets barely a mention, despite its wonderful effectiveness.

OL   One diarrhoea-causing agent you do not want to come into contact with is Ebola virus. The current epidemic in Guinea is caused by the Zaire form of the virus and has killed several hospital staff as well as dozens of people living in villages and several cities. This outbreak is described in a new online paper which represents a triumph of science and courage in an area which is still, 115 years after Conrad’s novel, close to being a Heart of Darkness. The case fatality rate was 86% among the early confirmed cases and 71% among clinically suspected cases, which is consistent with the case fatality rates observed in previous EBOV outbreaks. The virus comes from various fruit bats whose Latin names are way beyond anything I could invent: Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata.

OL   “It is easy to promote mammography screening if the majority of women believe that it prevents or reduces the risk of getting breast cancer and saves many lives through early detection of aggressive tumors. We would be in favor of mammography screening if these beliefs were valid. Unfortunately, they are not, and we believe that women need to be told so. From an ethical perspective, a public health program that does not clearly produce more benefits than harms is hard to justify. Providing clear, unbiased information, promoting appropriate care, and preventing overdiagnosis and overtreatment would be a better choice.” So say two authors from the Swiss Medical Board, and I applaud them.

JAMA  16 Apr 2014  Vol 311

1547   “Fibromyalgia is present in as much as 2% to 8% of the population, is characterized by widespread pain, and is often accompanied by fatigue, memory problems, and sleep disturbances.” This free review is the only piece I can find to comment on in this week’s JAMA. It is useful, because it goes through the mechanisms of central pain perception which probably underlie this distressing condition, and it has a very comprehensive list of treatment options. Fibromyalgia is one of those conditions where it is perfectly reasonable to try one treatment after another in a search for the one which might work. Tricyclics, gabapentin, duloxetine, maybe even low dose naltrexone. But just make sure your patient doesn’t end up on the entire list of everything that anyone has tried on them. And avoid opioids.

Lancet  19 Apr 2014  Vol 383

1404    An Australian survey conducted in schools across Victoria finds that almost a third of men and more than half of women had an episode of prominent depressive and anxiety symptoms at least once during mid-to-late adolescence. Almost everybody who has anxiety and depression later in life began having it in their teens or twenties. Yet conversely most people who were anxious or depressed as teenagers do not keep on being so all their lives. The authors of the study then conclude with a complete non sequitur: “The resolution of many adolescent disorders gives reason for optimism that interventions that shorten the duration of episodes could prevent much morbidity later in life.” Excuse me, what reasons for optimism? What interventions? Evidence?

OL   True to its fondness for headline-catching technical innovation, The Lancet has put two papers about tissue engineering on its website. One concerns the construction of new noses for patients who have had disfiguring cancer surgery. These were made by growing autologous chondrocytes on moulded collagen frames. The technique worked well in a small Swiss case series. Meanwhile, in Mexico, a team was creating autologous vaginas by similar means, for four patients with vaginal aplasia caused by Mayer-Rokitansky-Küster-Hauser syndrome. Which got the most press attention? You guessed it: The Vagina Autologs.

BMJ  19 Apr 2014  Vol 348

Feed antibiotics to intensively reared animals and you can increase their rate of weight gain by up to 73%. Feed a diverse range of antibiotics to undernourished human children and they have hardly any effect at all on growth. Here’s a great big meta-analysis of ten trials using metronidazole or aureomycin or penicillin or polymyxin B or cotrimoxazole. It makes me despair of meta-analyses.

So: here is another meta-analysis, this time of observational data. Something can definitely be taken away from this one. High blood pressure in women of childbearing age is a marker for something we don’t understand. It is associated strongly with adverse outcomes in pregnancy, increasing the risk of pre-eclampsia by 7.7, of preterm delivery by 2.7 and of perinatal death by 4.2.

If I despair of meta-analyses, what can I say about dietary surveys? Actually, they’re quite fascinating, though they rarely bear any definable relation to human health. Diet and religion are often closely aligned. The authors of this paper have got religion bad: “Diet is one of the fundamental risk factors for health, disease, and disability in the world. Indeed, given that trends in metabolic risk factors such as blood pressure, cholesterol, glucose, and body mass index are being largely driven by nutrition, suboptimal diet is the single leading modifiable cause of poor health in the world, exceeding the burdens due to tobacco and excess alcohol consumption combined.” They then go on to look at fat. Why, I know not. But it is quite interesting to see which countries eat what types of fat. Where people eat more saturated fat, they often eat more unsaturated fat. For all I know this may help to explain why nearly everyone everywhere is enjoying their food more and living longer.

OL   The only point worth mentioning about drugs for diabetes is that they will be taken for a long time by high risk people, so it is absolutely necessary to know what they do in the long term. For some reason this barn-door-obvious principle does not seem to have got through to those who are supposed to ensure the safety of drugs. Regulatory agencies and second-line agencies like NICE have been perfectly happy to license or recommend incretin mimetics for type 2 diabetes without any long-term safety data. For the sake of the millions who take them, I hope they really are safe: but all one can say at this point is that they don’t seem to increase the risk of pancreatitis, as at first feared. This meta-analysis admits its limitations but gives no clear danger signal. As for the risk of pancreatic cancer, cardiovascular events and so forth, we’ll just have to wait and see.

Plant of the Week: Ribes x gordonianum

This is the flashiest of the flowering currants, covered with flowers of spiky yellow and orange-red. Although it is extremely easy to propagate – just put a stout twig in the ground almost any time of the year – it is hard to find in nurseries and garden centres. Great was my joy when I tracked one down, and great was my chagrin when it flowered and turned out to be Ribes odoratum, with clove-scented yellow flowers of no great merit.

Ribes gordonianum has glossier leaves than most currants, and these are said to be aromatic. This is true, but their aroma is the typical currant-whiff of cat’s pee. But this smallish shrub still well worth having if you can find one: and do propagate it for your friends.


  • George

    What a perfect precis of the fat study.
    Do you think it even slightly possible that the decline in diabetic complications post 1995 represents a rise in the number of diabetics going low-carb after diagnosis?
    As far as I know, complications are rare in this group.

  • kidmugsy

    “promoting appropriate care”: a tautology, surely?