Richard Lehman’s journal review—3 July 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  29 Jun 2017  Vol 377

Electricity vs escitalopram

Two milli-amperes of direct current over half an hour is not a lot of electricity, but in a Brazilian trial this tiny zap delivered through the cranium (tDCS) not only relieved depression, but even induced mania in a few people with unipolar depression. It was applied over 15 sessions every day (with weekend breaks) and then weekly for 7 weeks. Meanwhile, other groups were receiving sham electrotherapy with escitalopram, or placebo. The depressed people who did best were those who got escitalopram 20mg daily, but the direct current was better than placebo. The investigators concluded that “non-inferiority could not be established” for tDCS compared with escitalopram, and it also tended to cause “nervousness,” and local reactions around the electrode sites. Maybe this trial’s main value is in showing that escitalopram actually works better than placebo for some people, and so does a tDCS for some. The really electrifying moment will come when we are able to match these treatments to individuals.

Are antibiotics laudable when letting out pus?

Pop goes the abscess, and out comes the creamy laudable pus. Youch, squeeze, and there’s a bit more. Put on a dressing and nature will usually do the rest. But not always: in this trial, 31% of small skin abscesses had not resolved by about three weeks after incision and drainage. That fell to 18% if the participants received either clindamycin or cotrimoxazole. In this American population, half the abscesses were caused by meticillin-resistant strains of Staphylococcus aureus. Clindamycin caused roughly twice the number of adverse effects as placebo or cotrimoxazole, so the latter seems to me the antibiotic of choice in this situation.

Aspirin to prevent pre-eclampsia

The title of this paper, “Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia” produced so many waves of dèja-vu that I wondered if I was having a temporal lobe fit. Here is why: “In 1979, a study showed that women who had taken aspirin regularly during pregnancy were less likely to have preeclampsia than women who had not. In the subsequent decades, more than 30 trials have investigated the benefit of low-dose aspirin (at a dose of 50 to 150 mg per day) for the prevention of preeclampsia; a meta-analysis of these studies showed that such therapy resulted in a 10% lower incidence of preeclampsia.” So why another trial with a placebo group? The answer lies in the definition of a “high-risk” group. Bear with me here: this may seem dweeby but I think it’s neat. You can use Bayes’ theorem to combine the a priori risk from maternal factors with biophysical and biochemical measurements obtained at 11 to 13 weeks of gestation. A study involving approximately 60,000 women with singleton pregnancies showed that such screening detected 76% of cases of preterm preeclampsia and 38% of cases of term preeclampsia, at a screen-positive rate of 10%. So the investigators selected their 1776 participants on this basis, and the crude figures speak for themselves: “Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin (150mg daily) group, as compared with 35 (4.3%) in the placebo group.”

JAMA 27 Jun 2017  Vol 317

Electroacupuncture to reduce urinary leakage?

In the prescientific era, non-drug treatments (bleeding and trepanning excepted) which had a big placebo effect were usually safer than treatment with toxic herbs and minerals. Acupuncture remains immensely popular in China and is widely offered in the West, especially in Germany. Add a little buzz of electricity and you may increase the effect. The most successful sham-controlled trials of electroacupuncture tend to come from China, like this one which reports that “real” acupuncture with electricity caused women to leak less urine at six weeks than “sham” acupuncture without electricity.

The proof is in the pee-value, which in this case was 7.3 mls. However, another Chinese trial of acupuncture which JAMA has seen fit to publish shows that acupuncture has no effect on fertility in polycystic ovarian syndrome. A sensible editorial discusses these trials in context, but lets itself down in the final sentence: “Clearly these ancient practices are helping reveal the complexity of the links between the mind and the body.” Unclearly would have been the better word.

Chest pain: more tests, same outcomes

You’ve heard this before in various forms, but it bears repeating. Testing everybody with chest pain “just to be on the safe side” results in more downstream procedures without any evident benefit. Here the cohort consists of 900,000+ privately insured Americans who presented to the emergency department with chest pain, but without an initial diagnosis of ischaemia. After risk factor adjustment, testing within 30 days was associated with a significant increase in coronary angiography (36.5 per 1000 patients tested) and revascularization (22.8 per 1000 patients tested) over the following year, but no significant change in admissions for myocardial infarction. But I don’t suppose that this massive demonstration of futility will make the slightest difference to practice.

The Lancet 1 July 2017  Vol 390

GETSET for another CFS/exercise controversy

Trials of exercise in chronic fatigue syndrome can get rapidly shrouded in the fog of war, as happened to the last one published in The Lancet. Prophylactically, the investigators of this one are seeking to make their data openly available as soon as possible. They recruited 211 adults who met the NICE criteria for CFS and randomised them to receive usual specialist care or a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). So this was a light-touch intervention requiring little professional time; and yet it made a clinically significant difference to fatigue scores at 12 weeks. The authors conclude that “graded exercise self-help  is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings.” Modesty, awareness of context and the need for replication, and willingness to share data: why can’t all researchers display these virtues?

Misoprostol v Foley catheter for inducing birth in India

Distending a Foley catheter balloon in the cervical canal is one way of inducing labour: giving oral misoprostol is another. The two methods were compared in two Indian hospitals, and the indication for induction was high blood pressure, either pre-existing or due to pre-eclampsia. Misoprostol induced labour more effectively and may have been safer in this setting, though the serious maternal and fetal events were too few to reach a definite conclusion.

The BMJ 1 July 2017  Vol 357

Melanoma & the pathologist’s word

As with the diagnosis of papillary thyroid carcinoma, the huge increase in diagnosis of early melanoma has not been accompanied by any significant change in cancer-specific mortality. If you attend Overdiagnosis-related conferences, you’ll be familiar with those charts showing a straight mortality line at the bottom and a 40 degree ascending diagnosis line above. But I bet if you had a dark skin lesion removed and the pathologist’s report came back with the word “melanoma” on it, you would lie awake feeling for lymph nodes and thinking about music for your funeral service. In both cases, the histological label is a large part of the problem. It’s hard to summarize the statistics from this study of the reproducibility and inter-observer agreement among American pathologists who looked at dark bits of excised skin under the microscope. Suffice to say that “Diagnoses spanning moderately dysplastic naevi to early stage invasive melanoma were neither reproducible nor accurate in this large study of pathologists in the USA.” Despite all the advances of modern molecular diagnostics, the word of the fallible pathologist remains law. We are still living in the Dark Mole Age.

High IQ children live longer in Scotland

If you can endure the climate, there are probably some advantages to a long life in Scotland: fresh fish, malt whisky, scenery and the sporadic occurrence of intelligent politicians, for example. To achieve this goal, it is best to be born with a high IQ. Most of the subsequent tendency to longevity can probably be attributed to avoiding smoking, becoming prosperous and perhaps eating more fruit and drinking wine. Some of these are discussed in this well-publicised paper.

Is this muscle pain caused by my statin?

This is one of the most enjoyable editorials I have ever read in a medical journal. It dances with good sense before concluding that the only way to find out if an individual’s symptoms (which need not be muscle pain but could include muscle fatiguability, for example) are due to statins is to do an n-of-one trial. If you are one of the many doctors or non-doctors who have experienced these symptoms, or know a patient who has, enrol in SAMSON via the website: travel (just twice) is paid. There are some questions this trial won’t settle, for example if the effects are very slow to develop or resolve, or if they are subtle changes in activity in old people with borderline function. But at least this starts to address the question from a non-pompous perspective. It begins with the presumption, “I’m sorry I haven’t a clue”: the antidote for Lancet panel games.

Plant of the Week: Hemerocallis “Berlin Red”

The day-lilies are a gardening beginner’s dream: imperturbably hardy, undemanding, fast-growing, easy to split and available in a huge range of colours. Each flower lasts a day, so in the evening you can go out and eat the already shrivelling petals, which are not just edible, but often sweet and peppery.

There are varieties which appear as early as May, but the tallish, stately “Berlin Red” usually waits until July. Like most plants, it is early this year. Its dark red flowers, streaked with sober buff yellow, are perfect among blues, yellows and whites. But I would not advise planting it near pink, orange or magenta subjects, unless you are a Great Dixterist and delight in offending the eye with random shrieky combinations.

The problem with day-lilies comes in the autumn, when their leaves flop and rot in welts of yellow slime. So although our garden was once a showcase for numerous varieties sold to us by the keeper of the National Collection, we now only have two kinds left. The autumn mess is thereby reduced, but so is the summer exuberance of our garden, and the pendulum may yet swing back to the day-lilies of years gone by.