Richard Lehman’s journal review—4 December 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 30 Nov 2017  Vol 377

An aura of hope for migraine

I’ve always been ashamed of having migraine. It seems such a poor excuse for not doing things. I used to plan my life around not getting overtired, or even elated, for fear of the zig-zags and the days of thudding pain and dejection that might follow. I’d stay on and work badly rather than admit to having an attack. It was better to be thought moody and difficult—which I am too of course. My story is a very common one, and nothing compared to the horrors endured by those with truly severe chronic migraine. The best narrative I’ve read (though I am biased) was recently written by my stepdaughter.

News of a potential breakthrough in migraine treatment will be welcomed by millions of women and men. I’m old enough to remember the arrival of triptans in the early 1980s. They had their uses—and weird effects—but haven’t proved the hoped-for panacea. Now come the mabs: erenumab, eptinezumab, fremanezumab, and galcanezumab. All of these target calcitonin gene–related peptide (CGRP), a widely distributed neurotransmitter which influences both neuronal modulation of pain and vascular activity.

If this sounds vaguely familiar, it is because of the gepants. These are not the famous pants worn by Superman to defy the G-force, but CGRP receptor antagonist drugs like olcegepant and telcagepant which have been around for a few years. So how do the new mabs perform? There have not been any head-on trials with the gepants (of course), but here are two short placebo-controlled studies with different end-points (sighs).

Fremanezumab is an antibody that goes straight for the peptide, and it was trialled in people with “chronic migraine”, i.e. lots of it every month. The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group. A lot of the press headlines have got confused over the arithmetic here, and no wonder. Spend a minute or two with the article itself.

The second trial used erenumab, which targets the CGRP receptor rather than the peptide itself, for episodic migraine. Again, the arithmetic takes some navigating. “The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through to 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group.” There seem to have been fewer injection site reactions compared with fremanezumab, but the real worry is that antibodies beget antibodies, and we don’t know how long these mabs will remain effective or what long-term harms they might have.  

JAMA  28 Nov 2017  Vol 318

Never mind what’s in them dear, just swallow the capsules

The capsules here contained wholesome faecal microbiome to prevent recurrent Clostridium difficile infection. A trial in 116 patients  shows they achieve the same 96.2% success rate as the same thing inserted via a colonoscope. Good shit, as we used to say back in the hippy days. The capsules were rated as “not at all unpleasant” by 66% of the Canadians in this trial, and 44% said the same of colonoscopy. The winters are so long there.

Fix hip fractures the same day

It’s a rather lean week in the journals, or I wouldn’t be reporting this retrospective observational study from 72 hospitals in Canada. They found 42,230 patients who had been operated on for hip fractures between 2009 and 2014. Patients who had their surgery within 24hrs had lower mortality at 30 days than those whose operations were delayed beyond that. Naturally, they matched patients by propensity scoring. But this is not an exact art, and the overall difference was 5.8% vs 6.5%: maybe not the most robust basis for a major quality indicator.

JAMA Intern Med Nov 2017

“No I won’t”: how to make patients cross

Like most doctors of my generation, I was never taught communication skills. I suspect the same still goes for most doctors around the world. And even in British general practice training, which probably leads the field, I don’t think many courses teach the gentle art of saying no. Here is a snapshot of one academic family practice organisation in North California, which collected data about denial of patient requests by 56 clinicians. This happened in 15% of encounters, and by and large it caused patients to leave dissatisfied. Who would have guessed? In 20 years’ time, will anything have changed? Only by a slow process of skills training and a culture shift which I’ve taken to calling the shared understanding of medicine (SUM).

Ann Intern Med 28 Nov 2017  Vol 167

More HPV tests, fewer smears

A large observational study from Kaiser Permanente reaches the conclusion that after one or more negative tests for human papillomavirus, screening for cervical cancer could be spaced out to every five years or longer. In the coming era of HPV vaccination and more accurate HPV detection, cervical cancer may become a true rarity. But the interim period may last a while yet, depending on the mix of local and national policies: trying to follow them takes more storage capacity than my brain has left.

The Lancet 2 Dec 2017  Vol 390

Getting the sperm to the egg helps conception

In a blog last month, Jeff Aronson described the arrival of the word de-adoption in the medical literature from 2006 onwards. 

His next column dealt with its ugly word-sisters exnovation and outroduction. But one of the hazards of evidence-based medicine is that debunking can sometimes be followed by rebunking, In 2013, the UK National Institute for Health and Care Excellence recommended that intrauterine insemination should not be routinely offered for couples with unexplained infertility. But here comes a study from Australia which shows that IUI with ovarian stimulation is a safe and effective treatment for women with unexplained infertility and an unfavourable prognosis for natural conception. Jeff may now need to write another column on re-reversal, de-exnovation or post-outroduction. Readoption or reintroduction will also do perfectly well, though rebunking is my favourite.  

The BMJ 2 Dec 2017  Vol 359

Aspirin doesn’t help leg ulcers

In New Zealand, 251 adults with venous leg ulcers who could safely be treated with aspirin or placebo were randomised to aspirin or placebo. There was no difference in healing or adverse events over 6 months. Being Kiwi means shutting up when you’ve said something. G’day.

The Which Guide to DOACs

Not very long after I began writing these reviews, oral anticoagulant drugs started to challenge the monopoly held by warfarin over decades. For many years they were called NOACs—novel oral anticoagulants—but now that the novelty has worn off, D standing for direct has taken the place of the N. Right from the start I argued that they should be priced to match the cost of warfarin plus its monitoring, so I am very happy to see this network meta-analysis concluding that “apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.” It’s taken a while, and something may yet happen to disturb the pecking order of this indirect comparison table, but we now know with reasonable certainty that for the majority of patients, DOACs carry a lower mortality than warfarin, without the need for dose monitoring.

Plant of the Week: Vinca major

The nobler kind of gardener uses the cold, damp, muddy weeks running up to Christmas to do some tidying up before the weather gets even worse for two months. So far, we have resisted any urge to follow their example. The down side of this cowardice is that we won’t make any discoveries of forgotten treasure hidden under heaped leaves. But we can still spot a few nice things as we sally out briefly in our overcoats.

Chief among these is the common periwinkle, which seems to flower the whole year round. We have a patch of these on a road bank. Perched high up, its blue flowers, though few in number, provide passers-by with a welcome reminder of life and beauty.

  • JDavidP

    How about a migraine combo? Use the direct acting mab with the receptor blocking mab. Better results?
    Wait. Worse results happened when combinind ACE inhibitors with ARBs. But is that the same??

    Not having a reversal agent for my apixaban makes me somewhat nervous, its high rating for better outcomes notwithstanding.
    You’re not nervous about that?