Richard Lehman reviews the latest research in the top medical journals

NEJM 26 Apr 2018

Tenecteplase v alteplase before stroke thrombectomy

Thrombolysis is widely recommended in stroke guidelines, though it remains contentious. John Mandrola’s recent piece about stroke thrombolysis is a masterly exercise in clear analysis. However, in many patients the simple procedure has now been superseded by thrombolysis plus clot retrieval: this applies to strokes caused by occlusion of the internal carotid artery, basilar artery, first segment of the middle cerebral artery, or second segment of the middle cerebral artery. In this publicly funded trial from Australia and New Zealand, two tissue plasminogen activators were compared as precursor therapy before thrombectomy. One was alteplase, which requires slow IV infusion over an hour, and the other was tenecteplase, a genetically modified variant of alteplase with greater fibrin specificity and a longer half-life, which permits bolus administration. As well as being simpler to administer, tenecteplase was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours.

Azithromycin for African children

“Children in the age group of 1 to 5 months had 24.9% lower mortality than with placebo.” That’s not just some children: it’s all babies under six months in countries with some of the highest child mortality rates in the world: Niger, Malawi, and Tanzania. The intervention was a single dose of azithromycin, and the trial was inauspiciously called MORDOR, Tolkien’s name for the kingdom of evil and the Anglo-Saxon word for murder. Here it’s made to stand for Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance. After the first six months, dosing with azithromycin twice a year prevents trachoma, and has a smaller—but still very significant—effect on mortality in pre-school children. The wonderfully wide-ranging benefit of this antibiotic was discovered in earlier trachoma prevention trials. Babies throughout the poor world should now get this treatment as routine, and I would argue for trials in high income countries too. But what about “avec un Oeil sur la Résistance”? Well obviously keep an eye out for resistance; but that is going to happen anyway in a world currently obsessed with the dangers rather than the benefits of antibiotics.     

Has my patient been exposed to novichok?

Here’s the irresistible NEJM guide to the symptoms and signs of chemical weapons poisoning. It is behind a paywall, which should be lifted for doctors in the Salisbury area and Syria. The rest of us will only be reading out of idle curiosity, hopefully.

JAMA 24 Apr 2018

Type 2 diabetes drugs and longevity

Comparing drugs for type 2 diabetes is tiresome work, let me tell you. When I tried it some years ago, it taught me a lot about inadequate surrogate end-points, skewed comparators, atypical populations and publication bias. Things have improved a bit since, and time has allowed data to accumulate about important outcomes for the new drug classes. I really admire the work that has gone into this network meta-analysis of all-cause mortality in trials of three classes of glucose lowering drugs: sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 Inhibitors. The DDP-4 inhibitors seem to produce the worst outcomes, though there is much devil in the detail.

Getting PAD patients walking

This trial aimed to improve walking distance in people with peripheral arterial disease. The exercise intervention group (n = 99) received 4 weekly medical centre visits during the first month followed by 8 months of a wearable activity monitor and telephone coaching. The usual care group (n = 101) received no onsite sessions, active exercise, or coaching intervention. The mean change from baseline to 9-month follow-up in the 6-minute walk distance was 5.5m in one group vs 14.4m in the other. Have I changed the order round, as Archie Cochrane famously once did in front of an audience of cardiologists? No, I haven’t: usual care was a lot more effective than regular badgering. There is a lesson in here somewhere.

Precisely how abnormal are you?

You’re not normal: get used to it. The long-predicted day when enough tests can be done to ensure universal abnormality has been reached, even without invoking genomics. But John Ioannidis and two colleagues are not as negative about this as you might expect. In a short article they propose a major rethink of diagnostics in the era of big data. This is the opposite of the woolly hype we usually get on the subject, and required reading for anyone interested in the future of medicine.  

JAMA Intern Med Apr 2018

Wisdom and blood pressure

In my younger, funnier days I sometimes attacked the guideline industry head-on, but now I think it’s time to leave it to die on its own. An immense amount of effort and good will goes into the creation of huge documents which consist of lumps of evidence held together by a weak mortar of expert opinion (I think I’ve used this metaphor before, but that won’t deter me): then a bit of Polyfilla falls out or the evidence changes, and the whole thing crumbles and the process starts again. An astonishing example is the deletion of large parts of the stroke guideline only just published by the American Heart Association (AHA)/American Stroke Association (ASA). Another came with the American Medical Association’s failure to agree with the ACC/ AHA’s threshold changes in blood pressure lowering. Quite right too, as you will find if you read this sensible take on the matter by three wise Australians who previously wrote a key paper on changing disease definitions. 

Ann Intern Med 24 Apr 2018

Sigmoid screening and Norwegian women

“Offering sigmoidoscopy screening in Norway reduced colorectal cancer incidence and mortality in men but had little or no effect in women.” I’d like to offer a prize for the person who comes up with the most plausible explanation for this. For the time being, it just serves as another example of the fact that in medicine, few things are predictable. If you want to know what is going to happen, you have to try it out, and then compare it with what happened elsewhere. I’d be intrigued to see if this crazy phenomenon can be confirmed from other sigmoidoscopy screening databases.

The Lancet 28 Apr 2018

Dr Mesmer’s magnetic brain cure

A doctor promising to cure everything with a big magnet makes a cameo appearance in Mozart’s The Magic Flute (1791). Since then, magnetotherapy has skulked in the twilight zone betwixt medicine and quackery, but it is now making a bid to become part of mainstream psychiatry. Don’t be put off by the theta bursts. They may sound like something from Scientology, but intermittent theta burst stimulation (iTBS) is a new form of repeated transcranial magnetic stimulation that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. In this Canadian trial it halved the depression scores of people with treatment-resistant depression, at the expense of transient post-magnetic headache.

Say no to O2

Since Joseph Priestley first revived asphyxiated mice with dephlogisticated air, oxygen has been seen as the way to restore life in all emergencies. Here’s a systematic review of 25 randomised controlled trials which enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery.

“In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy.” We’ll know the culture has changed when TV dramas start showing medics shouting “Quick, take away that oxygen!”

The BMJ 28 Apr 2018

Old surgeons and good outcomes

Watching snooker on the television is a harmless pastime, though you must be sure to press the mute button. Then you can listen to music, or trawl through lists of references, or have a snooze. Such are the diminishing pleasures of elderly life. Should you happen to watch the game, you will find that younger players tend to become overconfident and take on shots which, when missed, lead to their eventual downfall. Older players simply go for safety, and end up winning. Here is a study which shows that surgeons are the same. “Using national data on Medicare beneficiaries in the US, this study found that patients treated by older surgeons had lower mortality than patients treated by younger surgeons. There was no evidence that operative mortality differed between male and female surgeons.” Strange there are so few female snooker players.

Plant of the Week: Clematis macropetala

There are no prettier clematis flowers than those of the genus macropetala, and the mother of the tribe is a pale blue. From her, nurserymen have raised seedlings of deeper blue, pink, and purple. Ours have usually succumbed before they have flowered. We used to put this down to clematis wilt, which is a fungus that attacks at ground level, but I think the problem may have been slugs. This spring there are few slugs, despite the constant rain. And we are delighted to find macropetala clematis shooting up where we’d almost forgotten we’d put them.

They have delicate cut pale green leaves as well as adorable dainty flowers. The only thing they lack is fragrance. But you can easily remedy this by putting a blue one to grow through a big example of Skimmia “Kew Green”.  As you place the blue clematis flowers amidst the big yellow-green heads of the skimmia, you will die a little death of scent intoxication.