Richard Lehman’s journal review—2 January 2018

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 21-28 Dec 2017  Vol 377

When to clamp the cord in preterm babies

The result of this trial is nice and simple: “Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping.” Nevertheless I managed to struggle with it, due to the word “gestation.” These babies had been out of the womb for 6+ weeks before they reached the outcome point, because they were all born before 30 weeks’ gestation. They had been randomised as fetuses (sorry Mr Trump, it just slipped out) in mothers who were at high risk of preterm birth. So just to repeat the Australian trial’s message for Pommie simpletons like me: when babies are born before 30 weeks’ gestation, they are not disadvantaged (oops, done it again) by immediate rather than delayed cord clamping, as judged by outcomes at 36 weeks. Not being an obstetrician, I don’t know whether this has changed the climate (damn) of opinion in the specialty.

MRI magnets and cardiac devices

I spent Christmas week trying to follow an intellectual biography of Michael Faraday, to whom we owe the invention of immensely powerful electromagnets like those found in MRI machines. He would have been fascinated by the idea of magnetic resonance imaging, though it involves quantum effects which remain deeply counterintuitive, even after nearly a century. That would not have fazed him because he kept an open mind about deep theory throughout his life. Faraday instead would have gone on to devise simple experiments and observations which open the way to more fruitful speculation. I think he would have liked this simple experiment performed at the Johns Hopkins Hospital in Baltimore. Never mind the quantum stuff: does a magnetic force strength of 1.5 Tesla pose any threat to the health of patients who have implanted old-generation pacemakers or defibrillators? The answer, happily, is no.

JAMA 19-26 Dec 2017  Vol 318

Necessary pessary?

Now we return to the art and mystery of obstetrics and preterm birth. It’s a known fact that women with short cervices are at risk of premature delivery, but it isn’t clear whether this can be prevented by the use of a supporting pessary. Past trials have had mixed results, but have generally been of poor quality and mixed together primiparous women with those who have had a previous premature delivery. Here’s a study from Naples, splendidly conducted as befits that wonderful city. Some visitors there see only dirt, danger and dilapidation, but I taste perfect mozzarella, shining fresh fish, incomparable pizza and exquisite ice cream. Cervical length was measured three times in primiparous women of gestation between 18-24 weeks. Those with a measurement of 25mm or less were randomised to pessary fitting or no pessary. The pessary group had significantly fewer births before 34 weeks.  

Broad spectrum antibiotics and old lessons

After 75 years of widespread clinical use, penicillin ought to be utterly useless by now. But what actually happened after its introduction was that the bugs which could neutralize it (usually by producing beta-lactamases) went ahead and did so within 5-15 years, and the rest remain sufficiently susceptible to make penicillin a useful drug even in 2018. That’s even truer of amoxicillin, which (as its metabolite ampicillin) came into use in 1961. I must have prescribed it every working day in general practice from 1979 to 2015 without any noticeable diminution of effect. Most of these prescriptions, I cheerfully admit, may not have made very much difference, though many undoubtedly did. What I won’t concede, however, is that the prescription of these drugs by GPs has any place in the popular narrative of catastrophic antibiotic resistance, except to cast doubt on it. Here is a magnificent study of antibiotic prescribing for children with otitis media, group A streptococcal pharyngitis and/or acute sinusitis. It was carried out in Pennsylvania and New Jersey and looked at outcomes for 30,159 children retrospectively and 2472 prospectively, according to whether they have been prescribed penicillin or amoxicillin (“narrow spectrum antibiotics”) versus a macrolide, a cephalosporin, or amoxicillin-clavulanate (“broad spectrum”). There was no difference in treatment failure (3.1% for narrow, 3.4 for broad) but more adverse effects in the broad-spectrum group.

Single shot antibiotic for metalwork removal

Of course, how you choose and use antibiotics can make a big difference to outcomes—success, failure, or resistance. In this trial, patients with fracture fixation metalwork below the knee were given a single 1g shot of intravenous cefazolin 15-60 minutes prior to its surgical removal. This made no significant difference to rates of local infection over the next 30 days, compared with normal saline, even though the great majority of organisms isolated were sensitive to cefazolin. Perhaps you need to give some more of the stuff post-op. Or perhaps it just doesn’t work as prophylaxis.

Vit D + calcium does not prevent fractures

Deprescribing can be difficult, but here is an easy first step which you can take with the next old lady who comes through your door. “In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people.” Just a matter of swallowing hard and admitting you were wrong to prescribe them in the first place.

JAMA Intern Med Dec 2017

Guidelines and escalation

For the last 20 years, guidelines have acted as vectors for overtreatment. They also represent a huge duplication of effort, as shown by this research letter which identified 22 guidelines for diabetes and cardiovascular disease promulgated in the US alone between 2012 and 2016. Over 70% of their recommendations involved intensification of treatment, while 29% involved deintensification. Guidelines take misshapen stones of evidence and set them in a weak mortar of opinion. As the mortar crumbles, they slap on some more. This is no way to build an enduring cathedral of knowledge.

More CTs, fewer kidneys

Just before the holidays, the NEJM went out of its way to publish an article attacking the Less-is-More crusade (sic) in medicine. This was obviously an attack on JAMA Internal Medicine which has long hosted a series of articles under this heading, and on Dartmouth College which is mentioned by name as a leading centre for this “crusade”. It’s rather delightful therefore to see JAMA IM publishing this first-rate analysis by Gil Welch et al (Dartmouth) of rates of nephrectomy and the use of chest or abdominal CT scanning. Since the introduction of these investigations, which produce images of the kidneys as a by-product, the rate of kidney removal in the USA has doubled while mortality from renal cancer has remained unaltered. Here the investigators show that the more CTs done in any given region, the higher the rate of nephrectomy. The NEJM piece’s title asks “Are we overmedicalizing or oversimplifying?” I’ll leave you to make up your mind in the light of the conclusion to Gil’s paper:

“We should emphasize that surgeons are not deliberately performing unnecessary surgery any more than radiologists are purposely engaged in overdiagnosis. Many clinicians understand the downside of incidental detection. Nevertheless, they are caught in a complex web of forces promoting earlier cancer diagnosis and earlier intervention: strong financial incentives, fear of litigation, and unquestioning beliefs among the public about the value of early diagnosis and treatment.”

Ann Intern Med 19 Dec 2017  Vol 167

Preventing Alzheimer’s (spoiler alert)

This issue of the Annals contains four systematic reviews of interventions to prevent cognitive decline or Alzheimer-type dementia:   

  1. exercise training 
  2. cognitive training 
  3. over-the-counter supplements 
  4. pharmacological interventions 

What do they all have in common?

(For extra points, who was the Prime Minister before last?

What did he pledge to cure/prevent by 2025?)

Achieving BP reduction

A while ago, I had the pleasure of discussing statins with the irrepressible Darrel Francis. Moving in the highest circles of British cardiology (rather him than me), Darrel was struck by the fact that there were two factions who were completely irreconcilable, no matter how long and hard they tried to understand each other. One side took it for granted that they were in the business of preventing cardiovascular disease, and that this mandates urging as many people as possible to take statins. The other side felt that it must be a personal decision based on individual level of risk, and that there would be variations in uptake driven not by ignorance but by informed choice. To me, it seems that exactly the same arguments apply to the treatment of blood pressure. The key factors are: level of SBP, aggregated risk, and options to reduce that risk according to its components. But that would take time and stepwise shared thinking, whereas it is much easier to settle on a single SBP threshold for everyone and use any means available to achieve it. In both cases, though, there arises the question of how best to achieve the agreed-on BP. A useful systematic review shows that doctors alone are not the best people for the job: team uptitration of drugs achieves the best results, especially if physicians are excluded.

The Lancet 23 Dec 2017  Vol 390

Screening to prevent hip fractures?

Falling and breaking a hip is common and unpleasant prelude to death in many older women, with a one-year mortality of 20%. Other osteoporotic fractures are less lethal but very common and incapacitating. In the SCOOP trialwomen aged 70-85 were screened using the Fracture Risk Assessment Tool (FRAX), and this was then used to decide whether or not a participant should be invited for a dual energy x-ray absorptiometry (DXA) scan to assess bone mass density. Treatment was recommended for 14% of the screened group but there was no reduction in the total number of fragility fractures compared with a matched non-screened group. However, hip fractures did show a reduction reaching statistical significance. Time for a national screening programme? No, but room for some more big trials.

Triple antiplatelet therapy and TARDIS

Why use only two antiplatelet agents for cerebral ischaemia when you can use three? Because the TARDIS trial shows that if you mix aspirin, clopidogrel and dipyridamole you get extra bleeding for no clinical benefit.