Richard Lehman reviews the latest research in the top medical journals

NEJM 15 Mar 2018

Forever seeking Zika
Here is a study of pregnancy outcomes following Zika virus infection (ZIKV) in France. Yes, you read that right. I don’t mean European France of course; but Guadeloupe, Martinique, and Guyane are all officially departments of France, two of them in the Caribbean and the third on mainland South America. This paper belongs to the rare category of a twenty-first century colonial case series, consisting of pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. In these countries, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. This is very much in line with other estimates from other areas, but much lower than estimates from the original Brazilian outbreak.

Levitating ventricular assist devices
Pulselessness is a state we will all reach some day, but for a few it denotes the continuation of life by other means. Mechanical-bearing axial-flow pumps which do the work of the heart have been around for many years now, pushing out a continuous output at a relatively high risk of mechanical breakdown or stroke. Their new competitors are magnetically levitated centrifugal-flow pumps, which should have lower rates of such events. And so they do, according to a two-year randomized trial testing one Abbott-manufactured device (HeartMate II) against another (HeartMate 3). All the patients, who had advanced heart failure, took aspirin and warfarin after device implantation. Device replacement was markedly lower for the newer device, and the overall stroke rate was less; but the rates of disabling stroke and death were similar.

JAMA 13 Mar 2018

Healthcare spending: lessons from the USA
This article is a very good summation of what is known about advanced health care systems and how they compare with the USA. “The United States spent approximately twice as much as other high-income countries on medical care, yet utilization rates in the United States were largely similar to those in other nations. Prices of labor and goods, including pharmaceuticals, and administrative costs appeared to be the major drivers of the difference in overall cost between the United States and other high-income countries.” In fact the problems are so deeply embedded that it would take a truly radical—even socialist—administration to address them. That seems pretty impossible now: but if the right person were to appear, who knows?

Sodium and potassium in the US diet
The most reliable way to find out what electrolytes go into the body is to measure those that come out. I am sceptical about any study of the effect of sodium or potassium on human health that does not use this method: it is part of the reason why, for example, there are two Cochrane reviews of the effect of salt on health which reach opposing conclusions. Here is a benchmark setting study of 827 American adults. Men over there excrete an average of 4.2g of sodium a day in their urine (90% of the total) and women average 3g. The figure for potassium in both sexes is about 2.2g. The broader epidemiological context here is that levels of BP in the population have been declining slowly over several decades, and levels of cardiovascular disease have dropped steeply since 1980. However sodium-loaded American food tastes to an outsider, the American cardio-renal system seems to cope.

BP targets in diabetes
This article on blood pressure targets for people with diabetes ends by saying that “open discussion and debate regarding the diagnosis and treatment of hypertension are essential, as is ongoing research to define optimal diagnostic and therapeutic approaches. As the process proceeds, individualization of patient goals and targets should be placed at the center of discussion.” Three years ago I tried to say this to a leading professor in the field and was greeted with incomprehension. Now he is saying the same thing. I don’t think that has anything to do with me. The climate has mysteriously changed as everyone begins to recognize that mass medication of the population needs to be accompanied by shared understanding. But this is hard work. The article is a commentary on the differences between the guidelines of the American Diabetes Association and those of the American College of Cardiology/American Heart Association relating to blood pressure targets in diabetes. The elders of these tribes met together for many months of deep thought and discussion, based on the same evidence base, and came up with a set of different conclusions. People who had these conditions were kept out. And this will continue to happen for many decades unless we develop a science of the Shared Understanding of Medicine.

JAMA Int Med Mar 2018

Selective publication, again

The Shared Understanding of Medicine should begin with data sources that are clean and complete. But it can take heroic levels of effort to overcome the concealment and obfuscation which are still rife in medical research. Here Deborah Zarin—who is a true hero—and her team look at a sample of drug trials to discover where the results can be found. Clinicaltrials.gov was a unique source of results for nearly one-quarter of sampled drug trials and more than one-tenth of sampled sponsor-drug-condition trial sets. However, results remain unavailable in Clinicaltrials.gov or PubMed 7 or more years after study completion for nearly one-quarter of sampled drug trials and more than one-tenth of sampled sponsor-drug-condition trial sets. Remember: this is not some technical nicety. We are talking about the foundations of evidence-based medicine.

Ann Int Med 13 Mar 2018

Colonoscopy and mortality

I am temperamentally averse to screening, and also to having things put up my bottom. Nevertheless, I am prepared to keep an open mind on screening for colorectal cancer by colonoscopy. This case-control study from the US Veterans’ Administration shows a large effect on mortality from colorectal cancer in the screened group compared with those who were not screened: the odds ratio for left sided cancer was 0.28 and for right-sided cancer 0.54. But people who turn up for screening have different characteristics from those who don’t. In randomised trials, outcome differences were usually smaller or non-significant.

The Lancet 17 Mar 2018

Dual anti-platelet drugs after stenting: 6 months or 12?

Drug-eluting stents occlude more frequently than bare metal stents unless patients take dual anti-platelet therapy (DAPT). The duration of this was an important issue when clopidogrel was still an expensive drug: it still is an issue in some contexts. So it would have been nice if this South Korean trial had shown that 6 months of DAPT produced the same results as 12 months. But alas there was a slight absolute increase in the risk of myocardial infarction in the six-month group.

The BMJ 17 Mar 2018

Don’t be a checkpoint Charlie

Immunologists love to discover pathways that might lead to new treatments, and often give them dweeby names (hedgehog signalling will always be the favourite). In the first paragraph of this exceptional systematic review you will learn about checkpoint inhibitors, especially those aimed at the programmed cell death 1 (PD-1) pathway. You will make the acquaintance of nivolumab and pembrolizumab (how do you do—haven’t we met before somewhere?) and avelumab, atezolizumab, and durvalumab. By now you may be thinking of pouring your wine into a plant pot and trying to sneak out of the party, but I won’t let you. I know you’re not an oncologist, but these guys are really interesting, both for the good and their harm that they do. And this review is a rare and laudable example of a really thorough exploration aimed at discovering the adverse effects they can cause in people who are taking them to extend life by a few months on average. Most of this information comes from clinicaltrials.gov and it is far from complete. Now OK, I understand that your babysitter has fallen ill and you have to go, but please bear this in mind for another occasion.

Endovascular treatment for stroke: looking good

One of the biggest medical advances in recent years has been the development of endovascular treatment for strokes due to proximal intracranial vessel occlusion in the anterior circulation. Here’s a follow-up study of 1488 patients included in the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) Registry who had received endovascular treatment, including stent retriever thrombectomy, aspiration, and all alternative methods for acute ischaemic stroke within 6.5 hours from onset of symptoms between March 2014 and June 2016. Rather confusingly, this registry also contains data from patients who had these procedures in routine clinical practice in the Netherlands after the end of the trial, and this article compares the two subsets. The conclusion is satisfying: in routine clinical practice, endovascular treatment for patients with acute ischaemic stroke is at least as effective and safe as in the setting of a randomised controlled trial.

Plant of the Week: Daphne pontica

On the occasional still sunny day in March, the native British woodland daphne, D laureola, produces a haunting spicy scent from the little green flowers that hide under its leaves. For the rest of the year, it is a typical daphne, a bit straggly and modest to the point of sulkiness. Its main merit is that unlike the rest it is fairly indestructible and easily propagated from cuttings.

Daphne pontica is a similar evergreen plant from South Eastern European woods, but has the great advantage of holding its little bunches of scented flowers where you can see and sniff them, and of having a compact habit which is attractive all year round. It seems reliably hardy in England, but you may have to look around specialist nurseries for it, as it isn’t at all the kind of shouty plant that attracts garden centres.