Richard Lehman’s journal review—19 June 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  15 June 2017  Vol 376

Single nephrons are all alike

This is the time of year when our thoughts should turn to the kidney. However, I must report with sadness that just the smell of them on the barbecue usually elicits wrinklings of the nose and sharp remarks from the one I love. And this is a problem, since one man alone cannot consume the entire contents of a supermarket packet of lamb’s kidneys on a single occasion. Human kidneys are also harvested, though not for the barbecue. A study of 1388 kidneys from living donors at the Mayo Clinic gives us new insights into the function of their basic constituent, the nephron. By combining CT scanning and biopsies with functional measurements, we now know that the mean number of nephrons is 860,000±370,000 per kidney and that each one filters 80±40 nl per minute. The surprise is that nephrons look and perform similarly in donors of all ages, heights, and weights. The main exception is in people more than 190cm tall, who have better performing nephrons. The Texan nephron.

Abiraterone for prostate cancer

Abiraterone is an agent that blocks CYP17A1 and so prevents the intracellular production of androgen in prostate cancer cells. It was developed from ketoconazole in the 1990s. When oral ketoconazole was available in the UK, it cost about £14 per month. Abiraterone costs about £750 per month. Just saying. Following the success of abiraterone plus prednisolone in trials in advanced metastatic prostate cancer, two trials were set up to cover all groups of newly diagnosed prostate cancer. One was a publicly funded trial in which nearly half the men did not have metastases. The other was a Janssen funded trial in which all of them had metastatic castration-sensitive disease at diagnosis. In both trials abiraterone produced a significant increase in all-cause survival over a period of more than two years. So now a massive market beckons. Can we look forward to a price reduction down to dandruff-shampoo levels? It would be such a nice gesture to men with prostate cancer.

Canagliflozin: saving hearts, losing feet

As I’ve mentioned a couple of times recently, the sodium–glucose cotransporter 2 inhibitors (gliflozins) are showing promise as drugs which lower cardiovascular risk in people with type 2 diabetes. Janssen produces the one called canagliflozin and did a couple of big trials labelled CANVAS in over 10,000 people with T2DM at high CV risk. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. From about two years on, there is a statistically significant difference in favour of canagliflozin for this composite outcome. But there was also a near doubling of risk for lower extremity amputations in this group—(6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. That would need to feature in any shared decision tool, and needs rapid checking with observational databases to see if it might apply to all drugs in this class: a process which nowadays shouldn’t take more than a few days.

JAMA  13 June 2017  Vol 317

Not so FAST: ultrasound for blunt abdo injuries in kids

The question addressed by this randomized trial is: Does the focused assessment with sonography for trauma (FAST) examination safely improve care when used in the emergency department (ED) evaluation of hemodynamically stable children with blunt torso trauma? And the answer is no. It does not. Don’t bother with the abdominal ultrasound unless you have good reason to.

A higher score with FeSO4

In this double-blind, randomized clinical trial that included 80 patients, those who received ferrous sulfate for 12 weeks had a 1.0 g/dL greater increase in hemoglobin concentration than those receiving iron polysaccharide complex.” That’s quite a difference. So who were these 80 patients? They were actually American babies and young kids up to 4 years old attending a tertiary hospital clinic for nutritional anaemia. The evil reputation of ferrous sulfate as a gastric irritant was mitigated here by keeping the dose low.

JAMA Intern Med  June 2017  Vol 177

Education and cardiovascular risk

Alexander Pope wrote that a little learning is a dangerous thing, but this observational study of 14,000 American adults over a period of 26 years suggests that any learning reduces cardiovascular risk in a linear fashion. A little learning is good, and more learning is better. “Educational attainment was inversely related to the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities.” I have absolutely no idea what the second sentence means. Schools not statins? Perhaps a public health physician can help me out.

The Lancet  17 June 2017  Vol 389

Let’s bomb some hospitals

Wars get more sickening the longer they go on. By the time the Germans came to suppress the Warsaw Uprising in 1944, their first targets were buildings used as hospitals, where they indiscriminately killed all the occupants, including their own wounded. Now the same is happening in the long-running war in Syria. A careful analysis shows that “between early November 2015, and 31 December 2016, 938 people were directly harmed in 402 incidents of violence against healthcare: 677 (72%) were wounded and 261 (28%) were killed. Most of the dead were adult males (68%), but the highest case fatality (39%) was seen in children aged younger than 5 years. 24% of attack victims were health workers… Aerial bombardment was the main form of attack. A third of healthcare services were hit more than once. Services providing trauma care were attacked more than other services.”

Aspirin: bleeding dangerous in the old

This follow-up study of 3166 patients in the OXVASC study is a wake-up call to all doctors who prescribe aspirin. This is a dangerous drug for people over 75. But perhaps even more, this study is a wake-up call to all researchers, politicians, and public health savants not to rely on routinely collected data. In OXVASC the data on bleeding were collected by face-to-face encounters at 30 days, 6 months, and years 1, 5, and 10 by a study nurse or physician. There were 405 bleeding episodes in this cohort, and 78% of these led to hospital admission. But a full 37% of these had escaped administrative coding. More than a third! So much for a data-rich NHS: it is more like a data collander with very big holes. This is an immensely important paper for that finding alone. As for those poor over-75s with major GI bleeds, most of them ended up dead or disabled. The authors point to a meta-analysis which shows that 75% of these bleeds could have been prevented by co-prescription of a proton pump inhibitor. I’d suggest that every GP practice in the country should now do an audit of 75+ year old patients, to decide which of them really need an anti-platelet agent, and whether those who do are on a PPI.

The BMJ 17 June 2017  Vol 357

Maternal obesity and birth malformations in Sweden

I hope data collection in Sweden is better than in the UK, because I’m a great fan of their population studies and would be very miffed if they all turned out to be rubbish. Here is one to increase the gloom of mothers-to-be who are overweight or obese. “Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range.” Questions: does this study prove causality? Reversibility? How do rates of these abnormalities differ between Sweden and the UK, where rates of maternal obesity are much higher?

Incretin based drugs and diabetic outcomes

I’ve spent the last nine years pointing out the evidence that reducing blood glucose per se does not reduce macrovascular or even microvascular events in type 2 diabetes. What started as rank heresy is now commonly acknowledged, even as the search goes on for better sugar-lowering drugs. At the moment, simple absence of harm comes as a relief: this systematic review concludes: “Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.”

Plants of the Week: Delphiniums

The point of delphiniums is to add to the bliss of June by producing blue spires across the garden. This contribution lasts through the summer and is an intrinsic element in the classic English “cottage garden”. Like most hallowed British garden traditions, this one started in the 1880s, when tall delphinium hybrids began to appear in the seed catalogues.

Choose the ones you most like: personally, clear pale blue is what I most adore in a delphinium. Hybridists have produced yellows, reds and oranges, though you have to look hard for them. I would suggest you don’t bother. Similarly, a delphinium isn’t greatly improved by being so double that it is frilly, though that may suit some knicker-pink varieties, if those are your thing. Many delphiniums have centres of black – making them look bee-blessed – or off white. All good.

Graham Stuart Thomas points out that these delphiniums are caviar to slugs, and for years we struggled to get any leafage to remain on ours. Last year I watered some nematodes into our soil – just the once, and later in the season than the packaging suggested. This year we have hardly any slugs, and the delphiniums are already over a metre high. Time to get out there and stake them.

Although they have no scent in themselves, they should rise among fragrant roses. And mock oranges. And honeysuckles. And summer-flowering magnolias. June is just one miraculous glut for the senses.