Richard Lehman’s journal review—14 May 2018

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 10 May 2018  

Blocking veins to heal ulcers

British surgeons are doing rather well in the NEJM just now. This week’s print copy features the ground-breaking PRECISION trial of prostate MRI which I commented on a couple of weeks ago, while queuing on the journal’s website we have the EVRA trial of early versus delayed vein surgery for varicose ulcers. Pooling and retrograde flow of blood in the legs is thought to be the mechanism which maintains skin breakdown in people with varicose ulcers. That’s the logic of ablating superficial leg veins in the hope that the blood then diverts to the deeper veins and allows the ulcer to heal faster. The hypothesis that early ablation would result in faster healing than deferred ablation was tested in 20 hospitals around the UK. And it did: median healing time 56 days versus 82 days.

Arteries make the best CABG

Gosh: a systematic review has sneaked its way into the New England Journal. Or should we say “snuck”, as this is America. Conveniently for surgeons who wish to bypass blocked coronary arteries, the human extremities contain two spare vessels: the radial artery and the saphenous vein. There have been a number of small randomised controlled trials comparing outcomes from the two, but none of sufficient size to be definitive. But now the NEJM has discovered this thing called individual patient data meta-analysis, which can solve the problem by, well, combining individual data from trials. There was no mortality difference between 534 patients with radial-artery grafts and 502 patients with saphenous-vein grafts, but the use of radial-artery grafts for CABG resulted in a lower rate of adverse cardiac events and a higher rate of patency at 5 years of follow-up.

Fluids in major abdominal surgery

And now from Australia and New Zealand, a third surgical paper from the NEJM website, imparting useful knowledge for practice. Fashions in fluid replacement are always changing, and current guidelines for patients undergoing major surgery recommend a restrictive intravenous-fluid strategy to promote recovery. But why, when there is no evidence one way or the other? Too often guidelines are about what eminent people think: Claude Bernard’s reply would have been “Why think, when you can do the experiment?” So the Ozzies and the Kiwis did the experiment and lo! “Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury.”

JAMA 8 May 2018

Water cure for kidney disease?

In 1945, the US Board for Food and Nutrition declared that the ideal fluid intake of a human being is 2.5L a day. The concept that humans can’t rely on thirst to tell them how much to drink has taken on a strange life of its own, and the survival of Western humanity has come to depend on the constant consumption of water from plastic bottles. Moreover, in recent years, a large percentage of people have been found to have an estimated glomerular filtration rate of between 30-60 mL/min per 1.73m2, conferring on them the status of “stage 3 kidney disease”. Should they be coached/coaxed into increasing their water intake even further? In a Canadian trial, the coaxed group produced more urine, but their kidney function was the same after a year as the uncoaxed group. Time for a trial among the inhabitants of the Kalahari desert.

Instil gemcitabine for early bladder cancer

Hurrah for a trial called SWOG SO337. I’ve long since given up on working out what trial acronyms are supposed to mean, and I don’t even know if this counts as an acronym. Sufficient that it is a SWOG. It’s the label of a fairly useful study showing that gemcitabine by intravesical instillation is better than saline at reducing recurrence after resection of low-grade non-invasive urothelial carcinoma. The discussion section is usefully modest and the authors point out the need for more single-instillation trials of other cytoxics in this situation.

JAMA Intern Med May 2018

Grouped treatment for grouped pain

Pain is a solitary experience. Group effects may tell you which treatment is most likely to work for people in general, but not what treatment will actually take away your own pain or that of the individual you are trying to help. Expect analgesic failure; pursue analgesic success is a great essay setting out these principles, though since it was written in 2013 its authors have sometimes slid back into discussing analgesia in terms of conventional meta-analytics. Here’s a systematic review of psychological interventions for pain which comes up with few insights except that group therapy tends to be more effective than individual therapy. This suggests that the loneliness of pain becomes part of the pain for many people.

The Lancet 12 May 2018

Immunoscore for colon cancer

A new prognostic score for people with stage I-III colon cancer combines the efforts of more than 100 authors, one of whom is now dead.

This huge consortium has been at work since 2012 and its conclusions are based on data from 2681 patients. “The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I–III colon cancer.” Studies like this always make me feel a bit dim and very old. It took a while for it to dawn on me that the sentence quoted means that the total of the tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts IS the Immunoscore, not just a part of it, and the comparator is the old TNM classification. I was expecting some extra immune receptor bells and whistles, but if these exist, they don’t feature here. And I still wonder if clinicians actually use such scores, and if so for what? And with rapid advances in treatment, aren’t they going to be out of date before the ink is dry on the print-out? As for the patients, the authors claim that “the Immunoscore provides a reliable estimate of the risk of recurrence”, but with the wide 95% confidence intervals they cite, it does no such thing. It’s just an incremental improvement on the usual TNM score, with huge uncertainties for individual patients.  

Bare metal stents for saphenous grafts

I’ve also tried to apply my fading powers to coronary stents for 20 years, but I still haven’t worked out who is the winner. Yes, I know that drug-eluting stents were declared better than bare-metal stents about 15 years ago, but it’s the why that escapes me. Could the whole cardiology community have been wrong? Well, perhaps; I’m afraid it has form. But here is a nice clear comparative trial that compares bare metal stents with drug-eluting stents in a post-CABG population. “In patients undergoing stenting of de-novo saphenous-vein-grafted lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found.”

The BMJ 12 May 2018

Stroke risk from AF is never “resolved”

The problem addressed by this excellent database study is not really a clinical one, but an artefact of the awful payment incentive system which applies in this country: “In England.. patients with a record of resolved atrial fibrillation are excluded from the Quality and Outcomes Framework atrial fibrillation (AF) register, a scheme that incentivises appropriate management of patients with atrial fibrillation in primary care; guidance issued by NHS England states that patients with resolved atrial fibrillation should be ‘removed from the register.’” But the fact is that you can never be certain that AF has “resolved” unless you have your patient wear a monitor indefinitely, night and day. The principal finding of the study is that in patients with a diagnosis of resolved atrial fibrillation, the rates for stroke or TIA are lower than in patients with unresolved atrial fibrillation, but are 60% higher than in patients with no history of atrial fibrillation. These figures are derived from The Health Improvement Network (THIN), a database covering about 14 million people registered with NHS general practitioners. The answer: (a) abolish QOF, (b) abolish the term “resolved AF” and (c) ensure that everybody taking anticoagulants for AF knows their risk whether currently in overt AF or not.

Sham vertebroplasty rules

Osteoporotic compression fracture of a vertebral body often causes severe pain and incapacity, and the urge to do something has driven the widespread adoption of percutaneous vertebroplasty, despite a shaky evidence base. This latest trial from the Netherlands shows that the procedure works—but only as well as a sham procedure.

Plant of the Week:Magnolia sinensis

There are three very similar magnolias with exquisitely beautiful and highly scented pendent flowers at this time of the year. This one is simply named for China: the other two are named after the great plant hunters Wilson and Siebold. How—or indeed whether—you distinguish them depends on what book or article you read, and whether you are at heart a botanist or a gardener.  

The temptation to which I foolishly yielded was to plant sinensis on a bank which we proceeded to crowd with other things. The idea was to be able to get under the branches to enjoy the incomparable flowers right from the start. But now it is a rather stunted, lanky fellow. What you should really do is give this tree as wide an area as it likes—say 6 metres—and just wait for it to grow until you can easily get under its many trunks and branches. O to be young again, and rich enough to plant whole groves of them!