Richard Lehman’s journal review—28 November 2016

richard_lehmanNEJM  24 Nov 2016  Vol 375


It grieves me to say it, but there are certain things that American medicine does better than British medicine. Repairing abdominal aortic aneurysms seems to be one of them. It’s not that men on the whole live longer over there, but only a third as many die from a ruptured AAA in the USA as in England, according to a study using linked databases on both sides of the ocean. In America they tend to go in and repair at 58mm whereas we tend to wait until 64mm, and they do twice as many repairs, suggesting a screening effect. Perhaps as our screening programmes gather momentum, we will see a gradual levelling of difference; but for the time being, America definitely trumps England. Damn, I must learn to stop using that expression.

The ART and graft of cabbage

Another British study features on the NEJM website, this time from Oxford cardiothoracic surgeons who set up a multinational trial 12 years ago in 28 cardiac surgery centres. If trials must have acronyms, at least make them short and sensible: Arterial Revascularization Trial (ART) is neat, even artful. The primary objective of the trial was to compare 10-year survival rates associated with bilateral and single internal-thoracic-artery grafting for coronary artery disease (CABG). The 10 years haven’t yet fully elapsed for the recruited patients but the 5 year results show no difference in outcomes, with more surgical complications when two arterial graft sites are used. A noble endeavour with useful results, though actual rates of CABG surgery will have fallen even more by the time the 10 year figures appear.

Levitating heart pump

In Western Christian tradition, St Jude is the patron saint of desperate cases and lost causes. By coincidence there is a medical device manufacturer called St Jude, which makes left ventricular assist devices for use in advanced heart failure. Its axial continuous-flow pump, HeartMate II, has run into problems with thrombosis inside the device, so they ran a trial comparing it with a new fully magnetically levitated centrifugal continuous-flow circulatory pump, HeartMate 3, which was engineered to reduce shear stress on blood elements and avert pump thrombosis. Here are the 6-month results, and they show no thromboses in the new device, and fewer reoperations for pump malfunction. Otherwise, patient important outcomes were similar over this short period.

JAMA 22 Nov 2016 Vol 316

Quantifying the benefit of palliative care

Mention palliative care research, and my instinct is to drop what I’m doing and discuss it. Britain is supposed to be the best place in the world to die in, but looking back over 35 years, it is the failures to achieve a “good death” which stick in my mind. That period saw a large growth in palliative care provision, yet it was clear from the start that most of it was based on clinical tradition and humane intent rather than on randomised controlled trials. I’ve always wanted to do an RCT on symptom control in advanced heart failure, for example, but choosing the interventions and the outcome measures is formidably hard. A big meta-analysis looks at 43 randomised trials of palliative care in a variety of contexts. Reviews like this remind me of William Blake’s great dictum “He who would do good to another must do it in Minute Particulars: general Good is the plea of the scoundrel, hypocrite, and flatterer, for Art and Science cannot exist but in minutely organized Particulars.” Each dying patient is an individual challenge to the art and science of medicine, expressed through minutely organized actions. If you look for General Good in trials of palliative care, this is what you get:”Palliative care was associated with improved quality of life and symptom burden but not with improved survival. However results were attenuated and some of these associations were no longer significant when analyses were restricted to trials at low risk of bias.”

Drugs that send you to A&E

If you haven’t read previous studies about the drug classes that send people to hospital emergency departments, then this one is as good a start as any. It’s based on US nationally representative survey data covering 2013-4, and it shows that about four emergency room attendances related to prescribed drugs occurred per 1000 individuals annually. Three usual suspects always appear on lists for adults: drugs for diabetes, especially insulin; warfarin and newer oral anticoagulants; and opioid analgesics. But for children and adolescents, it’s quite different: the top culprit classes are antibiotics, followed by antipsychotics. The answer must be to prescribe fewer of the first, and almost none of the second.

JAMA Intern Med  Nov 2016

Glucose levels & decline in nursing homes

There’s a systematic review in The BMJ this week (see below) which shows—not for the first time—that untreated blood glucose levels show a continuously distributed relationship to cardiovascular risk. This has some importance for free-living individuals as a contribution to their total risk over time. But when you get admitted to a nursing home, your life expectancy is on average one year. Disease labels largely cease to matter, though if you are labelled diabetic the staff are likely to check your blood sugar every few hours or days. Or perhaps, in post-Brexit, post-NHS England, you will just be put into a disused factory and fed once a day. Back to the topic. Here’s a research letter showing that “In a national sample of residents in Veterans Affairs nursing home residents with diabetes from 2005 to 2011, the degree of glycemic control was not associated with persistent functional decline or death in the 2 years of the study. Our results suggest that an HbA1c level even greater than 9% may not increase the risk of persistent functional decline in nursing home residents with diabetes, suggesting that stringent glycemic control is not beneficial for these patients.”

BP drugs and fractures

It’s over a quarter of a century since observational studies first raised the possibility that thiazide diuretics taken in low doses to reduce blood pressure would also reduce the risk of fractures in older people. A Cochrane review of the literature to the end of 2008 concluded that “Thiazides appear to reduce the risk of hip fracture based on observational studies. Randomized controlled trials are needed to confirm these findings.” Since then, several massively expensive new treatments for osteoporosis have appeared, but there has still been no RCT of thiazides for fracture reduction. Faute de mieux, here is a post-hoc analysis of the ALLHAT trial looking at hip fractures in the groups randomised to blood pressure reduction using chlortalidone, amlodipine or lisinopril. The mean in-trial follow-up for the 22.180 participants was nearly 5 years, but observational follow-up went on a while longer.

The chlortalidone group had about 25% fewer hip and pelvic fractures, but despite the size of the trial, this teeters on the edge of statistical significance. Since then, thiazides have fallen out of favour for blood pressure control, with the exception of chlortalidone, which is not quite a thiazide anyway. Come on, public research funders: don’t just moan about the cost of osteoporosis drugs, fund a big prospective study using chlortalidone at £20 per year for high risk adults. You’d probably find a reduction in stroke, heart failure and kidney stones as well as fractures.

Dementia trends in USA

Why is it that the same newspapers that virulently support Brexit and run scare stories about refugees and EU workers also run scare stories about the inexorable rise of dementia and great British breakthroughs in the treatment of Alzheimer’s disease? There couldn’t be a more dismal illustration of the victory of lies and lobbying. Dementia prevalence declined by 12% between 2000 and 2012, according to representative survey of older Americans. Of 244 drugs developed for Alzheimer’s over the same period, only one was licensed.

Lancet  26 Nov 2016  Vol 388

One in the ear for Menière’s

Prosper Menière first described a condition characterized by spells of vertigo and gradual loss of hearing. His son decided to spell his surname Ménière, and so does The Lancet. People in a hurry omit both accents. Let us respect this great man of learning and get his name right, whenever we can remember to. Menière’s disease is probably overdiagnosed, but for some patients with the true syndrome it can be desperately life-disrupting. They would rather hasten the unilateral deafness than keep falling over and vomiting with little warning, and intratympanic gentamicin is sometimes used for this. But it may be possible to reduce the recurrent vertigo without inducing deafness, using intratympanic methylprednisolone instead. A small double-blinded trial randomised patients to injection of one drug or the other. Results among the 60 patients were somewhat mixed, and two people from the steroid group crossed over and opted for gentamicin. Interpretation: “Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière’s disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances.” I hope this can be read as an oblique reference to shared decision making.

BMJ  26 Nov 2016  Vol 355

Saturated fat revisited

Butter is the basis of good cooking. Lard, goose fat, and beef dripping also have noble parts to play. Olive oil is essential for many purposes, and for a few dishes walnut oil can be valuable. So long as your kitchen contains these fatty elements, you can cook anything you like, simply and deliciously every day, accompanied by wine and salad and followed by fresh fruit. I don’t know what female nurses and male doctors ate in the United States between 1984 and 2012, but I suspect it was not precisely on these lines. I could find out by reading their food diaries, which were sampled every four years or so. These were interrogated for clues about daily saturated fatty acid intake, using pretty sophisticated longitudinal analysis. The paper is full of terms like “beneficial macronutrients” which simply amount to value judgements, and despite their hard work I don’t think we are much further in understanding whether any food (other than sugar, perhaps) really has much to do with cardiovascular risk. It certainly has a lot to do with enjoying life.

“Prediabetes” again

Just now, most of the world is eating better and living longer than ever before. Population levels of plasma glucose are rising. People are getting heavier. You can say that everyone in the developed world is at risk of pre-diabetes, while about 40% actually have pre-diabetes and about 10% have diabetes. You could shift the threshold values and alter the percentages, or use different types of measurement such as HbA1c or fasting glucose or some kind of glucose challenge. You can crunch the figures and rediscover—again and again—that these thresholds don’t really mean anything in themselves up to the point where they signal an irreversible inability to metabolize glucose. At that point the metabolic, cardiovascular, and microvascular effects become large enough to warrant a special category of risk. We are really quite bad at classifying this. “Diabetes” covers many grades and trajectories, and needs an entirely new terminology. “Pre-diabetes” is an entirely useless expression, as I tried to explain—a little simplistically—in a recent blog. I’ll leave it at that.

Plant of the Week: Papaver orientale

Why praise oriental poppies in late November? They are one of the innumerable joys of June, flowering exuberantly for a week or two, and then just turning into big clumps of floppy cut-edged foliage. It’s amazing how well these plants from the dry Near East flourish in our cold wet gardens. Once they’ve established themselves, they will come through anything, including deliberate attempts to dig them up or destroy them.

It is this survivorship quality that you can put to good use if you want a second crop of flowers from your oriental poppies. As soon as they have flowered in early summer, cut them back to the ground. You will think you have killed your precious subjects, but after a few weeks those characteristic leaves will start to reappear. Then, late in autumn, you will be suddenly startled by some flamboyant apparition of papery red, orange, pink or white with a grand black splash in the middle. Ours appeared on a neglected grassy bank following two hard frosts. These are true treasures of the orient, fit for the Three Kings.