Richard Lehman’s journal review—16 April 2018

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 12 Apr 2018
Fish oils and dry eyes
In this trial of ingesting omega 3 fatty acids to alleviate dry eyes, the oils were derived from fish rather than snakes, no doubt for reasons of convenience. Now I balk at the expression “snake oil ” when it comes to selling useless drugs at enormous prices. Nineteenth century snake-oil salesmen were noble entrepreneurs by comparison with today’s gaggle of price gougers. They led a precarious peripatetic existence selling a potentially useful product at prices their auditors could afford. Some may even have died of snakebite. Anyway, I digress: this trial was not about selling high priced drugs. Participants with dry eyes were randomised to consume a daily oral dose of 3000 mg of n−3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). Symptom scores over one year improved similarly using fish oil or olive oil. Hence the conclusion: “Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n−3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo.” Note that there was actually no true “placebo” group for these “diseased” “patients.” They all ate fish oil or olive oil, and they got a bit better to the same extent. People with dry eyes should be advised to consume salted raw herrings in olive oil covered with chopped fresh onion and dill and eaten with plain potatoes and lots of sour cream. It is a Polish delicacy that is famed for making people’s eyes water.

JAMA 10 Apr 2018
Best options for problem asthma
In two big meta-analyses, Diana Sobieraj and colleagues survey six strategies for persistent asthma, mostly in adults. To me, these are a dismal reminder of how poorly we understand this heterogeneous condition, and how poorly the evidence base matches patient need as opposed to the sales pitch of inhaler merchants. Everyone in the 31 trials covered was taking a corticosteroid by inhaler: if perchance they switched to oral steroids, that was considered an event. Oral steroids are a surrogate for exacerbations, which in turn are a surrogate for poor asthma control. Meta-analyses can only work by comparing recorded outcomes, and exacerbations are always reported, whereas other patient-important outcomes are often not.

Now what happens if you add regular inhaled long-acting muscarinic agonists (LAMAs) to regular inhaled steroids in adults with uncontrolled persistent asthma? Overall, you may reduce the use of oral steroids by about a third. However, in head-to-head comparisons with long-acting beta-adrenergic agonists (LABAs), the two drug classes come out about equal. Combining both with an inhaled steroid (triple therapy) brings no advantage.

The second meta-analysis looks at the strategy called SMART (single maintenance and reliever therapy) compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy. Read that twice if you need to. In reality, it is a bundle of 15 trials, mostly manufacturer sponsored, of budesonide and formoterol in a dry-powder inhaler; plus one other trial. By using this product continuously, you are likely to have fewer exacerbations than if you use a higher dose steroid inhaler continuously with a β-agonist as a reliever when needed.

These commercial inhaler games have been going on for 40 years and show no sign of stopping.

JAMA Intern Med Apr 2018
Young women and MI outcomes
Here’s a survey of myocardial infarct outcomes for women in the so-called “transitional countries” of Europe—mostly from what used to be known as the “communist bloc.” Rapid percutaneous intervention is now the standard in most of these countries, but the old epidemiological truth remains: younger age was associated with higher 30 day mortality rates in women, even after adjustment for medications, primary PCI, and other coexisting comorbidities, but this difference declined after age 60 and was no longer observed in the oldest women.

Dialysis and humility
A few months ago, I confessed that I did not understand nephrology. This was pounced on by a number of nephrologists who suggested that I keep my ignorant views to myself. I shall gladly do this. Here is a cohort study of 11 215 US armed forces veterans with kidney failure. Receipt of specialist nephrology care through Medicare was associated with 28% higher frequency of dialysis initiation and a 5% higher frequency of death.

Given the many unknown factors, the decision on when it is best to initiate dialysis should evoke humility. The goal should be to encourage thoughtful, joint decision making by nephrologists and their patients. The system should reinforce the careful weighing of pros and cons by supporting healthcare professionals in caring for patients with very low eGFR.

In case you think me presumptuous, I should point out that this was written by two nephrologists.

The Lancet 14 Apr 2018
Short measures for a long life
If the effect of alcohol consumption on longevity is of interest to you, then it’s worth looking carefully at this massive analysis of 83 prospective studies

They provide data from nearly 600K current drinkers and their mortality in relation to self-reported alcohol intake on one or more occasions. It’s amazing how precisely the press has extrapolated from this fuzzy collection of associations to years of life to be gained by dropping a weekly unit of alcohol. It’s true that the data are broadly consistent. They tell us that for the longevity of the whole population, it’s best to aim at an alcohol intake below about 200 g/week. Some have even argued for 100 g (12.5 units), but they tend to be public health professionals who see their job as postponing death for as long as possible in the highest number of people. I am not sure that I belong among them. Pore over the figures (esp. 1 and 4) and make up your own mind. The authors even hint at the need for a randomised trial. Would you enrol?

COPD in China
Chronic obstructive pulmonary disease is a ragbag of conditions, few of them treatable but almost all of them preventable. In China, there are nearly 100 million adults with spirometry-defined COPD, according to extrapolation from data collected by the China Pulmonary Health (CPH) study. The authors conclude that “our data indicate that COPD is highly prevalent in the Chinese adult population. Cigarette smoking and air pollution are major preventable risk factors for the disease. Prevention and early detection of COPD using spirometry should be public health priorities in China, to reduce COPD-related morbidity and mortality.” I half agree, though I remain to be convinced that early detection using spirometry really is a useful strategy for reducing COPD. Prevention certainly is, but it has a lag time of 20-30 years. But that shouldn’t deter nations for racing each other to eliminate the causes of COPD—smoking, indoor and outdoor air pollution. This would also immediately reduce disease exacerbations and progression, and prevent a lot of cardiovascular disease.

Plant of the Week: Anemone nemorosa “Parlez-vous”

For those living in Britain, the next week promises to be one of the most blissful of the year. The sunlit fields will be full of lush grass, broken here and there by fast running rills of shining water. Black faced lambs will run to their mothers. In copses and woods, dappled sunlight may fall on a carpet of wood anemones with stars of pure white flowers, perhaps joined by the odd native daffodil or early bluebell.

It was not so for Frank Waley exactly 100 years ago. Like a million other British men, he was retreating from the German Spring Offensive of 1918 in desperate conditions. The woods around him would have been a collection of shattered stumps, but somewhere among them he found a pale blue wood anemone of unusual size and beauty. To this he gave the name “Parlez Vous” after the well known (but seldom repeated) soldiers’ song, Hinky-Dinky Parlez Vouz. One of the more printable stanzas runs:

Oh, Mademoiselle from Armentieres,
Parlez-vous :
She’s the hardest working girl in town,
But she makes her living upside down!

Frank Waley himself survived action with the rank of Captain, and seems to have led a rather more respectable existence. He must have been wounded not long after finding his anemone, since while recovering from his wounds one of the nurses gave him a new form of Narcissus pseudonarcissus. This is said to have fired a passion for plant collecting up to his death in 1987, at the age of 94. His own name (rather than that of a hard working girl) is given to another lovely wood anemone, this time pale yellow, Anemone ranunculoides “Frank Waley.” Frank was awarded an MC and became the first chairman of Westminster Synagogue.