Richard Lehman’s journal review—10 July 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  6 July 2017  Vol 377

The world gets fatter

The Global Burden of Disease studies are a triumph of hard work and Gates funding, and it’s good to see one appear in the NEJM. Sadly they always end up a bit like sausage meat. This article has the title “Health Effects of Overweight and Obesity in 195 Countries over 25 Years.” Using the unsatisfactory measurement called the body mass index, recorded with varying degrees of accuracy and completeness in these 195 countries, the study quantifies the upward trend in overweight and obesity across the world. It also shows that this trend is most obvious in children and adolescents, which is truly alarming because we can only guess at the long term consequences. And this is associated with various increases in classes of condition and kinds of mortality. But context is everything, and I would love to know more about the spread of effects in associations between specific conditions and levels of BMI in different countries. There is also very limited stratification of effect by age and sex for these individual conditions. This is not a criticism of the authors, rather a general criticism of papers which try to summarize a vast array of heterogeneous data. Such attempts lead to modging. The antidote for modging is to go to the data website, inspect each piece of meat entering the sausage factory, and reach one’s own conclusions. But there are so many other ways to spend a sunny weekend.

Endometriosis or oestrogen depletion?

When can it be good to induce a chemical menopause in young women? The answer, according to the manufacturers of elagolix, is when they have moderate or severe endometriosis-associated pain. Elagolix is an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist which switches off oestrogen production in most women. It does this better at a dose of 200mg b.d. than 150mg o.d. In two trials the price for reduced endometriosis pain was—would you believe it—higher rates of hot flushes, higher levels of serum lipids, and greater decreases from baseline in bone mineral density than in those who received placebo. So when the FDA inevitably approves this drug, I hope they ask Abbevie to produce a decision aid explaining the trade-offs, and the fact that if she takes the drug for more than six months she will be entering unknown territory.

Mastering the jargon of multiple-aimed studies

Imagine a French Impressionist painting where a woman stands waiting for a rural train, holding an umbrella in one hand and a basket of eggs in the other. Hold this in your mind, for it will help you remember that a master protocol may be an umbrella, a basket, or a platform. Ah master, I hear you ask, how can such a thing be? Mon cher enfant, it is because trial dweebs have a passion for giving things silly names. Let them explain in their own words: “Master protocols may involve one or more interventions in multiple diseases or a single disease, as defined by current disease classification, with multiple interventions, each targeting a particular biomarker-defined population or disease subtype. Included under this broad definition of a master protocol are three distinct entities: umbrella, basket, and platform trials. All constitute a collection of trials or substudies that share key design components and operational aspects to achieve better coordination than can be achieved in single trials designed and conducted independently.” Have you lost the will to live? If so, move on to the next item or go out and play. Are you intrigued by this new way of getting the most value out of human experiments, aka clinical trials? Then read the paper.

JAMA 4 July 2017  Vol 318

Radiofrequency denervation for back pain

According to the BUPA website, radiofrequency denervation (also called facet rhizolysis or radiofrequency ablation) is a procedure to help treat back or neck pain that comes from your facet joints. Sadly, they will now have to remove “back” from this statement, since the three Mint trials published here show that it doesn’t work for chronic low back pain originating in the facet joints, sacroiliac joints, or a combination of facet joints, sacroiliac joints, or intervertebral discs. I wonder how long it will take for this procedure to be de-adopted following Mint? I guess we’ll just have to suck it and see.

SWITCH insulin and reduce hypos

Pork or beef was the basic question put to people with diabetes for the first sixty years after the isolation of insulin by Banting and Best. These insulins worked very well: one of Banting’s original patients was still getting her insulin from our practice in the 1980s. And these excellent insulins remain available in the UK, though at surprising prices. Insulin degludec costs about four times as much and here are two large multinational trials (SWITCH 1 and 2) comparing it with insulin glargine, which costs half way between. In both types of diabetes, it appears to cause fewer episodes of symptomatic hypoglycaemia.

JAMA Intern Med  July 2017 

Sharing is the future of medicine

What would happen if we tried to reshape medicine in such a way that every output of our encounters with patients generated new and better knowledge? And that this endeavour was openly shared with each person who comes to seek our help? How can clinicians help themselves and the people they meet to understand both the options available and the uncertainties surrounding them, and be attentive to discover what is most important to each individual? These are only some aspects of Sharing Medicine, the title of a series I have had the privilege of putting together for JAMA Internal Medicine. In this opening piece, I set out my stall. There will be six more Viewpoints over the coming weeks. Please let me know what you think.

Communication in life-shortening illness: the agenda

To my delight, JAMA IM has adopted the “Sharing Medicine” label for a range of articles where sharing with patients is a major theme. Here is a terrific example. It’s a deeply considered exploration of the research agenda for communication between healthcare professionals and patients living with serious illness. “Sharing Medicine” articles will be open access at least for the first month after posting on the website, so if you have any interest in this subject, I’d suggest you download this piece right away. If you have no interest in this subject, download it anyway: we all die of some kind of serious illness, and so do those we love: and a common cause of distress in most cases is poor communication.

The Lancet 8 July 2017 Vol 390

NSAIDs for hip and knee arthritis

Working with Cochrane UK these past three years, I’ve come to the conclusion that no meta-analysis can be perfect, and that meta-analysis by its very nature is a blunt tool for clinical decision making. “Network” meta-analysis is a method of combining data to provide comparisons when head-to-head randomised trials may be lacking or impossible to carry out. I think this one on the effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis (which is not a Cochrane) is nearly as good as it gets. Paracetamol alone is unlikely ever to have a useful effect on knee or hip pain: agreed. Diclofenac, the GP and patient first choice of days gone by, is the most likely to provide the most relief. Such a pity that it quadruples cardiovascular risk. Next in line are etoricoxib and rofecoxib. These too carry a risk of increasing CV events and like all NSAIDs should never be used in people with heart failure. So we go round the houses: should we use paracetamol combined with a weak opioid? How do we share these decisions in the complexity of real life in old age?

Azithromycin AMAZES in asthma

Macrolides have anti-inflammatory, antibacterial, and antiviral effects, according to the editorial which accompanies this report of a trial of azithromycin in uncontrolled adult asthma.

So they sound just the ticket for both asthma and chronic obstructive pulmonary disease. This Australian trial AMAZES us by proving this true for asthma. Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks, and the main adverse effect was an increased incidence of diarrhoea. And we know it works for COPD too. Some enterprising young man needs to remarket azithromycin as shkrelizumab and sell it for $20 a day.

The BMJ 8 July 2017  Vol 358

Benign benzos

This week, the “bad” habits of us older GPs are being proved reasonable, one by one. We’ve seen that diclofenac really is the best NSAID for arthritis pain (though probably the most dangerous), and that continuous antibiotics (macrolides at least) do reduce exacerbations in asthma and COPD. Now it’s the turn of benzodiazepines. Yes, they do cause dependency, and they should be avoided where there are better alternatives. But this huge US cohort study shows that they do not increase mortality in older people, as has been repeatedly suggested. The few GPs remaining have better things to do with their time than try to wean old ladies off the diazepam they have taken every day for twenty years, in order to meet some arbitrary prescribing target.

Earlier palliative care and outcomes

Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis“. I ran a similar title past a GP/palliative medicine colleague recently. “That’s like doing a systematic review called ‘Effect of orthopaedics on bones'”. True. So I shall say no more.

Plant of the Week: Gypsophila paniculata “Rose Fairy”

 Gypsophila, as you probably know, is the frothy flower that appears in wedding bouquets and is commonly called baby’s breath. Think of all the words used about Mendelssohn’s music – elfin, gossamer, filigree, etc—and you get the picture. It provides a wonderful effect in the garden if you can achieve it, but in England the odds are not good.

Although G paniculata is hardy, it hates waterlogged soil in winter. By chance rather than by foresight, we planted one at the top of a small sunny bank in soil that was mostly light compost and sand. It loves it there and spreads an airy cloud of flower half a metre in every direction. Go, reader, and do likewise.

  • A Geriatrician

    “The few GPs remaining have better things to do with their time than try to wean old ladies off the diazepam they have taken every day for twenty years, in order to meet some arbitrary prescribing target”

    There are very good reasons to continue trying to wean benzodiazepines in older people, including reducing the risks of falls and fractures, let alone the risks to their cognition. All of these negative outcomes are certainly of interest to older people (sometimes moreso than mortality benefit).

  • Fiona French

    I hope that the perspective of a patient who has been left with brain damage after benzodiazepine withdrawal can be included here. I assume the BMJ is interested in the patient experience as well as the opinions of doctors. Many, many patients have been harmed by benzodiazepines, many of those seriously harmed. I therefore think it is a mistake to write about “benign benzos” without reviewing the quality of the paper which gave rise to that comment. In 1988, the Committee on Safety of Medicines recommended that benzodiazepines should be prescribed for only a matter of weeks because of the high risk of dependency and the severity of withdrawal. That guidance continues to be flouted in 2017 and patients continue to suffer. Online benzodiazepine support groups are flourishing like never before as patients are unable to find help or support from their prescribing doctors. Indeed, they are met with denial and disbelief that they could be suffering in such a horrendous way. Many are dead, having committed suicide, unable to tolerate withdrawal symptoms. Benzodiazepines are anything but “benign”.