Richard Lehman’s journal review—16 May 2016

richard_lehmanNEJM 12 May 2016 Vol 374
Smoake is dangerous to ye Lungs
1811 A new study of smokers with preserved pulmonary function finds that a lot of them have lung symptoms. And even if they don’t fulfil the criteria for chronic obstructive pulmonary disease (COPD), they still experience the familiar pattern of exacerbations and limitation of activity and end up using the same medications as people with COPD. Nothing has changed in the 412 years since King James I of England declared smoking to be “A custome lothsome to the eye, hatefull to the Nose, harmefull to the braine, dangerous to the Lungs, and in the blacke stinking fume thereof, neerest resembling the horrible Stigian smoke of the pit that is bottomelesse.”

Caregivers of critically ill, a year later
1831 Here’s a nice example of research based on the “subjective” experiences of real people, which is published in the NEJM because it hides its qualitative heart beneath a cloak of conventional sampling methods and statistics. The people described are caregivers (60% spouses, 70% women) of patients who had received seven or more days of mechanical ventilation in intensive care units across 10 Canadian hospitals. Anyone who has been in this situation will know how stressful it can be, and the net effect of prolonged severe stress in most people is what we label as depression. The bottom line of this study is that 67% of caregivers had high levels of depressive symptoms one week after patients were discharged from ICU, and 43% still had these at one year. These are useful figures, signifying a massive and enduring burden to thousands of individuals. But if you really want to know what it feels like to look after someone who has been in ICU, you’ll get a much better idea from the qualitative research that went into the collection of interviews from the Oxford Health Experiences Research Group.

Childhood asthma & later on
1842 I’ve just seen a retweet of Stephen Senn’s 2014 classic: “I’ve been studying statistics for over 40 years and I still don’t understand it. The ease with which non-statisticians master it is staggering.” I feel the same about the diagnosis of asthma in children, or the differentiation between chronic asthma and COPD in adults. Why, after 40 years, do I find it so difficult, when so many others blithely pin on the labels and prescribe away? I think it’s the idolatry of the surrogate, in yet another guise. If the practice nurse, using a machine, has put down certain figures for peak flow or FEV1 on a certain day, then these numbers trump any amount of history taking or reassessment. And once “preventive” treatment has been started, it is a brave doctor who stops it. And yet there is definitely a true syndrome of chronic asthma in children, which we understand poorly. Back in the 1990s, the CAMP trial used fairly rigorous selection criteria to select children with persisting asthma to receive treatment with inhaled budesonide, nedocromil, or placebo. These kids have been followed up ever since. The treatments made no difference to their long term lung function. Just 25% of them showed the normal increase in lung function followed by an early adult plateau and then slow decline. A quarter of them showed the increase, followed by an earlier decline. The remaining quarters either had an impaired increase followed by early decline, or an impaired increase followed by no early decline. By the time they reached 26, 11% of the cohort met the standard criteria for COPD. These long term data on natural history are very welcome, but they don’t fill me with hope that the classification and treatment of childhood asthma will be sorted in my lifetime.

A cathedral of data
There are an awful lot of articles awaiting publication on the NEJM website, but I’ll just make brief mention of a newly arrived quartet on the subject of data sharing. Ever since the famous “data parasites” editorial, the journal has shown a certain unease on the subject, which is not much allayed by these new articles. They are long on the problems and short on the solutions that already exist. The longest is a description of how data sharing might look if a new entity called Vivli (sic) was created by a Harvard group to house and curate databases from all sorts of research bodies—industrial, academic, charitable etc.
This kind of “cathedral of data” is exactly what the world should be starting to build. Cathedrals often take a few hundred years to complete, and that is fine: after all, scientific medicine as we know it is only about 150 years old. The Yale Open Data Access project has been going for four years and I’m delighted and privileged to be part of it. I’m an apprentice mason learning on the job. Perhaps if Vivli is to get started, it will need to begin this way. Plans alone will not build it.

JAMA 10 May 2016 Vol 315
68 Strategies for precision medicine
1941 There are two prevailing visions of the future of medicine. One is that we are nearing the limits of what is possible using a top-down, innovation driven approach to single diseases, and that we will learn how to care for people better if we step back, question many types of disease category, accept uncertainty, and listen to the varied and ever changing stories and priorities of individual patients. The other vision is called “precision medicine” or “bench-to-bedside” medicine, where the personalisation of medicine is not seen in terms of ever changing stories and priorities at all, but as never changing genomic patterning, with treatments tailored to match. Neither approach is complete, and in fact the deterministic element in “precision medicine” is finding itself under attack from genomics itself. Is there a grand unifying theory of medicine that unites the two?
Here is an open access article called “Convergence of Implementation Science, Precision Medicine, and the Learning Health Care System.” I was taught English by strict Yorkshire schoolmasters over 50 years ago and I’m subject to piercing, toothache-like pain when chewing on sentences such as “The vision of the learning health care system can address this, by repositioning the formal health care delivery sector as a set of nimble organizations that focus on ongoing system improvement by capturing data at the clinical encounter and using those data to inform ongoing clinical and community practice.” I think this is meant to mean “Learn from your successes and failures,” though I may not have fully captured the focus on its nimbleness. I am relieved to learn later that “68 strategies, grouped into 6 different categories—planning, education, financing, restructuring, quality management, and attention to policy contexts—offer promise to support genomics implementation in a range of health care systems.” That means it cannot possibly ever happen. But perhaps with just one, or at most two, strategies based on internalised values, a fruitful combination of patient priority setting and therapeutics can be achieved. And every now and again, genomics might come in handy for that.

Apple juice to keep the doctor away
1966 Here’s a “Randomized, single-blind noninferiority trial conducted between the months of October and April during the years 2010 to 2015 in a tertiary care pediatric emergency department in Toronto, Ontario, Canada. Study participants were children aged 6 to 60 months with gastroenteritis and minimal dehydration.” These little ones with mild D&V were randomised to an electrolyte replacement mix or dilute apple juice. They tended to prefer the latter, and thanks to this teaching hospital trial we can rest content in the knowledge we already had: that kids in rich countries with mild D&V get better whatever they are given or choose to drink.

BMI news from Denmark
1989 Last week I commented on The BMJ’s long term study of BMI in the population, which I tweeted out as “People who stay slim all their lives live longest. We must try not to hate them.” I promised not to report any more such studies unless they favoured weight gain. I haven’t had long to wait. A study of three cohorts from Copenhagen shows that over nearly three decades, the BMI associated with greatest longevity drifted upwards from 23.7 to 27. I think I was that once.

JAMA Intern Med May 2016 Vol 176
Door knobs, toilet seats, & MRSA
OL In my childhood, antibiotics were new and germs were still greatly feared. They were divided into family germs, which were harmless and could be shared by eating the same bit of cake, versus other people’s germs, which were disgusting and could kill you if you weren’t careful with door knobs, toilet seats, or even public library books. Obviously, “good homes” would be less of a risk than places frequented by the lower classes. I’m reminded of this by a study from Columbia University Medical Center, which sought to determine the role of household contamination in recurrent community acquired MRSA infection. All household members from the dwellings of 82 index patients were swabbed and so were door knobs, the television remote, the living room light switch, toys, the couch, the computer or radio, the house telephone or index cellular phone, the bathroom sink, the toilet seat, the kitchen towel, and kitchen appliance handles. Thirteen out of 35 patients with recurrent MRSA infection came from the 20 households found to be “dirty,” as opposed to the 62 that were “clean.” You can never be too careful.

Lancet 14 May 2016 Vol 387
Parenteral diclofenac for renal colic
1999 Apologies if I’ve told you this before, or if it’s more than you need to know. I get ureteric colic every three to four years. Over the years I’ve found that diclofenac works better and longer than opioids, provided it’s given deep in the gluteal muscle or per rectum. This is generally true and has been known for over 20 years. I’m surprised that a trial comparing parenteral morphine, paracetamol, or diclofenac for “renal” colic in Qatar was deemed worthy of publishing in the Lancet in 2016. Two points to remember though in connection with NSAIDs for acute severe pain. One: the more rapidly they act, the better they work—so oral preparations are largely useless. Two: there is now a formulation of diclofenac that can be given subcutaneously, so avoiding the need for deep IM injection, which I find myself unable to do to myself while rolling on the floor.

Human but acellular dialysis access
2026 I normally avoid Lancet articles that hype bionic advances, but I do sympathise with renal doctors who have to find new modes of access to be able to haemodialyse very sick patients. A novel bioengineered human acellular vessel implanted into the arm seems to hold promise, and for once I won’t moan about a phase 2 trial appearing in this august journal, as precursor to a full trial.

Hysteroscopic futility
OL I don’t know how common it is for fertility clinics to carry out routine hysteroscopy before IVF. But judging from a pair of trials on the Lancet website, it is time they stopped. The Dutch inSIGHT trial shows that routine hysteroscopy does not improve live birth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. A cross-European trial called TROPHY shows that outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the live birth rate. So this procedure should go on the Choosing Wisely bin list for NHS gynaecology, and anyone being charged for it privately should contest their invoice.

The BMJ 14 May 2016 Vol 353
Dietary association studies & breast cancer
Say you want to show an association between some disease and lifestyle choices in a free living population. You’ll need a cohort with lots of accurate data and complete follow-up. You’ll need to think of every possible confounding factor. But since you can’t actually do that, you’ll need to widen your confidence intervals and be very humble about your findings. In a Danish study of postmenopausal women over a five year period, “results support the hypotheses that alcohol intake is associated with increased risk of breast cancer and decreased risk of coronary heart disease.” Well, yes, but remember that self-reported alcohol intake in the population accounts for about one third of actual alcohol sales. If you want an even more inaccurate dietary measurement, ask people about their fruit and vegetable intake when in their teens. Then match that with their incidence of breast cancer. Why? You can’t build anything on studies like these. You can only count them up and see how many agree with your preconceived ideas.

OL Some friends across the Atlantic have said they’re looking forward to my comments on the analysis article alleging that medical error is the third commonest cause of death in the US. I am afraid I shall have to disappoint them. I think I have already been beastly enough to The BMJ for one week.

Plant of the Week: Magnolia “Yellow Fever”

We were arrested by the sight of this beautiful tree in one of the most beautiful places in the world: the gorge of Bodnant gardens in North Wales. “What a terrible name,” said my wife, and so it is. Perhaps Magnolia “Dengue Fever” will follow.

Hardy, deciduous, yellow flowered magnolias have been around for about 60 years, although they are still uncommon in British gardens. The first was “Elizabeth,” a hybrid between M denudata and M acuminata (1956). It is still one of the best, free flowering and beautifully scented. “Yellow River” is much more recent, and has so much denudata in its parentage that it is sometimes classed as a variety of the species. “Yellow Fever” is another cross with acuminata, again with pale cream flowers. All of them are lovely, but if you want a deeper yellow you may be best with “Yellow Bird,” a cross between acuminata and a hybrid known as M.x brooklynensis ‘Evamaria.’