Richard Lehman’s journal review—27 May 2014

richard_lehmanNEJM 15-22 May 2014 Vol 370
1944  The introduction of pay for performance in the NHS attracted great interest in the USA, which is still trying to come up with similar schemes of its own. Martin Roland and Stephen Campbell both helped the UK government to set up the Quality and Outcomes Framework for primary care in 2004, and ten years on they reflect on its “successes and failures.” American readers should try to stick with this piece, which I suspect they will find a bit boring in places: as they read along, they need to look for the “successes.” It is just possible that initially, the QOF incentivized some poorer performing practices to do better at some genuinely useful things. After about two years, however, results levelled off at exactly the level of incentivization. And the government felt it had been conned into overpaying GPs. In succeeding years, the QOF has led to a dreadful downward spiral of gaming, financial retrenchment, meaningless overload, worsening accessibility, tick-boxing, depersonalized care, and deprofessionalized doctors. Americans, reform your system some other way. Britons, get rid of this cancer on the body medical.

2023  The kind of thing that keeps British GPs sane is hoarding disorder. To be honest, until this article appeared, I didn’t know it had reached the level of a diagnostic category (in DSM-5). The stressed British GP often exhibits hoarding disorder, and occasionally sees it when visiting patients in their homes. Iatric hoarding disorder (which will feature in DSM-6) is most prevalent in male doctors aged over 40. Diagnostic features include a desk so piled with paper that it cannot be used, and shelves on which every NICE guideline ever issued has been placed, still in its cover. Because the guidelines are wider than the shelves, the point is reached when vibrations from a toddler playing nearby overcome the weak frictional forces holding them together and they fall on the toddler. This is known as a significant event. The guidelines thereafter remain on the floor for health and safety reasons. Since the average weight of useless material received daily by each GP exceeds one kilogram, it does not take long before the practice manager has to step in and take special measures, such as sectioning the GP or telling the cleaner to throw everything out while he is on holiday. Believe me, I know.

JAMA 14-21 May 2014 Vol 311

1853  “A Bigger Threat than Global Warming.” As usual, the headline last week ( in The Times I think) was about the imminent arrival of universal microbial resistance to antibiotics. There are a number of reasons why this will never happen, some of which are mentioned in this sane and upbeat viewpoint. It is a battle of our wits versus their genes, as Joshua Lederberg once said. Our wits have won up to the present and they have grown far more powerful. There are plenty of new antibiotics and vaccines in the pipeline. Worry about global warming instead—that really is happening, and urgently demands the best our wits can offer.

1859  A couple of years ago, I was amazed to find that there was no Wikipedia entry for Avedis Donabedian, so I set to reading his works in order to write one. I never did manage to track down his poetry, but I did come across the extraordinary quotation which begins this piece called Filling Buckets. Donabedian spent his life trying to define and examine quality in medical systems, and at the end of his life wrote “Ultimately, the secret of quality is love.” Everything else he wrote is so rigorous, nuanced, endlessly detailed, and scrupulously analyzed that this simple, heartfelt assertion comes as a shock—and yet of course it explains what drove his immense effort. Do read this article: it is not soppy at all, though it deals with the central question in our lives as doctors. With so much suffering around us, and often so little we can do about it, how can we get the affirmation we need to carry on? It comes, of course, from the gratitude, understanding, and acceptance of the human beings we try to help. Take that away, and we are finished. So why is it not a central aim of every health system to nurture this exchange of compassion and mutual understanding? Answer: because it is the opposite of commerce.

1870  “This trial was funded by Amgen Inc, which was responsible for the design and conduct of the study as well as data collection and interpretation, management, and analysis.” For some reason, JAMA, which rarely get papers like this, chose to print this statement way down amongst the final credits. Well, you kind of knew it anyway. When it takes 198 sites in 17 countries to collect just over 2000 people with the commonest kind of “dyslipidaemia” and the trial is run for just 12 weeks with a surrogate marker as the primary outcome, you know this is an old fashioned, business-as-usual, spread-our-influence, place-our-product type of exercise. The stuff, by the way, is called evolocumab and it will be many years before we know if it helps or harms people in the long term, besides lowering LDL-cholesterol. Let’s hope it isn’t licensed until we do know.

1889  I guess the secret of giving up alcohol is wanting to give up alcohol. I have never had any compelling reason to want to, so I don’t know how difficult it is. I used to give acamprosate to people and they said it helped. So does oral naltrexone, according to this systematic review. Compared head to head, the two drugs perform equally well/badly.

JAMA Intern Med May 2014

OL  “Invecchiare in Chianti” means “to grow old in Chianti,” a part of Tuscany I have not visited for a very long time. It brings images of hillsides where well spoken English couples decay agreeably in small farmhouses behind fading Laura Ashley curtains. But the invecchiati studied in the InCHIANTI seem to have been locals: 783 wrinkly bronzed inhabitants from two villages, aged 65 and over, who had all sorts of measurements done on a regular basis. One of these was their level of 24 hour urinary resveratol metabolites. This turned out not to be associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all cause mortality; which rather blights the theory that resveratol is the beneficial ingredient in chocolate and red wine. Go for the real thing. When growing old in Chianti, find a good local winemaker and buy in bulk.

OL  Hypoglycaemia has overtaken hyperglycaemia as a cause of Medicare diabetic admissions in the USA. The figures are taken from the records of almost 34 million beneficiaries aged 65 or over, analyzed from 1999 to 2010, and the first author of the study is Kasia Lipska, a young diabetologist from Yale. I must declare an interest because she has been a friend ever since she first welcomed John Yudkin and me on our first trip to Yale. This is a great bit of outcomes research, reflecting changes in the management of elderly diabetics over that period. It will be interesting to map trends over the next 10 years, as patient-centred care gradually pervades this corner of medicine.

OL  Some things are already going right with diabetes care. Another Yale paper looks at mortality trends in diabetic patients admitted to Yale New Haven hospital over the same period, 1999-2011. Here the trend is very striking indeed: for most of that period, you were twice as likely to die in hospital if you had diabetes, but in the last four years the difference has disappeared.

Lancet 17/24 May 2014 Vol 383

Two print issues and nothing worth comment—that’s quite unusual. Here are a couple of things from their Online First website:

OL  Unless you know someone with it, Friedreich’s ataxia is a condition that just sticks in your head from medical school. It affects one person in 30-50 000, so no company is ever going to make money out of it. Any treatment will have to come off the shelf, or as a spin-off. Nicotinamide has long sat on shelves as vitamin B3. Now in 97% of cases, Friedreich’s ataxia is caused by the pathological expansion of a GAA triplet repeat within the first intron of both alleles of the frataxin (FXN) gene, which results in partial silencing of the gene, leading to frataxin protein deficiency. And we know that nicotinamide can remodel the heterochromatinised FXN locus and significantly upregulate FXN expression in primary cells from human beings, cell lines, and a mouse model for Friedreich’s ataxia. So two London teaching hospitals did an open label exploratory study of high dose nicotinamide for 10 people with Friedreich’s ataxia for eight weeks. Up went the frataxin levels, and up go the hopes that this may be a breakthrough: time will tell.

OL  Cardiovascular remodelling in coronary artery disease and heart failure is a favourite topic with cardiologists on both sides of the Atlantic—hi over there, yes, make that remodeling and favorite. The article begins: “‘The heart is the beginning of life, for it is by the heart the blood is moved…the source of all action,’ wrote William Harvey in 1673.” Since Harvey died on June 3, 1657, this is very remarkable. The article ranges widely, and probably isn’t of huge interest to most generalists, but for those who like this sort of thing, there is a wealth of mechanistic detail which goes much further than the usual simple accounts of cardiac remodelling. In fact the main focus is more on the arterioles and the microvasculature. Therapeutic consequences from all this new knowledge are repeatedly described as “disappointing.”

BMJ 17/24 May 2014 Vol 348

When I saw this Dutch network meta-analysis of the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma, my heart sank. When I saw the list of industry affiliations at the end of the paper, it sank further. Whatever else it says about the authors, it gives them all a vested interest in the “continuous prevention” paradigm of asthma treatment. After treating adults with asthma for nearly 40 years, I still find difficulty with many of the concepts others seem to have no problem with: “asthma” itself, “exacerbations,” “safety,” “maintenance”—they all beg so many questions. And as for “network meta-analysis,” this just means indirect treatment comparison. It jettisons the benefits of randomization to allow broad comparisons between dissimilar trials. The conclusions of network meta-analyses therefore have even less relevance to individual patients, each of whose “asthma” is something unique to themselves. It was such a relief to turn to Chris Cates’ excellent Editorial that concludes, “Above all, patients with chronic asthma need treatment that is carefully tailored to their clinical needs. Health professionals still need to work with individual adults to titrate their dose of inhaled corticosteroid up or down according to the severity of symptoms. It would be unwise to rely too heavily on rankings from a network meta-analysis dominated by indirect evidence when making decisions about treatment.” There speaks the kind of doctor that all patients with asthma need to have.

The more massive a meta-analysis, the more it will tend to reach a generalized and predictable result. Few topics are more important than supporting maintenance of weight loss in obese adults and assessing the evidence for the effectiveness of these interventions. From a massive literature, the authors selected 46 studies involving 7788 subjects. Their conclusion: “Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance.” Yup.

Oh dear, more about meta-analyses. The best they can tell you is the sum effect of an intervention on a group of populations. The best you can hope to gain from looking at them is something that might possibly apply to patients you see. This might then in turn apply to the individual person you are actually seeing. You cannot know: the evidence can never allow you to extrapolate—it just gives you a flavour of the odds you may be dealing with. The odds for any individual getting gastric cancer in the UK are very small: in Japan they are much higher. The odds for any individual in either country of carrying H pylori are very high—perhaps 40%. In the world as a whole, gastric cancer is the third commonest cancer and H pylori carriage exceeds 50%. So it is impossible to generalize about the value of H pylori screening and eradication for preventing gastric cancer. Which is what this meta-analysisconcludes.

Wherever you look, you don’t find ’em. John Ioannidis set his team looking for vaccine trials over the last eight years. The proportion of trials published 12, 24, 36, and 48 months after completion was 12%, 29%, 53%, and 73%, respectively. Not too bad, you may think; but the other way to look at it is that more than a quarter of trials of important interventions on large at risk populations are not reported on within two years.

Plant of the Week: Paeonia “Garden Treasure”

English gardens are nearing their peak of beauty and variety, just as the sun has gone in, the skies are grey and lowering, and every day brings wind and rain. The flowers that dazzle in the gloom are the yellows—especially the Welsh poppies, which seem to have evolved specifically to cheer the Welsh on their cold wet mountainsides. But peerless among all yellow flowers is this unbelievably beautiful new peony.

Here you are seeing the product of perhaps the longest process of plant culture in the world—the selective breeding of peonies in China and Japan, which began well over a thousand years ago. It has been a slow process of hand pollination, selection, and division, with grafting too in the case of tree peonies. The process that nobody was able to master is the cross-pollination of herbaceous and woody peonies, until Toichi Itoh found a way of doing it (with a <1% success rate) in the 1940s.

Until quite recently, the Itoh hybrids (known as “intersectional” peonies) were rare and might cost up to $1000 in their year of introduction. We bought “Garden Treasure” for £85 three years ago. This year it can be had for £30. Don’t hesitate! You don’t need to move an inch: just go to RHS Plant Finder and order a bare root plant for autumn delivery. In the spring, you will watch its beautiful cut leaves appear in dark copper-bronze, turning a luxurious deep green as the first flower-buds appear. And then prepare to be dazzled. For several weeks each year – perhaps for more than a hundred years – this plant will produce more and more flowers. You can bring them in and they will last several days in water. People who inherit your garden will thank you long after you are dead.