Richard Lehman’s journal review – 6 June 2012

Richard LehmanNEJM  31 May 2012  Vol 366
2065    “Hey postman, I just saw that parcel move!” “Don’t worry buddy, that one’s fulla chicks.” Such exchanges cannot be uncommon in a country where live poultry is sent cheeping through the post at the rate of more than a million kilos per year; and how these poor fluffy creatures ever reach their destinations alive is a mystery to me, given the vagaries of the US postal system. More and more Americans want to keep poultry in their yards or even in their homes. Enter Salmonella enterica serotype Montevideo, a rather feeble bug which has trouble infecting adults but can cause nasty gastroenteritis in children who fondle infected chicks. There have been various sporadic outbreaks of salmonellosis due to this strain in the USA over the last 8 years, and here the NEJM publishes the results of the incredibly patient detective work which traced nearly all of them to a single Hatchery C in the western USA. Worthy reading for a wet Jubilee afternoon: you will learn all sorts of things you never knew about how chicks from one hatchery can be labelled as from another, and above all take home the vital lesson that “Consumers wishing to reduce their risk of illness should practice meticulous hand hygiene and encourage this behavior in children. High-risk groups, including children younger than 5 years of age, elderly persons, and immunocompromised persons, should not handle or touch chicks, ducklings, or other live poultry. Live poultry should not be allowed inside a residence, in bathrooms, or in areas where food or drink is prepared, served, stored, or consumed.” Get out of my bathroom at once, vile duckling.

2074    From the moment that radiotherapy was first used to treat cancers – and that’s over 100 years ago – debate sprang up about whether to use it before, during, or after surgery. In those days, the question was addressed by individual case series, and so never conclusively settled: now we used randomized controlled trials, and in most cases throw in some adjuvant chemotherapy as well. Oesophageal cancer is getting commoner, for reasons we don’t understand, so anything that improves cure rates is most welcome. Thanks to this nice Dutch RCT, we now know that preoperative chemoradiotherapy comes under that heading.

2102    Phlebas the Phoenician, a fortnight dead,
Forgot the cry of gulls, and the deep sea swell
And the profit and loss.
So begins the section of TS Eliot’s Waste Land called Death by Water. One theory has it that the Phoenicians were descendants from Bedouin tribesmen who made their first tentative steps on to the sea in Egyptian vessels carrying cedar wood from Tyre and Sidon. Eventually they became bold sailors travelling all the way to Cornwall. Drowning must have been a common end for Phoenician merchants, and pearl-eyed Phlebas would have had many companions on the floor of the Mediterranean or the Atlantic. This excellent clinical update on drowning put me right on several counts: drowning in sea water is little different from drowning in fresh; you are likely to survive longest in water that is near freezing point; resuscitation (CPR) attempts following drowning are no more or less likely to succeed that CPR in other situations.
Consider Phlebas, who was once tall and handsome as you.

Lancet  2 Jun 2012  Vol 379
2053    The massacre of the surrogates continues, and it is tempting to stand by and gloat, like King Herod or Genghis Khan. But there was a time when I really wanted to believe in these things, as the short cuts that medicine needed to move faster. This wishful thinking was widespread, and much encouraged by the pharmaceutical industry—which is busy inventing new surrogates to this day, hoping to avoid the lengthy trials needed to achieve true knowledge based on hard outcomes. How nice it would be if all that we needed to predict cardiovascular outcomes was the progression of carotid intima-media thickness. But contrary to popular belief, this measurement has no useful predictive value. The conclusion of this meta-analysis of individual patient data is unusually clear: “The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.” So how come the entire medical community fell under this delusion?

2063    Another meta-analysis from Germany looks at the widespread practice of keeping patients with schizophrenia on continuous medication to prevent relapse. Believe it or not, there are 65 trials which address this issue by including a placebo arm, with a mean size of 100 subjects. There is, however, no equipoise in this question: antipsychotic medication clearly prevents relapse, with a NNT of 3. The main issue is to determine which drug is best for which individual: usually a matter of trial and error and psychiatrist preference. We will know that psychiatry has become a science when these choices can be illuminated by good evidence of harms and benefits, and even a degree of shared decision-making.

I paste the following from the electronic version of this week’s Lancet:
What can be learned from China’s health system?
The Lancet today publishes a themed issue devoted to China to coincide with the third anniversary of the country’s 2009 health reform plan.

Slight problem—there is no themed issue on China this week.

BMJ  2 Jun 2012  Vol 344
John Ioannidis leads his Stanford team in an exploration of 20 different articles on cardiovascular risk scores. So which scores as the Score of Scores in this score of scores? Impossible to say, he concludes, as they are all derived in different ways and have only one characteristic in common: “authors always reported better area under the receiver operating characteristic curves for models that they themselves developed.” If someone as sharp as John can’t pick a favourite, what hope for the rest of us? I guess my own for UK use is QRISK2, but don’t all pelt me with tomatoes. I will do whatever you say.

A Dutch study compares memory clinics with general practitioner care for dementia. Follow-up by specialist clinics seems to confer no benefit in terms of treatment of coordination of care.

I never much liked giving corticosteroid injections for plantar fasciitis, and was glad when a study appeared a few years ago showing that the best long-term results were from graded exercises supervised by a podiatrist. I was always amazed when patients returned for a second round of steroid, because they would writhe in pain while I went ahead by guesswork. Just as with tennis elbow, the injections work for a month but may prolong the condition. This Australian study was a bit more humane: it used ultrasound guidance, first to deliver a posterior tibial nerve block and then to guide placement of dexamethasone or saline (double-blinded). The steroid group did better, but usually returned a few weeks later.

An observational study from 26 tertiary hospitals in Japan confirms common sense and previous evidence: the thing that matters in ST elevation myocardial infarction is not door-to-balloon time but onset-to-balloon time—and that beyond 2 hours, there is little difference in outcomes of death and heart failure at 3 years.

As there is so little original research in the journals this week, forgive me for puffing two superb pieces by friends in this week’s print BMJ: Preventing Overdiagnosis; how to stop harming the healthy by Ray Moynihan, Jenny Doust and David Henry, and The drug industry is a barrier to diabetes care in poor countries by John Yudkin. Putting these pieces behind a paywall is also a barrier to care in poor countries.

Finally, in response to a specific plea, I am travelling to the BMJ website to comment on the already famous paper about chocolate consumption in people with high cardiovascular risk. Ever since delicious solid chocolate was invented in Britain in the late 1840s, people have used it for modelling. This has given rise to the highly inventive Yorkshire term of derision, “Ee, th’art as much use as a chocolate fireguard.” This paper takes the process a step forward. It uses a Markov model to predict the effects of dark chocolate on cardiovascular outcomes over 10 years in high-risk individuals, based on the known effects of chocolate on blood pressure and lipids over a period of 2 to18 months. Now at least you can eat a chocolate fireguard, as my wife was quick to point out. But it’s impossible to swallow this Markov model, however hard you try. Henceforth we will be able to call all modelling studies that make wild extrapolations “as much use as a chocolate Markov model.” And although this is written up as a serious study, I wonder if the Australians who wrote it didn’t have their tongues firmly in their cheeks. Maybe they are now all laughing into their Fosters at pulling one over so many credulous Poms and Yanks.

Arch Intern Med  28 May 2012  Vol 172
761    Arguing about glycaemic control with diabetologists is sometimes rather heart-rending: they have convinced themselves for years that tight glucose control has to be of benefit and just can’t understand how anyone can be so irresponsible as to suggest otherwise. I have been accused – by implication – of not caring about renal failure or blindness. If tight control doesn’t prevent macrovascular events in type 2 diabetes, they argue, at least we know that it slows microvascular damage. Actually we only know about some weak surrogate outcomes, as this landmark meta-analysis of intensive glucose control and renal outcomes shows. And the further you mount the surrogate ladder, the weaker the effect becomes. Lowering HbA1c reduces microalbuminuria; it has a similar effect on macroalbuminuria; it has no effect on doubling of creatinine; and there is no evidence at all that it prevents end stage renal disease. So why do we assume that any drug that lowers blood sugar is of benefit to people with type 2 diabetes? Usually because their manufacturers offer chocolate Markov models based on wild extrapolation from weak surrogates over long periods of time.

773   Here it is in print: that astonishing study of intensive telemonitoring in the elderly with multiple comorbidity. Remember, it was associated with a fourfold increase in deaths.

799   A couple of papers to complement the BMJ Moynihan piece on overdiagnosis. If you measure thyroid function in lots of people—something we all end up doing—you will find some people (4.2%) with a low TSH but normal levels of circulating T3 and T4. Conversely you will find lots of people with a high TSH and normal circulating levels of T3 and T4. This study estimates cardiovascular and mortality risk in the first group from pooled cohort studies. There is a small increase in total mortality and quite a large (40%) increased risk of atrial fibrillation. So what do we do? Nobody knows, but at least we can create a new disease label—subclinical hyperthyroidism.

811   Subclinical hypothyroidism is common—about 10% of the adult population has this non-disease—and some British GPs treat it with small doses of levothyroxine. Others do not. So by comparing the two groups via the UK GP Research Database (which has now morphed into the Clinical Practice Research Datalink, CPRD), you can run a comparison of outcomes in the treated and the untreated groups. Hardly a randomized controlled trial, but there is some weak evidence of benefit from treating younger people with this finding. So the authors claim that a randomized trial is warranted.

Plant of the Week: Magnolia macrophylla

There is a full grown specimen of the bigleaf magnolia outside the Yale-China Center, not far from where we have been living for the past year. It has just come into flower and the surrounding air is filled with the most enticing smell of melons and honey.

This is a great choice for the spot, since China and the USA are between them home to most of the world’s magnolias. It has huge leaves and great white flowers with loose lanceolate petals and looks for all the world as if it came from a remote Himalayan mountainside in Yunnan province. In fact it comes from the forests and mountains of Florida.

The magnolias were among the first broadleaf trees to flourish soon after the dinosaurs died out. Their game plan is simple. Big leaves to maximize photosynthesis (this one is adapted for shady forests) and big white flowers with plenty of scent to attract insect pollinators by day and night. Seeds that just drop off and get eaten or hoarded by forest floor mammals. In the case of the bigleaf magnolia, it’s worked well for maybe 60 million years, but luck was running out until botanists came along and rescued it. There are only a few scattered occurrences in the wild, and few of its seeds germinate.

This is really a plant for mesic forest habitats in warm states, but I have seen a perfectly respectable specimen in the botanical gardens of Sheffield, seeming to flourish. Mesic, I should explain, is just botanese for moist. Sheffield is often mesic and darkish, so that may be why this plant likes it. It takes up a lot of room; its leaves become tattered in wind; it flowers for about two weeks. There is a smaller variety called ashei which may be more suitable for gardens. Leave this one to the botanists and the civic planters.