Richard Lehman’s journal review—19 January 2015

richard_lehmanNEJM 15 Jan 2015 Vol 372
201 “The main challenge is to ensure better systems [of sharing data] for the future. Because ‘the optimal systematic review would have complete information about every trial—the full protocol, final study report, raw dataset, and any journal publications and regulatory submissions, ‘a prospective system of research governance should insist on nothing less… These changes have been long called for, and delay has already caused harm. The evidence we publish shows that the current situation is a disservice to research participants, patients, health systems, and the whole endeavour of clinical medicine.”

Although there are technical hurdles, we need to change how we think about data. We need to view it as a community resource, much like a shared park, rather than as personal property. We need to recall every day that selfless volunteers put themselves at risk to advance medical science by enabling the data to be gathered. To honor that sacrifice, we need to turn those data into applicable knowledge; somebody else may well find something useful in your trial data that have been sitting idle for years. Let’s share and find out.”

The first quote is from an editorial in The BMJ of Jan 2, 2012, written with Elizabeth Loder on the back of work I was doing with Harlan Krumholz at Yale, who earlier that year had already begun to address the “technical hurdles” that Jeffrey Drazen refers to in the second quote, from Jan 16, 2015. It is nice to see progress at last, thanks to the new report from the Institute of Medicine. But that progress could have been a lot faster if the same people had been listening three years ago.

JAMA 14 Jan 2015 Vol 313
156 In a population cohort from Wisconsin, 22 of 81 participants with asthma experienced incident obstructive sleep apnoea over their first observed four year follow-up interval compared with 75 of 466 participants without asthma. So if you are wheezy in Wisconsin you are likely to be sleepy too. This is quite a startling figure: if over a quarter of a cohort get something within 4 years of observation, how many are likely to be unaffected after say 20 years? I blame the weather and the cheese.

165 There was once a single thing called breast cancer. Then there were two, depending on oestrogen receptor status. Then came extra classifications by progesterone receptor (PR) status and ERBB2 status (formerly HER2 or HER2/neu). And all the time we are learning about other distinct genomic characteristics, so that for all I know there may now be 57 kinds of breast cancer, complete with a Heinz index. Which is not funny if you happen to have the condition. It also makes it very difficult for a non-specialist to understand what anything means any more, especially the epidemiology of survival. I think that about all I can usefully say about this (open access) report from the SEER database, which covers about a quarter of all breast cancer diagnosed in the USA, is that there were significant racial differences in tumour detection and survival, mostly accounted for by the known biological differences in tumour type. What I can’t find in this report are the differences between screening diagnosed and clinically diagnosed cancers.

174 “Medical research in the United States remains the primary source of new discoveries, drugs, devices, and clinical procedures for the world, although the US lead in these categories is declining. For example, whereas the United States funded 57% of medical research in 2004, in 2011 that had declined to 44%.” A lengthy paper traces this relative decline and of course laments it from a transatlantic perspective. Personally I don’t mind how much the USA dominates medical research, provided there are benefits for everybody. But thinking over the last ten years, I’m not seeing many. Health costs seem to be rising out of all proportion to benefits. That’s despite a certain de-adoption of useless procedures such as much arthroscopy, PCI and CABG. There is now a cure for hepatitis C affordable to 0.001% of those affected. There are some cancer drugs that give you a few weeks at the cost of an average house. The biggest advance by far is bariatric surgery, but I don’t think that was a US invention. And e-cigarettes—but they don’t count as biomedical products, though they certainly are, and I suspect they will save more lives than all the innovations from the US biomedical industry over the coming ten years. Most definitely if they lead to all forms of combustible tobacco being banned.

The Lancet 17 Jan 2015 Vol 385
231 I do wish the world was run by New Zealanders. Unassumingly tough, kind and sensible, uninterested in adopting other people’s bad habits and neuroses, they are just wonderful at getting on with life. When old Kiwis have falls, they look at what they might fall over and what they might hold on to. Result: “a 26% reduction in the rate of injuries caused by falls at home per year exposed to the intervention.” OK, this has been done before. But it needs doing a lot more.

239 Richard Doll is famous for saying that death in old age is inevitable, but death before old age should be preventable. I like him even more for saying that “With all these diseases going around, it’s a wonder anybody gets out of this world alive.” I’m with Moses the Prophet and against Muir Gray in thinking that 70 is about the right threshold, and it’s the one chosen for this fascinating overview about avoidable mortality and how to reduce it. The authors propose, “as a quatitative health target, ‘Avoid in each country 40% of premature deaths (under-70 deaths that would be seen in the 2030 population at 2010 death rates), and improve healthcare at all ages.”’ I love The Lancet‘s new word “quatitative.” I shall use it whenever I can’t decide whether something is qualitative or quantitative; or as in this instance, a bit of both.

253 King Richard III of England was 32 when he died at Bosworth and then famously suffered the indignity of being buried in a Leicester car park. I think I probably drew your attention to this account of his post-mortem examination when it appeared online last September. Had Richard III been spared avoidable mortality in the form of a bashed-in skull and a spear through his spine, he would probably have needed a walking frame by the age of 70. He was never in the best shape:

I, that am curtail’d of this faire Proportion,
Cheated of Feature by dissembling Nature,
Deform’d, unfinish’d, sent before my time
Into this breathing World, scarse halfe made up,
And that so lamely and unfashionable,
That dogges bark at me, as I halt by them.
(from The Tragedy of Richard the Third: with the Landing of Earle Richmond , and the Battell of Boʃworth Field by Wm Shakespeare c.1592, First Folio text 1623)

With his nasty scoliosis and his habit of moving around castles with smoky rooms and no hand rails on the stairs, Richard III would have needed an OT assessment and a dosset box containing all the drugs which are now compulsory for elderly people in the UK:
simvastatin 40mg to add 2 days to life and cause muscle aches
tramadol 50mg to fail to ease pain & cause dependency, falls, confusion
naproxen 500mg to cause GI bleeds and fluid retention
furosemide 20mg to reduce fluid retention due to naproxen
omeprazole 20mg to prevent GI bleeds, encourage C diff
senna 7.5mg to counter tramadol constipation
citalopram 20mg to cause serotonin syndrome with tramadol
trazodone 50mg for agitation due to serotonin, to worsen it & cause falls
gababentin MR 800mg to see if it will help pain
paracetamol 500mg because it hasn’t helped the pain
tamsulosin 400mcg for nocturia due to age and furosemide
lisinopril 5mg for “grade 2 CKD” due to furosemide & naproxen
Seretide inhaler for low FEV1 due to scoliosis
My kingdom for a bit of horse-sense.

The BMJ 17 Jan 2015 Vol 350

This paper must have one of the longest titles in The BMJ‘s history: “Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation.” I think “Avoidance” would have been a better first word, but no matter: let’s just go the bottom line of this Dutch study: “In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates.” Which means that all methods were equally good and there weren’t many multiple births, right?

Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods.” This is big stuff: “The consequences of overdiagnosis include unnecessary labeling of people with a lifelong diagnosis as well as unneeded treatments and surveillance that cause physical and psychosocial harm. A patient who is overdiagnosed cannot benefit from the diagnosis or treatment but can only be harmed.” I absolutely agree, but it is so hard to get this message across to a public who are currently being told that all cancer is going to be curable soon, that early detection is the key and that is why the UK lags behind the rest of the world. And the evidence tends to be so partial and contestable. It’s like a nightmare where you find yourself lost in unfamiliar streets only to realize that you have no clothes on and you’ve forgotten what your hotel is called. Help! “We need internationally agreed standards for ecological and cohort studies and a multinational team of unbiased researchers to perform ongoing analysis.” Phew, some pants at last.

I am all for individual participant meta-analysis to answer important medical questions. This massive multi-author review seeks to discover if people who work longer hours tend to drink more alcohol. They do. I am glad to hear it: they deserve their reward. I hope they can afford to drink better alcohol, too. Most 2010 Bordeaux classic growths are worth laying down now but they won’t be ready for drinking for a few years yet. But if you have good white Burgundy older than six years, I would advise drinking it now, because so many from before 2006 turn out to have oxidized.

Plant of the Week: Coronilla valentina subsp. glauca “Citrina”

I have often heard elderly patients refer to their “bastard senna” either because it didn’t work or because it worked too well, but I didn’t realize that there is actually a plant that bears such a name, and this is the one. I’ve grown it two or three times, but it always dies with us, the bastard. It is a lovely little climber with pretty pea-foliage and sweetly scented yellow flowers, borne from now and on until the early summer.

I have no idea if the pods of bastard senna have laxative qualities like those of the true senna. All I know is that it can provide winter joy and also comes in a variegated form.