Richard Lehman’s journal review—17 April 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  13 Apr 2017  Vol 376
Diabetes, death, and cardiovascular disease in Sweden
“Diabetes mellitus is a complex and heterogeneous group of chronic metabolic diseases that are characterized by hyperglycemia.” That’s a good intelligent sentence to begin a good intelligent analysis of outcomes in Sweden for people labelled with diabetes over the period 1998-2012.

Figure two summarises what happens to people with type 1 and 2 diabetes in a civilised country with decent modern healthcare. For cardiovascular outcomes, the story is one of steady improvement: events and hospital admissions for all patients with diabetes are falling compared with population controls. The main exception, however, is all cause death (per two year period) in people with the label of type 2 diabetes. This was going down up until 2008 and then something happened to stop it dropping. I would love to know why. Were the Swedes doing something right and then started doing something wrong? What non-cardiovascular factors are causing this anomaly? It should be very easy to check from the mortality registers on this database.

Diabetes in American youth
And now, with due foreboding, let’s fly to the US. Here the incidence of diabetes is rising, especially in the young. In this survey of Americans aged 10-19, the overall rise between 2002 and 2012 was 1.4% annually for type 1, and 7.1% annually (4.8% after adjustment) for type 2. But for two ethnic groups, the rise in T2DM was spectacularly larger than for white American youth: native Americans and black Americans. Early onset T2DM has a pretty terrible prognosis, even when ideally treated—and optimal treatment is unlikely to be affordable for many of those worst affected. Here is another driver towards ever greater health disparities by race in the US.

JAMA 11 Apr 2017  Vol 317
Middle life risk factors for later brain amyloid
Florbetapir: the word to remember this week. Florbetapir is a chemical that crosses the blood-brain barrier and attaches itself to amyloid. It is produced in a cyclotron in the morning and will have decayed by the evening, because the crucial ingredient is 19F, an isotope of fluorine with a half-life of 109 minutes. That’s just enough time to get your subject into a positron emission scanner and look for amyloid in the brain. Over two years, this was done to 322 participants in the Atherosclerosis Risk in Communities cohort, which was set up in 1987-9 and measured cardiovascular risk factors sequentially in US adults without overt cardiovascular disease at baseline. Now this is very impressive, but bear in mind that florbetapir uptake on positron emission tomography (PET) is just a surrogate for amyloid deposition, which in turn is just a surrogate for so called Alzheimer’s disease. This in turn has become a catch-all label for dementia, and is very different from the case described by Alzheimer in 1906. Florbetapir uptake is very common in older people: in this cohort of mean age 76, it was present in 31% of those with no CV risk factors in midlife and in 61% with two or more risk factors. So this study shows two things: florbetapir PET picks up a lot of brain amyloid that has no obvious clinical meaning, and amyloid deposition is associated strongly with traditional CV risk factors rather than being something which discriminates clearly between “vascular” and “Alzheimer’s” dementia.

Back pain & manipulation
When I get back pain I become tetchy and needy. I want somebody to take it away so that I can become the calm, amiable, easy to live with person I would like to be. Fortunately, I don’t often get back pain. Instead I find other excuses for being tetchy and needy. But if I got back pain all the time, I can see why I would be manipulated, although this systematic review provides a weak signal that spinal manipulation can help in acute episodes of back pain. As with so many kinds of symptom relief, it’s not the population effect I’d be looking for if I were the person with back pain, it’s what might work for me. That is why the world is full of manipulators for when you become tetchy and needy.

JAMA Int Med  Apr 2017  Vol
Hospital based primary care is more wasteful
I’m a strong advocate of breaking down the barriers between primary and secondary care in Britain. It would be nice to think that the good features of general practice could spread into hospitals: a broader view of diagnosis, more continuity of care, acceptance of uncertainty, frugality with testing, give and take based on personal knowledge of patients. But there are dangers too, as this American survey shows. “Primary care” in the US is something else, and it is often co-located with hospital services that make money from doing things to patients. This large sample of primary care visits by Americans shows that those who go to hospital based clinics are more likely to be overinvestigated, especially using radiography and MRI, and referred needlessly to specialists. Primary care doctors can be infected by their environment. When the NHS is forced into its next phase of disintegration, it could easily happen here. And you will be paying a lot more for it.

US hospital initiative works
Just occasionally, incentives achieve what they set out to do. An example seems to be the Medicare Hospital Readmission Reduction Program in the US. This was a voluntary scheme, which provided financial incentives to reduce readmissions in participating hospitals. It had a number of components and it proved very popular. In 2010, none of the 2837 hospitals in this study were participating in the programs. By 2015, all of them were involved with some of the components. Using some sophisticated analytics, the investigators show that the degree of participation correlates with a fall in 30 day readmissions following myocardial infarction, heart failure, and pneumonia.

The Lancet  15 Apr 2017  Vol 389
Alcohol in England
Here is a wide ranging and well written survey of how alcohol affects the health of people in England. It is modestly billed as “A rapid evidence review of the effectiveness and cost-effectiveness of alcohol control policies: an English perspective,” but it is much more than that. It provides a panoramic survey of what is known about drinking in England and how public institutions assess its costs and harms. As for interventions, the evidence is sensibly summarised at the start: “Although there is variability in research design and measured outcomes, evidence supports the effectiveness and cost-effectiveness of policies that address affordability and marketing. An adequate reduction in temporal availability, particularly late night on-sale availability, is effective and cost-effective. Individually-directed interventions delivered to at-risk drinkers and enforced legislative measures are also effective. Providing information and education increases awareness, but is not sufficient to produce long lasting changes in behaviour.”

Death from breathing
Now from drinking to smoking, and from England to the world. A quarter of men around the world still smoke, which is a 28% reduction from 1990. Smoking has fallen everywhere since then, except for Congo and Azerbaijan (for men) and Kuwait and Timor-Leste (for women). Despite the absolute decline, the relative contribution of smoking to overall disease burden is growing, especially in lower income countries. There is no excuse for this. Nicotine addiction can be satisfied in safe ways, which don’t involve the inhalation of toxins. Selling combustible tobacco is mass murder.

There is slightly more excuse for air pollution, which is largely a legacy of our long dependence on burning hydrocarbons for energy. Another Gates funded global survey lists particulate air pollution as the fifth ranking mortality risk factor in 2015. Again, successes in rich countries are counterbalanced by increases in pollution in low to middle income countries. At least there is the general will to find technological solutions for this, based as much on a common fear of global warming as on concern for people inhaling toxic air.

Celecoxib vs naproxen in high risk patients
So here’s a fairly common clinical scenario: you have a patient who’s had a cardiovascular event for which aspirin is indicated. They also would like to take a non-steroidal anti-inflammatory drug (NSAID) for arthritis. But they have had an episode of upper gastrointestinal bleeding. So if you continue their present treatment, they will need to take a proton pump inhibitor. As for the NSAID, you could opt for naproxen, because of its greater cardiovascular safety, or celecoxib, because of its greater GI safety. Which is it to be? A hospital in Hong Kong collected 514 such patients over seven years and randomised them to one or the other, in addition to aspirin and esomeprazole. The title blazons the fact that this was an industry independent trial. Good. But it wasn’t sufficiently powered to determine cardiovascular events. It did, however, show that celecoxib was significantly less likely than naproxen to cause upper GI bleeds over an 18 month period.

The BMJ 15 Apr 2017  Vol 357
Attentive readers of The BMJ will remember reading about Quick-Wee in Minerva last September. And here is Quick-Wee again, in a biggish randomised trial rather than the earlier 40 baby series in the Emergency Medicine Journal. Infants were randomised to either gentle suprapubic cutaneous stimulation (n=174) using gauze soaked in cold fluid (the Quick-Wee method) or standard clean catch urine with no additional stimulation (n=170), for five minutes. The method resulted in a significantly higher rate of voiding within five minutes compared with standard clean catch urine (31% v 12%, P<0.001). I like the pee value. It means we can agree that Quick-Wee is a wee improvement in getting wee tots to pee when we see the need to test their wee.    

Short course steroids are not harmless
“A few days on pred to see them through” is a very common strategy in the US, as I’m sure it is here. In fact, one fifth out of a million and a half adults in an American commercial insurance plan were given prescriptions for short term use of oral corticosteroids during a three year period. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The absolute risk may be small, but these relative risks are pretty alarming, especially for sepsis.

Uncertain about adult tonsillectomy
It’s nice to see an Uncertainties article in this week’s BMJ, especially a meaty one with some good graphics. It covers the evidence base for tonsillectomy in adults with recurrent tonsillitis. There are some rather poor randomised trials and some good retrospective case series. The tables are good, but where is the decision tool to be used directly with patients? I hope that future articles will go the whole way and put The BMJ right at the forefront of shared decision making by turning evidence synthesis into adaptable, shareable infographics.

Plant of the Week: Koelreuteria paniculata “Coral Sun”
The Indian Golden Rain tree is named in honour of Joseph Gottlieb Kölreuter (1733 –1806), who spent most of his life doing experiments on hybridisation in plants. This form of it is not a hybrid but a natural mutation with red stems and coral-pink finely divided leaves in spring, which turn pale green in the summer and are then joined by sprays of yellow flowers. In autumn, red returns to the leaves and the flowers will have turned into interesting bladder-like fruits.

So here is a tree for all seasons: well, three seasons anyway. And in nurseries it is becoming commoner and cheaper by the year. When we saw one on sale for £12.99 the other day, we bought it at once, though we have no idea where to put it. Our garden is not very warm, and our life expectancy is not infinite, so we will be lucky to see it grow to 3m, perhaps. In a favoured spot, over a longer time, you could easily double that. I suspect that the further north in England you go, the less well this tree will perform. It likes sun. Somewhere above Nottingham, it will probably just get mardy* and die.

I haven’t yet seen this particular variety in a garden, but perhaps in time it will be as common a sight in our suburbs as laburnum. General practitioners of the future may look forward to its shrimpy leaves in April and its rain of golden flowers in August, as they drive along familiar town roads to familiar town patients. It will take a decade or more to tell if this is the kind of tree you want in your own front garden or would rather see in other peoples’.

*Mardy is a word of obloquy, which creeps in around Nottingham and Derby and is used sporadically in other places that Southern people rarely visit. It means sulky and unsociable. Often (but not necessarily) combined with “baby,” “bugger,” “bum,” or “pants.”