Posts filed under Medical news (262)

November 18, 2014

Cholesterol is bad for you

That doesn’t sound like a very interesting headline, but an important clinical trial whose results were released today has made definite steps towards re-convincing researchers on this point.

The trial, IMPROVE-IT, looked at adding a new drug, ezetimibe, to one of the standard statin drugs for cholesterol lowering, in people who had previously had a heart attack. Ezetimibe works by blocking cholesterol absorption in the gut, a completely different mechanism to the statins, which block cholesterol synthesis. The drug had previously shown unconvincing results in a preliminary study, made even less convincing by the behaviour of the manufacturer. There was increasing uncertainty that the cholesterol-lowering effect of the statins was really how they prevented heart disease, since no other drug appeared to be able to do the same thing.

Now, IMPROVE-IT has found a reduction in heart attacks and strokes. It’s very small — only 2 percentage points, even in this high-risk group of patients — but it looks real. Given the price of ezetimibe it probably won’t be widely used immediately, but it comes off patent in a few years and then use might spread a bit.  The results are also encouraging for dietary approaches to lowering cholesterol by reducing absorption: some cereals, and spreads with plant sterols.

Other stories: Forbes, New York Times 

November 12, 2014

Africa? Can you be more precise?

From the Telegraph (via many people on Twitter)



Seeing this at the same time as hearing about Bob Geldof’s Band-Aid reboot really emphasises the point that Africa isn’t a single place. The first Band-Aid recording was intended to help people in Ethiopia; the new one is for the Ebola-stricken regions of West Africa. The distance from Freetown to Addis Ababa is about the same as Auckland to Dili in East Timor, or Los Angeles to Bogota (or Addis Ababa to Prague).

On the other hand, the graph does make an important point. Syphilis, starvation, and TB are all very inexpensively treatable. Malaria and HIV are largely preventable, also at low cost. An effective treatment for Ebola will help, especially for medical personnel who are otherwise at very high risk, but in the long run it isn’t going to be enough. If we can’t deliver penicillin effectively, we won’t be able to deliver Ebola drugs. To make a real difference, we need a vaccine that’s good enough to prevent outbreaks.

November 7, 2014

What overdiagnosis looks like

An article in the New England Journal of Medicine talks about screening for thyroid cancer in South Korea. There has been a massive increase in diagnosis, mostly of very small tumours that are probably harmless — there was been no change in the thyroid cancer deaths.


As the authors say:

Thyroid-cancer surgery has substantial consequences for patients. Most must receive lifelong thyroid-replacement therapy, and a few have complications from the procedure. An analysis of insurance claims for more than 15,000 Koreans who underwent surgery showed that 11% had hypoparathyroidism and 2% had vocal-cord paralysis.


October 30, 2014

Cocoa puff

Both Stuff and the Herald have stories about the recent cocoa flavanols research (the Herald got theirs from the Independent).

Stuff’s story starts out

Remember to eat chocolate because it might just save your memory. This is the message of a new study, by Columbia University Medical Centre.


Sixteen paragraphs later, though, it turns out this isn’t the message

“The supplement used in this study was specially formulated from cocoa beans, so people shouldn’t take this as a sign to stock up on chocolate bars,” said Dr Simon Ridley, Head of Research at Alzheimer’s Research UK.


There’s a lot of variation in flavanol concentrations even in dark chocolate, but 900mg of flavanols would be somewhere between 150g and 1kg of dark chocolate per day.  Ordinary cocoa powder is also not going to provide 900mg at any reasonable consumption level.

The Herald story is much less over the top. They also quote in more detail the cautious expert comments and give less space to the positive ones. For example, that the study was very small and very short, and the improvement in memory was just in one measure of speed of very-short-term recall from a visual prompt, or that this measure was chosen because they expected it to be affected by cocoa rather than because of its relevance to everyday life. There was another memory test in the study, arguably a more relevant one, which was not expected to improve and didn’t.

Neither story mentions that the randomised trial also evaluated an exercise program that the researchers expected to be effective but wasn’t. Taking that into account, the statistical evidence for the effect of flavanols is not all that strong.

October 28, 2014

Absolute, relative, correlation, cause

The conclusions of a recent research paper

Delivery by [caesarean section] is associated with a modest increased odds of [autism], and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of[caesarean section] implies that even a small increase in the odds of disorders, such as [autism] or ADHD, may have a large impact on the society as a whole. This warrants further investigation.

The Herald

Babies born through Caesarean section are more likely to develop autism, a new study says.

Academics warn the increasingly popular C-section deliveries heighten the risk of the disorder by 23 per cent.

There’s a fairly clear difference in language: the news story is fairly clearly implying that caesarean sections cause autism; the research paper is being scrupulously careful not to say that.

Using a relative risk is convenient in technical communication, but in non-technical communication makes the impact seem greater than it really is. The US Centers for Disease Control estimate a risk of 1 in 68 for autism spectrum disorder (there aren’t systematic NZ data).  If the correlation with C-section really is causal, we’re talking about roughly 14 kids with autism spectrum disorders per 1000 without a C-section and about 17 per 1000 with a C-section. The absolute risk increase, if it’s real, is about 3 cases per 1000 C-sections.

It’s also important to be clear that this correlation cannot explain much of the recent increases in autism. A relative risk of 1.23 means that if we went from no C-sections to 100% C-sections there would be a 23% increase in autism spectrum disorder. The observed increase is about five times that, and since  C-sections have only increased about 10 percentage points, not 100 percentage points, the observed increase in autism is about 50 times what this correlation could explain.

There are (I’m told by people who know the issues) good reasons to think there are too many C-sections.  This probably won’t be one of the most important ones.


October 22, 2014

Screening the elderly

I’ve seen two proposals recently for population screening of older people. They’re probably both not good ideas, but for different reasons.

We had a Stat of the Week nomination for a proposal to screen people over 65 for depression at ordinary GP visits, to prevent suicide. The proposal was based on the fact that 70% of the suicides were in people who had visited a GP within the past month.  If the average person over 65 visits a GP less than about 8.5 times a year, this means those visiting their GP are at higher risk.  However, the risk is still very small: 225 over 5.5 years is 41/year, 70% of that is 29/year.

To identify those 29, it would be necessary to administer the screening question to a lot of people, at least hundreds of thousands. That in itself is costly; more importantly, since the questionnaire will not be perfectly accurate there will be  tens of thousands of positive results. For example, a US randomised trial of depression screening in people over 60 recruited 600 participants from 9000 people screened. In the ‘usual care’ half of the trial there were 3 completed suicides over the next two years; in those receiving more intensive and focused help with depression there were 2. The trial suggests that screening and intensive intervention does help with symptoms of major depression (probably at substantial cost), but it’s not likely to be a feasible intervention to prevent suicide.


The other proposal is from the UK, where GPs will be financially rewarded for dementia diagnoses. In contrast to depression, dementia is pretty much untreatable. There’s nothing that modifies the course of the disease, and even the symptomatic treatments are of very marginal benefit.

The rationale for the proposal is that early diagnosis gives patients and their families more time to think about options and strategies. That could be of some benefit, at least in the subset of people with dementia who are able and willing to talk about it, but similar advance planning could be done — and perhaps better — without waiting for a diagnosis.

Diagnosis isn’t like treatment. As a British GP and blogger, Martin Brunet, points out

We are used to being paid for things of course, like asthma reviews and statin prescribing, and we are well aware of the problems this causes – but at least patients can opt out if they don’t like it.

They can refuse to attend a review, decline our offer of a statin or politely take the pill packet and store it unopened in the kitchen cupboard. They cannot opt out of a diagnosis.


October 9, 2014

…and to divide the light from the darkness

Q: There’s a story that charging your phone in your bedroom make you fat.

A: Yes, there is.

Q: Why?

A: Because it looked like a good headline.

Q: No, why does it make you fat?

A: Melatonin. The theory is that any light at night time makes your body not produce enough melatonin and that this is bad.

Q: How much more did people who charged their phones in their bedroom end up weighing?

A: There weren’t any people involved.

Q: Ok, so they had mice with cellphones in their bedrooms?

A: Rats. And not cellphones.

Q: Some other light source of a similar brightness?

A: No.

Q: What, then?

A: They put melatonin in the rats’ drinking water.

Q: So that should make them lose weight. Did it?

A: Not that they reported.

Q: Can you work with me here?

A: They measured the conversion of fat under the rats’ skin from ‘white’ to ‘brown‘, which is theoretically relevant to energy use and perhaps to diabetes and heart disease. It’s interesting research. (abstract)

Q: So it could be relevant, but doesn’t the generalisation seems a bit indirect?

A: Yes, “a bit.”

Q: Do international patterns of cellphone use match patterns of obesity?

A: Not really, but maybe in East Asia they use different chargers or something.

Q: Is the LED on a charger really enough to make a difference?

A: That’s what the story lead implies, but the second paragraph talks about research involving phone screens, laptops, artificial lighting, and street lights, so I’m guessing there’s a bit of a bait and switch going on.

Q: Couldn’t it be enough? I mean, in nature, it would be completely dark at night, like they say.

A: Only up to a point. There was another relevant story today, too.


October 3, 2014

Antibiotics, kids, and obesity

Earlier this week, the Herald had a story about antibiotics and childhood obesity. No-one involved really covers themselves in glory here, but probably the reporter comes out best.

The headline (Antibiotics ‘link to child obesity’) with appropriate claim quotes, and the lead

Children who are given antibiotics in the first two years of their lives are at greater risk of becoming obese in early childhood, a study suggests.

are fine, though there’s a sub-headline “Study finds some treatments kill bacteria that affect rate at which toddlers gain fat” that manages to be wrong in every respect.

The story goes on

The United States research is based on the medical records of 65,000 children between 2001-2013.

Researchers found infants who were given broad-spectrum antibiotics at least four times in their first two years were 16 per cent more likely to be obese by the age of 5.

That is in the research paper, but it’s much less impressive in context


The circles are the observed ratios of rates of obesity, the lines give the margin of error. You can see that, compared to no exposure, one exposure seems bad, two or three not so bad, and four or more worse.  They’ve looked at a lot of comparisons that don’t show a clear pattern, and picked out the biggest number.

There are other quibbles, for example, ‘broad spectrum’ doesn’t mean what it usually means, it means ‘everything except penicillin and amoxicillin’, but the biggest problem is confounding.  There are lots of things related to obesity and to antibiotic prescription, and it wouldn’t be at all surprising for one of them to explain this relationship.

More importantly, there’s no way this explains any meaningful fraction of the increase in childhood obesity.  Only about 3% of children were in the ‘4+ broad spectrum exposures’, so even if the ratio of 1.16 was true, the antibiotics would only be responsible for about half a percentage point of the obesity rate.  Even less of the the obesity increase would be explained, since antibiotics aren’t actually completely new.  Differences between countries also don’t seem to fit this as an explanation. For example, South Korea used to have a serious antibiotic overuse problem, which was reduced by new regulations in 2000. They don’t have much of a childhood obesity problem.

Still, there’s no reason the result couldn’t be true to some extent.  Antibiotics do affect gut bacteria, and gut bacteria are important in metabolising food. It might be true, but it’s definitely being oversold, and there are more urgent reasons not to over-use broad spectrum antibiotics.

The other part of the story that’s disappointing for the light it casts on science communication is some of the response

Some New Zealand experts are sceptical. Fight the Obesity Epidemic founder Dr Robyn Toomath noted that the latest study was funded by the American Beverage Foundation for a Healthy America, founded by the soft-drink industry.

“This is the industry buying crap science,” she said. “People who are poor get sick and get more antibiotics. They are more likely to be fat and a lot of other things as well.”

I’m in favour of scientists commenting on public issues, and I don’t see anything wrong with advocacy, but I think public allegations of intellectual dishonesty need a bit more detailed backup than this. You’d almost get the impression that the research hadn’t looked at number of doctors visits or any indicators of poverty.

September 26, 2014

Screening is harder than that

From the Herald

Calcium in the blood could provide an early warning of certain cancers, especially in men, research has shown.

Even slightly raised blood levels of calcium in men was associated with an increased risk of cancer diagnosis within one year.

The discovery, reported in the British Journal of Cancer, raises the prospect of a simple blood test to aid the early detection of cancer in high risk patients.

In fact, from the abstract of the research paper, 3% of people had high blood levels of calcium, and among those,  11.5% of the men developed cancer within a year. That’s really not strong enough prediction to be useful for early detection of cancer. For every thousand men tested you would find three cancer cases, and 27 false positives. What the research paper actually says under “Implications for clinical practice” is

“This study should help GPs investigate hypercalcaemia appropriately.”

That is, if a GP happens to measure blood calcium for some reason and notices that it’s abnormally high, cancer is one explanation worth checking out.

The overstatement is from a Bristol University press release, with the lead

High levels of calcium in blood, a condition known as hypercalcaemia, can be used by GPs as an early indication of certain types of cancer, according to a study by researchers from the universities of Bristol and Exeter.

and later on an explanation of why they are pushing this angle

The research is part of the Discovery Programme which aims to transform the diagnosis of cancer and prevent hundreds of unnecessary deaths each year. In partnership with NHS trusts and six Universities, a group of the UK’s leading researchers into primary care cancer diagnostics are working together in a five year programme.

While the story isn’t the Herald’s fault, using a photo of a man drinking a glass of milk is. The story isn’t about dietary calcium being bad, it’s about changes in the internal regulation of calcium levels in the blood, a completely different issue. Milk has nothing to do with it.

Paracetamol and ADHD reporting

Everyone has a story about the new Auckland findings of correlation between paracetamol use in pregnancy and ADHD in kids.

Almost uniformly they don’t make it easy to the find actual (open-access) research paper, not even naming the journal: NZ Doctor’s reprint of the press release does best, with

“The study was published [date] in Plos One online at this link;” [sic]

without a link or a date. The paper is here.

The other thing the stories don’t really make clear is that this finding is important only because it confirms the surprising finding from a big Danish study published earlier this year. The evidence from the New Zealand research wouldn’t be at all convincing on its own, but the replication of an association with paracetamol but not other commonly-used medications is potentially important.   Even the Science Media Centre didn’t really make this clear in their post, though the University of Auckland website does better.

It’s still quite possible that chance or confounding explains this association, and we don’t know if other groups tried to replicate the association and failed, but the replication is a significant step.