Posts filed under Medical news (279)

February 25, 2015

Measuring what you care about

If cannabis is safer than thought (as the Washington Post says), that might explain why the reporting is careful to stay away from thought.



The problem with this new research is that it’s looking at the acute toxicity of drugs — how does the dose people usually take compare to the dose needed to kill you right away.  It’s hard to overstate how unimportant this is in debates over regulation of alcohol, tobacco, and cannabis.  There’s some concern about alcohol poisoning (in kids, mostly), but as far as I can remember I have literally never seen anti-tobacco campaigns mentioning acute nicotine poisoning as a risk, and even the looniest drug warriors don’t push fatal THC overdoses as the rationale for banning marijuana.

Alcohol is dangerous not primarily because of acute poisoning, but because of car crashes, violence, cancer, liver failure, and heart damage. Tobacco is dangerous not primarily because of acute poisoning, but because of lung cancer, COPD, heart disease, stroke, and other chronic diseases.

It’s hard to tell how dangerous marijuana is. It certainly causes dependence in some users, and there are reasons to think it might have psychological and neurological effects. If smoked, it probably damages the lungs. In all these cases, though, the data on frequency and severity of long-term effects are limited.  We really don’t know, and the researchers didn’t even try to estimate.

The conclusions of the researchers — that cannabis is over-regulated and over-panicked-about relative to other drugs — are reasonable, but the data provide very little support for them.  If the researchers had used the same methodology on caffeine, it would have looked much more dangerous than cannabis, and probably more dangerous than methamphetamine. That would have been a bit harder to sell, even with a pretty graph.


[story now in Herald, too]

February 21, 2015

If it seems too good to be true

The Herald (from the Daily Telegraph) has a story about a new high-antioxidant chocolate

Its makers claim it can change the underlying skin of a 50 to 60-year-old into that of someone in their 20s or 30s.

Actually, in an uncontrolled short-term trial in 400 people they say

“We used people in their 50s and 60s and in terms of skin biomarkers we found it had brought skin back to the levels of a 20 or 30-year-old

The target market is

“elegant, educated and affluent” city-dwelling women in their 30s and businessmen “to support their appearance in a stressful environment and on their business travels”.

or, in other words, people who would be willing to bore on about how young and beautiful their skin biomarkers are, in case you can’t tell by looking.

To be fair, there is independent expert comment (which is not entirely convinced). If you read right to the last sentence you get the real highlight:

Nutrition experts at UCL also warned that previous trials showed that astaxanthin worked better when applied directly to the face rather than ingested.


Updated to add: the story was also on Prime News, where they made explicit the point that this really has nothing to do with the chocolate. They could have put the astaxanthin in a pill, but they thought it would be more attractive if they put it in chocolate. A spoonful of sugar makes the medicine go down, etc,

February 20, 2015

Why we have controlled trials



The graph is from a study — a randomised, placebo-controlled trial published in a top medical journal — of a plant-based weight loss treatment, an extract from Garcinia cambogia, as seen on Dr Oz. People taking the real Garcinia cambogia lost weight, an average of 3kg over 12 weeks. That would be at least a little impressive, except that people getting pretend Garcinia cambogia lost an average of more than 4kg over the same time period.  It’s a larger-than-usual placebo response, but it does happen. If just being in a study where there’s 50:50 chance of getting a herbal treatment can lead to 4kg weight loss, being in a study where you know you’re getting it could produce even greater ‘placebo’ benefits.

If you had some other, new, potentially-wonderful natural plant extract that was going to help with weight loss, you might start off with a small safety study. Then you’d go to a short-term, perhaps uncontrolled, study in maybe 100 people over a few weeks to see if there was any sign of weight loss and to see what the common side effects were. Finally, you’d want to do a randomised controlled trial over at least six months to see if people really lost weight and kept it off.

If, after an uncontrolled eight-week study, you report results for only 52 of 100 people enrolled and announce you’ve found “an exciting answer to one of the world’s greatest and fastest growing problems” you perhaps shouldn’t undermine it by also saying “The world is clearly looking for weight-loss products which are proven to work.”


[Update: see comments]

February 16, 2015

Pot and psychosis

The Herald has a headline “Quarter of psychosis cases linked to ‘skunk’ cannabis”, saying

People who smoke super-strength cannabis are three times more likely to develop psychosis than people who have never tried the drug – and five times more likely if they smoke it every day.

The relative risks are surprisingly large, but could be true; the “quarter” attributable fraction needs to be qualified substantially. As the abstract of the research paper (PDF) says, in the convenient ‘Interpretation’ section

Interpretation The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies

Let’s unpack that a little.  The basic theory is that some modern cannabis is very high in THC and low in cannabidiol, and that this is more dangerous than more traditional pot. That is, the ‘skunk’ cannabis has a less extreme version of the same problem as the synthetic imitations now banned in NZ. 

The study compared people admitted as inpatients in a particular area of London (analogous to our DHBs) to people recruited by internet and train advertisements, and leaflets (which, of course, didn’t mention that the study was about cannabis). The control people weren’t all that well matched to the psychosis cases, but it wasn’t too bad.  The psychosis cases were somewhat more likely to smoke cannabis, and much more likely to smoke the high-THC type. In fact, smoking of other cannabis wasn’t much different between cases and controls.

That’s where the relative risks of 3 and 5 come from.  It’s still possible that these are due at least in part to some other factor; you can’t tell from just this sort of data. The atttributable fraction (a quarter of cases) comes from combining the relative risk with the proportion of the population who are exposed.

Suppose ‘skunk-type’ cannabis triples your risk, and 20% of people in the population use it, as was seen for controls in the sample. General UK data (eg) suggest the rate in non-users might be 5 cases per 10,000 people per year. So, in 100,000 people, 80,000 would be non-users and you’d expect 40 cases per year. The other 20,000 would be users, and you’d expect a background rate of 10 cases plus 20 extra cases caused by the cannabis. So, in the 100,000 people, you’d get 70 cases per year, 50 of which would have happened anyway and 20 due to cannabis. That’s not exactly the calculation the researchers did — they used a trick where they don’t need the background rate as long as it’s low, and I rounded more — but it’s basically the same. I get 28%; they got 24%.

The figures illustrate two things. First, the absolute risk increase is roughly 20 cases per 100,000 20,000 people per year. Second, the ‘quarter’ estimate is very sensitive to the proportion exposed. If 5% of people used ‘skunk-type’ cannabis, you can run the numbers again and you get 5 cases due to cannabis out of 55 in 100,000 people: only 9% of cases due to exposure.

Now we’re at the ‘interpretation’ quote from the research paper.  In this South London area, 20% of people have used mostly the high-potency cannabis and 44% mostly have used other types, with 37% non-users. That’s a lot of pot.  Even if the relative risks are correct, the population attributable proportion will be much lower for the UK as a whole (or for NZ as a whole).

Still, the research does tend to support the idea of regulated legalisation, the sort of thing that Mark Kleiman advocates, where limits on THC and/or higher taxes for higher concentrations can be used to push cannabis supply to lower-risk varieties.


February 12, 2015

Two types of brain image study

If a brain imaging study finds greater activation in the asymmetric diplodocus region or increased thinning in the posterior homiletic, what does that mean?

There are two main possibilities. Some studies look at groups who are different and try to understand why. Other studies try to use brain imaging as an alternative to measuring actual behaviour. The story in the Herald (from the Washington Post), “Benefit of kids’ music lessons revealed – study” is the second type.

The researchers looked at 334 MRI brain images from 232 young people (so mostly one each, some with two or three), and compared the age differences in young people who did or didn’t play a musical instrument.  A set of changes that happens as you grow up happened faster for those who played a musical instrument.

“What we found was the more a child trained on an instrument,” said James Hudziak, a professor of psychiatry at the University of Vermont and director of the Vermont Center for Children, Youth and Families, “it accelerated cortical organisation in attention skill, anxiety management and emotional control.

An obvious possibility is that kids who play a musical instrument have different environments in other ways, too.  The researchers point this out in the research paper, if not in the story.  There’s a more subtle issue, though. If you want to measure attention skill, anxiety management, or emotional control, why wouldn’t you measure them directly instead of measuring brain changes that are thought to correlate with them?

Finally, the effect (if it is an effect) on emotional and behavioural maturation (if it is on emotional and behavioural maturation) is very small. Here’s a graph from the paper
PowerPoint Presentation


The green dots are the people who played a musical instrument; the blue dots are those who didn’t.  There isn’t any dramatic separation or anything — and to the extent that the summary lines show a difference it looks more as if the musicians started off behind and caught up.

February 4, 2015

If drink we lack

As I’ve often said on StatsChat, if you’re eating dark chocolate or drinking red wine primarily for the health benefits, you’re doing it wrong. Now the problem is spreading to beer. Stuff has a headline “Could beer help fend off Alzheimer’s and Parkinson’s?” As you’d expect, the answer is “Not really.” 

The story is unusually light on information, not giving the journal name, the names of any of the researchers, or the names of any of their institutions.  Through Google, I found a story in the Telegraph, where the headline is even worse — “Beer could help ‘protect brain against Parkinson’s and Alzheimer’s'” — but at least they link to a press release.

The press release headline “Beer compound could help fend off Alzheimer’s and Parkinson’s diseases”  looks less extreme than the newspaper ones, but the lead is

The health-promoting perks of wine have attracted the spotlight recently, leaving beer in the shadows. But scientists are discovering new ways in which the latter could be a more healthful beverage than once thought.

They, finally, do link to the research paper, in the Journal of Agricultural and Food Chemistry. If you think that sounds a slightly strange place to publish research about the health effects of beer, well, it would be if that was what the research was about.  The abstract says

As an active component in beers, [xanthohumol]’s presence has been suggested to be linked to the epidemiological observation of the beneficial effect of regular beer drinking.

That is, the research assumes a beneficial effect of beer and is trying to work out what the mechanism might be. The research wasn’t in people, or even in mice, or even in mouse brain cells. It was in a standard lab cell line of nerve-like cells originally from a cancer of the adrenal gland in a rat.

You might also ask if there’s any research closer to live people. Last year, scientists at Oregon State University studied high doses of xanthohumol in mice.  They found it improved cognitive function in young mice, but not in old mice, and also pointed out

 the levels of xanthohumol used in this study were only possible with supplements. As a fairly rare micronutrient, the only normal dietary source of it would be through the hops used in making beer, and “a human would have to drink 2000 liters of beer a day to reach the xanthohumol levels we used in this research.”

That’s not really compatible with the new drink-driving limits.


February 3, 2015

Spotty coverage

Here’s a graph from the Economist showing the impact of the measles vaccine:


The number of measles cases fell from over half a million per year to about 100 per year when the vaccine was introduced. That’s a 99.98% reduction, in a disease that (in a healthy population) kills about two people in a thousand.


Here’s a graph from the Centers for Disease Control showing that little blip in 1990 on an expanded scale:


They say

The most important cause of the measles resurgence of 1989–1991 was low vaccination coverage. Measles vaccine coverage was low in many cities, including some that experienced large outbreaks among preschool-aged children throughout the early to mid-1980s. Surveys in areas experiencing outbreaks among preschool-aged children indicated that as few as 50% of children had been vaccinated against measles by their second birthday, and that black and Hispanic children were less likely to be age-appropriately vaccinated than were white children.

Vaccine coverage isn’t as bad as that now, but the profile of unvaccinated kids is different. Black and Hispanic children are just as likely as white children to have had at least one doses of the measles vaccine, and children in poverty have a rate only 1.5 percentage points lower. Now, a substantial chunk of the problem is parents who are anti-vaccine.

Kieran Healy has an interesting post on the ‘personal belief exemption’ data for kindergarten children in California.  They are only 3.36% of children, but they cluster.  That’s important because US is just on the edge of having high enough vaccine coverage to stop an epidemic from spreading, at least if the unvaccinated were evenly spread through the population. They aren’t:

the number of kindergarteners with PBEs, even in Berkeley, is not huge—about 67 kids out of 850 in the city. But 20 of those 67 are in the same school, and probably the same room.

Anti-vaccine hysteria is more prominent in the US than New Zealand: partly because our mainstream media don’t go in for it, and partly because everything is more prominent in the US. Similarly, reaction to the risks posed by unvaccinated children has been more prominent in the US. However,  New Zealand has a similar rate of measles vaccination. Our schools or early childhood services cannot refuse enrollment based on vaccination (no special paperwork is required as in California), and (like California) can only temporarily exclude unvaccinated children if they are known to have been exposed.

Last year, New Zealand had 283 cases of measles. Scaled for population, last year in NZ was about half as bad as the US in 1990, and about thirty times bigger than the current US outbreak (so far).

January 30, 2015

Probably not

The Herald (from the Daily Mail) asks “Has an 8-year-old found a cancer cure?

According to the story,

Michael Lisanti asked his eight-year-old daughter how she would cure cancer, and it seems she may have got it right.

Camilla Lisanti suggested using antibiotics, “like when I have a sore throat”.

Her parents, a husband-wife cancer research team were sceptical at first but tested out her theory in their Manchester University lab. And to their surprise, several cheap and widely-used antibiotics killed the most dangerous cancer cells.

That’s not what they say in their research paper, where the idea is presented as coming from a large-scale objective search

These observations are also consistent with the idea that cancer is essentially a disease of “stemness” gone awry

Based on this rather simple premise, using unbiased quantitative proteomic profiling, we have focused on identifying a global phenotypic property of cancer stem cells (CSCs) that could be targeted across multiple tumor types. We have identified this property as a strict dependence on mitochondrial biogenesis, for the anchorage-independent clonal expansion and survival of the CSC population.

Here, we show that 4-to-5 different classes of FDA-approved antibiotics, which inhibit mitochondrial biogenesis as an “off-target” effect, can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types 

Either way, are these antibiotics (which aren’t the ones recommended for ‘when I have a sore throat’)  a new idea that’s going to cure cancer?

Well, doxycycline, the apparent favourite, has been proposed before, based on at least two other theories about why it should work. A simple Google search would tell you that. A slightly more sophisticated search would tell you that this mechanism has been proposed before (in 1984)

Tetracyclines have even been tested before. A review article in 2011 says

Here we review the efforts to determine the efficacy of tetracyclines as chemotherapeutics in human cancer trials. While the majority of clinical trials have yielded disappointing results, tetracyclines have been shown to be generally well tolerated and have significant anti-proliferative effects in certain cancer types.

On the other hand, those trials were done in tumours chosen based on a different theory, and mostly used different tetracyclines. It would be wonderful if doxycycline did better in new trials, but I wouldn’t say that’s the way to bet.

January 28, 2015

Tracking medical results to their source

From the Herald

A study from the Garvan Institute in Australia demonstrates that a diet rich in coconut oil protects against ‘insulin resistance’ (an impaired ability of cells to respond to insulin) in muscle and fat and avoids the accumulation of body fat caused by other high fat diets.


Suppose we wanted to find this study and see what it really demonstrates. There’s not a  lot to go on, but the Google knows all and sees all. When you have more information — researcher names, journal names, words from the title of the paper — Google Scholar is the best bet (as Jeff Leek explains here).  With just “Garvan Institute coconut oil”, Google Scholar isn’t very helpful.

However, since this study is popular among coconut lobbyists, an ordinary Google search does quite well. For me, the top hit is a press release from the Garvan Institute. The press release begins

A new study in animals demonstrates that a diet rich in coconut oil protects against ‘insulin resistance’ (an impaired ability of cells to respond to insulin) in muscle and fat. The diet also avoids the accumulation of body fat caused by other high fat diets of similar calorie content. Together these findings are important because obesity and insulin resistance are major factors leading to the development of Type 2 diabetes.

I’ve highlighted two key phrases: this was an animal study, and the coconut oil diet did well compared to another high fat, high calorie diet.

What’s more, the Garvan press release links to the research paper. The abstract is open-access; here are two quotes from it

Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals.

In rats, isocaloric feeding of MCFA or LCFA HF diets induced hepatic insulin resistance to a similar degree, however insulin action was preserved at the level of LF controls in muscle and adipose from MCFA-fed animals.

That is, in mice, coconut oil was better than the same amount of lard (though not as good as a low-fat diet); in rats coconut oil was as bad as lard on one measure of insulin resistance, but was comparable to the low-fat diet on another measure.

If the results translated to humans, this would show a diet high in coconut oil was better for insulin resistance than one high in animal fat, but worse than a low-fat diet.

January 27, 2015

Benadryl and Alzheimers

I expected the Herald story “Hay fever pills linked to Alzheimer’s risk – study” to be the usual thing, where a fishing expedition found a marginal correlation in low-quality data.  It isn’t.

The first thing I noticed  when I found the original article is that I know several of the researchers. On the one hand that’s a potential for bias, on the other hand, I know they are both sensible and statistically knowledgeable. The study has good quality data: the participants are all in one of the Washington HMOs, and there is complete information on what gets prescribed for them and whether they fill the prescriptions.

One of the problems with drug:disease associations is confounding by indication. As Samuel Goldwyn observed, “Any man who goes to a psychiatrist needs to have his head examined”, and more generally the fact that medicine is given to sick people tends to make it look bad.  In this case, however, the common factor between the medications being studied is an undesirable side-effect for most of them, unrelated to the reason they are prescribed.  In addition to reducing depression or preventing allergic reactions, these drugs also block part of the effect of the neurotransmitter acetylcholine. The association remained just as strong when recent drug use was excluded, or when antidepressant drugs were excluded, so it probably isn’t that early symptoms of Alzheimer’s lead to treatment.

The association replicates results found previously, and is quite strong, about four times the standard error (“4σ”) or twice the ‘margin of error’. It’s not ridiculously large, but is enough to be potentially important: a relative rate of about 1.5.

It’s still entirely possible that the association is due to some other factor, but the possibility of a real effect isn’t completely negligible. Fortunately, many of the medications involved are largely obsolete: modern hayfever drugs (such as fexofenadine, ‘Telfast’) don’t have anticholinergic activities, and nor do the SSRI antidepressants. The exceptions are tricyclic antidepressants used for chronic pain (where it’s probably worth the risk) and the antihistamines used as non-prescription sleep aids.