Posts filed under Medical news (341)

From the Herald, under the headline “Could you have the binge drinking gene?”

It’s long been known that a penchant for alcohol may be in the genes, and scientists say they may now be a step closer to understanding why.

They have found that a faulty gene may cause binge drinking – and that mice with the mutation overwhelmingly prefer the taste of alcohol to water.

This story is from the Daily Mail again; the Herald’s own reporters write better medical science stories.

In fact, the research is looking at mice to see the effect of mutating one of the genes encoding something called the GABA-A receptor. There’s some genetic evidence that differences in this gene are related to alcohol dependence (not binge drinking, which isn’t the same thing) in humans, and the researchers are interested in how the effect might work. They say

Our understanding of the genetic and molecular basis of alcohol dependence is incomplete. Alcohol abuse has long been associated with facilitation of neurotransmission mediated by the brain’s major inhibitory transmitter, GABA, acting via GABAA receptors (GABAARs). Recently, a locus within human chromosome 4, containing GABAAR subunit genes… associated with alcohol dependence in humans. … However, the neurobiological basis by which genetic variation translates into alcohol abuse is largely unknown.

This research into how the genetic differences might work is interesting and has potential applications in treatments for addiction, but we know that variants in this particular gene predict almost nothing about alcohol dependence in humans. That’s typical in modern large-scale genetics: genetic variants common enough to study in large numbers of people usually have very small effects, and they are important because they provide tiny points of light illuminating the complex biological mechanisms of health and disease.

You can get another useful bit of context by searching on “binge drinking gene”

• Daily Mail, March 2011: It has long been believed that alcoholism runs in the family – now scientists have pinpointed why. They have identified a binge-drinking gene, offering new hope in combating the growing social problem, it was revealed today.
• Daily Mail, December 2012:  A newly discovered addiction gene could be fuelling teenage binge-drinking, research suggests. The mutant version of the RASGRF2 gene makes the brain more sensitive to habit-forming rewards such as alcohol, studies have shown.

We were clearly due for identifying the binge drinking gene again about now. But if you want to know if you are at risk of binge drinking, counting your drinks will be much more informative than measuring your genes.

The US Food and Drug Administration has sent a letter to 23andme, one of the companies that will genotype you and provide lots of information from the sample, telling them to stop. It’s a tricky situation.

This product is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body. For example, your company’s website at www.23andme.com/health  (most recently viewed on November 6, 2013) markets the PGS for providing “health reports on 254 diseases and conditions,” including categories such as “carrier status,” “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer. Most of the intended uses for PGS listed on your website, a list that has grown over time, are medical device uses under section 201(h) of the FD&C Act. Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions.

On the one hand, I can’t see any valid social interest in stopping people from knowing their genotypes if they want to. On the other hand, the FDA has a point about marketing.

They raise two isssues.  The first is that 23andme make lots of (fairly weakly supported) claims about the usefulness of the results in disease prevention. The second is that some of the genotype information is actually clinically relevant and that they have not demonstrated sufficient accuracy in their results. The first issue is essentially a misleading advertising problem; the second is a quality assurance problem.

There are two things that can go wrong with the clinically useful results. The first is simple error: the genotype assay could give the wrong result, or you could be given results from someone else’s sample. This should be low probability, but it’s important to know how low — 1 in a 1000 would definitely be too high.

The second issue is interpretation. Suppose you have a lot of family members with breast cancer, and you suspect a BRCA1 mutation is responsible. You might be relieved if you test negative, and think your risk isn’t especially high, but that’s only a reliable conclusion if your family’s cancer risk was actually due to a BRCA1 mutation, not to some other genetic risk factor.

Update: I should probably note that 23andme could fix what I think are the actual problems, but this wouldn’t necessarily satisify the FDA.  The FDA aren’t currently being unreasonable oppressive Luddite statist bureaucrats, but they’re probably happy to be to if that’s the option on offer.

From online site Games and Learning

A massive study of some 11,000 youngsters in Britain has found that playing video games, even as early as five years old, does not lead to later behavior problems.

This is real research, looking at changes over time in a large number of children and it does find that the associations between ‘screen time’ and later behaviour problems are weak. On the other hand, the research paper concludes

 Watching TV for 3 h or more at 5 years predicted a 0.13 point increase (95% CI 0.03 to 0.24) in conduct problems by 7 years, compared with watching for under an hour, but playing electronic games was not associated with conduct problems.

When you see “was not associated”, you need to look carefully: are they claiming evidence of absence or just weakness of evidence. Here are the estimates in a graphical form, comparing changes in a 10-point questionnaire about conduct.

The data largely rule out average differences as big as half a point, so this study does provide evidence there isn’t a big impact (in the UK). However, it’s pretty clear from the graph that the data don’t provide any real support for a difference between TV and videogames.  The estimates for TV are more precise, and for that reason the TV estimate is ‘statistically significant’ and the videogames one isn’t, but that’s not evidence of difference.

It’s also interesting  that there’s mild support in the data for ‘None’ being worse than a small amount. Here the precision is higher for the videogame estimate, because there are very few children who watch no TV (<2%).

The Institute for Health Metrics, at my previous university  in Seattle, has a new tool for visualising the causes of death and disability across the world with interactive graphics.

This pair of maps is for cancer in women.

The lower map is just cancer deaths per 100,000 women.  That’s the easiest sort of number to obtain, but the problem with it is obvious: the orange and red countries are mostly just the places where the female population is older than average.

The upper map is age-standardised deaths per 100,000 women. That is, you take the rate in your country for women of a particular age, say 72 years old , and multiply by the proportion of 72-year olds in the UN’s standard reference population. When you do this for each year of age and add up the results, you get an estimate of what the cancer rate differences really are like, averaged over ages.

The map looks completely different after standardising by age. In particular, there’s a lot less variation between countries. The lowest rate is in Saudi Arabia, which is wealthy enough to afford good medical care but still has low rates of many cancer risk factors in women. The highest rate is Papua New Guinea, which has very high rates of cervical cancer (affecting younger women than many cancers).

While some traditional herbal medicines (foxglove, opium, willow, qinghaosu) turn out to actually work when studied carefully, others don’t. The most likely explanation for the reported benefits in some ineffective herbal products is some sort of placebo effect. That’s become more likely following recent research that tested 44 herbal products on sale in the USA and found that a third of them were completely missing the active ingredient, with some of the others containing inactive fillers such as oats or potentially active (or allergenic) plants other than those on the label.

The researchers used DNA barcodes: measurements of short DNA regions that are variable enough to distinguish most plant species, they didn’t measure the putatively active compounds in the herbs.  The DNA approach is much more efficient, but it can give an unrealistically favorable view of the situation: it’s possible that even where the right plant was present, it didn’t have a meaningful concentration of the right compounds.

There was a bit of publicity over this when it came out a few weeks ago (I wrote about it on my blog), but now the New York Times has picked the story up and has a lot more detail.

Everyone knows that areas with more fast-food stores have more overweight people, and it certainly makes sense that fast food is bad for you. Like almost everything else, though, it gets more complicated when you start looking carefully.

Firstly, earlier this year Eric Crampton wrote in NBR about some research by an economics PhD student, Rachel Webb, who was trying to take advantage of this well-known relationship to unpick some aspects of correlation vs causation in the relationship between mother’s weight and infant’s birthweight. She found that, actually, areas in New Zealand with more fast-food outlets didn’t have more obesity to any useful and consistent extent.

Secondly, there’s new research on diet and fast food using data from the big NHANES surveys in the USA.  It confirms, as you might expect, that people who eat more fast food also eat less healthily at other times.

From Stuff, under the headline ‘One in 10 Kiwis now alcoholic‘

One in 10 New Zealanders could now be considered “alcoholic” according to new diagnostic criteria – but the majority of those with a drinking problem are unlikely to recognise it because the issue is so common.

The new estimate of 400,000 “alcoholics” in New Zealand – around 10 per cent of our 4.4 million population – was tallied up by Professor Doug Sellman from the National Addiction Centre at the University of Otago.

It is significantly higher than the Ministry of Health’s 2006 estimate which says 3 to 6 per cent of the population has an alcohol issue.

Sellman’s figures are based on the new diagnostic criteria for “alcohol use disorder” recently published in the fifth edition of the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association.

From the president of the American Society for Addiction Medicine, in a review of DSM-V

DSM-5 has “Alcohol Use Disorder,” which comes in mild, moderate and severe flavors, suggesting the inadequate pyramid approach. There are 11 possible symptoms of the “use disorder,” of which two are necessary to achieve a mild specifier, four for moderate and six for severe. “Alcohol use disorder is defined by a cluster of behavioral and physical symptoms,” the authors of DSM-5 state. I have no problem with that except that some may confuse “alcohol use disorder” with addictive disease or with alcoholism

Some may, indeed.

There’s a story in the Herald arguing for mass vaccination in NZ against group C meningococcal disease.  There’s a good case for the vaccination — it’s a really nasty disease and there aren’t any other good treatment or prevention approaches — but I don’t see how the cost-effectiveness claims in the story can be right.

Dr Gravatt is quoted as saying there would be zero net medical cost for the vaccination program

Dr Gravatt estimated the net cost of vaccinating children at 12 months and again at 18 years would be zero for each “quality-adjusted” year of life saved at a vaccine price of $25 to $40 per dose. The listed prices were around $43 to $87, but discounts would be likely in a bulk contract.

He refers to a British vaccine study — which one isn’t specified.  However, there are cost-effectiveness analyses of the whole British group C meningococcal vaccination program (they vaccinate against group C but not group B, the opposite of NZ).  One, from 2002, estimates  a cost per life year saved of £6259. The second, from 2006, considers a wider range of possible vaccination programs: for the one that’s most similar to what Dr Gravatt proposed it estimates net medical costs of £9082 per quality-adjusted life year, and for the cheapest one, £3653 £2760 (update)per quality-adjusted life year. And that’s assuming the vaccine costs only £12 per dose, and in a country where group C meningococcal disease was slightly more common than it is here.

Another way to look at it: there are about 60000 births per year in NZ, so after the initial catch-up phase we’d be paying for 120000 doses per year. Even at $25 per dose, that comes to $3 million per year. According to the Herald’s story there are about 25 cases per year, so for the vaccination to be cost-neutral even at this lowest suggested price, the average disease case would have to cost the healthcare system $120000. That’s more than ten times what the UK cost-effectiveness study estimated (roughly £4000) including both the immediate cost of treating the disease and the cost of treating the long-term effects.

The vaccine looks to be a lot more cost-effective than, say, the prostate cancer drug that Campbell Live was pushing last week, and because herd immunity is important for this disease, there’s a relatively stronger case for vaccinating everyone, but that would be because the cost is worth it, not because the cost is zero.

Updates, including a lot more technical detail:  (more…)

The Herald tells us

Sunscreen provides 100 per cent protection against all three types of skin cancer and also safeguards a so-called superhero gene, a new study has found.

That sounds dramatic, and you might wonder how this 100% protection was demonstrated.

The study involved conducting a series of skin biopsies on 57 people before and after UV exposure, with and without sunscreen.

There isn’t any link to the research or even the name of the journal, but the PubMed research database suggests that this might be it, which is confirms by the QUT press release. The researcher name matches, and so does the number of skin biopsies.  They measured various types of cellular change in bits of skin exposed to simulated solar UV light, at twice the dose needed to turn the skin red, and found that sunscreen reduced the changes to less than the margin of error.  This looks like good quality research, and it indicates that sunscreen definitely will give some protection from melanoma, but 100% must be going too far given the small sample and moderate UV dose.

I was a also bit surprised by the “so-called superhero gene”, since I’d never seen p53 described that way before. It’s n0t just me: Google hasn’t seen that nickname either, except on copies of this story.

A good story in Stuff today about mortality rates.

A Ministry of Health report shows while death rates are as low as they have even been since mortality data was collected, men are far more likely to die of preventable causes than women.

Heart Foundation medical director Professor Norman Sharpe said it is a gap that will continue to widen as a “new wave” of health problems caused by obesity start showing up in the statistics.

The latest mortality data, gathered from death certificates and post-mortem examinations, shows there were 28,641 deaths registered in New Zealand in 2010.

While the number of actual deaths is increasing, up 8 per cent since 1990, this was because of a growing and ageing population.

Death rates overall have dipped about 35 per cent, meaning statistically we are more likely to survive to a ripe old age.

There aren’t any of the problems I complained about in last year’s story on this topic: there’s a clear distinction between increases in rates and the impact of population size and aging, and the story admits that the problems with preventable deaths it raises are projections for the future.

While on this topic, I will point out a useful technical distinction between rates and risks.  Risks are probabilities; they don’t have any units and are at most 100%. Lifetime risks of death are exactly 100%, and are neither increasing nor decreasing.  Rates are probabilities for an interval of time; they do have units (eg % per year). Rates of death can increase or decrease, as the one death per customer is spread out over shorter or longer periods of time.