Posts filed under Medical news (315)

November 20, 2015

Headline inflation

The breakthrough of the decade doesn’t happen most years, and the breakthrough of the year doesn’t happen most weeks, but you still need to put out a health news section.  If you do it by hyping whatever turns up, your headlines end up not having a lot of information value.

So, today, “Blood test for ovarian cancer ‘100% accurate‘” in the Herald is grade inflation.  The researchers at Georgia Tech have some impressive findings, but their test still hasn’t been evaluated on anyone other than the 95 women whose cancer status was known in advance and whose blood was used to develop the test. As the research paper says

…because the disease is in low prevalence in the general population (~0.1% in USA), a screening test must attain a positive predictive value (PPV) of >10%, with a specificity ≥99.6% and a sensitivity ≥75% to be of clinical relevance in the general population

That is, they want the test to give no more than 4 false positives per 1000 healthy women. So far, they’ve only looked at 49 healthy women.

The story is better than the headline on how significant this is, with an independent expert.

Dr Simon Newman, of Target Ovarian Cancer, said: “It is exciting preliminary research. It’s crucial to diagnose ovarian cancer promptly, as up to 90 per cent of women would live for five or more years if diagnosed at the earliest stage.

“However, this highly promising discovery needs significant further development and validation in large clinical trials before we know if it is suitable for screening the general population and works as well as predicted.

Even that’s exaggerated. We just don’t know what the survival would be with early diagnosis. At the moment, you have to be very fortunate to have your ovarian cancer detected at the earliest stage, and these tumours might be very non-representative.  We’ve seen real but smaller-than-expected benefits from screening in other cancers.

There are worse problems with the story than a bit of exaggeration, though. It gets the scientific idea completely wrong, saying:

But when Georgia Institute of Technology researchers looked at the blood of 46 women in the early stages of the disease and that of 49 healthy women, the cancerous samples contained different levels of 16 proteins compared with the healthy ones.

The innovative step in this research was to not use proteins. As the press release says

“People have been looking at proteins for diagnosis of ovarian cancer for a couple of decades, and the results have not been very impressive,”

Instead, the researchers looked at ‘metabolites’, smaller molecules produced by cell processes. Their hypothesis was that tumours might have varying genetic changes and varying proteins, but if they ended up as cancer they would have some cellular processes in common.


November 10, 2015

New blood pressure trial

A big randomised trial comparing strategies for treating high blood pressure has just ended early (paper, paywalled).  There’s good coverage in the New York Times, and there will probably be a lot more over the next week. It’s a relatively complicated story.

The main points:

  • Traditionally, doctors try to get your blood pressure below 140mmHg, but some people always thought lower would be better.
  • The study, funded by the US government, randomly allocated over 9000 people with high blood pressure and some other heart disease risk factor (but not diabetes) to either try to get blood pressure of 140mmHg or try to get 120mmHg.
  • A previous trial with the same targets, but in people with diabetes, had been unimpressive: the results slightly favoured more-intensive treatment, but the difference was small, and well within the variation you’d expect by chance.
  • In the new trial blood pressure targeting worked really well: the average blood pressure in the low group was 122mmHg, and in the normal group was 135.
  • Typically, people in the low group took two or three blood pressure medications, those in the normal group typically took one or two — but in both cases with quite a lot of variation.
  • There were 76 fewer ‘primary outcome events’:  heart attack, stroke, heart failure, or death from heart disease in the low BP group, and 55 fewer deaths from any cause.
  • From the beginning, the plan was to stop whenever the difference in number of ‘primary outcome events’ exceeded a specified threshold, unless there was a good reason based on the data to continue. The difference had been just barely over the threshold at the previous analysis, and they continued. In mid-September it was clearly over the threshold, and they stopped.
  • Stopping early will tend to overestimate the benefit, but the fact that they waited for one more analysis reduces this bias.

I’m surprised the benefit from extreme blood pressure reduction is so large (in a relative sense), but even more surprised that they managed to get so many healthy people to take their treatments that consistently for over three years.  As context for this, data from a US national survey in 2011-12 showed only about two-thirds of those currently taking medications for high blood pressure even get down to 140mmHg.

In an absolute sense the risk reduction is relatively small: for every thousand people on intensive blood pressure reduction — healthy people taking multiple pills, multiple times per day — they saw 12 fewer deaths and 16 fewer ‘events’.   On the other hand, the treatments are cheap and most people can find a combination without much in the way of side effects. If intensive treatment becomes standard, there will probably be more use of combination pills to make multiple drugs easier to take.

There’s one moderately worrying factor: a higher rate of kidney impairment in the low BP group (higher by a couple of percentage points). The researchers indicate that they don’t know if this is real, permanent  damage, and that more follow-up and testing of those people is needed. If it is a real problem it could be more serious in ordinary medical practice than in the obsessively-monitored trial.  This may well explain why the trial didn’t stop even earlier:  the monitoring committee would have wanted to be sure the benefits were real given the possibility of adverse effects — the sort of difficult decision that is why you have experienced, independent monitoring committees. 

November 9, 2015

Fish and chips might be bad for you

From the Herald (from the Telegraph)

Martin Grootveld, a professor of bioanalytical chemistry and chemical pathology, said his research showed “a typical meal of fish and chips”, fried in vegetable oil, contained as much as 100 to 200 times more toxic aldehydes than the safe daily limit set by the World Health Organisation.

In contrast, heating up butter, olive oil and lard in tests produced much lower levels of aldehydes. Coconut oil produced the lowest levels of the harmful chemicals.


That’s in the lab. In July, Professor Grootveld reported the same type of analysis for a BBC program, but on oil as actually used by home cooks. From the press release at De Montfort University

Professor Grootveld’s team found sunflower oil and corn oil produced aldehydes at levels 20 times higher than recommended by the World Health Organisation. 

Olive oil and rapeseed oil produced far fewer aldehydes as did butter and goose fat.

So, about an order of magnitude less bad than the current story.

The story talks about turning current food advice on its head. The most… the two most… among the several most important things wrong with that claim are: first, that oils high in monounsaturated fats (such as olive oil and rapeseed/canola) are the current food advice; second, that the advice to eat less saturated fat is based on studies of actual disease, not just on lab biochemistry;  third, Prof Grootveld published research on this lipid oxidation phenomenon in 1998, so his reported surprise at the findings is a bit strange; and fourth, “a typical meal of fish and chips” hasn’t been regarded as health food since basically forever.



November 5, 2015

New source for medical/science news

STAT ( is not, sadly, a statistics news site. On the upside, it’s a very promising site covering medicine and medical science.  It’s owned by the same person as the Boston Globe, but is a separate venture.

Their front page has a lot of news items already; for a look at the sort of more detailed story they can handle, there’s one on whether antioxidants have positive or negative effects on cancer. That’s by Sharon Begley, a highly-regarded and award-winning science writer.

STAT has recruited, either as staff or columnists, a lot of impressive people. It’s definitely worth looking at.


October 22, 2015

The wine when it is red

Q: Are you going to have a glass of wine tonight?

A: You mean as a celebration?.

Q: No, because a glass of red wine has the same benefits as a gym session. The Herald story?

A: Yeah, nah.

Q: What part of “Red wine equal to a gym workout – study” don’t you understand?

A: How they got that from the research.

Q: Was this just correlations again?

A: No, it was a real experimental study.

Q: So I’m guessing you’re going to say “in mice”?

A: Effectively. It was in rats.

Q: They gave some rats red wine and made others do gym workouts?

A: No, there wasn’t any red wine.

Q: But the story… ah, I see. “A compound found in red wine”. They gave the rats this compound directly?

A: That’s right

Q: And the gym workouts?

A: Basically, yes. The rats did treadmill runs, though they don’t report that they had headphones on at the time.

Q: So the resveratrol group ended up fitter than the exercise group?

A: No, both groups got the workouts. The resveratrol plus exercise group ended up fitter than the group just getting exercise.

Q: So, really, it’s about a glass of red wine plus a gym workout, not instead of a gym workout? If it was people, not rats?

A: Well, not “a glass”.

Q: How many glasses?

A: The rats got 146mg resveratrol per kg of weight per day. One standard conversion rate is to divide by 7 to get mg/kg in humans: about 20. So for a 60kg person, that’s about 1200mg/day of resveratrol.

Q: How much is in a glass of wine?

A: It depends on the size, but at 5 glasses per bottle, maybe 0.3 mg

Q: So we might need bigger glasses, then.

A: At least you’ll get plenty of exercise lifting them.

October 12, 2015

Elephants and cancer: getting it backwards

One News had a story tonight about elephants. This is how it starts

NZ anchor: An American researcher thinks he may have come up with a new weapon in the fight against cancer, inspired by a trip to the zoo. He remembered that elephants almost never get cancer and wondered whether what protects them could also help us.

US reporter: Elephants have survived 55 million years on this earth. They’ve evolved to beat cancer, and they might just help us beat it too

That’s a nice story, but it’s basically backwards from the more-plausible story in Nature News, and the (open-access) paper in JAMA.

The distinctive feature of elephant blood, according to either version of the story, is that elephants have many more copies of the tumour-suppressor gene p53. This gene makes a key protein in the mechanism that causes cells with DNA damage to kill themselves rather than reproducing and turning into tumours.  A large proportion of tumours have mutations in p53, and people who inherit a damaged copy of the gene tend to develop cancer (including some unusual forms) early in life.  We’ve known about p53 for a long time — decades — so while it is a target for drug development, it isn’t by any means a new target.  We haven’t got far with it because it’s hard to mimic the effect of a protein that acts inside the cell nucleus.

The story in Nature News is that the American researcher, Dr Jordan Schiffman, specialises in treating children with familial cancer, including ones who have inherited mutations in p53 (Li-Fraumeni syndrome). He heard a talk about elephants having many copies of p53. He then went to his local zoo to find out what the cancer rate was in elephants, and confirmed it was low.   This is important;  lots of people will tell you that sharks, for example, don’t get cancer, and that’s just not true.  Elephants, on the other hand, really do seem to have a surprisingly low rate of cancer.

Since elephants have a lot of cells and live a long time, you’d expect them to have a lot of chances to get cancer. Studying elephants makes sense as a way to find completely new ways of treating or preventing cancer. Unfortunately, it seems that a major reason elephants don’t get cancer  is that they have lots of redundant p53 genes, which isn’t a new treatment target. (Other reasons may be that they don’t smoke and they eat vegetarian diets.)

So, while it’s true that elephants have multiple copies of the p53 gene, everything else in the story is basically backwards. Looking for new cancer treatment targets in elephants is a good idea, but that’s isn’t quite what they did. The findings are good news for elephants but they are bad news for us; p53 isn’t a promising new treatment target, it’s one of the oldest ones we have.

August 30, 2015

Genetically targeted cancer treatment

Targeting cancer treatments to specific genetic variants has certainly had successes with common mutations — the most well known example must be Herceptin for an important subset of  breast cancer.  Reasonably affordable genetic sequencing has the potential for finding specific, uncommon mutations in cancers where there isn’t a standard, approved drug.

Most good ideas in medicine don’t work, of course, so it’s important to see if this genetic sequencing really helps, and how much it costs.  Ideally this would be in a randomised trial where patients are randomised to the best standard treatment or to genetically-targeted treatment. What we have so far is a comparison of disease progress for genetically-targeted treatment compared to a matched set of patients from the same clinic in previous years.  Here’s a press release, and two abstracts from a scientific conference.

In 72 out of 243 patients whose disease had progressed despite standard treatment, the researchers found a mutation that suggested the patient would benefit from some drug they wouldn’t normally have got. The median time until these patients starting getting worse again was 23 weeks; in the historical patients it was 12 weeks.

The Boston Globe has an interesting story talking to researchers and a patient (though it gets some of the details wrong).  The patient they interview had melanoma and got a drug approved for melanoma patients but only those with one specific mutation (since that’s where the drug was tested). Presumably, though the story doesn’t say, he had a different mutation in the same gene — that’s where the largest benefit of sequencing is likely to be.

An increase from 12 to 23 weeks isn’t terribly impressive, and it came at a cost of US$32000 — the abstract and press release say there wasn’t a cost increase, but that’s because they looked at cost per week, not total cost.  It’s not nothing, though; it’s probably large enough that a clinical trial makes sense and small enough that a trial is still ethical and feasible.

The Boston Globe story is one of the first products of their new health-and-medicine initiative, called “Stat“. That’s not short for “statistics;” it’s the medical slang meaning “right now”, from the Latin statum.

August 20, 2015

The second-best way to prevent hangovers?

From Stuff: “Korean pears are the best way to prevent hangovers, say scientists.”

This is precisely not what scientists say; in fact, the scientist in question is even quoted (in the last line of the story) as not saying that.

Meanwhile, as a responsible scientist, she reminded that abstaining from excess alcohol consumption is the only certain way to avoid a hangover.

At least Stuff got ‘prevention’ in the headline. Many other sources, such as the Daily Mail, led with claims of a “hangover cure.”  The Mail also illustrated the story with a photo of the wrong species: the research was on the Asian species Pyrus pyrifolia,  rather than the European pear Pyrus communis. CSIRO hopes that European pears are effective, since that’s what Australia has vast quantities of, but they weren’t tested.

What Stuff doesn’t seem to have noticed is that this isn’t a new CSIRO discovery. The blog post certainly doesn’t go out of its way to make that obvious, but right at the bottom, after the cat picture, the puns, and the Q&A with the researcher, you can read

Manny also warns this is only a preliminary scoping study, with the results yet to be finalised. Ultimately, her team hope to deliver a comprehensive review of the scientific literature on pears, pear components and relevant health measures.

That is, the experimental study on Korean pears isn’t new research done at CSIRO. It’s research done in Korea, and published a couple of years ago. There’s nothing wrong with this, though it would have been nice to give credit, and it would have made the choice of Korean pears less mysterious.

The Korean researchers recruited a group of young Korean men, and gave alcohol (in the form of shoju), preceded by either Korean pear juice or placebo pear juice (pear-flavoured sweetened water).  Blood chemistry studies, as well as research in mice by the same group, suggest that the pear juice speeds up the metabolism of alcohol and acetaldehyde. This didn’t prevent hangovers, but it did seem to lead to a small reduction in hangover severity.

The study was really too small to be very convincing. Perhaps more importantly, the alcohol dose was nearly eleven standard drinks (540ml of 20% alcohol) over a short period of time, so you’d hope it was relevant to a fairly small group of people.  Even in Australia.


August 6, 2015

Feel the burn

Q: What did you have for lunch?

A: Sichuan-style dry-fried green beans

Q: Because of the health benefits of spicy food?

A: Uh.. no?

Q: “Those who eat spicy foods every day have a 14 per cent lower risk of death than those who eat it less than once a week.” Didn’t you see the story?

A: I think I skipped over it.

Q: So, if my foods is spicy I have a one in seven chance of immortality?

A: No

Q: But 14% lower something? Premature death, like the Herald story says?

A: The open-access research paper says a 14% lower rate of death.

Q: Is that just as good?

A: According to David Spiegelhalter’s approximate conversion formula, that would mean about 1.5 years extra life on average, if it kept being true for your whole life.

Q: Ok. That’s still pretty good, isn’t it?

A: If it’s real.

Q: They had half a million people. It must be pretty reliable, surely?

A: The problem isn’t uncertainty so much as bias: people who eat spicy food might be slightly different in other ways.Having more people doesn’t help much with bias. Maybe there are differences in weight, or physical activity.

Q: Are there? Didn’t they look?

A: Um. Hold on. <reads> Yes, they looked, and no there aren’t. But there could be differences in lots of other things. They didn’t analyse diet in that much detail, and it wouldn’t be hard to get a bias of 14%.

Q: Is there a reason spicy food might really reduce the rate of death?

A: The Herald story says that capsaicin fights obesity, and the Stuff story says bland food makes you overeat

Q: Didn’t you just say that there weren’t weight differences?

A: Yes.

Q: But it could work some other way?

A: It could. Who can tell?

Q: Ok, apart from your correlation and causation hangups, is there any reason I shouldn’t at least use this to feel good about chilis?

A: Well, there’s the fact that the correlation went away in people who regularly drank any alcohol.

Q: Oh. Really?

A: Really. Figure 2 in the paper.

Q: But that’s just correlation, not causation, isn’t it?

A: Now you’re getting the idea.



August 5, 2015

What does 90% accuracy mean?

There was a lot of coverage yesterday about a potential new test for pancreatic cancer. 3News covered it, as did One News (but I don’t have a link). There’s a detailed report in the Guardian, which starts out:

A simple urine test that could help detect early-stage pancreatic cancer, potentially saving hundreds of lives, has been developed by scientists.

Researchers say they have identified three proteins which give an early warning of the disease, with more than 90% accuracy.

This is progress; pancreatic cancer is one of the diseases where there genuinely is a good prospect that early detection could improve treatment. The 90% accuracy, though, doesn’t mean what you probably think it means.

Here’s a graph showing how the error rate of the test changes with the numerical threshold used for diagnosis (figure 4, panel B, from the research paper)


As you move from left to right the threshold decreases; the test is more sensitive (picks up more of the true cases), but less specific (diagnoses more people who really don’t have cancer). The area under this curve is a simple summary of test accuracy, and that’s where the 90% number came from.  At what the researchers decided was the optimal threshold, the test correctly reported 82% of early-stage pancreatic cancers, but falsely reported a positive result in 11% of healthy subjects.  These figures are from the set of people whose data was used in putting the test together; in a new set of people (“validation dataset”) the error rate was very slightly worse.

The research was done with an approximately equal number of healthy people and people with early-stage pancreatic cancer. They did it that way because that gives the most information about the test for given number of people.  It’s reasonable to hope that the area under the curve, and the sensitivity and specificity of the test will be the same in the general population. Even so, the accuracy (in the non-technical meaning of the word) won’t be.

When you give this test to people in the general population, nearly all of them will not have pancreatic cancer. I don’t have NZ data, but in the UK the current annual rate of new cases goes from 4 people out of 100,000 at age 40 to 100 out of 100,000 people 85+.   The average over all ages is 13 cases per 100,000 people per year.

If 100,000 people are given the test and 13 have early-stage pancreatic cancer, about 10 or 11 of the 13 cases will have positive tests, but so will 11,000 healthy people.  Of those who test positive, 99.9% will not have pancreatic cancer.  This might still be useful, but it’s not what most people would think of as 90% accuracy.