Occasional reflections on Life, the World, and Mathematics

Posts tagged ‘medicine’

Medical hype and under-hype

New heart treatment is biggest breakthrough since statins, scientists say

I just came across this breathless headline published in the Guardian from last year. On the one hand, this is just one study, the effect was barely statistically significant, and experience suggests a fairly high likelihood that this will ultimately have no effect on general medical practice or on human health and mortality rates. I understand the exigencies of the daily newspaper publishing model, but it’s problematic that the “new research study” has been defined as the event on which to hang a headline. The only people who need that level of up-to-the-minute detail are those professionally involved in winnowing out the new ideas and turning them into clinical practice. We would all be better served if newspapers instead reported on what new treatments have actually had an effect over the last five years. That would be just as novel to the general readership, and far less erratic.

On the other hand, I want to comment on one point of what I see as exaggerated skepticism: The paragraph that summarises the study results says

For patients who received the canakinumab injections the team reported a 15% reduction in the risk of a cardiovascular event, including fatal and non-fatal heart attacks and strokes. Also, the need for expensive interventional procedures, such as bypass surgery and inserting stents, was cut by more than 30%. There was no overall difference in death rates between patients on canakinumab and those given placebo injections, and the drug did not change cholesterol levels.

There is then a quote:

Prof Martin Bennett, a cardiologist from Cambridge who was not involved in the study, said the trial results were an important advance in understanding why heart attacks happen. But, he said, he had concerns about the side effects, the high cost of the drug and the fact that death rates were not better in those given the drug.

In principle, I think this is a good thing. There are far too many studies that show a treatment scraping out a barely significant reduction in mortality due to one cause, which is highlighted, but a countervailing mortality increase due to other causes, netting out to essentially no improvement. Then you have to say, we really should be aiming to reduce mortality, not to reduce a cause of mortality. (I remember many years ago, a few years after the US started raising the age for purchasing alcohol to 21, reading of a study that was heralded as showing the success of this approach, having found that the number of traffic fatalities attributed to alcohol had decreased substantially. Unfortunately, the number of fatalities not attributed to alcohol had increased by a similar amount, suggesting that some amount of recategorisation was going on.) Sometimes researchers will try to distract attention from a null result for mortality by pointing to a secondary endpoint — improved results on a blood test linked to mortality, for instance — which needs to be viewed with some suspicion.

In this case, though, I think the skepticism is unwarranted. There is no doubt that before the study the researchers would have predicted reduction in mortality from cardiovascular causes, no reduction due to any other cause, and likely an increase due to infection. The worry would be that the increase due to infection — or to some unanticipated side effect — would outweigh the benefits.

The results confirmed the best-case predictions. Cardiovascular mortality was reduced — possibly a lot, possibly only slightly. Deaths due to infections increased significantly in percentage terms, but the numbers were small relative to the cardiovascular improvements. The one big surprise was a very substantial reduction in cancer mortality. The researchers are open about not having predicted this, and not having a clear explanation. In such a case, it would be wrong to put much weight on the statistical “significance”, because it is impossible to quantify the class of hypotheses that are implicitly being ignored. The proper thing is to highlight this observation for further research, as they have properly done.

When you deduct these three groups of causes — cardiovascular, infections, cancer — you are left with approximately equal mortality rates in the placebo and treatment groups, as expected. So there is no reason to be “concerned” that overall mortality was not improved in those receiving the drug. First of all, overall mortality was better in the treatment group. It’s just that the improvement in CV mortality — as predicted — while large enough to be clearly not random when compared with the overall number of CV deaths, it was not large compared with the much larger total number of deaths. This is no more “concerning” than it would be, when reviewing a programme for improving airline safety, to discover that it did not appreciably change the total number of transportation-related fatalities.

The world’s easiest job

In six US states — Arizona, Idaho, Arkansas, Georgia, Mississippi, and South Dakota — pharmacists are permitted to refuse to fill prescriptions to which they have moral or religious objections. In Idaho they can still be required to fill the prescription in life-threatening situations if no one else is available, and in Arizona they must at least return the prescription so they can get it filled from another pharmacist. In the other four, apparently they don’t even have to do that much.

So, I’m thinking, there’s hardly an easier job that Christian Scientists, in the last four states particularly, if they’re looking for easy work should apply to pharmacies. No matter what prescription anyone brings to them they can toss it in the bin and go back to playing solitaire, or reading the works of Mary Baker Eddy.

(You may think they’d have difficulties getting hired, and they may indeed have to acquire some formal qualifications. No lunch is completely free, though presumably they can obtain religious exemptions from most of the requirements of their course. But the drug store can’t refuse to hire them on religious grounds.)

Political doping

Who would have imagined that elections could be swayed by political-performance-enhancing drugs?

Trump, in full “unshackled” mode, told a crowd of supporters in Portsmouth, New Hampshire that Clinton, who has won both presidential debates according to most polls, seemed “pumped up” at the beginning of the second debate last Sunday, but that he thought her energy then waned as the debate went on. So, in Donald Trump’s reality, it of course stands to reason that she was thus “pumped up” on some kind of performance-enhancing drugs, and they should both take drug tests before the third debate.

I dispute the claim that this is fully unshackled. If Trump were fully unshackled, he would demand that Clinton be subjected to a medical gender test, like South African runner Caster Semenya. After all, as Trump has so eloquently put it in the past

Frankly, if Hillary Clinton were a man, I don’t think she’d get 5 percent of the vote.

(“Frankly” is great. He’s giving us the straight dope now, as opposed to the politically correct pabulum that he is otherwise forced to espouse.) She should have to prove, then, that she’s not a man. It clearly wouldn’t be fair to allow Hillary Clinton to run for president as a woman, with all the advantages that women are known to enjoy in presidential campaigns, while actually benefitting from a higher testosterone level than her male opponent.

Imagine if it didn’t come out until after the election that Hillary was doping. What would we do then? Would her victory be annulled? Would she be banned from political competition for four years? If her testosterone levels are too high, would she be forced to take suppressing hormones? Would she be required campaign as a man? Perhaps she’d have to sexually assault a campaign worker, to even things out? The mind boggles.

Donald Trump’s prodigious prostate

Let us accept for a moment the claim that Donald Trump’s medical condition is uniformly excellent. You might still expect that random medical test results should be about average for a healthy man. (Not meaning BP or heart rate or god-forbid testosterone, which you would expect to reflect his hyperpowerful masculinity.) I was looking at this report, released a few weeks ago, which included Trump’s test result for PSA (prostate-specific antigen). High levels can be signs of an enlarged prostate, or prostate cancer. But Trump’s doctor reports his level at 0.15. According to this study men over 70 with normal prostate have a median level of 1.9 (it doesn’t seem to depend much on age above 70). If we make the very conservative assumption that the distribution falls off linearly from 1.9 down to 0, we would estimate that less than 1% of men have PSA scores below 0.2.

Maybe Trump has no prostate.

Alternatively, he should really be compared with a younger reference group, because his pact with Mephistopheles and/or regular consumption of the blood of virgins keeps him youthful.

Chinese towels

Another thought about Elizabeth Holmes and Theranos: Her billion-dollar medical-testing company based on secret and unproven technology in her twenties depended largely on a board of well-connected politicians and former politicians, notable for their lack of any relevant scientific expertise. But before she got to that point she needed to turn the heads of some scientists. According to the New Yorker, she caught the attention of dean of engineering Channing Robertson in her freshman year at Stanford:

One day, in her freshman year, Robertson said, she came to his office to ask if she could work in his lab with the Ph.D. students. He hesitated, but she persisted and he gave in. At the end of the spring term, she told him that she planned to spend the summer working at the Genome Institute, in Singapore. He warned her that prospective students had to speak Mandarin.

 “I’m fluent in Mandarin,” she said.

“I’m thinking, What’s next? She’s already coming into the research group meetings at the end of her freshman year with my Ph.D. students. I find myself listening to her more than to them about the next experiments to be done and the progress that’s been made. I realized she’s different.”

Clearly scientific acumen was exceptional. But what is the role of Mandarin? (This is the second story in the article about how she impressed people with her knowledge of the language.) I am reminded of the famous passage in The Hitchhiker’s Guide to the Galaxy:

A towel, it says, is about the most massively useful thing an interstellar hitchhiker can have. Partly it has great practical value… More importantly, a towel has immense psychological value. For some reason, if a strag (strag: non-hitchhiker) discovers that a hitchhiker has his towel with him, he will automatically assume that he is also in possession of a toothbrush, face flannel, soap, tin of biscuits, flask, compass, map, ball of string, gnat spray, wet weather gear, space suit etc., etc. Furthermore, the strag will then happily lend the hitchhiker any of these or a dozen other items that the hitchhiker might accidentally have ”lost”.

Is speaking Mandarin (assuming you’re not yourself Chinese) the intellectual equivalent of having your towel? Is that what he means by “What’s next?” He’s thinking, I’m dean of the engineering school at Stanford, and I don’t speak Mandarin. She’s only 18 and she’s managed to learn to speak fluent Mandarin. She must know all kinds of things that I have no inkling of.

Is that the reason why the chic private schools in the UK all seem to be teaching Mandarin?

How to do it: Medical testing edition

I was commenting just recently on the cult of big ideas, where people whose life experiences have given them hierarchical power are suckers for “ideas” that are mostly blather, lots of words about the irrelevant bits of the problem, distracting attention from the real difficulties. And now Theranos is in the news. I read about this company, started by the obviously charismatic Elizabeth Holmes, in The New Yorker about a year ago. My immediate reaction was, this must be a joke. It was very much in the spirit of Monty Python’s How to do it.

Theranos, a Silicon Valley company[…], is working to upend the lucrative business of blood testing. Blood analysis is integral to medicine. When your physician wants to check some aspect of your health, such as your cholesterol or glucose levels, or look for indications of kidney or liver problems, a blood test is often required. This typically involves a long needle and several blood-filled vials, which are sent to a lab for analysis… [Theranos] has developed blood tests that can help detect dozens of medical conditions, from high cholesterol to cancer, based on a drop or two of blood drawn with a pinprick from your finger. Holmes told the audience that blood testing can be done more quickly, conveniently, and inexpensively, and that lives can be saved as a consequence.

Sounds wonderful. Quick. Convenient. Inexpensive. Saving lives. How is she going to do all that? Well, she wears “a black suit and a black cotton turtleneck, reminiscent of Steve Jobs”. She dropped out of Stanford. She has a board of directors full of highly influential aged former politicians, but no scientists, so far as I can tell. She “is in advanced discussions with the Cleveland Clinic. It has also opened centers in forty-one Walgreens pharmacies, with plans to open thousands more. If you show the pharmacist your I.D., your insurance card, and a doctor’s note, you can have your blood drawn right there…. A typical lab test for cholesterol can cost fifty dollars or more; the Theranos test at Walgreens costs two dollars and ninety-nine cents.” (more…)

The politics of impatience

What does it mean when someone who is himself significantly responsible for solving a problem expresses his “impatience” for a solution? I think of this because today’s Times has on page 2

George Osborne lost patience with the pensions industry yesterday, announcing action against insurers who blocked savers from accessing their cash.

And on page 4 we read of

news of a fresh delay of up to a year in publication of the Iraq inquiry, prompting Mr Cameron to say that he was “fast losing patience”.

Perhaps this outbreak of impatience is somehow related to the front-page story, which says

the very best they can expect is that it will take them time — but time is not on their side.

That one is about the pervasive decline in sperm quality due to plastics in packaging, sunscreens and cosmetics.

Every three minutes

From a Guardian article on a new theory about the aetiology of Alzheimer disease:

It is thought that this year one person every three minutes will develop dementia.

It’s hard to explain statistics in a way that they feel real to people, but is “one person every three minutes” really a useful way to think about a disease that develops gradually over many years, as opposed to, say, muggings? Perhaps they meant to say “one person every three minutes will be diagnosed with dementia”.

Do all babies look alike?

And if not, why don’t they have any privacy rights with regard to their photographs?

Here is the illustration provided by the BBC on its home page for a report on the decision to approve fertility procedures that take genetic material from three different people:

Not a three-parent baby, but they are expected to look similar to this one.

Not a three-person baby, but manufacturers promise they will look similar to this model.

One wonders what purpose this photograph serves. Are there readers who see the headline and think, “Wait, babies, I’ve heard of them. Can’t quite remember what they look like…” In what sense is this an illustration of the article? It’s not even a newborn infant. They might as well have shown a 90-year-old lady, because making three-person babies inevitably leads to the eventual creation of three-person 90-year-olds. It might be even more relevant to show an elderly person, because that’s the goal: the purpose of the procedure is to improve the health and longevity of the humans so conceived.

They could have used their stock photograph of weirdly lighted lab technicians pipetting something into a test tube instead.

I’m wondering, who is this baby who is standing in for a “three-person baby”? I’m used to seeing children have their features blurred out in news photos. But, of course, this one was presumably a “volunteer” model. One baby can stand in for all babies. (As long as it’s white, of course.)

What does an anti-vaccine activist want?

With the swelling of interest in the anti-vaccine movement, inspired by the recent California measles outbreak, I’ve seen a number of opinions published similar to this one from Ian Steadman in the New Statesman

Then there’s also this to think about: if somebody’s distrust of scientific and/or political authority is so great, for whatever reason – maybe they’ve been scared by sensationalist stories in the media, or maybe they sincerely believe the government has no moral right to dictate health choices to citizens – that they’re willing to significantly increase their child’s risk of catching a (possibly fatal) illness, then calling them names and telling them scientists and politicians disagree with them is probably futile. Arguing that “the science is settled” with someone whose stance is predicated on the belief that the standards of proof used by scientists are flawed is definitely futile.

The article is excellent, but I don’t entirely agree with this sentiment. Living in Berkeley and Oxford, I have encountered some vaccine refuseniks, and it’s not clear to me that they have anything as definable as a belief about “the standards of proof used by scientists”. Rather, I think that they have a desperate need to feel special, protected not by mass vaccination — and definitely not by anything as infra dig as “herd immunity” — but by their special virtue, which may be Christian purity or organic health-food purity. (more…)

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