Map of life expectancy at birth from Global Education Project.

Tuesday, May 31, 2011

Hang up and read

I feel compelled to comment on the massive worldwide freakout over the WHO's International Agency for Research on Cancer declaring that cell phone use might be a cause of brain cancer. I have not made any deep study of this issue but I can step up and give you some clarity and perspective that generally seems to be lacking.

As you ought to know, I am the last person in the world who would ever shill for the mobile phone industry. (I do own 20 shares of AT&T stock, which doesn't exactly make me their punk, I don't think.) I have been outspoken here more than once about the very substantial risk of talking on the phone while driving, which for some reason doesn't seem to bother people; and the profound idiocy of talking on the phone all the time about trivial nonsense when you could be actually existing in the world. I make phone calls when I have a good reason, and save the idle chit chat for when I'm just hanging out with people who are actually sharing my region of the space-time continuum.

But let's get real here. What the IARC has said is that very heavy, long term cell phone use might be associated with a slightly elevated risk of a rare brain cancer called glioma. The press release refers to as yet unpublished results from the so-called Interphone study, which might suggest to readers that the study found out something really scary.

Okay, here's what the Interphone study found. It's a case control study, which means that the proper way to look at the conclusion is that it's telling you the risk of having used a cell phone that is associated with being diagnosed with glioma. If that sounds kind of backwards, that's because it is. So no matter what, it can't prove causation: maybe cell phone users tend to have something else going on that's associated with cancer. At most it can be suggestive.

But it's not even all that suggestive. In fact, the odds of ever having regularly used a cell phone are lower for people with glioma than for people without it, as are the odds for people with another kind of cancer called meningioma. Both these results are statistically significant. But they don't want to say that means cell phone use at moderate levels protects you against cancer, which would be the obvious conclusion. Instead they say this possibly reflects "participation bias or other methodological limitations." So they make this observation, but they don't believe it, without specifying any plausible reason, just guessing there might be one.

But, they also found that there was an elevated association between glioma and the highest reported decile of recalled cumulative call time over ten years, and odds ratio of 1.4, although it was barely statistically significant. As I've told you a million times, you're likely to see a supposedly significant finding in a sub-group comparison that is actually spurious, because you're making multiple comparisons and you could just stumble across a coincidence. And they say, "there are implausible values of reported use in this group." So maybe people with brain cancer have problems with memory or understanding the questions? But they aren't willing to suggest that this result possibly reflects any methodological limitations.

Finally, although for technical reasons the case control study can't directly output the actual population risk, but only the odds ratio for the study population. But I can tell you that there are about 10,000 gliomas diagnosed in the U.S. each year, which means the risk you will be diagnosed this year is 3.3 in 100,000. The odds ratio is almost identical to the risk ratio for such a rare event so the actual elevated risk from implausibly heavy cell phone use over ten years is 1.3 cases in 100,000 people per year. If I have done all that correctly. Okay, it's higher than that because we probably shouldn't include children, maybe twice as high if we're limiting this to adults.

Feel better now? Can you think of anything you maybe should be more worried about? That maybe we aren't talking about?

Monday, May 30, 2011


As I was paying for my lunch on Friday, the clerk said "Happy Memorial Day!" I objected that Memorial Day is not supposed to be about happiness. It was originally, as the name makes clear, supposed to be a day to remember the casualties of war, but in most communities it has become a celebration of militant nationalism and an affirmation of war. Bands play stirring patriotic tunes, people line the streets waving flags, and soldiers march by displaying weapons. When I was a child, in fact, they used to drive tanks down the main street of Branford, Connecticut. I was actually kicked out of my high school marching band for wearing a black arm band in the parade -- making the apparently politically offensive point that we were supposed to be mourning, not celebrating.

Similarly, I do everything in my power to avoid celebrating Christmas. It's not because I am not a Christian. I would honor the sentiments of friends and family, even if I didn't share them, but Christmas is not a religious holiday at all. It is a grotesque celebration of materialism, a massive orgy of buying and possessing stuff, most of which the people who end up with it don't actually want or need. Christmas is essential to the economic system, but it is the precise opposite of any message I read in the gospels.

So no, I'm not having a happy Memorial Day. Nobody is paying any attention, but the flag covered boxes are still landing at Dover AFB. Of course it's a lot worse for the people who live in the countries where those young Americans are getting killed. It isn't glorious, it isn't honorable, it isn't even a necessary evil. It's just evil.

Friday, May 27, 2011

Will the FDA finally get it about surrogate endpoints?

As you have likely heard, there is bad cholesterol (Low Density Lipoprotein, LDL) and "good" cholesterol (High Density Lipoprotein, HDL). Elevated LDL in the blood is associated with increased risk of heart disease and strokes. No doubt about it. Conversely, in observational studies, elevated HDL is associated with lower risk. Truth.

So, we know that statins, which lower LDL, are associated with reduced risk of heart attacks and stroke, probably cost-effectively in people who already have heart disease, maybe or maybe not worth it for people who just have risk factors. But there's definitely an effect.

So, obviously, a pill that raises HDL will also help. For years, doctors have prescribed time-release niacin (nicotinic acid) for this purpose. It has some unpleasant side effects, but it's worth it to raise your HDL and save your life, right?

Sadly, no. A randomized controlled trial has been stopped early because adding Niacin to a statin regimen actually seems to result in increased risk of stroke, even though, yup, it raises HDL.

We've seen this again and again -- drugs are approved because they have an effect on some biological indicator which is hypothesized to yield a health benefit. But then it turns out it doesn't after all. Meanwhile the drug companies have raked in billions and patients have experienced unpleasant or even deadly side effects, for no benefit.

It's easy to think of reasons why we can be misled in this way. For example, a lot of vigorous aerobic exercise tends to raise HDL. Maybe it was associated with reduced risk in observational studies because it is a marker of fitness. But raising it with a pill doesn't make you physically fit! It just makes you have elevated HDL, which appears to be beside the point.

The FDA must change its policy and require actual evidence of a health benefit before approving new drugs. And maybe there are a lot more old ones that should come off the market. Of course everybody is lining up to defend Niaspan, even though it doesn't work, because a) there's big bucks involved and b) they don't want to admit they were wrong. Grow up folks.

Thursday, May 26, 2011

Like I'm a tell yuh

Sadly, due to taking a new job and not yet being able to sell my place in Boston, I'm making a ridiculous commute every day from what was supposed to be my weekend home in Connecticut to Providence. A secondary adverse effect is a serious NPR overdose. This morning I had to listen to Mara Liasson or Marr Eliason or whatever her name is explain that even if Paul Ryan's plan to cut Medicare wasn't popular with the voters the Democrats weren't serious because they didn't have a plan to cut Medicare and Medicare needs to be cut whether the voters like it or not, and Bill Clinton is a wise statesman for congratulating Paul Ryan on being serious because Medicare is going to ruin us all. (And what the hell is wrong with Clinton all of a sudden anyway?)

Listen Marr, the Democrats do have a strategy for containing Medicare costs and they even managed to sneak some of it into the health care reform act whereupon the Republicans accused them of cutting Medicare by $500 million dollars and thereby took control of the House, where they will absolutely not allow any of the very necessary and beneficial actions we can take, right now, to rein in the cost of Medicare without hurting beneficiaries. But either you don't understand anything about health care policy, or you just pretend not to for the sake of Fairness and Balance, or a little bit of both.

Here Dr. Rita Redberg explains it so even an NPR "reporter" can understand it. Medicare spends a whole lot of money on stuff that doesn't benefit patients, and might even harm them. Doctors and drug companies and medical device companies pocket that money, which is why Republicans start screaming about death panels and socialism and bureaucrats telling your doctor what to do every time anybody tries to do anything about it. The new structures created by the Affordable Care Act -- the Patient Centered Outcomes Research Institute and the Independent Payment Advisory Commission -- could do something about this, but Congress intentionally made them toothless because they collect too much money from the industries that want to keep the gravy flowing; and/or they're scared to death of the ads accusing them of "cutting Medicare" and setting up death panels and being communists.

So here's what we need to do. Stop using the language of "cutting" Medicare because that doesn't work. Start using the language of preserving Medicare, making it secure, making it efficient, making it do what's best for patients and taxpayers at the same time, making save money by taking better care of patients. This is not a contradiction at all: saving money and taking better care of people are the same thing. If Nancy Pelosi can find a way to get that message through the concrete skull of people like Marr Eliason or whatever her name is, there may be hope for us.

Wednesday, May 25, 2011

Short cuts

It's probably just a coincidence, but it seems that every time I extoll reason and repudiate faith, I lose a follower or two. So this link probably won't help.

The Patient Centered Outcomes Research Institute, described here, is an important component of the health care reform act. With all the excrement about the individual mandate going through the ventilator, it's gotten surprisingly little attention from the Grand Oligarchy Party. I say surprisingly little because here is the actual Death Panel, with names and everything -- the Board of Governors of PCORI.

The Affordable Care Act directs money to PCORI, in a way that Congress can't prevent without repealing the Act, to sponsor research into what works and what doesn't work so well in health care. And this is, of course, what the Republicans call "rationing" and "death panels." Believe it or not, their insane rhetoric was so intimidating that the Act explicitly forbids Medicare from taking into account anything PCORI finds out in making coverage and payment decisions. So we'll just have to trust doctors to keep up with the latest and do the right thing. Since something like 20-30% of medical spending is wasted, we can probably do a lot to constrain Medicare spending if they'll just pay attention. Good luck with that.

And here's some concrete evidence: The best way to cut health care costs is to improve quality. The fact is, we can spend less on health care and give people better care and better results. But every attempt to do that is met by Republicans screaming that Democrats want to put Granny on the ice floe, while of course that is precisely their own nefarious plot. We'll see if they can continue to get away with it.

Tuesday, May 24, 2011

Possible, but impossible

One of the major takeaways from the International Conference on HIV Treatment and Prevention Adherence, where I am at, was pretty much laid out in the beginning by keynote speaker Wafaa el-Sadr. She is among other accomplishments the winner of one of those McCarthur Foundation genius awards, so I guess she must be a genius. So listen up.

We were discussing a few days ago the eradicability of certain diseases. Smallpox has already been eradicated, and we've been just on the verge with polio for a few years now. (It's very disappointing that we haven't made it, due mostly to political obstacles, and it will be a catastrophe, in my view, if polio again becomes widespread and we have to once again start immunizing kids all over the world. So let's get this thing done.) Jimmy Carter, who is an excellent former president, is behind the near eradication of the guinea worm, which will likely be completed soon enough.

To be eradicable, a disease needs to have no non-human reservoirs. Guinea worm spends part of its life cycle in water, but needs a human host to complete it. There also must be a means either to prevent transmission. A vaccine is most convenient, but in the case of the guinea worm it's done by purely mechanical means: filtering drinking water, and making sure that the worms, when they emerge from their host, do not have an opportunity to get back in the water and reproduce.

There is no vaccine for HIV, but it turns out -- and people really weren't sure of this until now -- that if an infected person rigorously adheres to an anti-retroviral medication regimen, so that there is no detectable virus in the blood plasma, there will also be no virus in the genital mucosa and secretions and they will be almost entirely non-infectious. We know this from studies with sero-discordant couples. Evidence for non-infectiousness by sharing injection equipment is only circumstantial and there are good reasons to think it may not be so complete. Also injection drugs users are less likely to be adherent to their medications.

Nonetheless you don't need to achieve 100% non-transmission to stop an epidemic. If transmissibility is low enough, chains of infection will be short and the pathogen will eventually die out. Also, if people are in treatment it's much easier to augment prevention by education and needle exchange. People who are in treatment are actually less likely to engage in transmission risk behavior. This may seem counterintuitive, but basically, it means they have come to terms with their situation and are dealing with it. They don't want to be reinfected or get an STI, and they don't want to infect others. If they are addicts, they are more likely to stop or at least practice harm reduction.

But, can we treat our way out of this epidemic? Almost certainly not. Here's why.

First, everybody who is infected will have to know it. In the U.S., 20% or more of infected people are unaware of their status. The number is higher elsewhere, particularly in sub-Saharan Africa and South Asia. Then, every one of them must be immediately linked with medical care. You get a big fall of there, even in the wealthy countries where many people go through an initial period of avoidance and denial.

Then, they have to get treatment. This is tricky because it isn't clear that it's in the individual's own interest to begin treatment immediately. Right now the standard of care calls for initiation when the CD4+ cell count -- those are the kind of white blood cells that are preferentially infected and destroyed by HIV -- falls below 350/ml. There are indications that long term outcomes might be better if you start earlier, around 500, but it's not clear that it makes sense to start earlier. The pills have long-term side effects that can eventually catch up to you, mostly abnormalities of lipid metabolism that can cause disfiguring fat redistribution, weight gain, hypercholerstolemia, and diabetes. Also there is the danger of acquiring drug resistant virus if adherence is less than perfect. It isn't considered ethical to ask people to do something for the benefit of public health that might harm them personally, and a lot of people probably wouldn't do it anyway. You can intervene to influence behavior at that point, but you'll never be 100% effective.

Then, the people need to adhere strictly to their prescribed regimen, which is difficult to do and a lot of people don't do it. Recent data indicate that if you miss two or three days consecutively on typical regimens, you risk viral rebound. Longer treatment interruptions carry even higher risk.

So, right now, in the United States, only about 19% of HIV infected people have suppressed viral load and are essentially non-infectious. In Africa, of course, it's far worse, and in fact we're falling further behind as the rate of new infections exceeds the rate at which people can be offered treatment. And treating people earlier means few people could be treated altogether given fixed resources.

So no, we won't eradicate HIV by treating it. But, the more people we can treat, the fewer new infections there will be. It's a virtuous circle, even if it won't be entirely closed. That makes it a good investment. But like many good investments, the depraved state of our current politics means we aren't going to make it.

Monday, May 23, 2011

Back in Action

Things have been a little hectic around these parts -- in fact I am now in Miami Beach for the annual International HIV Adherence Conference, so yesterday was spent strapped into aluminum cocoons and running through airports in between. Anyhow here are a couple of items.

I wrote recently that Scientific American has dumbed it down for the contemporary declining intellect but is still worth your while. However, they have gone beyond the sin of mere middlebrowitude to an outright assault on the cause of science by running a fawning interview with climate change denialist Richard Muller, which noted climatologist Michael Mann is calling libelous. I'll let Joe Romm (at the link) do the dirty work for you.

They have flirted with climate change denial before, and I must say that I cannot remember a serious piece on climate recently. Naturally people are wondering what the hell is going on. Sold out to their advertisers, maybe? Sure looks like it.

On another subject, everybody treated the Harold Camping doomsday prediction with ironic detachment and deadpan humor, but hey, it's no joke. This psychopath destroyed thousands of lives -- not just people foolish enough to believe him, but in many cases their spouses, children and other loved ones who did nothing to deserve it. And his scam raked in hundreds of millions of dollars. However, it isn't criminal because it's religious, get it? I don't see any clear distinction from other religions, but maybe this will help a few people see that there's something essentially dangerous and destructive about faith.

I'll give you the latest from the conference later today.

Friday, May 20, 2011

Yabbut they probably knew it wasn't going to happen

Continuing to peruse my old SciAms I find, in February 1994, Philip Morrison, Kosta Tsipis and Jerome Weisner telling us that "U.S. forces were shaped for conflict with a superpower. The emerging multilateral world calls for a smaller, more flexible, and far less expensive military."

That's right folks, "When the Soviet Union imploded in 1991, the U.S. was still spending more than $300 billion a year for a military that included 350 ships, 16 active army divisions, more than 3,00 planes, and more than 25,000 nuclear warheads. Such massive forces place an unacceptable burden on the American economy and saddle the nation with a military built around an unrealistic scenario of vast global conflict."


Wednesday, May 18, 2011

Critical Condition

The new JAMA features two commentaries viewing with alarm the prospects for primary care as the health care reform legislation takes effect. Liselotte Dyrbye and Tait Shanafelt frame their concern around physician "burnout," which basically means the doctor feels a lot of work related stress, has difficulty empathizing with patients, and wants to quit. Joel Zinberg puts the problem in more straightforward terms: physicians will be increasingly squeezed financially.

The burnout problem comes mostly from excessive caseloads. There is a shortage of primary care physicians and once more people who are currently uninsured start showing up, they'll either get turned away or the docs will just have to work even harder and neglect the rest of their lives even more.

The money problem is a bit more complicated. The legislation expands the population eligible for Medicaid but once the 100% federal funding for the expanded population goes away in 2016, the states are going to have to pick up part of the cost and they are a) largely broke and b) not necessarily inclined to spend more on Medicaid anyway. Medicaid already pays less than other insurance and the states will no doubt respond by ratcheting down reimbursement even further. Second, Medicare reimbursement rates are scheduled to decline, which is not actually a feature of the Affordable Care Act but is one of the assumptions about how to pay for it. The original idea was to gradually decrease the spread in payment between specialty procedures and primary care but Congress kept putting it off so now we face a cliff.

The Act does propose lower payment rates to specialists which is supposed to reflect productivity improvements, but Zinberg argues that the result will be a reduction in physician income. Finally, the Independent Payment Advisory Board can recommend reductions in spending starting in 2014 if Medicare spending exceeds the overall rate of medical inflation, and until 2020, all of that effect will fall on physicians.

Zinberg doesn't think physicians are overpaid, given their medical school debt and delayed entry into the workforce associated with long training. That's debatable, in the case of many specialties, which is exactly the point here. We need to increase the supply of primary care providers, and we need to give them better pay and more satisfying working conditions. At the same time, we have too many specialists, who do too much, and they are overpaid relative to primary care providers. So I would say that hidden in Zinberg's essay is what really amounts to a plea for the privileges of specialists, which he happens to be. (He is a surgeon.)

We do face a real challenge in meeting the primary care needs of the population, and it does threaten to undermine health care reform and cause real hardship for patients and primary care providers. It's a difficult political challenge in part because medical specialists are well to do and politically powerful, and they aren't willing to give up their $200,000 a year plus incomes. Actually they might not have to if there were fewer of them and they did fewer unnecessary or harmful procedures, such as CABG and stenting and prostate removal and imaging -- all of which are overdone, among others. But primary care docs do have a real gripe. Graduating students aren't going into primary care even as more and more older doctors are retiring, so the situation is just going to get worse, at least in the near future.

But getting from the current situation with its powerful vested interests to where we need to be, well, there's no clear road.

Tuesday, May 17, 2011

We're all sick

No doubt you have heard all about this Korean study that finds the prevalence of autism to be 2.6%, astounding the world.

Well now. "Autism" is defined as meeting certain criteria based on a structured interview and observational protocol. It turns out that in the sample of kids from the general school population -- not those who had already been assigned to special needs programs -- the average IQ and academic performance of the kids with "autism" was indistinguishable from those without it, and in fact the proportion with superior IQs was higher than average. They were labeled as "autistic" because they had trouble making friends, and didn't have great social skills, basically.

Is this a "disease"? Does it have anything whatsoever to do with classic autism, which includes profound deficiency in language development; bizarre, perseverating and often self-destructive behaviors; and typically low IQ? There's no reason to think so.

Some kids are socially talented, some are mathematically talented, some are musically talented, some are athletically talented, etc. Most of us don't have it all going on, but I don't consider myself to have a disease because I can't dunk a basketball. There's probably something to be said for giving some form of extra help or coaching for children who are socially awkward and aren't popular, but I don't think labeling them as diseased is necessarily helpful.

Ray Moynihan, in the new BMJ, discusses this phenomenon of disease creep. It's particularly pronounced in psychiatry, but it's found everywhere. He writes, "we may sometimes be pushing boundaries too wide, and setting treatment thresholds so low, that people with mild problems or modest risks are exposed to the harms and costs of treatment, with little or no benefit." He gives as examples not only psychiatric diagnoses, but also "pre-hypertension," which afflicts 60% of the adult population; and expansion of the definition of Type 2 diabetes.

The panels that create these disease definitions, it turns out, have been populated heavily by people who get big bucks from drug companies. For example, 56% of DSM-IV panelists, and 100% of those on the sub-panel for mood disorders. (Have a Prozac.) Allen Frances, who chaired the panel, now tells Moynihan he has regrets. "He now believes that the edition unwittingly contributed to an explosion of unnecessary diagnoses in the areas of attention deficit, autism and bipolar disorder." He's worried the DSM-V will be even worse. (It's enough to give me intermittent explosive disorder.)

Of 12 panelists who created the "pre-hypertension" diagnoses, 11 got drug company money. Ditto for a 12-member panel on diabetes that, in 2009, promulgated a low blood sugar target and supported use of rosiglitazone, which is now banned in Europe and discouraged for use in the U.S.

As Moynihan suggests, we could fix this. Just ban people with conflicts of interest.

Monday, May 16, 2011

plus ça change

I am a nearly lifelong subscriber to Scientific American, since my grandparents gave me a gift subscription when I was 13. For some reason, when I was in college, I got in the habit of saving them. I recently moved from my home of 25 years and since I was handling all those back issues I started to take a look at them.

It's very interesting to see the state of science 30 years ago, compared with where it is today. Broadly, I would say that the rapid technological change we've experienced in that time obscures the lack of any major revolutions in basic science. In the April, 1981 issue Howard Georgi provided a complete exegesis of the Standard Model of the elementary particles and forces which is essentially unchanged today. Particle physicists have been pursuing his vision of a unified theory, but the building blocks of nature as we know it were already understood.

Other issues from that era describe the DNA-RNA-protein mechanics, the life of the cell, the immune system, and the other essentials of biology. All we've done since really is fill in more and more detail. Inflationary cosmology, as explained by Alan Guth, is still largely accepted. To be sure, cosmologists have run into some difficulties, labeled dark energy and dark matter, but these are new mysteries, not new conclusions. Complex systems dynamics ("chaos") was discovered in the '80s, the "RNA world" hypothesis of the origin of life was also discussed in the April 1981 issue by Manfred Eigen and colleagues, the quantum theory was fully developed, computer science was actually further developed than you might think -- the April 1981 issue also includes an article on speech recognition software. And yes, they knew about anthropogenic climate change caused by burning fossil fuel way back then.

But there are some pretty big differences between SciAm of 1981 and SciAm of today. For one thing, the articles back then were longer, and more challenging. They have more mathematics, and take you down closer to the bare metal of the specialized ideas. There was Martin Gardner's Mathematical Games column which gave readers substantial intellectual challenges every month. The magazine is still worth your while, but it has been dumbed down, a lot, to conform to shorter attention spans and less erudition. The basic courses in biology, physics, and astronomy have changed hardly at all in 30 years -- but fewer people have a grasp of them, and fewer still invest the time to keep up.

Oh yeah, I meant to mention this ad, from the April 1981 issue. It's from Texaco, and it features a picture of the totally irrelevant Bob Hope:

America's got enough coal to keep your lights on for hundreds of years. And Texaco's coal gasification process could mean you won't have to worry about how it affects the environment.

One of the main problems with burning coal to generate electricity has been, of course, to burn it in an environmentally acceptable manner. But Texaco's developed a process to turn our most plentiful energy resources into clean-burning fuel gas which can be used to produce power for generating electricity.

We've already proven the gassification proces in small-scale plants. Now Texaco is working with other companies and organizations to build a large coal gasification/electrical generating plant in the Mojave Desert. It will turn thousands of tons of coal a day into electricity. Some years from now, Texaco's investment in coal gasification technology will mean you'll have the electricity you need -- without having worrying about environmental effects.

Uh huh. Just remember: There's no such thing as clean coal.

Saturday, May 14, 2011

People are stupid

Isaac Asimov spoke at my college back in the day, and those were the first three words of his talk. Anyhow, as you probably know, Judgment Day is one week from today. Lots of people -- nobody seems quite sure how many but it sure seems like hundreds, at least -- have quit their jobs, abandoned their families, and are assiduously planning to spend their last dime by 5:59 pm on May 21. (The apocalypse starts at 6:00 pm, rolling across time zones, apparently.)

This got me to thinking. There's been a lot of conversation lately about how belief is largely impervious to evidence. For some reason this article by Chris Mooney has brought this inconvenient truth to attention, although the studies Mooney discusses have all been reported on before. Who knows why something suddenly hits the zeitgeist big time but anyway, this has.

The basic idea is that when people who are committed to a belief confront facts that don't fit, they just dig in deeper. They find a way, either to dismiss the fact, or reinterpret them, or somehow cram them into their framework. Although this is usually discussed with obligatory Fairness and Balance, it's pretty clear to me that people do this to varying degrees, that some minds are more open than others, and that there is a correlation with the conventional left-right political spectrum. (And no, I don't consider doctrinaire Communists to be actual liberal thinkers.) But that aside ...

There must be some degree of getting smacked in the face by the cold fish of reality that will get through to just about anybody, right? I mean, suppose (I know it seems unrealistic but bear with me) that Harold Camping has miscalculated and dawn breaks on May 22 with the world going on as before? What are these people going to think, and say?

So what would it take to break through global warming denial? Record setting droughts, floods, tornadoes, in every corner of the planet, haven't done it. But surely there is some tipping point where Rush Limbaugh and the Koch brothers just won't be able to fool people any longer, because what's in front of their faces is as plain as day. Where might that be?

Wednesday, May 11, 2011

Time for a percutaneous cerebral intervention?

I've written before about this scandal of cardiologists doing revascularization procedures -- usually that means basically reaming out a coronary artery and implanting a metal stent to help keep it open -- inappropriately. What is really strange about this, but maybe not so much after all, is that many cardiologists, most of the general public, and even health care journalists, believe that these procedures prevent heart attacks and extend life. They absolutely do not. Nortin Hadler has written about this frequently and he always attracts a barrage of outrage from physicians who claim he's wrong. The same thing has happened to me when I've commented on blogs, and gotten into e-mail wars.

But there is no doubt about this. As William B. Borden and a multitude write in their report in today's JAMA (you are scum and may only read the abstract) "[A] meta-analysis of 11 trials concluded that there was no benefit of PCI in preventing myocardial infection or death in patients with stable CAD [coronary artery disease]." Yes, if you've just had a heart attack, it's called for, otherwise the only benefit may be symptomatic relief of angina. And there are costs and risks.

So, the right thing to do is first to try so-called "Optimum Medical Therapy" (OMT) -- basically give people statins and beta blockers and aspirin and see how they do. If they don't have symptoms they can't live with, Bob's your uncle.

So Borden and friends find, based on a large database of information about PCI procedures, that less than half of them were getting OMT before they got the PCI. They are mystified why this keeps happening when it's so well-known that it's the wrong thing to do.

Well it's no mystery to me. That's what interventional cardiologists do. It's what they get paid to do. So they do it.

This is why, while it's nice to do comparative effectiveness research -- which is how we know that you ought to try OMT before even thinking about PCI -- it isn't enough. We need a method to get pointy headed bureaucrats to come between you and your doctor. Why? Because your doctor isn't in business for his or her health, and apparently not for yours either. If you want to pay for a PCI out of your own pocket, even if it isn't in your own best interest, nobody ought to stop you I suppose.

But why should I pay for it, from my taxes and my own insurance premiums? What exactly is supposed to be "libertarian" about that? And that's what we're talking about here Dr. Paul -- forcing everybody to pay for inappropriate medical procedures. Insurance companies and Medicare should make a rule -- we won't pay for PCI for people with stable CAD unless you document either that you tried OMT first, or it was counter-indicated; and that the patient complains of angina and understands that the procedure is for symptomatic relief only. If that isn't in the record, you don't get paid.

Unfortunately, that seems to be what it's going to take. Either that or injecting responsibility into their brains.

Tuesday, May 10, 2011

Stuff a sock in it

Here's my sage advice. After you get done killing the world's most wanted terrorist, your next step should be to STFU.

Immediately describing various events during the raid which later turned out not to have happened was the one, guaranteed method to make people a) doubt everything else you might say and b) sow confusion about the propriety and ethics of the action. (These are legitimately questionable but we should have these conversations on good information.)

Bragging about the terabytes of data -- "equivalent to a small college library!" whatever that means -- you have captured is the perfect way to make sure that everybody who thinks there's a remote possibility their name and address is in there somewhere will immediately skedaddle. By the time they got done going through the first few gigabytes 17 graduate students had already flown home from Germany to Saudi Arabia and the Emirates; and Ayman al-Zawahiri and Mullah Omar had ordered up a police escort and moved their entourages closer to Pakistani military headquarters, if not right on an army base where U.S. helicopters really won't want to land. Anyway, you know perfectly well that 90% of it is garbage -- the kids playing World of Warcraft, bin Laden looking at pictures of nekkid ladies, the wives downloading recipes, or whatever it is they were doing.

Finally, please do not announce that bin Laden's lair turned out to be an "operational command headquarters" when the only operational command that appeared to be going on there was vague discussion of somebody somehow derailing a train somewhere some day. Especially because the instantaneous reaction is for Senators to start talking about No Ride Lists (as far as I know, you derail a train from the outside, not the inside) and pretty soon, we'll be submitting to cavity searches to board the commuter train.

That's exactly what the whole al Qaeda thing is about, get it? They threaten, possibly credibly and possibly not, to do some nasty thing that amounts to a little more than a minor nuisance compared to the risks of death, injury and sickness that we face every day; and we waste untold billions of dollars on useless charades to make people think we're doing something to prevent it, such as invading Iraq and fighting in a civil war in Afghanistan against people who don't give a shit about the U.S. but only want to govern their own country, not to mention having to get to the airport 2 hours early.

Here's what you do. You kill the guy, then you engage in an eloquent, elegant silence. That would be smart.

Monday, May 09, 2011

Crank magnetism

That's the inexplicable tendency of one for of crankery to be associated with others, within the same individual. Here I give you Dr. Marc Siegel, Fox News's answer to Dr. Gupta, who is one of the most vocal proponents of the idea that trying to allocate medical resources efficiently and effectively is tantamount to murdering your grandmother. It turns out that's not the only way in which he is nuts. I received the following e-mail:


- Mind-Body Control The Key Says Dr. Marc Siegel – Prayer And Faith Can Help

In a new thought provoking, sure to be controversial book, Dr. Marc Siegel, Associate Professor of Medicine at the New York University School of Medicine and a Fox News Senior Correspondent says that cancer, heart disease and even death can be prevented by people understanding and recognizing their “inner pulse.”

The just released book, The Inner Pulse, explores the mysterious connection between body, mind, and spirit in the health and healing process.

“You don’t have to get sick, don’t have to die and can rise out of your wheelchair to walk again. Prayer counts, meditation matters, exercise is crucial, and understanding your inner pulse can allow you to master your body, and defeat many illnesses which modern doctors will tell you are uncureable,” says Siegel. “You can defy the odds by learning to know your inner pulse and responding to what it tells you. Disprove anyone who would write you off too soon.”

Dr. Marc Siegel is the author of several acclaimed books on the effect of pandemic viruses and how to prepare for them; his latest, The Inner Pulse, explores the mysterious connection between body, mind, and spirit in the health and healing process. Dr. Siegel is an Associate Professor of Medicine at the New York University School of Medicine, the Founder and Medical Director of Doctor Radio and a columnist for the Los Angeles Times and USA Today.

Diana Lombardi


So now he's a faith healer. You don't need no stinking Medicare (even though controlling Medicare spending is murder), prayer will cure your heart disease and cancer! To take this more seriously than it deserves, there was some interest in the idea that optimism and equanimity and all those good vibes might be associated with longer cancer survival and reduced risk of heart attacks, but it's been carefully studied and it just isn't true. This sort of quackery is particularly pernicious because it tells people that if they are sick, it's their own fault for not having achieved the proper spiritual state.

As for prayer, that's been tested too -- why I don't know -- and no, it doesn't work either.

This guy is a fascinating stew of mismatched offensive stupidity, that's all I can say.

Update: Just for kicks, I ran Siegel through the Quackometer.

Sunday, May 08, 2011

The end of the world

As we know it, that is. And I'm not talking about May 21. Jeremy Grantham is an investment manager, and this is his quarterly newsletter for investors. (His firm, GMO, does not stand for Genetically Modified Organism but rather Grantham-Mayer-Van Otterloo, in case you care.)

The overall perspective and purpose of Grantham's analysis may not be exactly what readers of this blog are looking for -- he's advising you about investing in commodities and, longer term, resources and resource efficiency. But whatever his motivation and values, he's paying attention to what is actually going on in the world instead of the sideshows that seem to have the undivided attention of our political class and the "journalists" who take dictation from them.

Basically, we're running out of the stuff -- principally petroleum but a lot of metals and fertilizer as well -- that fueled the human population explosion starting in about 1800 and created the anthropocene geological age. As Grantham explains, "The fact is that no compound growth is sustainable." He asks us to imagine the ancient Egyptians, "whose gods, pharaohs, language and general culture lasted for well over 3,000 years." Suppose they started with one cubic meter of possessions, and experienced just 4.5% annual growth. Three thousand years later they would have 10^57 cubic meters of physical possessions, more than the volume of a billion solar systems. Even much lower exponents result in impossibilities.

Grantham sees the price of commodities having no place to go but up, long term, although he expects a short term correction a buying opportunity. But there is no escaping it -- within a few years, just the coming decade, we are going to enter a new world. "From now on, price pressure and shortages of resources will be a permanent feature of our lives. This will increasingly slow down the growth rate of the developed and developing world and put a severe burden on poor countries."

That's a rather dry way of putting it. Malthus appeared to be mistaken only because the age of fossil fuels intervened to briefly eliminate all restraints. That's over folks. It's over. It's time to realize we are being hanged, and focus the mind.

Friday, May 06, 2011

Cross of Gold

There are no conspiracies and there are no coincidences. That's what a friend of mind once proclaimed in a chemically induced state. I don't know what he meant but he seemed to think it was very important. Anyway, by either conspiracy or coincidence or some ineffable mechanism, both NEJM and BMJ feature essays this week addressing the limitations of Randomized Controlled Trials as guidance for medical practice and reimbursement policy.

Because you are mere riff-raff, you are only allowed to read the abstracts, so let me fill you in on the basic ideas, which aren't actually difficult. I don't want to bore you with stuff you already know, but just to make sure everyone is on the same page the so-called "gold standard" for deciding whether a therapy works is the Randomized Controlled Trial (RCT). That's what you have to do to get a drug approved by the FDA, and it's the basis for comparable drug licensing systems throughout the world. It's also usually an RCT that is responsible for reversing some conclusion based on observational epidemiology, such as the anti-oxidant supplement flapdoodle.

The basic idea is that you take a bunch of people who meet eligibility criteria, and randomly divide them into groups -- in the simplest design, that would be 2 groups. One group gets the drug, the other gets a pill that is identical in appearance but contains only inert (presumably) ingredients. Nobody involved in the trial -- not the patients, no their doctors, not the people who collect data -- knows who is taking what. They systematically collect data on baseline and subsequent indicators of disease severity or symptoms or whatever, and then they declare the drug superior to placebo or not. This can be done, in principal, for cure, symptom relief, or prevention of disease, although the latter obviously tends to require large numbers and long-term follow-up.

We've talked here a lot about the statistical pitfalls -- something can appear to work just by coincidence, you can go rooting around for some apparent benefit and you're likely to find something even though it's spurious, small effects that aren't really worth it can be statistically significant, we're comparing only to placebo and not to alternative treatments in most cases, unfavorable results don't get published, yadda yadda yadda.

But there's another category of problem I haven't talked much about, and that's the main focus of these two essays. RCTs just aren't like the real world.

1) The eligibility criteria usually exclude large numbers of people who typically have the disease to be treated or the risk to be reduced, in other words they aren't necessarily typical of the people who will get the prescription once the thing is licensed. It's easier to interpret the results if the participants are fairly homogeneous in terms of disease or risk severity, age range, maybe gender, they may and other characteristics, and are likely to adhere to the treatment. That's convenient for the investigators, but threatens what we call external validity: does this result apply to other sets of people?

2) Not only are the subjects chosen because they are likely to adhere -- i.e. take the pills on schedule - their adherence is closely monitored and actively supported. In the Real World (RW), half the people don't take the pills the way they are supposed to.

3) Another important eligibility criterion, which I decided merited its own place in the list, is usually little or no comorbidity. To get cleanly interpretable results, you don't want people who have a lot of other sources of symptoms or risk. But that's not the RW either, obviously. In fact, as we grow older, most people have comorbidity, they're taking other meds, and oh yeah, they're getting yet older. That can totally mess things up.

So what's the answer? Real world observational trials would seem to help. Of course then you've got all the problems RCTs are designed to eliminate -- the people know what they're taking, or maybe they aren't taking it, maybe it's comorbidity that kills them or makes them sick, maybe the pill is actually helping in some way other than how we think it is . . . . The latter sounds weird but actually it's quite plausible. For example, many people think that statins reduce the risk of heart disease more because of anti-inflammatory than anti-cholinergic effects. And it's hard to know what you're comparing the results to, if you aren't carefully controlling who does and who does not get the pill. Maybe it's not the pill, but rather who happens to end up getting a prescription, that really matters.

So the point I'm trying to make here is that there is no diamond bullet of truth. Coming to scientific conclusions depends on putting together a mosaic of evidence. That includes trying to understand the biological mechanisms of disease and a mode of action of a drug that makes sense given that understanding; RCT observations that support the so-called "efficacy" of the drug -- that it works under controlled conditions; and real-world observations that support its "effectiveness" -- that indeed it works in the RW.

Of course you can't get the last one unless you go ahead and license it and try it on a large scale for a while. That's why many people support provisional drug licensing, during which time the compound is not used indiscriminately but only in the context of closely observed pilot "pragmatic" trials. We'd also pick up unanticipated adverse events that way before large numbers of people could be harmed.

Politically, however, this seems a hard sell. Drug companies obviously hate it because it delays their chance to make big fat profits and totally eliminates the chance to make big fat profits from stuff that doesn't work after all. Since that happens to be where a very large share of their profit comes from (Celebrex and HRT, anyone?) it's not popular with them. And it's not popular with patients and doctors either, who are always clamoring for the latest miracle.

This stuff is hard.

Thursday, May 05, 2011

Pussyfooting around

No, I'm not referring to what you probably think I'm referring to. James Chambers and Peter Neumann, in the new NEJM, discuss a treatment for prostate cancer approved by the FDA in April 2010. Sipeucel-T, brand name Provenge, offers a median survival benefit of 4.1 months and costs $93,000 for a usual course of 3 treatments.

Chambers and Neumann (Peter to me -- we were colleagues at Tufts) wander around the relevant regulatory issues. CMS did a review of its coverage policy for Provenge that wasn't completed until March of this year, and maybe that was inefficient, couldn't CMS and FDA have worked together? Well, not really, they have different responsibilities. On the other hand, as long as the FDA has approved it CMS can only consider limiting coverage to cases where it is indicated as effective and can't take cost into account, so if we are worried about the cost what can we do? Maybe we can merge Medicare Part B into Part D and then private insurers can negotiate over the price, which Medicare is not allowed to do . .. Yadda yadda yadda.

What we can't do, and what they can't really talk about because it's apparently a societal taboo -- and it's certainly not within the bounds of current law or policy and it's congress won't go near it -- is a) let Medicare negotiate for a better price and b) let Medicare consider whether $93,000 might be better spent on something else.

Uh oh. Reducing the profits of drug companies = socialism, which is un-American. And actually considering whether taxpayers should spend $93,000 to extend the life expectancy of people who are already very sick by 4 months is rationing = death panels = murder.

Curiously, however, considering not giving people who can't afford it any health insurance at all is perfectly okay, in fact it's the way to defend our freedom against socialists and death panels. Those unlucky people who aren't rich enough won't get Provenge either, but that isn't rationing, it's fiscal responsibility.

See the difference?

Wednesday, May 04, 2011

Science staggers on

During my morning commute, NPR spent a full hour reporting that Osama bin Laden is still dead. I guess that means it's time to move on to another subject and this one is for sure interesting. It seems a couple of good sized, medium term prospective cohort studies in Europe find that dietary sodium consumption is inversely associated with heart disease and cardiac mortality. In other words, according to these observations, people who eat more salt are less likely to get heart disease or to die from it.

Increased sodium intake did have a modest association with increasing systolic, but not diastolic, blood pressure. The authors hypothesize that restricting dietary sodium sufficiently to reduce blood pressure is associated with other adverse effects on the body's regulatory systems that overcome any benefit from reduced blood pressure. The suggestion is that maybe people shouldn't worry about sodium intake and just do what their body wants them to do when it comes to eating salt.

As I always say, I'm not a real doctor and I'm not giving out advice. However, I should point out that 100% of the subjects were white Europeans and that Africans have long been known to be more salt sensitive, so even if this is absolutely correct, it might not apply to everybody.

With that out of the way, here's the main point I want to make. The arguments of a large public health benefit from reducing salt in the typical diet were based on the observed association of sodium intake with blood pressure; multiplying that by the observed association between blood pressure and disease; and extrapolating to the general population. There are some unexamined assumptions in there, and this research suggests pretty strongly that the assumptions are incorrect.

This doesn't mean that the biological science that led to a general recommendation to reduce salt intake was wrong. It does mean that people drew conclusions from what we did know that might have been unwarranted. (Just because of this one publication nobody should consider the issue settled. The authors review other studies and, while they show that there really hasn't been clear empirical support for an association between sodium intake and heart disease or mortality in the past, the picture has been murky.) Unfortunately, this is a common problem in public health.

At some point you have to decide that a recommendation is plausible enough to promote it publicly, because it would be irresponsible to allow continued injury to people that you truly believe is happening. But that point often comes before we have real certainty or clarity. That's why there is such a history of changing recommendations. Take antioxidant supplements! Whoops, never mind. Eat a low fat diet. Whoops! Avoid saturated fats and trans fats particularly, but vegetable oil is fine. Take post-menopausal hormone replacements. Whoops! You probably shouldn't.

And so on. This makes people cynical and distrustful of all these sorts of recommendations. Don't be. Sometimes they turn out wrong but the overall direction is progress. The mistakes eventually get fixed. It isn't true that everything causes cancer. Keep listening to the authorities because they're steadily getting it more and more right. That's the best we can hope for, but it's worth respecting.

Tuesday, May 03, 2011

I've heard about shit like this . . .

That is, a postdoc sabotaging a colleague's experiments. In fact, the specific tactic of pouring alcohol into the other guy's cell cultures is a cliche. These sorts of stories made me reluctant to embark on a conventional academic career path. The moral of the story, other than "some people are total schmucks," is that the perch on the lower rungs of the scientific career ladder is horribly tenuous. Thanks in part to the volatile fortunes of federal research funding, there are too many Ph.D.s for the available decent academic jobs. So we get this sort of nihilistic hypercompetitiveness.

I'm happy to say, however, that my own experience has been the precise opposite. Everybody helps and encourages everybody else. But that's probably a function of the culture established by the leadership of the places where I have worked.

On another subject -- the paper on which this news story is based is not available on-line yet, but that's okay, you'll probably get more out of the story than the journal abstract anyway. For the most part, you should avoid over the counter medications entirely. As the study shows, you probably don't know what's in them, they probably aren't doing you much good if any -- particularly if we're talking about cold remedies -- and you could very well be OD'ing on acetaminophen.

The distance between a therapeutic dose of acetaminophen (AKA tylenol) and a dose that's toxic to your liver is very narrow. Did you know that the only reason they put acetaminophen in Vicodin is to discourage junkies from taking it because the FDA counts on them to know it's poison? It's true! If you have osteoarthritis or other pain, talk to your doctor and get on an NSAID diet that you can tolerate, or whatever you and doc decide on. If you have a cold or a flu-like illness, drink ginger tea. But I say, stay away from the brand names, and know what you're taking.

Monday, May 02, 2011

Obligatory curmudgeonliness

You knew I would deliver.

Driving to work today I was a bit surprised by news of the crowds pouring into the streets all around the country in spontaneous celebration of the wacking of OBL. Of course people wanted him to be caught but I hadn't realized so many people's feelings were still so close to the surface. The people standing in the plazas and on the street corners chanting "USA, USA" reminiscent of the Olympic hockey team's victory over the Soviet Union rather than any more substantive event that I can recall. My own feeling was essentially that this removes an irritant to the rational conduct of foreign policy and U.S. electioneering, but I wasn't inclined to run out and get rowdy about it.

A few of the more thoughtful reactions I have come across call either for a quibble or for an endorsement. PZ Meyers is actively disturbed by the cheering crowds, because he is thinking of the hundreds of thousands who are dead essentially because GW Bush used Al Qaeda as a pretext to invade Iraq. After wading through rivers of blood, we kill one man who was thousands of miles away the entire time. It seems a wrong occasion for celebration.

A fair point, but people aren't really thinking of that. Barack Obama is not George W. Bush, after all, and he was certainly obliged to hunt Bin Laden with all possible diligence. However, the pursuit and ultimate running to ground of Bin Laden in Pakistan turns out to be unrelated to both Iraq and Afghanistan, which really ought to lead to some serious soul searching once people get over their triumphalism.

Juan Cole reminds us of al Qaeda's origins in Ronald Reagan's cold war machinations. He also makes clear what many others have pointed out -- bin Laden was no longer of any substantive importance, al Qaeda has devolved into separate organizations in various places that did not answer to him or depend on him for resources, and essentially, this won't change anything. Maybe not, but it could if Obama takes advantage of the greater room this gives him to wind down the Afghanistan folly. It also exposes for anybody who is paying attention the collusion of the Pakistani military with al Qaeda and bin Laden specifically. Obviously they knew exactly where he was the whole time.

Magnifico at Daily Kos does an excellent job of rounding up the information available at this time and putting the story together. I find it particularly amusing that president Obama gave the order on Friday morning. He did seem to have a mysterious Mona Lisa smile throughout the White House correspondent's dinner. Now we know why.

Finally, although the U.S. is claiming that bin Laden was killed when he refused to surrender and resisted capture, we all know that the Seals had orders to kill, not capture him. The last thing the administration needed was to have bin Laden in custody. Those people who are regretting that there will not be a trial are being unrealistic. Yes, summary execution is against our principles and also against the rules. The Geneva Convention doesn't allow you to kill prisoners. But no politician or government is going to object to this, I think, for better or worse.

Just imagine the circus if they had shipped a breathing Osama bin Laden to Guantanamo, and had to figure out how to try him, kill him in an approved manner, and then presumably hand over the body to someone. It was pretty well understood all along that if the U.S. ever tracked him down, they'd just shoot him and throw his body into the ocean from a helicopter. Ugly, but over and done.