A common mistake in medical epidemiological studies is to mistake coincidence for causality. This is a very easy trap to fall into if the predicted cause-and-effect result is one that we already believe, or would like to believe, or that previous data leads us to expect. Again, the results of epidemiological studies should be used to formulate a hypothesis to be tested in the future, and not to prove a hypothesis.
With this in mind, let us evaluate a group of world-wide nutritional studies that was published by Lancet, the top English medical journal,the third week in February. They studied BMI's throughout the world. (for those of you in the non-medical world, this is (weight)/(height)(height), i.e. height squared. We have all been told that the greater the BMI (i.e. the heavier you are for a given height), the greater is the risk of heart disease and death. A recent anomaly reported elsewhere was a study that showed that those who were slightly overweight (BMI's between 26 and 30) had the best chance of surviving a heart attack. This result fit no theories, so it has not been further addressed, especially since this was the first evidence that maybe obesity wasn't the killer that it was claimed to be.
The Lancet study, which studied countries through the New World, the Old World, and the Far East came up with three results that held up statistically:
(1) Over the past 30 years the BMI is steadily increasing in all countries, almost monotonically.
(2) Over the past 30 years, the world-wide rate of heart attacks and cardiovascular deaths is decreasing.
(3) In the Far East, and only in the Far East, the greater the BMI, the LESS was your risk of heart attack or cardiovascular death.
This last result, indicating that overweight is cardioprotective, has many cardiologists and statisticians scrambling to find fault with it. However, except for saying they don't believe the result, there has been no significant rebuttal of the result. It is up to we doctors and researchers to try to understand the implications of this result, if we assume it represents a true state of affairs, but since the relationship was observed for over 30 years of studies, it is difficult to claim that it is not significant, and perhaps we should re-evaluate our definition of the "normal" range of BMI's.
Sunday, February 27, 2011
Saturday, February 26, 2011
Germ Warfare
I was stimulated to write this blog by the report circulated to me by e-mail by the ISID (International Society of Infectious Diseases), which said that there was an outbreak of at least 21 cases of a previously unknown phenotype of the measles virus in Turkey. The ISID (www.promedmail.org) performs an important information function. For instance, it was a Dutch physician recently returned from China who gave the first report of SARS, an epidemic the Chinese government tried to keep from the newspapers. Ibsen's play "Enemy of the People" always has the chance of occurring with real people and tourists, viz. the typhoid outbreak in Gstaad 20 years ago just before the beginning of the ski season.
This got me to thinking that the real danger to the world if a major war should break out is not atomic weapons (does anyone remember "duck and cover", and H. Rap Brown saying that "we are alive today because the Russians did not launch last night"?). The real problem would be unrestricted germ warfare. And the chosen method of attack would almost certainly be a virus, because (a) we have antibiotics that work against most bacteria, but few that work against viruses, and (b) except for a few exceptions such as anthrax spores, only viruses can be spread by fomites (inanimate objects), A further bonus is that except for the pneumonic version of the plague, it is much more difficult to spread acutely lethal bacterial infections, than to spread viruses (viz. the rapidity of the spread of many flu epicemics).
It is generally accepted that the first attempt at germ warfare occurred during the sieges of walled cities in the 14th and 15th centuries, when the besiegers catapulted plague victims over the walls. One U.S. cavalry officer after our Civil War gave blankets to the Indians on which people with measles had lain (effect unknown). And Lord Jeffrey Amherst here in the Northeast plotted to distribute smallpox-laden blankets among the Indians in an attempt to "kill them all". Again, there is no record of the results.
Now what would be the ideal virus, and what steps should the attacking country take to avoid "blowback"? The answer to the second question immediately answers the first. You would want to vaccinate your armed forces, police, and medical staff against your planned viral attack. The most efficient vaccine we have is for smallpox. It is also the most sensible one to use, because unlike measles it has no animal hosts, but only man (as far as we know). Therefore there is no risk of it hiding in the animal population. Smallpox has the added advantage of being rapidly spread, and quite lethal. The best way to spread it is to inoculate unvaccinated volunteers who are willing to die, wait for 7 to 10 days until their rashes appear, and they are maximally infective, and then fly them to the key cities of your chosen enemy and let them mingle among the people. Since we no longer vaccinate against smallpox this attack would be quick, very lethal, and probably unstoppable.
Let me assure my readers that this blog does not plant ideas into anyone's head, because no one will take it seriously. Tom Clancy wrote a novel in 1997 which climaxed with a Japanese pilot flying a fully gasoline-loaded 747 into the Capitol building and killing the president, etc. No one guarded against this, and voila, along came 9/11/2001. I should also mention that all members of our armed forces are fully vacccinated against smallpox, the plague, etc. In theory there are only a few stocks of live smallpox kept tightly guarded in the U.S., Russia, and England, and we all know that if this is what the governments tell us it is probably true.
This got me to thinking that the real danger to the world if a major war should break out is not atomic weapons (does anyone remember "duck and cover", and H. Rap Brown saying that "we are alive today because the Russians did not launch last night"?). The real problem would be unrestricted germ warfare. And the chosen method of attack would almost certainly be a virus, because (a) we have antibiotics that work against most bacteria, but few that work against viruses, and (b) except for a few exceptions such as anthrax spores, only viruses can be spread by fomites (inanimate objects), A further bonus is that except for the pneumonic version of the plague, it is much more difficult to spread acutely lethal bacterial infections, than to spread viruses (viz. the rapidity of the spread of many flu epicemics).
It is generally accepted that the first attempt at germ warfare occurred during the sieges of walled cities in the 14th and 15th centuries, when the besiegers catapulted plague victims over the walls. One U.S. cavalry officer after our Civil War gave blankets to the Indians on which people with measles had lain (effect unknown). And Lord Jeffrey Amherst here in the Northeast plotted to distribute smallpox-laden blankets among the Indians in an attempt to "kill them all". Again, there is no record of the results.
Now what would be the ideal virus, and what steps should the attacking country take to avoid "blowback"? The answer to the second question immediately answers the first. You would want to vaccinate your armed forces, police, and medical staff against your planned viral attack. The most efficient vaccine we have is for smallpox. It is also the most sensible one to use, because unlike measles it has no animal hosts, but only man (as far as we know). Therefore there is no risk of it hiding in the animal population. Smallpox has the added advantage of being rapidly spread, and quite lethal. The best way to spread it is to inoculate unvaccinated volunteers who are willing to die, wait for 7 to 10 days until their rashes appear, and they are maximally infective, and then fly them to the key cities of your chosen enemy and let them mingle among the people. Since we no longer vaccinate against smallpox this attack would be quick, very lethal, and probably unstoppable.
Let me assure my readers that this blog does not plant ideas into anyone's head, because no one will take it seriously. Tom Clancy wrote a novel in 1997 which climaxed with a Japanese pilot flying a fully gasoline-loaded 747 into the Capitol building and killing the president, etc. No one guarded against this, and voila, along came 9/11/2001. I should also mention that all members of our armed forces are fully vacccinated against smallpox, the plague, etc. In theory there are only a few stocks of live smallpox kept tightly guarded in the U.S., Russia, and England, and we all know that if this is what the governments tell us it is probably true.
Friday, February 4, 2011
Medical Research Errors, or Don't Believe all that you Read
I did physics research for over 10 years, and clinical medical research for over 25 years. I have reviewed physics papers (as assistant editor of a physics journal) and medical papers, especially for the Annals of Internal Medicine. As a physics reviewer, I could often suggest revisions that would make the paper publishable, but as a medical reviewer I found this to be impossible. During my 10 year tenure as a reviewer in my medical field, I would estimate that I rejected 90% of the papers I reviewed, usually for lack of scientific rigor, and my negative review was never overridden by the article being published in a medical journal of similar significance.
There are various problems with scientific rigor in medical journals, but the most serious is their improper use of statistics, followed by lack of reproducibility, i.e. other researchers cannot replicate the results. In science, this is usually due to fraud (black ink spots placed on mice) or self-delusion (N-rays in France), but in medicine it is usually a sign that the first result was not entirely correct. I always tell my patients who rush in breathlessly with the latest report of medical research to wait for the second and confirming report. The second report often does not confirm the first. I also tell them to beware of medical studies that look for surrogate endpoints (lowering of blood pressure or cholesterol) rather than significant clinical endpoints(stroke, heart attack).
There are too many books, articles, and TV shows including some authored by doctors, that are studded with phrases such as "the evidence suggests", "it seems reasonable that", "past history shows" or all patients with or without condition X did or did not have disease Y. None of these statements contains a scientific truth, and such phrases would never appear in a physics or chemistry journal. A hard fact is rarely stated, such as that 500mg 2 x day of Vitamin C will lower your uric acid level by approximately 1.0 and thereby reduce your risk of a gout attack (this latter statement has been substantiated by research). We have very little good clinical evidence about many medical conditions, although it is almost universally agreed that antibiotics can kill bacteria and save lives, and that vaccinations are beneficial.
We still don't understand why only 10% of smokers get lung cancer (although we know with 100% certainty that all smokers will develop emphysema if they smoke long enough---40 pack years is usually sufficient). We don't understand why different patients with high blood pressure develop problems in different organs: stroke, kidney failure, heart attack. We don't understand why one alcoholic gets cirrhosis of the liver, one dies of hemorrhagic pancreatitis, and one gets the Korsakoff Syndrome. Similarly, we cannot predict which organ will fail in a patient with insulin-dependent diabetes, or if in fact any of them will.
The main problem, of course, is that each patient is an individual biochemical laboratory, and no two patients react the same way to any medical intervention. This is always true if the patient is on three or more drugs, since almost all pharmacological studies are done on patients on no drugs. (And no one knows how all the over-the-counter health foods interact with anything.) Many medical recommendations are based on three or fewer studies, while there are over 50 verifications of Bell's Inequality in quantum physics, and hundreds of measurements of the speed of light. Furthermore the results of a medical study apply only statistically, in that not everyone is cured of strep throat by penicillin, and some people with strep throat recover without any antibiotic at all. If I were responsible for the treatment of 1,000,000 patients, I would have no hesitation in making certain recommendations, but if I am recommending treatment for just one person, I am never 100% certain if the treatment (a) will work, and (b) is necessary.
In a previous blog I carefully reviewed the mathematical and statistical flaws inherent in all meta-analyses, so let me just say here that every result suggested by any meta-analysis should be verified by double-blinded random testing, despite the rapidity with which the media trumpet the results of the study.
I should also mention the problem of confounding conditions. When we do a clinical intervention study, we try to make the treated and control patients physiologically as similar as possible. When we do not, we come to the false conclusion that coffee drinkers suffer more heart attacks than do non-drinkers, until it was realized that coffee drinkers also smoke more cigarettes than the non-drinkers. We still have conflicting studies on whether tall people live longer or shorter lives than short people, and are similarly lacking in knowledge about righties versus lefties. (But I do wonder why all left-handed tennis players seem to have a natural topspin on their forehand on television.) Many men gleefully reported to their wives and significant others the one study that seemed to indicate that frequent ejaculations had a protective effect against prostate cancer, but many fewer people and organizations trumpet the many studies that show that mild alcohol ingestion is protective against heart attacks, and the fact that NO study has shown that mild alcohol ingestion contributes to heart attacks.
And please ignore all studies reported at all medical conferences. Until these studies have been written up, reviewed and then published, there is no way for anyone to verify their accuracy. And beware doubly of the placebo effect: In the 1950's, before we had ethical treatment review boards, 12 patients with angina had open heart surgery (I will not name the surgeon or the institution). 6 patients had the "real" surgery, and the other 6 had "sham" surgery, in that they only had their sternum (chest) split open, and then were wired shut again without anything being done to their hearts. 4 out of 6 in each group had their anginal pain and symptoms relieved.
What I am trying to say is that doctors overstate the degree of medical certainty behind many of their medical prescriptions and suggestions. Remember that before 1973 homosexuality was a psychiatric disorder, and in the new DSM-V manual you will find that narcissism will no longer be one. (Although I expect that if a drug company develops a medicine to treat narcissism it will quickly become a disease again.)
Finally, if your internet searches seem to indicate that some doctor or institution has a "special" treatment for a disease, please remember that all doctors want to cure their patients, and many would not mind becoming famous. If someone had a new cure for lung cancer, or rheumatoid arthritis, it would not be kept secret, and doctors throughout the world would know about it. There is one case of medical secrecy in history: A family of French Huguenot doctors, the Chamberlens fled to England in the 16th century. One of them invented obstetrical forceps to aid with difficult births. (Remember that C-sections were almost uniformly fatal in those days.) They became famous for their work with difficult deliveries, and they kept the existence of obstetrical forceps secret for over 150 years. I do not think that this would be possible now.
There are various problems with scientific rigor in medical journals, but the most serious is their improper use of statistics, followed by lack of reproducibility, i.e. other researchers cannot replicate the results. In science, this is usually due to fraud (black ink spots placed on mice) or self-delusion (N-rays in France), but in medicine it is usually a sign that the first result was not entirely correct. I always tell my patients who rush in breathlessly with the latest report of medical research to wait for the second and confirming report. The second report often does not confirm the first. I also tell them to beware of medical studies that look for surrogate endpoints (lowering of blood pressure or cholesterol) rather than significant clinical endpoints(stroke, heart attack).
There are too many books, articles, and TV shows including some authored by doctors, that are studded with phrases such as "the evidence suggests", "it seems reasonable that", "past history shows" or all patients with or without condition X did or did not have disease Y. None of these statements contains a scientific truth, and such phrases would never appear in a physics or chemistry journal. A hard fact is rarely stated, such as that 500mg 2 x day of Vitamin C will lower your uric acid level by approximately 1.0 and thereby reduce your risk of a gout attack (this latter statement has been substantiated by research). We have very little good clinical evidence about many medical conditions, although it is almost universally agreed that antibiotics can kill bacteria and save lives, and that vaccinations are beneficial.
We still don't understand why only 10% of smokers get lung cancer (although we know with 100% certainty that all smokers will develop emphysema if they smoke long enough---40 pack years is usually sufficient). We don't understand why different patients with high blood pressure develop problems in different organs: stroke, kidney failure, heart attack. We don't understand why one alcoholic gets cirrhosis of the liver, one dies of hemorrhagic pancreatitis, and one gets the Korsakoff Syndrome. Similarly, we cannot predict which organ will fail in a patient with insulin-dependent diabetes, or if in fact any of them will.
The main problem, of course, is that each patient is an individual biochemical laboratory, and no two patients react the same way to any medical intervention. This is always true if the patient is on three or more drugs, since almost all pharmacological studies are done on patients on no drugs. (And no one knows how all the over-the-counter health foods interact with anything.) Many medical recommendations are based on three or fewer studies, while there are over 50 verifications of Bell's Inequality in quantum physics, and hundreds of measurements of the speed of light. Furthermore the results of a medical study apply only statistically, in that not everyone is cured of strep throat by penicillin, and some people with strep throat recover without any antibiotic at all. If I were responsible for the treatment of 1,000,000 patients, I would have no hesitation in making certain recommendations, but if I am recommending treatment for just one person, I am never 100% certain if the treatment (a) will work, and (b) is necessary.
In a previous blog I carefully reviewed the mathematical and statistical flaws inherent in all meta-analyses, so let me just say here that every result suggested by any meta-analysis should be verified by double-blinded random testing, despite the rapidity with which the media trumpet the results of the study.
I should also mention the problem of confounding conditions. When we do a clinical intervention study, we try to make the treated and control patients physiologically as similar as possible. When we do not, we come to the false conclusion that coffee drinkers suffer more heart attacks than do non-drinkers, until it was realized that coffee drinkers also smoke more cigarettes than the non-drinkers. We still have conflicting studies on whether tall people live longer or shorter lives than short people, and are similarly lacking in knowledge about righties versus lefties. (But I do wonder why all left-handed tennis players seem to have a natural topspin on their forehand on television.) Many men gleefully reported to their wives and significant others the one study that seemed to indicate that frequent ejaculations had a protective effect against prostate cancer, but many fewer people and organizations trumpet the many studies that show that mild alcohol ingestion is protective against heart attacks, and the fact that NO study has shown that mild alcohol ingestion contributes to heart attacks.
And please ignore all studies reported at all medical conferences. Until these studies have been written up, reviewed and then published, there is no way for anyone to verify their accuracy. And beware doubly of the placebo effect: In the 1950's, before we had ethical treatment review boards, 12 patients with angina had open heart surgery (I will not name the surgeon or the institution). 6 patients had the "real" surgery, and the other 6 had "sham" surgery, in that they only had their sternum (chest) split open, and then were wired shut again without anything being done to their hearts. 4 out of 6 in each group had their anginal pain and symptoms relieved.
What I am trying to say is that doctors overstate the degree of medical certainty behind many of their medical prescriptions and suggestions. Remember that before 1973 homosexuality was a psychiatric disorder, and in the new DSM-V manual you will find that narcissism will no longer be one. (Although I expect that if a drug company develops a medicine to treat narcissism it will quickly become a disease again.)
Finally, if your internet searches seem to indicate that some doctor or institution has a "special" treatment for a disease, please remember that all doctors want to cure their patients, and many would not mind becoming famous. If someone had a new cure for lung cancer, or rheumatoid arthritis, it would not be kept secret, and doctors throughout the world would know about it. There is one case of medical secrecy in history: A family of French Huguenot doctors, the Chamberlens fled to England in the 16th century. One of them invented obstetrical forceps to aid with difficult births. (Remember that C-sections were almost uniformly fatal in those days.) They became famous for their work with difficult deliveries, and they kept the existence of obstetrical forceps secret for over 150 years. I do not think that this would be possible now.
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