There has been a lot of talk and newsprint about the obesity "epidemic" that is occurring, but I feel that certain facts have been ignored, as well as certain principles of human behavior. Whenever patients tell me that doctors don't know much about human nutrition, I generally comment that neither does anybody else. There have been very few double-blinded studies about the effect of nutrition on human health and well-being, but that doesn't seem to stop people from being more certain about human nutrition than the facts will allow:
1) No one knows how many meals a human should eat each day: one, six, or whatever.
2) No one knows at what time of the day the largest meal should be eaten, (but if you eat within 2 hours of bedtime you increase your risk of reflux esophagitis).
3) If you eat only vegetables, you will die from pernicious anemia, aka vitamin B-12 deficiency, since vegetable cells contain NO vitamin B-12; vitamin B-12 is is needed for animal cell DNA synthesis, and not for vegetable DNA.
4) Nobody smiles in a vegetarian restaurant, but everyone looks ecstatic at a steak restaurant such as Peter Luger's.
5) The only vegetables that seem to benefit human health when added to the diet are alcohol (beer, wine or whiskey), dark chocolate, olive oil (the Mediterranean diet), and the bark of the willow (salicylic acid, which Bayer transformed into aspirin).
6) No one knows how much water/fluids a human should drink each day, but the general consensus is a minimum of 0.5 liters, since that is the urine volume required to excrete the products of oxidation in maximally concentrated urine.
7) In a hospital, the minimum IV should be D5/0.5NaCl with 20 meq of KCl at 125 cc/hr, and then adjust to the patient's condition.
8) Fat cells require cholesterol and preferentially absorb insulin, so if you are a diabetic or have a cholesterol problem, you should lose weight.
9) Cholesterol does not increase cholesterol, so egg yolks are OK, and, in fact, eggs have about the highest protein per gram of any food.
10) If you do not have high blood pressure and are not diabetic, then salt and sugar should cause you no problem.
11) Almost all my patients who on oral medicine for diabetes cannot/will not lose weight, even after I tell them that a 20m pound weight loss will probably (temporarily) cure their diabetes.
12) As you get older, your metabolism slows up, and your blood pressure, cholesterol and fasting blood sugar generally increase.
13) Most women find it impossible to lose the last 5 pounds necessary to get down to their pre-pregnancy weight.
14) Most men gain at least 10-15 pounds the first year they work or get married, in the first case from lack of exercise (8-10 hrs/day behind a desk), and in the second case from an increase in calories consumed at dinner.
15) Cigarette smoking increases your metabolism and decreases your appetite, so most men gain 10 pounds the first year they quit smoking and most women gain 15.
16) And this is key: The first pleasure all humans got was from being fed, either at their mother's breast or from a bottle. The first desire to be fulfilled was that created by hunger. Therefore, it feels good to eat, and it is difficult to deny yourself this fundamental pleasure and to feel hungry, which you must do in order to lose weight. The first time a woman's dress goes from size 6 to size 8, or a man's belt from 32" to 34", they rarely say "I must lose some weight". It has nothing to do with not knowing how many calories they are eating, or doctor-patient information, or lack of electronic medical records. Most patients don't care enough about how they look after gaining 10 pounds, or believe that there is enough increased health risk from added weight to lose the additional pounds. Men actually are less stressed by their appearance when overweight than are women: When a woman looks full face into a mirror, she sees the added weight that went to her hips, but when a man looks in a mirror the same way, he barely sees the added weight that went to his belly.Losing weight means being willing to suffer present pain for future gain, and the human brain is not geared to worry about the future, but rather to fasten the seatbelt 10 seconds before the car hits a brick wall. The same comment about future gain also holds true for exercise, but the average patient finds it much easier to exercise than to lose weight.
17) I also think the reason that almost all humans love ice cream is that it is rich in sugar and fat, just like mother's milk.
18) Don't you think that by the time he/she is 7 days old, a baby is addicted to sugar by Pavlovian conditioning: whenever he/she is hungry (or whatever is felt), this discomfort is assuaged by a warm sweet fluid, so that the baby associates warmth (chicken soup?) and sweets with a sense of comfort and well-being. It's difficult to see how an external message can easily overcome this dependence.
19) Final observation: based on my informal questioning of my patients, the majority of adults who loved chocolate ice cream as a child can curl their tongue (I can!), while the majority of patients who did not like chocolate ice cream cannot. I wonder what the genetic linkage is. I personally thought that my friends who preferred vanilla ice cream to chocolate could not have possibly tasted the same chocolate flavor that I did.
Wednesday, September 16, 2009
Saturday, September 5, 2009
Radiation, X-rays, Medicine, and Cancer
The question of the relationship between radiation, X-rays, cosmic rays, (radioactive) radon gas, and cancer is a murky one, and there are many unanswered questions. In some cases, exposure to radiation gives the patient an increased lifetime risk for cancer, and for reasons unknown to medical science, the risk for women is greater than the risk for men. Because of the very long time delays that can be involved (up to 45 years has been recorded), it would appear that radiation is a cancer potentiator, rather than a direct inducer.(But radiation itself can be an inducer for a cell that has already been potentiated.) In the cases (Hiroshima, Chernobyl) where a direct and short time correlation has been observed, it is probable that the intensity of the radiation is also important. We know that high energy, high intensity radiation is lethal to humans, and lower intensity radiation is lethal to cancer cells. We also know about radiation sickness. We have a rough idea of the lethal dose of radiation (which is different for alpha rays, beta rays, photons (gamma rays), neutrons, and cosmic radiation). We know how much radiation shielding astronauts need to keep them alive.
We do not know, and will never know, the LD50 dose for humans for any type of radiation. We cannot even measure human radiation exposure. The unit called the Sievert is used, but the Sievert depends on the type of radiation, the energy, and, most important of all, the amount of radiation energy absorbed by various tissues, and this latter term can only be estimated (and very poorly, at that) from animal studies. We also know that we are missing some scientific factor: The residents of Denver dwell 5,000 feet higher than the residents of NYC, and therefore have one mile less of atmospheric shielding from cosmic rays. How is it then that Denver residents do not have a significantly higher rate of cancer than do Manhattanites?
There was a recent article published in JAMA detailing the increased amount of radiation we are all getting over our lifetime from X-ray studies. In fact, the U.S. gov't has officially classified radiation as a carcinogen. Why is it then that no patient is ever given a release form to sign than delineates the estimated immediate and lifetime personal carcinogenic risk from the proposed X-ray study? (I once tried to generate and have my ER patients sign such a form, and I was immediately told by the chairmen of Radiology and Medicine to stop.)
Thirty years ago, when I was a physics professor, I started to do some experiments with a colleague of mine from Princeton. Since he had a joint appointment with Princeton Physics Dept. and the Princeton Plasma Physics Lab, which meant that he also worked on the Stellarator, our research was classified (and still is, for all I know). We then co-opted a physicist at Oak Ridge Nat'l Labs for good radioactive sources. We were trying to see if there is a minimum radiation dose below which there is NO cancer risk. The belief now as well as then was that there is not, and that there is no minimum safe dose of radiation. We were unable to come to a definite conclusion. We could not determine whether or not a certain straight line on a graph passed through the origin.
The universal fear of radiation is so great that MRI was initially called by its correct name NMR (Nuclear Magnetic Resonance), but NMR was changed to MRI so as to not scare patients away from the MRI. We could greatly decrease food poisoning and contamination with germs and bugs by subjecting wheat, fruit, etc., to killing levels of radiation, but again, the public is so fearful of the possible consequences of radiation that Congress has never passed a food-radiation enabling law, and we can therefore expect future lethal food outbreaks similar to the E. Coli in hamburgers. The one time we should have been fearful, we were not, and many women who licked camel's hair brushes to make a finer point before painting the numbers on a wristwatch with a radioactive chemical developed mouth and jaw cancers.
I guess this blog is written with mixed emotions, and no firm purpose. As a physicist I have the greatest respect for the dangers of radiation, and as a physician, I know its many beneficial uses. I wish we all knew more!
We do not know, and will never know, the LD50 dose for humans for any type of radiation. We cannot even measure human radiation exposure. The unit called the Sievert is used, but the Sievert depends on the type of radiation, the energy, and, most important of all, the amount of radiation energy absorbed by various tissues, and this latter term can only be estimated (and very poorly, at that) from animal studies. We also know that we are missing some scientific factor: The residents of Denver dwell 5,000 feet higher than the residents of NYC, and therefore have one mile less of atmospheric shielding from cosmic rays. How is it then that Denver residents do not have a significantly higher rate of cancer than do Manhattanites?
There was a recent article published in JAMA detailing the increased amount of radiation we are all getting over our lifetime from X-ray studies. In fact, the U.S. gov't has officially classified radiation as a carcinogen. Why is it then that no patient is ever given a release form to sign than delineates the estimated immediate and lifetime personal carcinogenic risk from the proposed X-ray study? (I once tried to generate and have my ER patients sign such a form, and I was immediately told by the chairmen of Radiology and Medicine to stop.)
Thirty years ago, when I was a physics professor, I started to do some experiments with a colleague of mine from Princeton. Since he had a joint appointment with Princeton Physics Dept. and the Princeton Plasma Physics Lab, which meant that he also worked on the Stellarator, our research was classified (and still is, for all I know). We then co-opted a physicist at Oak Ridge Nat'l Labs for good radioactive sources. We were trying to see if there is a minimum radiation dose below which there is NO cancer risk. The belief now as well as then was that there is not, and that there is no minimum safe dose of radiation. We were unable to come to a definite conclusion. We could not determine whether or not a certain straight line on a graph passed through the origin.
The universal fear of radiation is so great that MRI was initially called by its correct name NMR (Nuclear Magnetic Resonance), but NMR was changed to MRI so as to not scare patients away from the MRI. We could greatly decrease food poisoning and contamination with germs and bugs by subjecting wheat, fruit, etc., to killing levels of radiation, but again, the public is so fearful of the possible consequences of radiation that Congress has never passed a food-radiation enabling law, and we can therefore expect future lethal food outbreaks similar to the E. Coli in hamburgers. The one time we should have been fearful, we were not, and many women who licked camel's hair brushes to make a finer point before painting the numbers on a wristwatch with a radioactive chemical developed mouth and jaw cancers.
I guess this blog is written with mixed emotions, and no firm purpose. As a physicist I have the greatest respect for the dangers of radiation, and as a physician, I know its many beneficial uses. I wish we all knew more!
Sunday, August 23, 2009
Performance-Enhancing Drugs?
The question of the use of performance-enhancing drugs has been in the newspapers lately, especially as regards baseball players and anabolic steroids. We are here going to discuss the use of many "performance-enhancing" drugs, with regard to their utility (do they really improve performance?), their legality, and whether or not a particular sport bans them. This blog will not discuss the morality of such drug use. I would like to point out, however, that if a drug both improves performance AND has dangerous side-effects, then it may be unfair to force other athletes to risk their health to compete on the same level as a drug-user.
We are not here going to discuss in detail the problem of false-positive urine tests. For those interested in this topic, there was an article several years ago in JAMA, or you can go back in time and read Jerry Rubin's "Steal This Urine Test". We all recall the Seinfeld episode (based on true events) when Elaine tested positive for opium because she had eaten a poppy-seed bagel. There is also the problem of finding a possible drug-masking chemical in your urine (e.g. a diuretic can dilute your urine below the testing cutoff), so the presence of a diuretic can be considered evidence of an attempt to falsify the test. Some companies who refuse to hire cigarette smokers test their urine for co-nicotine, a metabolite of nicotine. Unfortunately, tomatoes and several other vegetables contain a high concentration of co-nicotine, so some vegetarians will test positive for this chemical. As I recall, Advil can give a false-positive urine test for marijuana, and Robitussin a false positive test for PCP.
The question of legality of the drug is an interesting one. Lasix, which reduces pulmonary hemorrhage in horses, is legal only in New York State horse races.
Some sports events permit the use of inhaled beta-agonists for preventing exercise-induced asthma, and others do not. Some drugs are available in certain countries only by prescription, while in other countries they can be purchased over-the-counter, and they may be illegal in a third country.
The first question is whether or not a drug actually enhances athletic performance. We immediately run into the placebo effect, which has been shown to be as high as 30% in some cases. That is, a drug may not actually improve performance, but if an athlete believes that it does, it may. This is not farfetched: if you tell a hypnotized person that you are going to burn them and touch their forearm with an ice cube, they will develop a blister and reddening, just as if they were burned. Or, you can tell a group of subjects that they are about to receive a sleeping pill (or a CNS stimulant), and many will fall asleep rapidly in one case, and stay awake in the other.
STEROIDS (Anabolic, i.e. chemically related to testosterone): I have seen no published research that anabolic steroids improve baseball performance, or any other peak athletic performance. Yes, they do increase muscle mass (so weight lifters and body builders will use them), but it has not been shown that it enables you to drive a baseball or golf ball further, or serve harder in tennis, or throw a football further. It can make football lineman heavier, but it has not been shown to make them any quicker.
GROWTH HORMONE: I have read three studies. One of the two done in older men showed an increase in lean muscle mass, and the other did not. The third was done in younger men, and again showed a slight increase in muscle mass, but increase in athletic performance was not tested for.
CAFFEINE: I suppose we all used No-Doz (= caffeine in two cups of coffee) in college to help us stay up all night to study and then be awake enough to take the test the next day. I know of one study that showed increased scores in the GRE's, and caffeine does increase overall mental alertness. It also may decrease reflex reaction time in some sports, so you can hit the tennis ball earlier, etc. Caffeine also potentiates the pain relieving effects of aspirin and acetimenophen.
BETA-BLOCKERS (INDERAL): These medicines block the effect of adrenalin in your body and, if the drug is lipophilic and crosses the blood-brain barrier (as does Inderal) can exert a CNS calming effect, and I find it especially useful to treat patients with Mitral Valve Prolapse with associated palpitations and/or anxiety attacks. Because it also reduces tremors, many solo concert violinists will take Inderal before a performance. However, in the Biathlon in the Olympics, beta-blockers are banned. In the Biathlon, you ski and then shoot at a target. Obviously, the sooner your heart rate decreases and your hand tremor decreases, the sooner you will have a more accurate shot.
RITALIN: This (and Strattera, Concerta, and several other methylphenidate congeners) are used for students with ADD or ADHD.It seems to enhance concentration and improve academic performance. Since there can be a genetic component, often when a male teenager is diagnosed with ADD, his father also tries Ritalin, and finds that he functions more efficiently at the office. From what I have seen, Ritalin and other CNS stimulants do improve concentration (think of it as a stronger and longer-lasting form of caffeine). It seems that Ritalin makes the brain function more rapidly and more efficiently, and one wonders if all students would be better students if they were on Ritalin. In addition, if one is diagnosed with ADD, then, in addition to Ritalin, the student is given more time to take the SAT's, LSAT's, etc., even though (and this is not a pejorative comment) in the real world a judge will not give a lawyer with ADD an extra week in which to write a brief.
BENZEDRINE: This and other CNS stimulants was issued by the U.S. Gov't. to pilots on long-range missions, and other military members for PRN use when falling asleep could be dangerous.
VIAGRA: (or CIALIS or LEVITRA): This definitely improves the rapidity of penile erection in response to direct physical stimulation, and makes the penis firmer for a longer period of time. The drug is also a direct dilator of the pulmonary artery and its branches in the lung, and has an accepted medical use to treat primary pulmonary hypertension (a disease that can be fatal) as well as prevent high-altitude pulmonary sickness.
HYPNOTICS: The use of sleeping pills is well-accepted, and the only arguments seem to be the length of time they should be used, and whether or not all early-morning awakening is a sign of depression.
ATIVAN/VALIUM/XANAX: I have several patients who will take one of these half an hour before giving a speech or attending a meeting when senior executives will be present. When taken for this reason, the anxiolytic prevents paralyzing anxiety attacks, and permits the patient to function more efficiently.
PROZAC/ZOLOFT/PAXIL: Social phobia and panic attacks are real phenomena. Patients who need this drug to function do function more efficiently. They are encouraged to also get psychiatric help, but often their HMO does not cover it. Whether their personality when they take the drug is the "real" them is, I think, a question for metaphysicians, not family doctors.
TESTOSTERONE: Both men and women manufacture testosterone. I baseline the free testosterone level of all my patients at 40 years of age. If their sex drive then decreases to the point that they are bothered, (whether or not they are depressed), I repeat the measurement, and I use testosterone gel if it has decreased. There have been several articles by a Canadian Ob-GYN showing that menopausal women will also have increased sexual satisfaction if their testosterone level is raised to their pre-menopausal level.
ESTROGEN: Pills or vaginal cream. Some women have a decrease in sex drive and/or severe vaginal dryness in menopause. Many of them benefit from topical or oral estrogen replacement (which may also lead to a decrease in urinary tract infections). I explain this to them and refer them to their gynecoligist.
DIET PILLS: Whether or not they work, they can act as a mild anti-depressant, much in the same way that psychiatrists will prescribe low-dose Dexedrine to nursing home patients to improve their appetites.
DIURETICS: Too dangerous for chronic use for weight loss, but this does not stop jockeys and wrestlers to "make the weight".
PROVIGIL: The latest CNS stimulant on the market. It is prescribed for sleep-shift disorders, or chronic daytime fatigue. It is very popular for medical interns and residents for this very reason. I am unaware of any studies vis-a-vis the improvement of one's abilities as a student.
One of my patients reminded me of Dupont's slogan: "Better living through chemistry". This is ultimately a moral question, of course, in addition to a medical one. Each and every patient is a different combination of biochemicals, brain-body interactions, thought processes and belief systems, so each prescription must be thoroughly discussed with the patient by his family physician, who should be aware of the patient's expectations and limitations, and re-evaluates the patient carefully at periodic intervals.
We are not here going to discuss in detail the problem of false-positive urine tests. For those interested in this topic, there was an article several years ago in JAMA, or you can go back in time and read Jerry Rubin's "Steal This Urine Test". We all recall the Seinfeld episode (based on true events) when Elaine tested positive for opium because she had eaten a poppy-seed bagel. There is also the problem of finding a possible drug-masking chemical in your urine (e.g. a diuretic can dilute your urine below the testing cutoff), so the presence of a diuretic can be considered evidence of an attempt to falsify the test. Some companies who refuse to hire cigarette smokers test their urine for co-nicotine, a metabolite of nicotine. Unfortunately, tomatoes and several other vegetables contain a high concentration of co-nicotine, so some vegetarians will test positive for this chemical. As I recall, Advil can give a false-positive urine test for marijuana, and Robitussin a false positive test for PCP.
The question of legality of the drug is an interesting one. Lasix, which reduces pulmonary hemorrhage in horses, is legal only in New York State horse races.
Some sports events permit the use of inhaled beta-agonists for preventing exercise-induced asthma, and others do not. Some drugs are available in certain countries only by prescription, while in other countries they can be purchased over-the-counter, and they may be illegal in a third country.
The first question is whether or not a drug actually enhances athletic performance. We immediately run into the placebo effect, which has been shown to be as high as 30% in some cases. That is, a drug may not actually improve performance, but if an athlete believes that it does, it may. This is not farfetched: if you tell a hypnotized person that you are going to burn them and touch their forearm with an ice cube, they will develop a blister and reddening, just as if they were burned. Or, you can tell a group of subjects that they are about to receive a sleeping pill (or a CNS stimulant), and many will fall asleep rapidly in one case, and stay awake in the other.
STEROIDS (Anabolic, i.e. chemically related to testosterone): I have seen no published research that anabolic steroids improve baseball performance, or any other peak athletic performance. Yes, they do increase muscle mass (so weight lifters and body builders will use them), but it has not been shown that it enables you to drive a baseball or golf ball further, or serve harder in tennis, or throw a football further. It can make football lineman heavier, but it has not been shown to make them any quicker.
GROWTH HORMONE: I have read three studies. One of the two done in older men showed an increase in lean muscle mass, and the other did not. The third was done in younger men, and again showed a slight increase in muscle mass, but increase in athletic performance was not tested for.
CAFFEINE: I suppose we all used No-Doz (= caffeine in two cups of coffee) in college to help us stay up all night to study and then be awake enough to take the test the next day. I know of one study that showed increased scores in the GRE's, and caffeine does increase overall mental alertness. It also may decrease reflex reaction time in some sports, so you can hit the tennis ball earlier, etc. Caffeine also potentiates the pain relieving effects of aspirin and acetimenophen.
BETA-BLOCKERS (INDERAL): These medicines block the effect of adrenalin in your body and, if the drug is lipophilic and crosses the blood-brain barrier (as does Inderal) can exert a CNS calming effect, and I find it especially useful to treat patients with Mitral Valve Prolapse with associated palpitations and/or anxiety attacks. Because it also reduces tremors, many solo concert violinists will take Inderal before a performance. However, in the Biathlon in the Olympics, beta-blockers are banned. In the Biathlon, you ski and then shoot at a target. Obviously, the sooner your heart rate decreases and your hand tremor decreases, the sooner you will have a more accurate shot.
RITALIN: This (and Strattera, Concerta, and several other methylphenidate congeners) are used for students with ADD or ADHD.It seems to enhance concentration and improve academic performance. Since there can be a genetic component, often when a male teenager is diagnosed with ADD, his father also tries Ritalin, and finds that he functions more efficiently at the office. From what I have seen, Ritalin and other CNS stimulants do improve concentration (think of it as a stronger and longer-lasting form of caffeine). It seems that Ritalin makes the brain function more rapidly and more efficiently, and one wonders if all students would be better students if they were on Ritalin. In addition, if one is diagnosed with ADD, then, in addition to Ritalin, the student is given more time to take the SAT's, LSAT's, etc., even though (and this is not a pejorative comment) in the real world a judge will not give a lawyer with ADD an extra week in which to write a brief.
BENZEDRINE: This and other CNS stimulants was issued by the U.S. Gov't. to pilots on long-range missions, and other military members for PRN use when falling asleep could be dangerous.
VIAGRA: (or CIALIS or LEVITRA): This definitely improves the rapidity of penile erection in response to direct physical stimulation, and makes the penis firmer for a longer period of time. The drug is also a direct dilator of the pulmonary artery and its branches in the lung, and has an accepted medical use to treat primary pulmonary hypertension (a disease that can be fatal) as well as prevent high-altitude pulmonary sickness.
HYPNOTICS: The use of sleeping pills is well-accepted, and the only arguments seem to be the length of time they should be used, and whether or not all early-morning awakening is a sign of depression.
ATIVAN/VALIUM/XANAX: I have several patients who will take one of these half an hour before giving a speech or attending a meeting when senior executives will be present. When taken for this reason, the anxiolytic prevents paralyzing anxiety attacks, and permits the patient to function more efficiently.
PROZAC/ZOLOFT/PAXIL: Social phobia and panic attacks are real phenomena. Patients who need this drug to function do function more efficiently. They are encouraged to also get psychiatric help, but often their HMO does not cover it. Whether their personality when they take the drug is the "real" them is, I think, a question for metaphysicians, not family doctors.
TESTOSTERONE: Both men and women manufacture testosterone. I baseline the free testosterone level of all my patients at 40 years of age. If their sex drive then decreases to the point that they are bothered, (whether or not they are depressed), I repeat the measurement, and I use testosterone gel if it has decreased. There have been several articles by a Canadian Ob-GYN showing that menopausal women will also have increased sexual satisfaction if their testosterone level is raised to their pre-menopausal level.
ESTROGEN: Pills or vaginal cream. Some women have a decrease in sex drive and/or severe vaginal dryness in menopause. Many of them benefit from topical or oral estrogen replacement (which may also lead to a decrease in urinary tract infections). I explain this to them and refer them to their gynecoligist.
DIET PILLS: Whether or not they work, they can act as a mild anti-depressant, much in the same way that psychiatrists will prescribe low-dose Dexedrine to nursing home patients to improve their appetites.
DIURETICS: Too dangerous for chronic use for weight loss, but this does not stop jockeys and wrestlers to "make the weight".
PROVIGIL: The latest CNS stimulant on the market. It is prescribed for sleep-shift disorders, or chronic daytime fatigue. It is very popular for medical interns and residents for this very reason. I am unaware of any studies vis-a-vis the improvement of one's abilities as a student.
One of my patients reminded me of Dupont's slogan: "Better living through chemistry". This is ultimately a moral question, of course, in addition to a medical one. Each and every patient is a different combination of biochemicals, brain-body interactions, thought processes and belief systems, so each prescription must be thoroughly discussed with the patient by his family physician, who should be aware of the patient's expectations and limitations, and re-evaluates the patient carefully at periodic intervals.
Friday, August 7, 2009
Medical Statistics, Research and News
As a former experimental physicist who did funded research for several years, published many papers in physics journals, and was on the editorial board of a physics journal for three years, I have several comments about the quality of medical publications and the interpretation of their results by the lay press.
First, it seems to be a common habit to publish data points in a graph without error bars. This makes it impossible to interpret the results properly. (For lay persons, the error bars show the range of +/- 2 standard deviations, which means that IF the data and error distribution is Gaussian, then there is a 2.5% probability that a repeat measurement would be above and a 2.5% probability of being below the range of the error bars.) Then this mistake is often compounded by connecting the data points by a sequential series of straight lines, rather than a French curve or a least squares fit.
When a result is presented as being "statistically significant", what is meant is that there is only a 5% probability of the result being incorrect (yes, I know I am simplifying here). However, a statistically significant result may not be clinically significant. It is easy to demonstrate that if you have enough subjects, something will be statistically significant. But is it really medically useful to know how to decrease your risk of being killed by a falling meteorite by 50%?
The lay press is also woefully ignorant of the concept of statistical variation. If you tabulate, for instance, cases of breast cancer in every county in a state, one county has to be the highest, and one has to be the lowest, without any "cause". Every time there is a clustering of cases (as in lymphoma in Passaic, N.J. about 15 years ago), there is a rush to find the cause.
Then the relative risk rather than absolute risk is emphasized. Again, if your chance by being killed by a falling meteorite is one in a million, then if I decrease your relative risk by 50%, I have only lowered your absolute risk by 0.0001%.
Finally, and this is the most egregious mistake of all, is the use of surrogate endpoints. For instance, in the study of the effect of lowering cholesterol by the use of Zetia, instead of looking at heart attacks or stroke as a primary endpoint, the thickness of the intima of the carotid artery was used as a surrogate endpoint. If the most common cause of arterial blockage is rupture of a plaque rather than embolic, then this surrogate endpoint is not medically useful. (Personally, I think the evidence points to the anti-inflammatory effects of ASA and statins as reducing the risk of plaque rupture and acute blockage, but no one has yet been able to detect such an acute event when it happens in humans.)
Actually, in fairness to medical researchers, I should mention the main limitation that they face. In physics, if an experimental result is published, other researchers rush to try to repeat the result by a different experimental technique, using different apparatus, to help establish the validity and uniform applicability of the result. Thus, after Wu, Ambler, Heyward and Hoppes verified the theoretically predicted non-conservation of parity in beta decay using electrons, Lederman and Steinberger verified it by studying the decay of muons (possibly aided by Garwin's suggestions). There have been at least ten different verifications of Bell's inequality, using different experimental setups and techniques, which verifies the "spooky" action-at-a-distance required by quantum measurement theory. As soon as Mossbauer announced his effect, physicists rushed to duplicate it around the world. The speed of light has been measured many, many times, as has the dilation of time predicted by the theory of special relativity. On the other hand, in medical research, there is only one direct way to do the experiment, since no other "experimental equipment" exists. This has at least two consequences:(1) there is less glory in verifying a medical result, even if it is done to higher probability by studying more people , and (2) if a result is "very convincing", then virtually no one will repeat it because it would seem to be a waste of money to the funding office, or a risk of malpractice to the research group.
I should also mention that some experiments are not done, because they are deemed not to be in the public interest:There have been several studies in Europe (usually published in Lancet) that seem to indicate that cigarette smokers have a lower incidence of Parkinson's Disease. This suggests a relationship between nicotinic receptors in the brain and dopaminergic neurons. But I predict that no one in the USA would receive federal funding to do a prospective study to see if, in fact, cigarette smoking does protect against Parkinson's Disease, or, indeed has any other benefit.
All studies of new drugs, and many studies of existing drugs, are done on pharmacologically naive patients, who are on no drugs at the time of the experiments. Since most of my patients are on at least four drugs, the results of the study may not apply to them, both as regards to benefits and side effects.(This is typified by the fact that if I have a patient with diabetes, hypertension, osteoarthritis, chronic hepatitis, and GERD, and try to follow all five of the government guidelines, drugs used to treat one problem conflict with the guidelines for another problem.)
Now that I have expressed several of my opinions, let me complete this article by reviewing definitions of several common words and phrases that you may see in research articles:
NNT---Number Needed to Treat---the statistically suggested number of patients to treat with the studied drug in order to achieve the expected outcome in one.
NNH---Number Needed to Harm---similar in concept to NNT,except it is the number to treat to get a bad outcome. If NNT is greater than NNH, you have a problem, unless, perhaps, the outcome in NNT is preventing certain death.
NNS---Number Needed to Sue----this is not generally listed in statistical textbooks. It is the number of patients out of a million who get a bad enough result that a malpractice lawyer thinks it worthwhile to start a class action suit.
Statistically significant---there is less than a 5% probability (one-in-twenty) that the result is due to chance. Alternatively, if you repeat the experiment 20 times, then you would expect to get the same "result" nineteen times.
Type I/Alpha Error---you conclude that there is a statistically significant difference between the control group and the treated group, when there is really NO difference. Similar in concept to a false positive conclusion.
Type II/Beta Error---you conclude that there is no statistically significant difference between the control and the treated group, when there really is. Similar in concept to a false negative conclusion.
Sensitivity---the probability that if you test positive for a disease, you have the disease; i.e. a test with a low false negative rate.
Specificity---the probability that if you test negative for a disease, you do not have the disease; i.e. a test with a low false positive rate.
Common clinical sense---tells you not to believe a positive test result in a particular patient. If you order a panel of 20 tests, each of which has a Gaussian distribution, then the odds are 50:50 that at least one of the tests will fall outside the "normal" range without indicating true disease.
Correlation/Causation---two events can be related in time or space without having a cause-and-effect relationship. Propinquity can always be coincidental, but can also suggest paths for future research.
Confounding---a factor not considered when looking for a cause-and-effect relationship that affects the effect. The best example would be the initial statistical demonstration that coffee drinkers had a higher rate of heart attacks, without allowing for the confounding effect that more coffee drinkers than non-drinkers smoked cigarettes. It is probably impossible to ensure the absence of all confounding effects, since we don't know about many confounding effects, and it is virtually impossible to test for their existence.
Confidence Interval---Similar in concept to error bars around a measured data point. The confidence interval of a result suggests to you the range of the result in which we expect 95% of the studied population to fall.
Intention-to-treat---included all patients who registered for the randomized drug study, whether or not they dropped out of the study.
Incidence---the percentage of the population that develops a given disease in a given period of time.
Prevalence---the percentage of the population that has the disease at a given time. Note that the prevalence of a disease helps to determine whether you want to emphasize avoiding a Type I error or emphasize avoiding a Type II error, as well as a test with high sensitivity or high specificity.
Endpoint---the result you are looking for to determine that a treatment "works".
First, it seems to be a common habit to publish data points in a graph without error bars. This makes it impossible to interpret the results properly. (For lay persons, the error bars show the range of +/- 2 standard deviations, which means that IF the data and error distribution is Gaussian, then there is a 2.5% probability that a repeat measurement would be above and a 2.5% probability of being below the range of the error bars.) Then this mistake is often compounded by connecting the data points by a sequential series of straight lines, rather than a French curve or a least squares fit.
When a result is presented as being "statistically significant", what is meant is that there is only a 5% probability of the result being incorrect (yes, I know I am simplifying here). However, a statistically significant result may not be clinically significant. It is easy to demonstrate that if you have enough subjects, something will be statistically significant. But is it really medically useful to know how to decrease your risk of being killed by a falling meteorite by 50%?
The lay press is also woefully ignorant of the concept of statistical variation. If you tabulate, for instance, cases of breast cancer in every county in a state, one county has to be the highest, and one has to be the lowest, without any "cause". Every time there is a clustering of cases (as in lymphoma in Passaic, N.J. about 15 years ago), there is a rush to find the cause.
Then the relative risk rather than absolute risk is emphasized. Again, if your chance by being killed by a falling meteorite is one in a million, then if I decrease your relative risk by 50%, I have only lowered your absolute risk by 0.0001%.
Finally, and this is the most egregious mistake of all, is the use of surrogate endpoints. For instance, in the study of the effect of lowering cholesterol by the use of Zetia, instead of looking at heart attacks or stroke as a primary endpoint, the thickness of the intima of the carotid artery was used as a surrogate endpoint. If the most common cause of arterial blockage is rupture of a plaque rather than embolic, then this surrogate endpoint is not medically useful. (Personally, I think the evidence points to the anti-inflammatory effects of ASA and statins as reducing the risk of plaque rupture and acute blockage, but no one has yet been able to detect such an acute event when it happens in humans.)
Actually, in fairness to medical researchers, I should mention the main limitation that they face. In physics, if an experimental result is published, other researchers rush to try to repeat the result by a different experimental technique, using different apparatus, to help establish the validity and uniform applicability of the result. Thus, after Wu, Ambler, Heyward and Hoppes verified the theoretically predicted non-conservation of parity in beta decay using electrons, Lederman and Steinberger verified it by studying the decay of muons (possibly aided by Garwin's suggestions). There have been at least ten different verifications of Bell's inequality, using different experimental setups and techniques, which verifies the "spooky" action-at-a-distance required by quantum measurement theory. As soon as Mossbauer announced his effect, physicists rushed to duplicate it around the world. The speed of light has been measured many, many times, as has the dilation of time predicted by the theory of special relativity. On the other hand, in medical research, there is only one direct way to do the experiment, since no other "experimental equipment" exists. This has at least two consequences:(1) there is less glory in verifying a medical result, even if it is done to higher probability by studying more people , and (2) if a result is "very convincing", then virtually no one will repeat it because it would seem to be a waste of money to the funding office, or a risk of malpractice to the research group.
I should also mention that some experiments are not done, because they are deemed not to be in the public interest:There have been several studies in Europe (usually published in Lancet) that seem to indicate that cigarette smokers have a lower incidence of Parkinson's Disease. This suggests a relationship between nicotinic receptors in the brain and dopaminergic neurons. But I predict that no one in the USA would receive federal funding to do a prospective study to see if, in fact, cigarette smoking does protect against Parkinson's Disease, or, indeed has any other benefit.
All studies of new drugs, and many studies of existing drugs, are done on pharmacologically naive patients, who are on no drugs at the time of the experiments. Since most of my patients are on at least four drugs, the results of the study may not apply to them, both as regards to benefits and side effects.(This is typified by the fact that if I have a patient with diabetes, hypertension, osteoarthritis, chronic hepatitis, and GERD, and try to follow all five of the government guidelines, drugs used to treat one problem conflict with the guidelines for another problem.)
Now that I have expressed several of my opinions, let me complete this article by reviewing definitions of several common words and phrases that you may see in research articles:
NNT---Number Needed to Treat---the statistically suggested number of patients to treat with the studied drug in order to achieve the expected outcome in one.
NNH---Number Needed to Harm---similar in concept to NNT,except it is the number to treat to get a bad outcome. If NNT is greater than NNH, you have a problem, unless, perhaps, the outcome in NNT is preventing certain death.
NNS---Number Needed to Sue----this is not generally listed in statistical textbooks. It is the number of patients out of a million who get a bad enough result that a malpractice lawyer thinks it worthwhile to start a class action suit.
Statistically significant---there is less than a 5% probability (one-in-twenty) that the result is due to chance. Alternatively, if you repeat the experiment 20 times, then you would expect to get the same "result" nineteen times.
Type I/Alpha Error---you conclude that there is a statistically significant difference between the control group and the treated group, when there is really NO difference. Similar in concept to a false positive conclusion.
Type II/Beta Error---you conclude that there is no statistically significant difference between the control and the treated group, when there really is. Similar in concept to a false negative conclusion.
Sensitivity---the probability that if you test positive for a disease, you have the disease; i.e. a test with a low false negative rate.
Specificity---the probability that if you test negative for a disease, you do not have the disease; i.e. a test with a low false positive rate.
Common clinical sense---tells you not to believe a positive test result in a particular patient. If you order a panel of 20 tests, each of which has a Gaussian distribution, then the odds are 50:50 that at least one of the tests will fall outside the "normal" range without indicating true disease.
Correlation/Causation---two events can be related in time or space without having a cause-and-effect relationship. Propinquity can always be coincidental, but can also suggest paths for future research.
Confounding---a factor not considered when looking for a cause-and-effect relationship that affects the effect. The best example would be the initial statistical demonstration that coffee drinkers had a higher rate of heart attacks, without allowing for the confounding effect that more coffee drinkers than non-drinkers smoked cigarettes. It is probably impossible to ensure the absence of all confounding effects, since we don't know about many confounding effects, and it is virtually impossible to test for their existence.
Confidence Interval---Similar in concept to error bars around a measured data point. The confidence interval of a result suggests to you the range of the result in which we expect 95% of the studied population to fall.
Intention-to-treat---included all patients who registered for the randomized drug study, whether or not they dropped out of the study.
Incidence---the percentage of the population that develops a given disease in a given period of time.
Prevalence---the percentage of the population that has the disease at a given time. Note that the prevalence of a disease helps to determine whether you want to emphasize avoiding a Type I error or emphasize avoiding a Type II error, as well as a test with high sensitivity or high specificity.
Endpoint---the result you are looking for to determine that a treatment "works".
Saturday, July 25, 2009
Thoughts re the Future of Single-Payer Medicine
I thought it might be useful to write down my observations and thoughts about the financial side of the practice of medicine, based upon 25 years of private and academic practice of internal medicine, 15 years with a partner, and the last 10 years solo.
First, I have been solo for the past 10 years, because no recent medical school graduate wants to practice (and I have a big-city practice and attend at a medical school) pure internal medicine without an enormous salary guarantee that only a large group can afford to offer (which includes fronting their malpractice insurance). The reason is that HMO's and MCR both pay much more for doing than for thinking and diagnosing, since the powers that pay can measure doing, but not thinking. It is ridiculous that MCR pays me more for a 5-minute rigid sigmoidoscopy than for a 15-minute intake interview. This is why dermatology is the most popular residency. Getting paid $500 for a Botox injection every 3 months is an annuity! And since no insurance pays for it, the physicians can charge whatever they wish. Man is an economic animal, and often will respond to economic stimuli. So when Massachusetts established state-wide health care, there were not enough primary care doctors, and the average wait for a new doctor was 60 days. Just imagine the shortage when the 45 million currently uninsured patients look for a new primary care doctor. We will need at least 10,000 new primary care doctors, and where will they come from? Actually, every doctor should do Botox and Restalen injections and skin biopsies one day a week, so he/she can practice the medicine they like the other four days. And since MCR pays psychiatrists less than they pay me for the same amount of office time, why would any psychiatrist ever want to see a new MCR patient?
Second, we have socialized medicine now, and it's called Medicare. Few MCR patients want to give it up. There are many advantages to the patient, and the main advantage to the physician is that we spend less time on paperwork, and time is our least fungible resource. For a MCR patient, unlike an HMO patient, I don't have to call anyone for permission to get an MRI,and I don't have to worry that the best shoulder surgeon I know is a Cigna MD, and my patient is an Oxford patient, so my patient can't get to see the physician I prefer. I don't have to ask the patient to fax me a list of the HMO ophthalmologists so I can see if I know anyone on the list.
Also, MCR patients get back 5 to 10 times the dollar amount in medical services of the MCR premiums they paid.The tobacco companies showed (but dropped the argument because it made for poor PR) that the government saves money on every patient who dies before reaching MCR age. I also (I hope) will not have to spend time asking someone for permission to prescribe a brand name rather than a generic drug, or to prescribe a brand name drug that is not on their formulary.
Third, if everyone has a private MD, they will "crash" in the ER less often with diabetes out of control, unstable angina, end stage renal disease, etc. If you look at ER visits in Canada vs. here, there are fewer (percentage-wise) visits for acute medical conditions. Having a private physician who you can visit regularly puts a basic floor under your medical condition, even if nothing more is done than blood pressure check, PAP smear, and stool for blood. Overall, since ER visits are extremely expensive because ER doctors do every test they can think of, since they don't want to miss anything (viz. the recent article in the July, 2009 issue of "Archives of Internal Medicine" on the ER workup of syncope in the elderly) we will save a lot of money.
Fourth, technology is expensive, but it works. No patient walks up to an orthopedic surgeon and says "I want a new hip". Instead, the doctor is told "I can't move without agonizing hip pain". No patient says "I need cardiac bypass surgery", or "I need cataract surgery".
Fifth point has to do with malpractice. The most common suit against a family MD is for failure to diagnose a condition. As far as I am aware, no physician ever got sued for doing a test, but only for not doing one. When I started practice,I used to spend 30 minutes to explain to a 40 year old man with no risk factors and atypical chest pain and a normal EKG why he did not need a stress test, and the problems that can result from false positive tests. Now I suggest a stress-echo, stress-thallium and consultation with a cardiologist to the same patient. Why risk being sued even if I know I will win the case? Why spend the time and stress?
As long as we have contingency fees, we will have malpractice cases, and doctors will do extra tests to minimize their exposure, as well as make any referrals any family member of the patient suggests.
Sixth, unless you have a boutique practice, the average MD has to see one patient every 10 minutes, which involves putting 4 patients into 4 rooms, and having the NP or PA take the interval history, do the vital signs, etc. No one can get proper medical care under these conditions. I was trained to spend 15-45 minutes in the office with my patient to take a history and discuss any family stresses, then examine the patient in the exam room, and then bring the patient back into my office to discuss the results. I don't know of any doctor under 60 who practices medicine in this way, and most patients don't know what they are missing.
Seventh, there is something very wrong with the practice of medicine when the majority of doctors advise their children not to go into medicine.
Eighth, every medical system in every country rations by money, time, or availability, since the demand for medical care is almost infinite. England NHS does not transplant kidneys over a certain age, so those who can afford it fly to India to buy a kidney. Some drugs are not allowed in England because the NHS pays for all drugs, and this is how the country caps pharmacy expenses. Canada rations hospitals as to how many open-heart surgeries they can do in a given month. Germany reduces the physicians state-paid salary if their patients' prescriptions cost too much. MCR pays for only so many physical therapy visits or hospital days a year.
Ninth, I still love the practice of medicine, and intend to see my patients as long as I am able.
P.S.: About 10 years ago, there was an article published in NEJM that showed that New Haven had 5 times as many cholecystectomies per capita as did Boston, while Boston had 5 times as many CABG's per capita as did New Haven. Did one city have too many operations, or did the other have too few? No one could determine the answer.
P.P.S. The best review of the current state of internal medicine was published by David. D. Norenberg, M.D., in the Annals of Internal Medicine(Ann. Int. Med. 2009; 150:725-726) accessible at www.annals.org: "The Demise or Primary Care". Please read it and share it with everyone you know, physicians, patients, and politicians.
First, I have been solo for the past 10 years, because no recent medical school graduate wants to practice (and I have a big-city practice and attend at a medical school) pure internal medicine without an enormous salary guarantee that only a large group can afford to offer (which includes fronting their malpractice insurance). The reason is that HMO's and MCR both pay much more for doing than for thinking and diagnosing, since the powers that pay can measure doing, but not thinking. It is ridiculous that MCR pays me more for a 5-minute rigid sigmoidoscopy than for a 15-minute intake interview. This is why dermatology is the most popular residency. Getting paid $500 for a Botox injection every 3 months is an annuity! And since no insurance pays for it, the physicians can charge whatever they wish. Man is an economic animal, and often will respond to economic stimuli. So when Massachusetts established state-wide health care, there were not enough primary care doctors, and the average wait for a new doctor was 60 days. Just imagine the shortage when the 45 million currently uninsured patients look for a new primary care doctor. We will need at least 10,000 new primary care doctors, and where will they come from? Actually, every doctor should do Botox and Restalen injections and skin biopsies one day a week, so he/she can practice the medicine they like the other four days. And since MCR pays psychiatrists less than they pay me for the same amount of office time, why would any psychiatrist ever want to see a new MCR patient?
Second, we have socialized medicine now, and it's called Medicare. Few MCR patients want to give it up. There are many advantages to the patient, and the main advantage to the physician is that we spend less time on paperwork, and time is our least fungible resource. For a MCR patient, unlike an HMO patient, I don't have to call anyone for permission to get an MRI,and I don't have to worry that the best shoulder surgeon I know is a Cigna MD, and my patient is an Oxford patient, so my patient can't get to see the physician I prefer. I don't have to ask the patient to fax me a list of the HMO ophthalmologists so I can see if I know anyone on the list.
Also, MCR patients get back 5 to 10 times the dollar amount in medical services of the MCR premiums they paid.The tobacco companies showed (but dropped the argument because it made for poor PR) that the government saves money on every patient who dies before reaching MCR age. I also (I hope) will not have to spend time asking someone for permission to prescribe a brand name rather than a generic drug, or to prescribe a brand name drug that is not on their formulary.
Third, if everyone has a private MD, they will "crash" in the ER less often with diabetes out of control, unstable angina, end stage renal disease, etc. If you look at ER visits in Canada vs. here, there are fewer (percentage-wise) visits for acute medical conditions. Having a private physician who you can visit regularly puts a basic floor under your medical condition, even if nothing more is done than blood pressure check, PAP smear, and stool for blood. Overall, since ER visits are extremely expensive because ER doctors do every test they can think of, since they don't want to miss anything (viz. the recent article in the July, 2009 issue of "Archives of Internal Medicine" on the ER workup of syncope in the elderly) we will save a lot of money.
Fourth, technology is expensive, but it works. No patient walks up to an orthopedic surgeon and says "I want a new hip". Instead, the doctor is told "I can't move without agonizing hip pain". No patient says "I need cardiac bypass surgery", or "I need cataract surgery".
Fifth point has to do with malpractice. The most common suit against a family MD is for failure to diagnose a condition. As far as I am aware, no physician ever got sued for doing a test, but only for not doing one. When I started practice,I used to spend 30 minutes to explain to a 40 year old man with no risk factors and atypical chest pain and a normal EKG why he did not need a stress test, and the problems that can result from false positive tests. Now I suggest a stress-echo, stress-thallium and consultation with a cardiologist to the same patient. Why risk being sued even if I know I will win the case? Why spend the time and stress?
As long as we have contingency fees, we will have malpractice cases, and doctors will do extra tests to minimize their exposure, as well as make any referrals any family member of the patient suggests.
Sixth, unless you have a boutique practice, the average MD has to see one patient every 10 minutes, which involves putting 4 patients into 4 rooms, and having the NP or PA take the interval history, do the vital signs, etc. No one can get proper medical care under these conditions. I was trained to spend 15-45 minutes in the office with my patient to take a history and discuss any family stresses, then examine the patient in the exam room, and then bring the patient back into my office to discuss the results. I don't know of any doctor under 60 who practices medicine in this way, and most patients don't know what they are missing.
Seventh, there is something very wrong with the practice of medicine when the majority of doctors advise their children not to go into medicine.
Eighth, every medical system in every country rations by money, time, or availability, since the demand for medical care is almost infinite. England NHS does not transplant kidneys over a certain age, so those who can afford it fly to India to buy a kidney. Some drugs are not allowed in England because the NHS pays for all drugs, and this is how the country caps pharmacy expenses. Canada rations hospitals as to how many open-heart surgeries they can do in a given month. Germany reduces the physicians state-paid salary if their patients' prescriptions cost too much. MCR pays for only so many physical therapy visits or hospital days a year.
Ninth, I still love the practice of medicine, and intend to see my patients as long as I am able.
P.S.: About 10 years ago, there was an article published in NEJM that showed that New Haven had 5 times as many cholecystectomies per capita as did Boston, while Boston had 5 times as many CABG's per capita as did New Haven. Did one city have too many operations, or did the other have too few? No one could determine the answer.
P.P.S. The best review of the current state of internal medicine was published by David. D. Norenberg, M.D., in the Annals of Internal Medicine(Ann. Int. Med. 2009; 150:725-726) accessible at www.annals.org: "The Demise or Primary Care". Please read it and share it with everyone you know, physicians, patients, and politicians.
Saturday, July 11, 2009
Vaccines and Immunizations for Adults
This blog is a general (search the archives of Morbidity and Mortality Weekly Report, or the CDC travel page, or www.immunizationed.org for more detailed info) review of the vaccinations/immunizations available for adults. I will be reviewing them in the order of the fatality rate for the infected but unvaccinated immunocompetent adults. WARNING: if you are pregnant, or immunosuppressed--e.g. on steroids, on cancer chemotherapy, have AIDS,etc., do NOT take any live virus vaccine without checking with your doctor, and avoid anyone who has had a live virus vaccine for 8 weeks after they have been vaccinated.
RABIES: Except for one fortunate female in Wisconsin, this disease has been 100% fatal once symptoms are evinced. The virus is carried in the salivary glands of infected meat-eating animals: bats, raccoons, skunks, foxes, dogs, cats,---.The vaccine is available from your state board of health, or vetinarians. You should seek vaccination for any bite or scratch from ANY unknown animal, as well as if you have been in the same room with a bat, since their needle-like teeth often can bite without your feeling it. It is also recommended for pre-exposure prophylaxis if you are traveling to a region where there is a high incidence of rabies in stray dogs, such as certain parts of Asia, including Katmandu, and India, Mexico, and other countries (check with CDC). Chloroquine, and possibly mefloquine, both used for malaria prophylaxis, may blunt your immune response to the vaccine, so be sure to notify the treating physician if you are taking either of these drugs, and ask for deep IM rather than SQ vaccination. Raccoons are nocturnal animals, so any raccoon seen in the daytime should be presumed to be rabid.
TETANUS: Last year there were over 50 fatalities from tetanus in the U.S., and there should be none.It is 100% preventable by an antitoxin shot (no longer made from horse serum, so there is little likelihood of a strong reaction). It is a paralysis caused by a toxin generated by an anaerobic bacterium that inhabits the soil, especially where there is horse manure. You should be vaccinated every 10 years, but there is no harm done if the ER vaccinates you whenever you come in with a laceration. More women than men die each year (often from a non-remembered puncture wound from a garden rose thorn, etc.): Since men get injured more often than women, they are more likely to have been in the ER and been re-vaccinated. If you don't remember when you received your last tetanus shot, please ask your doctor for one at your next visit. I should also mention that the only vaccine currently available in the USA is dT, so you are also re-vaccinated against diphtheria at the same time. It would take up too much space here to explain why, but the reason is not medical.
YELLOW FEVER: This is a LIVE vaccine, and the vaccination is good for 10 years. It is only available from physicians or centers certified by the US gov't. Yellow fever is endemic in many areas of countries in South America, Central America, and Africa. It is spread by mosquitoes both in jungles and cities and one infection confers lifetime immnunity. The case fatality rate can be as high as 50%, and there is no treatment, since we have no drugs that reliably attack flaviviruses. Therefore, when in doubt, take the vaccine. (As a historical point, at one time it was endemic in the United States, from New Orleans to Philadelphia.)
POLIOMYELITIS: The oral vaccine (OPV) is live, and the injected vaccine (IPV) contains inactivated virus. One dose if IPV is recommended for travelers to underdeveloped countries or those with poor sanitation (check with the CDC).
HEPATITIS B: This vaccine is recommended not only because Hepatitis B can progress to cirrhosis of the liver even with treatment, but also because infection with Hepatitis B (or C) is a proven risk factor for cancer of the liver. It can be spread by unprotected sex, exposure to blood, including transfusions, or sharing of needles by drug users. Because it is considered a STD, vaccination for all children has been recommended before they reach the age of sexual activity. As an adult, vaccination is recommended for those exposed to blood (ER workers, dental hygienists and dentists, etc.) and those with compromised immune systems, including those on renal dialysis. You should specifically ask your physician if you should have the vaccine. If you are immuno-incompetent, then it is recommended that you be tested for protective antibodies one month after vaccination. Unless you are tested annually for antibodies, it is unknown how long your protection will last.
N.B.: If you want to help your country, then please donate a unit of blood. The blood bank will test your blood, at no charge to you, for Hepatitis B and C, syphilis, AIDS, and a few other diseases. You will not be permitted to donate blood if you have been in a country where malaria is endemic (including Mexico, even if in a non-malarious area) within the previous 12 months.
SMALLPOX: A LIVE vaccine. No longer given routinely, except to U.S. military personnel. Cidofovir has shown some success in animal models of this disease. Case fatality rate at least 20%.
HPV: Vaccine against Human Papilloma Virus. This is considered to be permissive, if not an inducer for cancer of the cervix. There are many strains of HPV, and the vaccine does not protect against all of them, so women should still have pap smears, even if vaccinated. Recommended for all females before first menses, and any woman who has not received the vaccination.
INFLUENZA: Everyone should have annual vaccination with the regular flu vaccine.
Since the antibody levels decline after 4 to 6 months, I recommend biannual vaccinations to my all my patients. In the past, the vaccine was recommended only for those over 65, as well as health care workers and teachers, etc., because there was not enough to give everyone in the U.S. It is especially important to get this vaccine because Tamiflu is no longer effective against it.
AVIAN FLU: The government hopes to have a vaccine against this available by October, 2009. Fortunately, this flu virus is generally susceptible to Tamiflu. We are all sincerely worried about this flu strain developing resistance to Tamiflu so I(we) are not prescribing it to patients to have "just in case". Patients born after 1956 have no natural antibodies to this H1N1 strain, and so are at risk for death. Patients born before this date were probably infected with a strain somewhat homologous to avian flu, and therefore become less ill.
PNEUMOCOCCAL PNEUMONIA: Patients over 65, those without a spleen (either at birth or after surgery), patients with TB,diabetes and a host of other chronically ill patients are at risk of death from pneumococcal pneumonia. However, it was found that patients younger than 65 develop a stronger immune response than older patients, Most physicians now will give the vaccine to their (normal) patients when they reach age 60, and a booster is recommended 5 years later.
MENINGOCOCCAL MENINGITIS: Recommended for those traveling to areas where this is endemic. The antibody levels decline after 2 years. Saudi Arabia requires this vaccination for those traveling to Mecca.
JAPANESE B ENCEPHALITIS: May to September in Asia. Low risk of infection, and high rate of side effects and reactions. Discuss with your doctor.
PLAGUE: Recommended only for travelers in regions where it is endemic (but this does include the U.S. Southwest). Booster every 1 to 2 years.
TYPHOID: Oral vaccine. Spread by contaminated food and water. Suggested if you are going to be in underdeveloped country for 3 or more months, but you should still be careful what you eat and drink.
HEPATITIS A: Virtually never fatal, but it can ruin your vacation. Spread by contaminated food and water. can be combined with Hepatitis B vaccine.
SHINGLES/HERPES ZOSTER:LIVE virus. This is reactivation of the virus that gave you chicken pox. It lives in your body forever, and can be reactivated along pain nerves as you get older and your immune surveillance competence drops. Classically, it causes redness and blisters along the path of a pain nerve, but you can get non-eruptive zoster, wherein the virus re-activates WITHOUT the rash. The problem is extreme residual pain along the path of the inflamed nerve, and it seems that older patients get more severe pain. We recommend it for all patients, because the pain can be disabling. However, vaccination is not 100% protective. Also, a prior zoster attack does not prevent a second attack.
RABIES: Except for one fortunate female in Wisconsin, this disease has been 100% fatal once symptoms are evinced. The virus is carried in the salivary glands of infected meat-eating animals: bats, raccoons, skunks, foxes, dogs, cats,---.The vaccine is available from your state board of health, or vetinarians. You should seek vaccination for any bite or scratch from ANY unknown animal, as well as if you have been in the same room with a bat, since their needle-like teeth often can bite without your feeling it. It is also recommended for pre-exposure prophylaxis if you are traveling to a region where there is a high incidence of rabies in stray dogs, such as certain parts of Asia, including Katmandu, and India, Mexico, and other countries (check with CDC). Chloroquine, and possibly mefloquine, both used for malaria prophylaxis, may blunt your immune response to the vaccine, so be sure to notify the treating physician if you are taking either of these drugs, and ask for deep IM rather than SQ vaccination. Raccoons are nocturnal animals, so any raccoon seen in the daytime should be presumed to be rabid.
TETANUS: Last year there were over 50 fatalities from tetanus in the U.S., and there should be none.It is 100% preventable by an antitoxin shot (no longer made from horse serum, so there is little likelihood of a strong reaction). It is a paralysis caused by a toxin generated by an anaerobic bacterium that inhabits the soil, especially where there is horse manure. You should be vaccinated every 10 years, but there is no harm done if the ER vaccinates you whenever you come in with a laceration. More women than men die each year (often from a non-remembered puncture wound from a garden rose thorn, etc.): Since men get injured more often than women, they are more likely to have been in the ER and been re-vaccinated. If you don't remember when you received your last tetanus shot, please ask your doctor for one at your next visit. I should also mention that the only vaccine currently available in the USA is dT, so you are also re-vaccinated against diphtheria at the same time. It would take up too much space here to explain why, but the reason is not medical.
YELLOW FEVER: This is a LIVE vaccine, and the vaccination is good for 10 years. It is only available from physicians or centers certified by the US gov't. Yellow fever is endemic in many areas of countries in South America, Central America, and Africa. It is spread by mosquitoes both in jungles and cities and one infection confers lifetime immnunity. The case fatality rate can be as high as 50%, and there is no treatment, since we have no drugs that reliably attack flaviviruses. Therefore, when in doubt, take the vaccine. (As a historical point, at one time it was endemic in the United States, from New Orleans to Philadelphia.)
POLIOMYELITIS: The oral vaccine (OPV) is live, and the injected vaccine (IPV) contains inactivated virus. One dose if IPV is recommended for travelers to underdeveloped countries or those with poor sanitation (check with the CDC).
HEPATITIS B: This vaccine is recommended not only because Hepatitis B can progress to cirrhosis of the liver even with treatment, but also because infection with Hepatitis B (or C) is a proven risk factor for cancer of the liver. It can be spread by unprotected sex, exposure to blood, including transfusions, or sharing of needles by drug users. Because it is considered a STD, vaccination for all children has been recommended before they reach the age of sexual activity. As an adult, vaccination is recommended for those exposed to blood (ER workers, dental hygienists and dentists, etc.) and those with compromised immune systems, including those on renal dialysis. You should specifically ask your physician if you should have the vaccine. If you are immuno-incompetent, then it is recommended that you be tested for protective antibodies one month after vaccination. Unless you are tested annually for antibodies, it is unknown how long your protection will last.
N.B.: If you want to help your country, then please donate a unit of blood. The blood bank will test your blood, at no charge to you, for Hepatitis B and C, syphilis, AIDS, and a few other diseases. You will not be permitted to donate blood if you have been in a country where malaria is endemic (including Mexico, even if in a non-malarious area) within the previous 12 months.
SMALLPOX: A LIVE vaccine. No longer given routinely, except to U.S. military personnel. Cidofovir has shown some success in animal models of this disease. Case fatality rate at least 20%.
HPV: Vaccine against Human Papilloma Virus. This is considered to be permissive, if not an inducer for cancer of the cervix. There are many strains of HPV, and the vaccine does not protect against all of them, so women should still have pap smears, even if vaccinated. Recommended for all females before first menses, and any woman who has not received the vaccination.
INFLUENZA: Everyone should have annual vaccination with the regular flu vaccine.
Since the antibody levels decline after 4 to 6 months, I recommend biannual vaccinations to my all my patients. In the past, the vaccine was recommended only for those over 65, as well as health care workers and teachers, etc., because there was not enough to give everyone in the U.S. It is especially important to get this vaccine because Tamiflu is no longer effective against it.
AVIAN FLU: The government hopes to have a vaccine against this available by October, 2009. Fortunately, this flu virus is generally susceptible to Tamiflu. We are all sincerely worried about this flu strain developing resistance to Tamiflu so I(we) are not prescribing it to patients to have "just in case". Patients born after 1956 have no natural antibodies to this H1N1 strain, and so are at risk for death. Patients born before this date were probably infected with a strain somewhat homologous to avian flu, and therefore become less ill.
PNEUMOCOCCAL PNEUMONIA: Patients over 65, those without a spleen (either at birth or after surgery), patients with TB,diabetes and a host of other chronically ill patients are at risk of death from pneumococcal pneumonia. However, it was found that patients younger than 65 develop a stronger immune response than older patients, Most physicians now will give the vaccine to their (normal) patients when they reach age 60, and a booster is recommended 5 years later.
MENINGOCOCCAL MENINGITIS: Recommended for those traveling to areas where this is endemic. The antibody levels decline after 2 years. Saudi Arabia requires this vaccination for those traveling to Mecca.
JAPANESE B ENCEPHALITIS: May to September in Asia. Low risk of infection, and high rate of side effects and reactions. Discuss with your doctor.
PLAGUE: Recommended only for travelers in regions where it is endemic (but this does include the U.S. Southwest). Booster every 1 to 2 years.
TYPHOID: Oral vaccine. Spread by contaminated food and water. Suggested if you are going to be in underdeveloped country for 3 or more months, but you should still be careful what you eat and drink.
HEPATITIS A: Virtually never fatal, but it can ruin your vacation. Spread by contaminated food and water. can be combined with Hepatitis B vaccine.
SHINGLES/HERPES ZOSTER:LIVE virus. This is reactivation of the virus that gave you chicken pox. It lives in your body forever, and can be reactivated along pain nerves as you get older and your immune surveillance competence drops. Classically, it causes redness and blisters along the path of a pain nerve, but you can get non-eruptive zoster, wherein the virus re-activates WITHOUT the rash. The problem is extreme residual pain along the path of the inflamed nerve, and it seems that older patients get more severe pain. We recommend it for all patients, because the pain can be disabling. However, vaccination is not 100% protective. Also, a prior zoster attack does not prevent a second attack.
Wednesday, July 1, 2009
Aspirin, Lipoprotein A, CRP, Anti-oxidants, Heart disease
There have been a number of articles published recently in Lancet, Journal of the AMA, and newspapers about primary prevention of heart disease. By primary prevention, we mean the reduction of risk of a heart attack in patients who have not had a heart attack. Since the greatest risk for having a heart attack is having had one, the number of patients in a study of primary prevention has to be larger and last for a longer time than a study of secondary prevention, where aspirin, beta-blockers, statins, etc., have been shown to be of help.
I should also mention that the over-riding problem in prevention of any disease is not lack of communication between doctors and patients,or lack of information on the part of patients, but the unwillingness of patients to change their behavior (and no, I am not blaming the victim). Most patients know that they should exercise, lose weight, and stop smoking to reduce their primary heart attack risk, but how many do, even if, as in NYC, the amount of calories per dish is published in the menu of every chain restaurant?
1) C-reactive protein, or CRP. Numerous studies have shown a correlation between elevated CRP and heart attacks. This correlation is about as strong as that between elevated homocysteine and heart attacks. However, just as pulling down on the metal elevator arrow in the lobby of a skyscraper does not bring the elevator down, lowering the homocysteine has not been shown to lower heart attack risk. Whether the CRP as a marker for inflammation means that inflammation is a primary risk factor remains to be seen. A recent published genetic analysis (similar to the Lp(A) analysis) seem to show that lowering CRP does NOT lower the risk for heart disease.
2) Aspirin. First we have to decide if we mean 81mg/day, 325 mg/day, or 325 mg twice a day. Since aspirin blocks platelet clumping for 7 days, it is not clear why the studies involved daily aspirin, rather than once or twice a week. In addition, none of the studies to date controlled for aspirin resistance, where aspirin at the suggested dose does not prevent platelet clumping. It has been a "consensus" that absent any other risk factors (smoking, diabetes,etc.) that aspirin prevention should start at age 45 for men and 55 for women. However, a recent article Lancet cast severe doubt on this recommendation, so your guess is as good as mine.
3) Lp(A), or lipoprotein A. A recent article used genetic analysis to suggest that elevated Lp(A) is an independent risk factor for heart attacks. However, no one has shown that lowering Lp(A), prevents heart attacks, nor do we have a good drug to lower Lp(A). The same could be said in reverse about low HDL, the "good" cholesterol.
4) Anti-oxidants. The prophylactic use of anti-oxidants should be approached with caution. Prospective studies have shown that extra daily Vitamin E increases the primary risk for heart attacks, and prophylactic beta carotene increases the risk for lung cancer in cigarette smokers. A recent study at Memorial Sloan-Kettering showed in vitro that vitamin C inhibited the killing effect of chemicals on cancer cells. Selenium and vitamin E have been shown to have no protective effect against prostate cancer.
The conceptual problem is, of course, that correlation does not imply causation. Just recall how coffee drinking was "shown" to be a risk factor for heart attacks until it was realized that more coffee drinkers than non-drinkers smoke cigarettes. We always have to beware of confounding factors, as well as a common cause that elevates both the risk of disease and the marker. Does anyone really understand why female Pima Indians of the American Southwest have such a high incidence of cholecystitis, or the female Parsees of India (Zoroastrians transplanted from the Mideast) have such a high incidence of breast cancer?
I should also mention that the over-riding problem in prevention of any disease is not lack of communication between doctors and patients,or lack of information on the part of patients, but the unwillingness of patients to change their behavior (and no, I am not blaming the victim). Most patients know that they should exercise, lose weight, and stop smoking to reduce their primary heart attack risk, but how many do, even if, as in NYC, the amount of calories per dish is published in the menu of every chain restaurant?
1) C-reactive protein, or CRP. Numerous studies have shown a correlation between elevated CRP and heart attacks. This correlation is about as strong as that between elevated homocysteine and heart attacks. However, just as pulling down on the metal elevator arrow in the lobby of a skyscraper does not bring the elevator down, lowering the homocysteine has not been shown to lower heart attack risk. Whether the CRP as a marker for inflammation means that inflammation is a primary risk factor remains to be seen. A recent published genetic analysis (similar to the Lp(A) analysis) seem to show that lowering CRP does NOT lower the risk for heart disease.
2) Aspirin. First we have to decide if we mean 81mg/day, 325 mg/day, or 325 mg twice a day. Since aspirin blocks platelet clumping for 7 days, it is not clear why the studies involved daily aspirin, rather than once or twice a week. In addition, none of the studies to date controlled for aspirin resistance, where aspirin at the suggested dose does not prevent platelet clumping. It has been a "consensus" that absent any other risk factors (smoking, diabetes,etc.) that aspirin prevention should start at age 45 for men and 55 for women. However, a recent article Lancet cast severe doubt on this recommendation, so your guess is as good as mine.
3) Lp(A), or lipoprotein A. A recent article used genetic analysis to suggest that elevated Lp(A) is an independent risk factor for heart attacks. However, no one has shown that lowering Lp(A), prevents heart attacks, nor do we have a good drug to lower Lp(A). The same could be said in reverse about low HDL, the "good" cholesterol.
4) Anti-oxidants. The prophylactic use of anti-oxidants should be approached with caution. Prospective studies have shown that extra daily Vitamin E increases the primary risk for heart attacks, and prophylactic beta carotene increases the risk for lung cancer in cigarette smokers. A recent study at Memorial Sloan-Kettering showed in vitro that vitamin C inhibited the killing effect of chemicals on cancer cells. Selenium and vitamin E have been shown to have no protective effect against prostate cancer.
The conceptual problem is, of course, that correlation does not imply causation. Just recall how coffee drinking was "shown" to be a risk factor for heart attacks until it was realized that more coffee drinkers than non-drinkers smoke cigarettes. We always have to beware of confounding factors, as well as a common cause that elevates both the risk of disease and the marker. Does anyone really understand why female Pima Indians of the American Southwest have such a high incidence of cholecystitis, or the female Parsees of India (Zoroastrians transplanted from the Mideast) have such a high incidence of breast cancer?
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