Monday, December 21, 2009

Addiction, Part I

We are here going to discuss addiction and the various degrees and sub-categories thereof: dependence, habit, obsession-compulsion, drug abuse, enabler, conditioned reflex, and illegal drug use. We shall see that the categories are not clear-cut, boundaries of groups are not precise, and behavioral scientists disagree about definitions. This discussion will not include membership in religious sects and drug use in their rituals,since that will be discussed in a future blog.

Again, many of the above definitions are conditioned by our culture (see my previous blog on insanity). The old joke that an alcoholic is someone who drinks more than his doctor does is particularly relevant here. Many doctors forget that they define what is "normal" for their patients, and doctors, especially psychiatrists, have to be careful to maintain a "poker face". (It is trivial to add here that if you are demonstrating cardiac auscultation to a medical student on a female patient with a V/VI holosystolic murmur, you should refrain from using the phrase "a palpable thrill".)

First of all, the label of "enabler" should be stricken. The only way to influence the legal behavior of someone with whom you are involved is by request, by order, by saying "do it if you love me", or by threatening to leave if the behavior does not stop, i.e. basically by compulsion. I have found, for instance, in 25 years of practice that the only way to force a male alcoholic to stop is for his boss to threaten him with loss of his job, and, in the case of women, for the judge to threaten them with loss of their children. Only then is their ego threatened enough to change their behavior, and it still generally involves at least 30 days inpatient treatment. You are not responsible if your loved one continues self-destructive behavior, although their "right" to self-destruction does not mean that it is the "right" thing to do. Of course, if their behavior damages them permanently, you have the job of caring for them, which seems to be grossly unfair. As a simple example, if your spouse chews his/her fingernails, are you a fingernail-chewing enabler? I know that it is painful to watch such behavior, but as I often tell spouses, smokers know they shouldn't smoke, overweight people and diabetics know they should lose weight,etc.But once you tell them more than twice, you are nagging them, and my male patients tell me they react to such nagging with anger and passive-aggressive behavior. It is not enabling to stay with someone whose behavior you disagree with or you feel is self-destructive, any more than the person can be cured by your walking out. (When children are present, however, the answer may be different, and then case-by-case analysis and judgment is needed.)

Obsessive-compulsive behavior is best described as repetitive behavior that the patient wishes he/she could stop, or that interferes with the ability to work, love, or play (pace Freud). Again, I am deliberately omitting any discussion of religion, including the behavior of self-flagellation so brilliantly shown in "The Seventh Seal". This problem is very difficult to treat psychiatrically, since the behavior is a substitute to ward off anxiety, and the true cause cannot always be found. The unwanted behavior can range from going back home to make sure the oven is turned off, to washing your hands 20 times a day, to taking one hour to put on makeup, etc. Anorexia is probably the end-point of o-c worrying and behavior about one's weight and self-image. At what point does compulsive self-pleasuring become a true problem? (The latest data shows that 95% of college men self-pleasure , and the other 5% are liars.) If the o-c behavior is mild, the patient will probably not even admit it as such (how many baths a day is too many, when 100 years ago only upper-class Englishmen bathed as often as once a week?). If you are a compulsive gambler as Michael Jordan apparently may have been, but you can afford to lose $100,000/month, is it still a problem?

Habit is just mild o-c behavior that is socially acceptable, and later becomes reassuring to the user. It is not threatening or dangerous, and can even engender a sense of pleasure, similar to the baseball player who always makes sure to step on the foul line when leaving the playing field, and avoiding it upon entering. In fact, alteration of habits is often an early indication of mental change, whether the change is falling in love, or early Alzheimers.

Addiction is the most complex behavior of all, and the most difficult to define. Classically, addiction to a drug is defined as a combination of drug-seeking behavior, even if it is illegal, tolerance, and withdrawal effects upon abrupt cessation. (I once took care of a patient who was admitted at his request to help him break his addiction to a legal drug:he swallowed up to 40 nitro-glycerine tablets a day, because he enjoyed the sensation triggered by abrupt drops in blood pressure.)The worst withdrawal effects are seen with CNS depressants, such as alcohol, tranquilizers, and other "downers", since the brain generates counter-chemicals which stimulate the brain, and the abrupt cessation of the drug lets the self-generated stimulating chemicals run riot, and hence the shakes, sweats, DT's, and the like which can kill the patient. Some doctors would say that a truly addicting drug is one that kills you if you stop it abruptly, or one that makes you feel compelled to increase the dosage, because of tolerance, until it kills or seriously damages your body, such as methamphetamine or other "upper" use.
People also talk about "sex addiction", "gambling addiction", caffeine addiction, etc. None of these is acutely dangerous to the body (and, in fact, several studies have shown that caffeine is protective against adult-onset diabetes, especially in females). IMHO, all that is happening is that the immediate gratification and pleasure from the act far outweighs any thought of future problem. All babies demand instant gratification, and part of growing up is learning to defer this desire. However, it is extremely difficult to "prove" that hedonism is not a viable philosophy. The question of "rational" or Appolonian behavior vs. pleasure-seeking or Dionysian behavior is a motif that repeatedly recurs in human history. Euripides demonstrated the two sides in his play "The Bacchae", the 17th century English had the Cavaliers vs. the Roundheads, we had the Drys vs. the Wets,and today it is said that sex is a natural human occurrence in Europe, and an obsession in America. In South America, where the children are too poor to buy cocaine, they stuff rags in the gas tanks of autos and sniff the fumes to get high and escape their lives temporarily.
It is very odd that smoking cigarettes creates a pleasant feeling,
since the first few cigarettes make you cough horribly, so the pleasure is partly learned, as it is with marijuana. I also have trouble labeling it a true addiction (I know that most people disagree with me here) since anyone who takes a 12 hour plane ride stops smoking for at least that long, without any acute withdrawal symptoms. Most smokers "know" that cigarette smoking is health-threatening, but they feel that the particular cigarette they are about to smoke at this moment will not be especially damaging. Nicotine is an amazing drug about which we know very little: how does it both quench hunger and help one feel more comfortable after a full meal? Why does it have a calming effect? Why have various European studies shown that smokers apparently have a lower incidence of Parkinson's Disease? I tell my smokers that while they may not all get cancer, I can guarantee with 100% certainty the development of COPD/emphysema, and eventual dependence on an oxygen tank. In fact, sophisticated pulmonary function studies (not generally available outside of research labs) will show premature small airways closure in almost all smokers. Because of this, I prescribe Spiriva (ipatronium) inhalers for all my smoking patients. This drug has been demonstrated to slow the natural progression of symptomatic emphysema in non-smokers, and I can only hope that it will do the same for smokers.

At this point, I would like to show how some of the observed facts quoted above should suggest hypotheses which, in turn, require well-designed experiments to verify or disprove:
1) Why does coffee (? caffeine) drinking prevent or delay the onset of adult diabetes? Does it have to do with the effect of caffeine on the beta cells of the pancreas? We know that epinephrine (aka adrenaline in England) has an effect on these cells. Is there a local effect on potassium flux across the membranes of these cells? A proper experiment should tell us more about the nature of diabetes.
2) If cigarette smokers have a lower incidence of Parkinson's Disease, does this mean that stimulation of the nicotinic receptors in the human brain affects the dopaminergic neurons? Would a nicotine patch or daily use of nicotine gum have the same effect? We do know that smoking cigarettes seems to have a calming effect on some schizophrenics, so there is some nicotine---neural pathway or interaction occurring; we just don't know what it is, or if it can be stimulated without cigarettes.
3) It was simple observations that led the great scientists to marvelous concepts. Aristotle claimed that heavy bodies fell faster than lighter bodies, and Galileo asked himself (? the first gedanken experiment) what would happen if a heavy body were tied by string to a lighter body, and the two were dropped together. Einstein asked himself what the universe would look like if he rode on a beam of light at the speed of light, and developed the Theory of Special Relativity. He later used the Galilean result that all bodies fell at the same rate, and therefore had the same acceleration in a gravitational field. Since Force= (mass)x(acceleration)= (mass)x (gravity), this meant that inertial mass was equal to or equivalent to gravitational mass, and from this he developed the Theory of General Relativity.

I just realized that this blog is running longer than most of them, because this is a complex field, with much qualitative and little quantitative data. I will continue the discussion in a future blog. Just bear in mind that your brain tries to operate on the "seek pleasure, avoid pain" principle, and that it takes a lot of social training to prevent people from continual self-gratification, (see Freud's "Civilization and its Discontents"). When you were a baby you felt uncomfortable, cried, and your mother soothed you, usually with food or by holding you. Just like Pavlov's dog, we became conditioned to instant soothing, and it took a lot of training by our parents and schools to modify this. I'll leave you with the following experimental result: a biologist took lab rats, inserted an electrode into the pleasure center of their brains, connected the electrode to a battery, and connected the battery wiring to a bar in their cages. Every time a lab rat pushed the bar, the rat received an instant jolt of "pleasure". Every rat, without exception, pushed the bar repetitively and non-stop until death occurred from dehydration and starvation.This occurred even though rats, unlike humans, have no knowledge of death, and therefore no fear of it or need to blot such thoughts out by getting high.

Sunday, December 6, 2009


The first fact to realize about insanity is that it is a culturally defined disease, in the sense that the culture and/or society decide what "normal" is. If something is sufficiently unusual and uncommon, and not explicable by reason or understood as having a well-defined cause, then society will often label the action as evidence of an "unsound mind". For instance, until the American Psychiatric Society voted (and not by 100% to zero) that homosexuality was not a mental disease, homosexuals were often "treated" by psychiatrists. Similarly, in the 1950's and 1960's, if a Russian citizen claimed that communism was not the best political system, he was often classified as schizophrenic, confined to a mental hospital, and treated with Thorazine and other anti-psychotics. In the Southern USA before 1860, if a black slave wanted to run away, he was often labeled as "crazy because of 'escapitis'", because why would he try to run away if he were not insane.

You also cannot "prove" that you are sane. It generally takes the testimony of two psychiatrists who have examined you to certify that you are insane or not insane. The default assumption is that you are sane, unless a judge requires you to prove you are sane before he will let you stand trial. Of course, the psychiatrists are themselves culturally bound, so that an American who attempts suicide is considered to have a mental problem, while a Japanese who attempts hari-kari is not, and probably everyone who sees Shakespeare's "Julius Caesar" understands Brutus' suicide. If you saw and spoke with the image of your dead grandmother, you might be considered insane, unless you were a teenage girl from a Latin American culture, where such such events can occur on or near her fifteenth birthday.

Then we come to the insanity defense. I am not commenting pro or con on its use, but how can you decide today that someone was insane two years, ago, if he/she were not examined at that time. However, most doctors will label a person as having a drinking problem, if the patient has drinks more on a daily basis than does the doctor. Similarly, as I tell my residents time and time again, all prescribing is a negotiating process, so if a hospitalized patient refuses to take a prescribed medicine, this is not grounds for a psychiatric consult.

One problem that occurs frequently is with people who hear voices or see images and claim that such sensations came from God. Clearly one cannot "prove" by any logical process that they were not, any more than they can prove that they were. There is a condition called the "Jerusalem Syndrome", wherein pious Christians and Jews are so overcome with the holiness of Jerusalem when they land at Lod airport that they become instantly convinced that they are the Jewish or Christian Messiah. There is a ward of Jerusalem Hospital that has permanently set aside beds for members of this group. Bernadette of Lourdes and Joan of Arc had difficulty convincing the authorities that they were divinely inspired while Abraham had no difficulty believing that the Lord commanded him to sacrifice his son, nor did Joseph Smith have difficulty believing in the Angel Moroni. Since religion is part of every culture, ideations that might otherwise be considered manifestations of paranoia are acceptable when they occur in a religious context.

In Salem, Massachusetts, women were judicially killed for being witches. Such behavior is not condoned now in the United States. However, there is a mental condition that occurs in males from Asia (especially Japan) as well as males in West Africa: They become convinced that their penis is shrinking and being pulled up and vanishing inside their bodies. Some men even go so far as to tie weights with ropes to their penises to arrest this process. However, in Africa, this belief is considered as evidence that a witch has placed a curse on you, and the immediate cure is to kill the witch. This has occurred, and the males involved are never prosecuted. I might observe in all societies it seems that only female witches are executed, and never male warlocks.

I would like to close this blog with a comment on free will. Most of us believe that we have free will, but most psychiatrists do not so believe. They believe that we are bound up in childhood problems, and try to solve them in the adult world in which we live. We try to resolve the unsolved problems of childhood and therefore (they believe) we marry the person who is most similar to the parent with whom we had the most problems.
This raises the question/problem of how much free will any of us have if we are still trying to solve childhood problems as an adult, since we never recognize the displacement 1nvolved in the battle(s). Since the justice system can only function logically and properly and fairly if we all have free will, that is precisely the default belief of all justice systems. Therefore you are responsible for all of actions, unless you can prove that you are not. To have any justice system function, it must be assumed, incorrectly or not, that you are legally responsible for 100% of your actions; this is the same assumption we make on Voting Day, as well as when we choose members of a jury.

Tuesday, November 17, 2009

Mammograms, Zetia/Vytorin, Proscar,Folic Acid

I have received many phone calls from my patients and e-mails from readers on my bloglist about 3 different reports about medical research results: an article in the NY Times by Gina Kolata(Proscar), a report from a cardiac conference(Zetia/Vytorin), and recommendations from a medical study group (mammograms). I received no inquiries about an article in Lancet (folic acid), but I guess few people read British medical journals, even though Lancet antedates both NEJM and JAMA, and their letters to the editor are invaluable. My comments on these are probably applicable to many reports of medical results, and I leave it to my readers to evaluate any such reports.

First, some general comments. In many areas of non-precise science (I am therefore excluding mathematics, chemistry and physics) when recommendations are made, there is both a majority report/recommendation, and a minority report. However, in medicine, except as a rebuttal to a journal article (e.g. the discussion in Lancet as to whether or not reducing total salt in the diet saves lives) we never see the minority report. I doubt that 20 doctors (or 20 anyones) ever agree 100% on a committee report, and it would be nice to see the minority report (cf. the arguments about global warming) so we can try to make our own decision. Furthermore, most refereed journal articles require the authors to make the source data available on request, but this does not happen with medical committee recommendations, so we have no way to judge how they arrived at their recommendations, or what compromises were made (e.g. how did the government first decide that total cholesterol levels should be below 240?). Was it the same way that Congress decided on 27.5% as the oil depletion allowance, i.e. a compromise?

The recent recommendations on the starting age and frequency of mammograms are a case in point. There was no minority report, and the data on which the recommendations were made are not available. I only fear that HMO's will seize on this report to pay for fewer mammograms, as Medicare once did. I have never had a problem with ordering a test for a patient even if I was absolutely certain the result would be negative, because the patient's peace of mind is important to me.
There is absolutely no way to know for a given individual how often a mammogram should be done (why not every 6 months to detect fast-growing cancers?), or at what age the mammograms should start. I also have some 90 year old women who have never had a mammogram, and have never had breast cancer, and so far they are right as well.

The article about men not taking Proscar even though men on Proscar have a lower incidence of prostate cancer did not properly emphasize the fact that if prostate cancer does occur when a man is taking Proscar it is much more aggressive, and has a higher Gleason score. On the other hand, taking both Proscar and Flomax decreases a man's probability of needing a TURP of the prostate to relieve blockage caused by a growing prostate. Also, some men do not like taking Proscar because it diminishes the amount of fluid in the ejaculate by at least 50%, and these men do not enjoy the different sensation, because their orgasms are therefore shorter. Why not just say that men who do not take Proscar are "pharmacologically autonomous"?

Both Zetia and Vytorin decrease cholesterol, which is all the FDA required them to do. Studies on other statins as well as on Niacin showed that lowering cholesterol by these chemicals reduced the risk of second heart attacks and strokes, as well as the risk of first heart attacks. (I have never seen a study on diet, lower cholesterol, and heart attacks.) The FDA then assumed that any chemical lowering of cholesterol was beneficial, as does the entire medical establishment.
The study of Zetia/Vytorin showed that they did not cause regression of the narrowing of the intima of a major artery. However, this is a secondary surrogate marker for strokes and heart attacks. If heart attacks are caused by rupture of plaque (as many cardiologists believe) then stabilizing the plaque (are statins anti-inflammatory as aspirin is?) is more important than the lumen diameter, after a certain narrowing. No one has shown that lowering the cholesterol with Zetia or Vytorin does NOT reduce the risk of heart attack or stroke, just as no one has shown that intimal regression is a valid surrogate for MI's and CVA's.

The latest issue of Lancet reported a large study that showed that fortifying the diet with folic acid, which successfully lowered neural tube defects in infants, INCREASED the risk of cancer. I wonder what the USA and FDA will do with this study. It certainly should be repeated. But studies showing that vitamin ingestion can cause problems rarely make headlines in America. Maybe we should revise the recent recommendations which raised the RDA for folate from 0.4mg to 0.8mg?

Thought for the month: Why does the full moon appear larger when it rises in the East than it does when it is directly overhead?

Monday, November 16, 2009

Universal Health Care: What it Should Contain

Many patients and friends have asked me during the past months what I would like to see in universal health care. I only want a system that is best for my patients, and takes the least paperwork time for me. Any system, of course, will always pay less for thinking than for doing (i.e. operating) because it is difficult to measure thinking. I defer the question of outcome measurements to another blog.

1) We already have socialized medicine, and it is called Medicare and the VA Hospitals, and none of the users of the systems seems very much dissatisfied with it. And, in fact, middle-class parents paying to put their children thru college, etc., would find it difficult if not impossible to provide dollar for medical dollar coverage for their elderly parents, as they would have to do without Medicare.

2) You are allowed (by law) to keep your same cell phone number for life, if you want to, and don't have to change it every time you switch carriers. But when you are transferred from HMO A to HMO B because your company got a better premium deal from the second company,you suddenly have to scurry around and find a new internist, gynecologist, pediatrician, and any other specialist you are seeing. This is manifestly unfair, inefficient, and disrupts the smooth flow of medical care-taking. It's one thing if a patient chooses to leave a doctor, but to be forced to leave a doctor is unconscionable and stressful. And what if you are a Cigna patient but the world's expert is an Oxford surgeon? Then you have to pay his full bill, with no insurance deduction. You should be able to KEEP THE SAME FAMILY DOCTOR FOR LIFE!

3) Many patients are tied to their jobs thru their health insurance. If they stop working or switch their jobs, their wife and children may not be covered, or there may be very special coverage available only while they work for this particular company.

4) A minor point: why does the family coverage for your children stop when they are 23 years old?

4) A stronger point: If you and your wife both have paid premiums for a $100K fire policy on your house, and it burns down, you both get paid $100K., because you each have a policy. But if you and you wife both have paid medical premiums for a family policy, and you get a heart attack,you can only collect doctor and hospital bills from one of your policies. This means the other one was invalidated for this case, and all the premiums (10, 20 30 years' worth)are sheer profit for the company. Why should this be? It's like reverse double-dipping,only this time your pockets are the ones being directly dipped into.

5) I should not have to waste my time calling up for permission for MRI's. I don't have to do it for MCR, but most HMO's want me to expose a patient to cancer-causing Xrays of a CT exam before they allow an MRI, or I have to spend a lot of time (my least fungible recourse) convincing them otherwise.

6) I could also save time if I didn't have to call the drug management company to explain why the drug I chose for my patient is preferable to their chosen (and cheaper) drug. They don't know the patients. (Actually, must drug stores and wholesalers make a greater per cent profit on generics than brand names, because no one outside the field knows how cheap it is to make a generic.)

7) They should not make Electronic Medical Records mandatory until they have proved that they save money, or at least patient morbidity. There has been no clear evidence of this yet.All I know is that in the "good old days" I could admit a patient and write a set of orders with pen and paper in 5 minutes. Now with filling out the matrix in the computer form in the sequence of questions they ask me (e.g. what is my patient's flu vaccine status, a fact I always put down in my admitting note) punching in my date of birth xx-xx-xxxx (not a code) just more information collected, so all doctors tend to be born on 11-11-1911) it takes me at least 25 minutes to admit a patient. This is not progress, but more on the EMR on another blog.Sometimes when I get tired of all the pettifogging, if it is my personal patient, I just put down patient refuses".

In summary: keep the same doctor for life, and also solve the problem of who will pay for abortions, because as long as we have both men and women, married or unmarried, we will have unwanted pregnancies,

Friday, October 23, 2009

Stress and Somaticism

I have often noticed how stress wears my patients down, and causes multiple somatic symptoms. If the mind is unhappy and/or stressed, it will always make the body hurt. If you are fortunate, the discomfort induced by stress is always the same: IBS, headache, low back pain, etc., so that you can use the physical symptom as a signal to you that you are under stress, and try to abort a full-blown attack of pain by minimizing or avoiding the stress. I am most concerned that the brain will get so used to pain that the pain circuit becomes self-perpetuating, as it can in post-herpetic neuralgia. It is more difficult to reduce or eliminate the stress when the stress is due to a dysfunctional relationship. I look for situations that can produce stress in my patients' minds by asking a few simple questions at their first exam and at annual physicals: what do you do that you most dislike doing? when was your last vacation? do you look forward to coming home at the end of the day? do you look forward to going to work?

I have found that a frequent cause of stress is due to living with a person with a character disorder, whose view of the world is impervious to logic, manners, or sensitivity. Often the patient is unaware of how permanent the dysfunctional situation is. The most severe case of this is in the borderline personality. I recall that psychiatry attendings would comment that they would never allow first year residents to treat borderlines, because they invariably sabotage their treatment, which can trigger unresolved anger in the therapist.

As I was preparing this blog, I received an e-mail which described what it was like to live with a borderline personality. I think the writer described the household situation extremely well. I am therefore posting the link here, in the hopes that you all will click on it:

The title of the article is "Walking on Eggshells", and this phrase is a perfect analogy to what life is like when you live with a person with a borderline personality disorder. (I personally think that these borderlines have a tremendous amount of unrecognized anger, but that is for another blog.)

Monday, October 5, 2009

Screening Tests---Part I

This blog is the first of a staggered series in which screening tests will be discussed and analyzed. By a screening test, I mean a test done as part of a routine physical, perhaps suggested by the medical history. I define a useful screening test as one which detects a disease at such a time that medical treatment can cure the disease or prolong life.
Since one problem with screening tests is the occurrence of false positives, then either the screening test must be "very" sensitive (few false positives) or else the disease being tested for must have a "high" incidence. The definition of "very" and "high" depends on the disease, the doctor, the patient, the community, and the circumstances. We also would like the sensitive screening test to be able to be supplemented with a more precise test of high specificity (few false negatives). At the present,for instance,the Western Blot is the gold standard for the second test with both Lyme disease, and HIV/AIDS. (I should note parenthetically that the Blood Banks prefer tests of low sensitivity, since they do not want to risk transfusing infected blood.)
There are four reasons for doing screening tests (and again, I want to emphasize that I am NOT talking about diagnostic tests, where a disease is suspected).The reasons are:
a) To benefit the patient (obvious)
b) To benefit the patient's family (but then the patient must give informed consent, since the test will not benefit him directly)
c) To benefit society (again, the patient's consent is required)
d) The patient or a family member suggests it. In this case, it is vital to remember that NO DOCTOR EVER GOT SUED FOR DOING A TEST, but only for not doing one. It does no good to tell a jury that the odds of Leprosy were 1:10,000. If the patient asks for the nine-banded armadillo test, and you refuse, and the patient comes down with leprosy, then the jury will just see that the patient asked for a test, you refused, and he suffered preventable injury as a result.
I am not going to discuss the screening tests to be done on a female who plans to become pregnant, or who is pregnant, or a patient about to be immunosuppressed by steroids,or anti-cancer drugs, or organ transplant treatment, or asplenic patients, etc.
It goes without saying that before any test is done on a patient, he/she should know which tests you are ordering---kidney tests, liver tests, thyroid tests, etc.

Blood pressure---we know that treating high blood pressure (especially systolic) will help prevent strokes. Oddly enough, although there is an entity called hypertensive heart disease, there is not good data to show that lowering blood pressure prevents this.

CBC---detecting anemia leads to a search for the cause and treatment of both the anemia and the underlying cause. Detecting a persistently elevated or low white blood count or platelet count will generally lead to a bone marrow biopsy, which may yield a treatable disease on analysis.

BUN/Creat---elevated kidney tests leads to treatment of early kidney failure.

LFT---elevated liver tests and/or GGTP leads to testing for hepatitis, fatty infiltration of the liver, alcoholism, etc.

Uric acid---elevated in chronic alcoholism, and a warning of risk for gout.

PPD---for certain patients, a skin test for tuberculosis is appropriate.

VDRL---ditto for a screen for syphilis. Caveat: both syphilis and Lyme disease are caused by a spirochete, and Lyme disease is a common cause of a false positive syphilis test. The reflex test for syphilis is FTA-ABS, which turns positive when a patient has syphilis, and almost never reverts to negative. Second caveat: when doing a spinal tap for neurosyphilis, only do the VDRL; nobody knows what to do with a positive CSF FTA.

Stool for blood--- screens for CA of colon, but the most common cause of a positive stool for blood lies in esophageal or gastric irritation/ulceration. Over the age of 65, the cause for the positive stool is not found in 10% of the patients, even when angiodysplasia of the cecum is carefully looked for.

TFT---thyroid abnormality is very common in women, especially after pregnancy, and seems to follow in the female line.

25-OH Vitamin D---low values can contribute to osteoporosis, so females with osteoporosis (and probably those approaching menopause) should be tested.

PSA---as of now, there is no good evidence that treating prostate cancer saves lives, so this test is of doubtful use. Different medical groups recommend for (CA society, urologists) or against (Canadian Health Task Force, USPHS) it.

Fe/TIBC/ferritin---I test all menstruating females and vegetarians. ? if you should test everyone else once to screen for hemochromatosis.

Vitamin B-12----test vegetarians, Nordics, Latin Americans, and patients over 50.

Cholesterol/triglycerides/LDL----screen, and then discuss results with patient. there are no hard and fast rules for treatment, or, if there are, they change every three years. More about cholesterol in a future blog.

U/A----tremendous screen for many diseases. You can even use it to screen for diabetes.

Glucose---Enormous argument in literature about how intensively to treat diabetes, and the benefits thereof, but a patient with diabetes needs other special medical treatment, and needs to be made aware if it. Back it up with HgbA1C.

HgbA1C---probably the most efficient screen for diabetes.

CRP---as a complement to cholesterol panel---every other year a paper says that screening is beneficial, or is not beneficial. Flip a coin. Patients expect it now, so I do it.

ESR---a useful screen for inflammatory processes, e.g. bacterial infection, TB, CA, certain arthritidies. Very useful in the ER, since a normal ESR (and it does rise with age---10-20 for men, 10-30 for women, and then maybe 5 points every 10 years) raises the probability of a viral process. Over 100 means a serious process is going on.

Testosterone---serum and free---baseline it at age 50. Both men and women may need supplementation as they get older.

Blood test for pregnancy---on all hospital admissions and ER visits.

HIV/AIDS--screen and Western Blot follow-up on positives. For appropriate patients. Remember that there are reports in the literature that the Flu Vaccine can lead to a false positive screening test for HIV for 4 to 8 weeks after vaccination, but not a false positive Western Blot. I once had five fraternity brothers in December come to me, all of whom gave blood in a college blood drive, and all of whom had false positive HIV screens one month after flu vaccine.

Lyme disease---only when I suspect it, or the patient is unusually insistent. Reasoning is too involved to go into here.

Tissue Transglutaminase IgA (celiac screen) and lactose intolerance screen---really should be part of a work-up for every patient with Irritable Bowel Syndrome, as well as a stool for Giardia antigen. (I know, this is diagnostic, not screening per se, but no logical system is totally complete, according to Godel.)

Hg+---If a patient eats pelagic fish three or more times a week, I check the blood mercury level.

Blood type---useless. The hospital would never believe the patient's memory, and would re-type and cross-match before transfusion.

Sometimes a patient comes in who has had unprotected sex, or who is about to start with a new sexual partner, and wants to be tested for "everything". I always tell them to help their country by donating a unit of blood, and the blood bank will routinely screen for "everything" (e.g. Hepatitis A,B, and C, syphilis, AIDS, West Nile Virus, etc.) I also comment that the next insurance company that requests a copy of his/her medical records may wonder why tests for "everything" were done, and raise the premium.

I have deliberately not mentioned mammograms, EKG's, stress tests, Ca++/CT scans, USG of carotid arteries, etc. They will be discussed in a future blog.

If you know of a blood test you use for your screening that I have not mentioned, please e-mail it to me as a blog comment, so everyone can see it when it is posted. Feel free to use a pseudonmyn if you prefer. I promise to comment on all posts.

Wednesday, September 16, 2009

The Obesity "Epidemic" and Nutrition

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.

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!

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.

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".

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 "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 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.

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?

Thursday, June 25, 2009


I expect I will receive more e-mails from this blog than from all the others together. Nutrition is fundamental, not only to life, but, as per Freud, the first stage of mental development. Our first sensation of love, warmth, and security was at our mother's breast. Because it has such a fundamental connection with our psyche, this is probably why we have more and different personal habits and religious taboos over food than any other aspect of our lives. We also have magical thinking about "good" foods and "bad" foods.

Mother's milk is heavy in sugar and fat, which is probably why we all love ice cream. (Separate thought:I prefer chocolate to vanilla, and I often wonder if people who prefer vanilla taste the chocolate in the same way that I do.) Fat is appreciated because it adds flavor and substance to food It also markedly slows stomach emptying, so we feel fuller for a longer period of time if the meal contains fat. Some of my patients equate "low fat" to "low taste" especially low-fat mayonnaise.

There are eight essential amino acids, which are called "essential" because every animal cell needs all eight to make proteins,and cannot synthesize them. Vegetables have at most seven of these amino acids, which is why a complete vegetable dish contains rice + beans, or corn + peas (aka the American Indians' succotash); that is, at least two vegetables.

There are also two or three essential fatty acids (depending on your definition), and again any animal cell contains all of them, which again is why you need at least two vegetables if no meat is eaten. This is probably why no one looks truly happy in a vegetarian restaurant, because they sense they are missing something (or subconsciously are aware of the fact that tofu lowers men's sperm count because soy is a phytoestrogen). On the other hand, everyone is all smiles in a steak restaurant.

Everyone should be aware that Vitamin B-12 is necessary for an animal cell to synthesize animal DNA, but not vegetable DNA. Vegetables contain no vitamin B-12 whatsoever. Therefore, if you eat neither meat nor fish nor eggs, you will eventually die from pernicious anemia. It as also a curious fact that no one is literally addicted to eating meat, or can achieve an altered mental state by eating meat (licking Colorado toads being a notable exception). All the addicting or mind-bending foods are vegetables, with their totally different chemistry: nicotine, alcohol, caffeine, opium, marijuana ,peyote, "magic" mushrooms, etc. In fact, if you kill an animal or fish at random and eat it, the odds are that it will agree with you. But if you eat a random vegetable or berry, there are good odds that it will make you ill or kill you (mushrooms, choke cherries, oleander, foxglove, mistletoe, rhubarb, yew, manicheel), not to mention the severe contact allergies from poison ivy, oak and sumac.

As for cholesterol, it is an essential component of the membrane of every animal cell, through which all nutrients pass. (Plant cells have a cell wall outside the cell membrane, which contains no cholesterol whatsoever.) So when we chemically lower cholesterol, we lower a constituent of the membrane of every cell of the body. This in turn alters trans-membrane potentials, ion fluxes, molecular transport, and sensitivity to neural stimulation. This may explain why some patients develop leg cramps (muscle cell irritability and sensitivity), or altered liver tests (? inflammation of the cell membrane and enzyme leakage), and sometimes just don't "feel right"(altered electric potentials in brain cells). If cholesterol is lowered by weight loss, the body responds as a whole, and therefore there are no such side effects. When Wise's Potato Chips tried to advertise their chips as "having absolutely no cholesterol", which is a literal scientific fact, the FTC pulled their add, claiming that patients would confuse "no cholesterol" with "no fat".

We don't even know how many meals we should eat daily: one, two, three,or six. We don't know the proper time of day to eat the largest meal, even though we know that all our minerals and hormones have a diurnal cycle (cortisol is highest in the AM, serum iron in the PM, etc.). We don't know if the fact semi-starved rats exceed their natural life span applies also to humans. We don't understand why, if a normal BMI is optimal for health, how is it that people with an elevated BMI survive heart attacks better.

As for vitamins, a vitamin is a chemical which, if you do not ingest, you get ill and may die (scurvy, beri-beri, pernicious anemia, etc.), because your body needs it as a co-factor for essential enzymes, and cannot synthesize it.A,D,E, and K are fat-soluble vitamins, but C and all the B's will be excreted in your urine, if ingested in excess. Oddly enough, an excess of daily vitamin B-6 causes neurological symptoms, just as a deficiency of the same vitamin does. (cf article in NEJM, more than 10 years ago; research done at Albert Einstein Hospital)Since it is a pure chemical, your body cannot tell the difference between "natural" and synthesized vitamins. Since the FDA does not regulate or supervise vitamin manufacture, there is also absolutely no guarantee as to if a capsule labeled "400 U of Vitamin E" contains 0, 400, or 1200. And the idea that too much of a vitamin cannot hurt you never applies to fat-soluble vitamins, which are stored in your body. We have already seen studies of the coronary artery dangers of too much daily Vitamin E.

Finally, all the suggestions about "healthy" diets are based on retrospective and/or epidemiological studies, which all fail to remember that correlation does not mean causation. The only food intervention shown to lengthen life, mostly by preventing heart attacks, is alcohol. I have read studies with beer, scotch slivovitz, red wine, etc. It is the C2H5OH molecule that saves you. There was an article as far back in 1974 in JAMA, in which comparative autopsies showed that moderate male drinkers had larger diameter (i.e. wider and less clogged) coronary arteries than age and weight matched controls (non-smokers only). Every time a forward study (low fat, beta-carotene, selenium) has been done, the results have been nil, or even negative (especially with vitamin E).

The overall problem is that no prospective food study has ever been done with adult humans, so all are beliefs are just that; beliefs without a sound foundation in experimental fact.

Friday, June 19, 2009

Fatigue, Insomnia, Sleep Apnea, and Hypnotics

There are many beliefs about sleep, but not much verified knowledge. For instance, it is not true that one hour of sleep before midnight is worth two after.
It is true that a lot of fatigue is due to mental processes, rather than physical fatigue.
We are probably all underslept, since most adults have trouble getting "catch-up" sleep. When you were in high school or college, you could probably make up for the sleep deficit you incurred during the week by sleeping till noon or later on weekends. As we get older, we seem to lose this ability, while at the same time we awaken at night more frequently.
As a physician, I observe that my chronically underslept patients are more irritable, with degraded ego functions as well as more muscular pains and aches, and have some degree of depression. They also seem to function closer to baseline when doing well-known and repetitive tasks, but have trouble concentrating on crossword puzzles and the like. (Or as we used to say as interns, we could run a cardiac arrest with no sleep, but it was difficult to do an intake interview.)
Another danger of being underslept is falling asleep behind the wheel of your car, or making other errors. The government recognizes this by putting a limit on the number of consecutive hours a truck driver can drive, or a pilot can fly. The number of hours a medical intern can be on call at a hospital is also limited, but strangely enough a 60-year-old medical attending has no limits placed on his hours. In fact, if a patient called me at 10 at night and I told him/her that instead of getting my advice, because I had been awake for 16 hours ,they should go to the nearest emergency room where they could be seen by a well-rested doctor, they would be very upset.
Since lack of sleep is so corrosive and destructive, both mentally and physically, I see nothing wrong with the use of sleeping pills. I would prefer the use of sleeping pills to a patient falling asleep at the wheel of his/her car. Some patients are concerned about becoming dependent on sleeping pills, but I believe that many adults have "irritable sleep syndrome" and need some chemical help to get sufficient sleep.
Sleep apnea studies are in a curious position. They are reviewed by psychiatrists, neurologists, pulmonologists, and ENT doctors. The definition of sleep apnea is somewhat imprecise. (If you are not an overweight male who snores, the chance of your having sleep apnea is greatly lessened.) We all have apneas, generally defined as cessation of breathing for 10 or more seconds. The diagnosis is firmer if the oxygen saturation drops below 85% at the same time. There are also hypopneas, which are episodes of underbreathing without complete cessation. We have also known for a long time that everyone drops oxygen saturation during sleep, which is why we put nasal oxygen on all heart attack patients. Oxygen desaturation is a potent pulmonary artery vasoconstrictor, which overloads the right ventricle, which can tolerate volume overload better than pressure overload.
Since the number of apneas increases with age, the definition of sleep apnea depends in part on a patient's age. My two additional criticisms of all sleep apnea studies are:(1) no one asks the patient (usually a male) if he would be willing to wear a positive pressure sleep mask for the rest of his life, and (2) it would be more efficient to put a patient suspected of sleep apnea on a CPAP and then a BIPAP mask to see if they felt less tired, etc. the next day, but insurance and Medicare only pay for the mask if you first diagnose sleep apnea. In other words, unlike putting a patient on an antidepressant, CPAP cannot be used as a diagnostic/therapeutic treatment and test.
Before I send a chronically fatigued patient for a sleep apnea test, I try one month of Prozac or other SSRI, then one month on Effexor XR or Wellbutrin SR, and finally one month on Provigil, which is FDA approved for CNS stimulation of patients with sleep-shift disorder or chronic insomnia/fatigue, and seems to have no ischemic cardiac effects.

Sunday, June 7, 2009

Generic Drugs, Brand Names, and Tier I Drugs

Most people think that generic drugs always work, that all Tier I drugs of an HMO are pharmacologically equivalent,and that generic drugs are cheaper. Only the last statement is true, and the pharmacies also love generics because they have higher profit margins. (Brand name $80, charge to you $100, profit$20; generic $20, price to you $50, profit $30.) However, the generics do not always work as well as brand names, because there can be different "inert" compounds added to the parent drug to make the tablet. The FDA requires that the blood levels of the generic be the same as the brand name (+/- 10%), but only the brand name drug has been tested for clinical efficiency. There is no way of comparing tissue levels of the brand name drug to the generic, and this is especially important with drugs that act on the central nervous system (tranquilizers, sleeping pills, pain pills) after crossing the blood-brain barrier. Again, no generic is tested for clinical efficiency against the brand name drug.

The blood-brain barrier is nature's way of protecting the brain from noxious compounds that are dissolved in your blood. A drug has to cross the blood-brain barrier (through capillary walls) to reach the brain and achieve its effect. Whether a particular drug can do this is usually only determined by trial and error. For instance, penicillin readily crosses the blood-brain barrier, and is therefore extremely active in treating meningitis. Keflex, a cephalosporin, cannot cross the blood-brain barrier, and is therefore useless in treating meningitis, although it generally can treat any soft tissue infection or lung infection that penicillin does.
Within a particular class of drugs (e.g. beta-blockers) if a drug is lipophilic, this affects the ability of the brain to absorb the drug once it gets there. Marijuana is extremely lipophilic, so it is released very slowly from fatty tissue in the brain, and your urine can test positive for at least two weeks after inhaling it. There can also be subtle differences within a class of drugs: Coreg is the only beta-blocker shown to reduce microalbinuria in diabetic patients.

When it comes to other groups of drugs, there is wide human variation in responsiveness, since we are all biochemically different. Claritin and Zyrtec are over-the-counter (OTC) anti-histamines, and sometimes one will work on a patient's allergies, and sometimes the other, since they are chemically very different. Allegra is a prescription antihistamine, which works better in many patients, but unlike Medicare Part D, most HMO's ask me to certify that both OTC drugs did not work before they will pay for Allegra. The same problem arises is proton-pump inhibitors (PPI's) for acid reflux. The HMO's want me to try the patient on OTC Prilosec before paying for Prevacid, Aciphex or Nexium. Furthermore, if I want to prescribe Nexium at a double dose to suppress acid symptoms, which some patients need, I generally have to send them to a GI doctor to have the payment okayed. Remember, if you are forced to buy an OTC drug, your co-pay is 100%, and the cost to your HMO is $0.

The worst scenario is in CNS-acting drugs. In my experience, generic Ativan works less than 10% of the time, so if a patient does not respond to generic Ativan, I am not sure of the cause. I also have found that generic Prozac works less than 50% of the time, and there are treatment problems with generic Wellbutrin. If a patient responds well to the anti-depressant Lexapro, the HMO generally asks me to switch the patient to a generic form of Celexa, even though they are chemically totally different drugs. I have also found that the beta-blocker Nadolol is excellent prophylaxis against migraines, as is Inderal LA, but since only Inderal (which requires dosing 4 x a day) is available in a generic form, the LA Rx. is generally not paid for.

In your own case, I am certain that aspirin, Advil, and Alleve all work differently in you, even though they all are NSAID's (anti-inflammatories).

Viagra, Levitra, and Cialis all work to treat erectile dysfunction, but sometimes one drug will work, and sometimes another.

The main point is that drugs with the same physiological endpoint in the human body have different chemical structures, and they cannot all work equally well.