Tuesday, August 28, 2012

Are Medical Tests Overused?

     There have recently been a slew of articles about the overuse of  medical testing. Special attention has been directed towards radiological studies (including in-office ultrasound) and OTC testing kits sold to consumers. However, none of these articles takes the patients' views and wishes into account.

     One philosophical question arises when the patient asks for a test, blood or radiological, which the physician knows will be negative. Is there anything ethically wrong in ordering this test to give the patient peace of mind, assuming that the physician explains the probability of a false negative test and the problems and possible morbidity that can follow from acting on a false positive test? I think not. In some cases a negative test (e.g. a cardiac stress test in a patient suffering chest pain from a panic attack) will permit the physician to direct the patient's attention to the underlying problem. This is especially true in irritable bowel syndrome, where it has been my experience that it is very difficult for the patient to agree that the symptoms are purely functional.

     The thought of some diseases strikes such terror in patients' minds that they insist on screening tests, even though no study has shown that a positive test leads to a clinical intervention that either saves or prolongs life. Screening for ovarian cancer with the CA-125 blood test plus a vaginal ultrasound immediately comes to mind. OTOH, abdominal aortic aneurysms do enlarge, rupture and kill the patient (as in the case of Albert Einstein who refused surgical treatment). Medicare will pay for one abdominal USG in a patient's lifetime if the first test is normal. "Cost effectiveness" would limit this study to the highest risk group: male smokers over 65, especially if they have hypertension. However, although the group  incidence published in an article in Lancet was 11%, I am certain that if a patient was told that he/she had a 5% chance of having a possibly fatal condition, then they would want the ultrasound.

     We do know how to treat many infectious diseases, so screening for tuberculosis, syphilis, AIDS, hepatitis B and Hepatitis C, all of which can be fatal if untreated, would seem to make sense, although there are no studies as to how often these tests should be offered if negative. One would think that screening for chronic kidney disease, which problem can lead to dialysis, would also make sense, but in the latest issue of the Annals of Internal Medicine the United States Public Service Task Force has come out against this. We can't even show that screening for diabetes saves lives, but we are on firm ground when we state that treating hypertension prevents strokes. Oddly enough, although untreated high blood pressure can cause heart failure, there is no clinical study that demonstrates that treating hypertension prevents heart failure. And although "everyone" agrees that a chest Xray is not needed in a non-smoker with no pulmonary symptoms, many anesthesiologists insist on a chest Xray before surgery if general anesthesia is to be used.

     Every female of child-bearing age who comes to the emergency room is given a urine test for pregnancy. Should the same be done at every visit to a physician's office? Or before any Xray, including dental ones?
The prevalence of arteriosclerotic coronary artery disease at autopsy in 40 year old men is 10%. Should every man of this age have a stress-echo cardiogram as well as a thallium stress test? What about smokers and insulin-dependent diabetics and morbidly obese patients at age 30?

     It makes clinical sense to do a complete blood count, because anemia can be treated and its cause found, and many leukemias can be cured. Similarly, deficiencies of vitamin B12, vitamin D and iron  can be tested for and treated, as can elevated mercury, uric acid, and  calcium levels as well as  low magnesium levels. Whether patients who grew up in a country where parasites are endemic or who visited such countries should be screened for parasites has never been properly addressed, and such patients are usually only tested when they evince symptoms. I assume the physician would obtain the patient's permission before testing for such drugs as cocaine, amphetamines, opiates and benzodiazapenes. Another debated practice is that of obtaining a baseline EKG at the first office visit: no patient ever has a completely "normal" EKG, and it can make clinical sense to know what the EKG looks like before the patient's first visit to the ER with chest pain. And annual EKG's can detect the occurrence of a silent MI, but no studies have, to my knowledge, addressed the utility of this practice, although an unchanged EKG does bring a degree of mental comfort to the patient.

     I have saved the thorniest problem for last. There are more and more OTC tests sold for patients to test themselves not only for a particular disease, but for risk factors for the disease. This is a real problem if the disease in question has no satisfactory treatment. And unless the false positive and false negative percentages are explicitly stated on the package along with the prevalence of the disease in the patient's population, he may well be needlessly worried or reassured. Clearly these tests will continue to be sold, but the patient should be firmly instructed by the pharmacist not to jump to any conclusions before discussing the results with his/her physician.

     Let me close with an anecdote from my practice. When you donate blood, the Red Cross routinely screens for AIDS among other diseases, and confirms a positive screen with a Western Blot test which is the  "gold standard". The WB is not used for screening because it is more expensive and labor intensive, much as syphilis is screened for with the VDRL and confirmed with the FTA. In the past, the flu virus for the vaccine was grown in human cell culture, and because of cross-viral antibodies, patients who received the flu vaccine would test positive for the AIDS virus on the screening test but negative on the Western Blot; this false positive existed for three to six weeks after the flu vaccine. I received a panicked phone call one December from a patient of mine who was a fraternity member at a Florida university where the fraternities were competing with one another in a blood bank drive. He told me that he and 25% of his brothers had tested positive on the screen, and what were they to do? Thankfully I was able to reassure him about the false positive once I had learned that they had all gotten the flu vaccine the previous week, and could tell him to wait for the Western Blot result. Of course, he could never again give blood, because although the Red Cross would officially tell them the Western Blot was negative and that they didn't have AIDS, they still would not risk using the blood.


Wednesday, August 22, 2012

Radiation and Radiation Sickness Part II

     There are and will continue to be articles about the dangers of radiation, so I thought a few additional remarks about the basic physics of radiation and its effect on human tissue are in order. I will restrict my discussion to external radiation that occurs in the form of gamma rays, aka Xrays, and ignore alpha rays (helium nuclei), beta rays (electrons) and neutrons. I will just mention that the shorter the wavelength the higher the energy of the incident radiation, so that infrared rays have less energy than do  ultraviolet rays, which is why UV rays can penetrate the skin more deeply and thereby create Vitamin D.

     Xrays are a form of energy, travelling at the speed of light because they are composed of photons. We are exposed to Xrays from the earth's natural radioactivity, from medical Xrays, and from cosmic rays. Xray energy is often defined as the ability to ionize a column of air, but this definition from physics is not a useful definition for medical purposes. Instead we have the "rad" and the "rem", although "roentgen","curie", "gray" and "sievert" are in use in some places.

     The rad is a unit of absorbed radiation dose, in other words it is the dose of Xradiation that is needed for a certain sample (animal, vegetable or mineral) to absorb a certain fixed amount of energy per gram of material. It is thus clear that the rad depends on the wavelength, i.e. the energy of the incident radiation as well as the absorptive properties of the material. The rem, or "roentgen equivalent man" is a measure of the biological effects of the absorbed radiation, which is clearly not only dependent on the wavelength of the incident radiation but also on the tissue (brain, bone marrow, thyroid gland, etc.) that is absorbing the radiation. I should here mention that different countries and different international organizations have different conversion factors from rad to rem. It is also obvious that it is impossible to determine the precise rem value of incident radiation on man because we have no way to examine living human tissue after exposure to radiation to determine its biological effect, so the conversion factors are "guesstimates".

     The idea that the risk of cancer increases linearly with Xray dose rate is a consensus decided upon by international bodies, and has no demonstrated basis in clinical fact. The risk is really stochastic rather than deterministic. It is also stated, without clinical evidence, that the risk is higher for children and fetuses than for adults, and higher for women than for men. The international recommended "safe" exposure dose from medical Xrays and other sources over and above environmental exposure is 0.1 rem/year, but this is also a consensus number with no demonstrated basis in fact. For comparison, because of their higher altitude and therefore less shielding by the atmosphere, residents of Denver are exposed to an additional 0.3 rem/year, and airplane crews are exposed to between 0.5 rem/year to 1.0 rem/year, depending on their routes. BTW, the International Commission on Radiological Protection recommends evacuation of any area where the excess dose of radiation is greater than 0.1 rem/year, even though residents of Denver have a lower cancer incidence than do residents of the flatlands. I also have found no published clinical studies demonstrating that women who have mammograms have a higher incidence of breast cancer than women who never had a mammogram.

     Addenda: All granite contains some uranium and therefore exhibits low-level radioactivity. We have no good model as to whether or not Xradiation is teratogenic. The International Committee for Weights and Measures does not accept the rad as a unit of radiation exposure, but this unit is widely used in the U.S. The lethal dose of radiation depends upon the time frame over which it is delivered, which is why radiation therapy for cancer is spread out over weeks. In general, a dose of 1,000 rads delivered over a few hours will be lethal, and doses of 100 to 1,000 rads over a few hours will cause acute radiation sickness, with the probability of dying being greater of course at the higher dose.



Monday, August 20, 2012

The Joys of Caffeine

     Vegetables are a wonderful and mysterious kingdom, inhabited by an alien chemistry that has varied effects on our animal bodies. Many vegetable cells contain chlorophyll, while animal red blood cells have hemoglobin. Vegetable cells have both a cell wall and a membrane, while animal cells have only a membrane, and since humans cannot digest cell walls, vegetables make wonderful roughage. OTOH, no vegetable cells contain Vitamin B12, which is an essential cofactor in the production of DNA in animal cells. And if you eat a random animal, the odds are that you will not get sick, while eating a random vegetable is fraught with dangerous possibilities. Some vegetables are processed to make useful medicines: opium, marijuana, alcohol,  aspirin, chocolate, tea, coffee, artemisin, quinine, taxol, digitalis, and some contain dangerous poisons: opium, alcohol, digitalis, mistletoe, oleander, some mushrooms, nightshade, tobacco, LSD, nutmeg, peyote, cocaine, jimson weed, manicheel. As far as I am aware, the only addicting foods that can cause dependency and lead to severe withdrawal effects are from the vegetable kingdom (e.g. alcohol and opium/heroin). As an example of how unknowing we can be, when Bayer patented heroin, aka diacetyl morphine, it was touted and sold OTC as non-addictive morphine (and at the same time, in the 1900's, aspirin was available by Rx only).

     The benefits of coffee are many and varied, which is not to say that too much cannot produce unwanted and unwelcome side effects. Some of the benefits have been demonstrated in humans, while others have only helped laboratory rats. Some people will have a reaction similar to drinking coffee when they ingest chocolate, because theobromine is a xanthine, as is caffeine. PubMed is a website operated by the National Library of Medicine, and if you have questions about any of the studies I quote in abbreviated form, you can find an abstract of the pertinent clinical article and a reference to the whole article at this site.

     The following is a list of some of the reputed benefits of coffee (caffeine) ingestion. I can vouch for some of them, because we all took No-Doz in college and medical school when pulling an all-nighter studying for a test, and one No-Doz has the caffeine equivalent of two cups of coffee. And whether it worked or not, studies have shown that if you think you are drinking coffee, you show some of the benefits. I should mention that the caffeine in coffee starts to be absorbed 15 minutes after ingestion, reaches a peak blood level after 45 minutes, and its half-life is 6 hours. Ingestion of the antibiotic Levaquin or the antidepressant Luvox prolongs its half-life and significantly increases its peak level by competitive inhibition of the degradation of caffeine by your liver.

     1) Reduces the chance of developing adult-onset diabetes (greater effect in women than men)

     2) Reduces the appetite

     3) May reduce your chance of developing Parkinson's Disease. The confounding factor here is that smoking definitely reduces your chance of developing Parkinson's Disease due to the nicotine receptors in the brain, and more coffee drinkers smoke than do non-coffee drinkers.

     4) Improves motor skills in patients with Parkinson's Disease.

     5) Enhances the analgesic effect of all pain medicines.

     6) Reduces depression, and enhances a feeling of well-being

     7) May help dilate the bronchioles in asthmatic patients.

     8) Improves the on-the-job efficiency of shift workers who have staggered sleep schedules.

     9) Decreases mental fatigue from sleepiness.

     10) Extends the time to physical fatigue from exercise.

     11) Instant memory ability peaks in the morning and slowly decreases throughout the day. Morning coffee blocks this effect.

     12) Enables functioning at a higher work load than usual.

     13) Some studies show a quickening of brain cell synapse time, mostly in rats.

     14) Improves eye-hand coordination.

     15) Decreases the risk of some cancers.


Thursday, August 9, 2012

Diabetes Part II

     There is an excellent review of the diagnosis of diabetes in the current issue of the New England Journal of Medicine (Vol 367, pp 542-550, Aug. 9, 2012) so I thought I would summarize it here and add a few relevant. clinical facts as well.

     First, except for pregnant women, there is no good clinical evidence that screening and early treatment of "pre-diabetes" improves any clinical outcome. Two different tests are used to screen for diabetes and prediabetes: the fasting (8 hours) glucose and the glycohemoglobin (HgbA1C). Both the American Diabetes Association and the World Health Organization recommend confirming one test with another. The two-hour glucose tolerance test is generally not recommended except for pregnant women  because its reproducibility is poor and its variance is large.

     Once diabetes is diagnosed, stringent control of the glucose helps prevent the development of diabetic retinopathy (eye disease). Both the ADA and the WHO agree that a fasting glucose of 126 or greater or a glycohemoglobin of 6.5 or greater signifies diabetes. Both also characterize a fasting glucose of 100-125 as "pre-diabetes". The ADA calls a glycohemoglobin of 5.7-6.4  pre-diabetes, but the WHO does not, even though the test for HgbA1C is now standardized throughout the world.

     The only clinically proven sustained method for overweight diabetics to lose weight and reverse their diabetes is by bariatric surgery---i.e. stomach banding or partial surgical bypass.

     A retrospective clinical study published this week in JAMA showed that patients who are overweight when diagnosed with diabetes have a longer lifespan than patients who have normal weight when diagnosed.

     There is no general agreement as to what age to start screening for diabetes or how often.

     There are clinical conditions that can cause a falsely high or low HgbA1C. There also are medical conditions and drugs that can elevate or lower the fasting glucose.

     Since diabetes is synergistic with other causes of coronary artery disease, many physicians would screen patients who have other risk factor(s) for heart disease: elevated cholesterol, high blood pressure, etc.

     Blood pressure, cholesterol and fasting glucose often  increase with age, and no one has yet shown if treatment of pre-diabetes really prevents diabetes (but the diagnosis may raise your life insurance premium).

     Eating sugar will not make you diabetic unless you also are gaining weight.




Sunday, August 5, 2012

Do Xrays and Cosmic Rays Cause Cancer?

     I will review this topic wearing both my hats as a former physics professor (who also did research on the effect of ionizing radiation on tissue) and a former medical professor. I am not here going to criticize the statistical methods used to draw conclusions (e.g. in "Projected Cancer Risks From CT Scans..." Arch. Int. Med. Vol 169, pp 2071-2077, 2009.) Rather I will discuss the medical evidence for the carcinogenic effects of radiation and see if there is any valid scientific evidence that enables us to extrapolate these results downward so as to predict the possibly carcinogenic effect of  the Xrays we are exposed to by CT scans and cosmic rays. I understand that this is a "hot" topic (no pun intended), and as usual in such cases, the heat of an issue tends to be in inverse proportion to the light that experimental facts shed on the issue. As Voltaire famously mentioned, no one is burned at the state because people disagree with the statement that 7 x 8 = 56, although Giordano Bruno was burned at the stake for maintaining that the earth was not the center of the universe.

     I am going to restrict my discussion to adults. The different units of radiation measure will also not concern us directly, because we have no way of accurately determining how much of a given wavelength of Xradiation a body organ will absorb, let alone the DNA damage it will cause. All the hard data we have really comes from the development of cancers in the survivors of the two atomic bombs dropped on Japan, and we begin by assuming that the response of Caucasian and black tissue to radiation is the same as the response of Japanese tissue, insofar as its carcinogenicity is concerned, an assumption that is, thank God, not borne out by any accidents of nature or man. (Chernobyl is a special case, since the doses there were not comparable to those of diagnostic radiation, and a lot of the radiation damage and cancer were caused by ingestion of radioactive isotopes.)

     The question to which there has been no clinical answer is whether or not  the risk from the radiation released by an atomic bomb can be extrapolated down in a linear fashion to medical Xrays or our daily bombardment by cosmic rays. Is there a threshold, a level of radiation below which Xrays  will not induce cancer in humans? Is the only "safe" dose (i.e. non cancer-causing) of Xrays no  Xrays? This question has never been answered by any clinical study, and all the assumptions and estimations of the dangers of diagnostic Xrays are based upon the unproven assumption that there is no such threshold, and that even one photon in the Xray energy range can cause cancer in a human cell.This assumption   completely ignores the reparative capabilities of DNA. We also have never answered the question of whether or not the risk from successive Xrays is cumulative, so that we can add the putative carcinogenic risk of one Xray to the next one. Somehow this is counterintuitive, unless we are saying that 10 mammograms in 10 days  are no more dangerous than 10 mammograms each spaced a year after the previous one. This would seem to say that there is no DNA repair process for Xray damage, even though man lives his whole life exposed to very high energy cosmic rays.

     I would argue that there must be a threshold dose below which Xrays do not cause cancer, and therefore linear extrapolation downward from the cancer incidence in A-bomb survivors is invalid. We know that we are constantly bombarded by cosmic Xrays which have energies thousands of times higher than you are exposed to by an Xray machine. Note that I said energy, not intensity. (Intensity is measured in photons  per square centimeter per second.)  We are partially shielded from cosmic radiation by the ozone layer and by the earth's atmosphere. People living in Denver are a mile higher than denizens of New York City, and therefore have one mile less of atmospheric shielding. Nevertheless, the cancer rate in Denver is identical to that in the lowlands. Therefore the increased cosmic Xradiation that Denverians receive is not enough to measurably affect their cancer rate. It therefore follows that there is a threshold, and that we have no idea of what a safe dose of radiation is, except that "too much" can damage tissues directly by overheating and frying them.

     I can also adduce  evidence  that the cell damage from Xrays is cumulative. It is well known that as you get older, the incidence of cancer increases. But as you get older, you have been exposed to more and more cosmic Xrays originating from deep in the universe.  Is it possible that cosmic Xrays are the main cause of the increase in cancer with aging, in part by damaging the nuclei of cells in our body  and in part by damaging our immune system? For that matter, we know that the coronary arteries under the left breast have in increased rate of calcification if the breast is radiated for breast cancer. Could the exposure of all our arteries to the continuous rain of cosmic Xrays also be the explanation for the increased hardening of the arteries with age? Could this also explain the loss of brain cells with aging, and possibly contribute to Alzheimer's disease in that amyloid plaques are the body's attempt to heal radiation damage to the brain by creating scar tissue?
There has been no satisfactory explanation of why our cancer incidence increases with age, except to note that our immune system also weakens with age. But correlation is not causation, and, as I suggested above, we are then left with the question of why the immune system weakens with age. Since we know that radiation can damage the human immune system, then the continuous cosmic radiation is as good an explanation as any. It may even explain why few if any humans live beyond 120 years: the shortening of telomeres with age may also be a consequence of cosmic radiation bombardment, and we can never test this hypothesis because the energy of cosmic radiation is thousands of times higher than xrays we generate here on earth.

     In summary, there is no clinical evidence one way or another that our estimates of a "safe" dose of radiation are correct, and we have no way of determining the life-long effect on us of our bombardment by ultra high energy cosmic Xrays.