Friday, December 28, 2012

How to Lose Weight

     There has been a recent upsurge in articles advising people how to lose weight "successfully", i.e. to lose weight and keep it off. There are discussions and theories about fructose in the diet, about insulin resistance, about the relative merits of the Ornish and Atkins diet, about stomach-banding operations, about the role of exercise and heredity, etc. But we still know far too little about how the body processes ingested calories of all kinds---fats, proteins, and carbohydrates.

     What we do know is that the body has the enzymes necessary to interconvert carbohydrates and fats, protein and fats, and carbohydrates and protein, with the exception of  the eight essential amino acids and the three necessary fats. We will assume an adequate intake of these latter two as well as sufficient daily vitamin intake, be it contained in the food eaten or taken as a daily supplement. And let us recognize that eating is like breathing, in that there is an involuntary autonomic drive, which can be overridden by voluntary means.
Not to be obvious, but we always have examples of people who are grossly overweight and dangerously underweight, viz. sumo wrestlers and anorectic patients (and I am not here going to discuss the distorted body images that are involved).

     Let us first consider the marvelous caloric balancing act that the body does daily and therefore yearly without any conscious guidance. It is generally agreed that ingestion of approximately 3500 calories can be converted to one pound of flesh, and oxidation of one pound of flesh releases 3500 calories (remember that part of the food we eat daily is oxidized just to generate the heat needed to keep our body temperature fixed and comfortable). We also know that exercise generates heat, so that the body shivers when it is cold as a way of raising its temperature. Now there are about 350 days in a year, and if we divide 3500 calories by 350 days we see that the body must ingest fewer than 10 extra calories a day or burn it off in some manner if we don't want to gain weight. No one knows how the brain instructs the body to do this marvelous act, and yet most of us have weights that are fairly constant year to year, which means that the brain is micromanaging our caloric intake and expenditure in a way that we could not possibly do consciously. Could any of us eat the same amount of calories plus or minus 10 calories on a daily basis? I think not, no matter how committed we were. Remember that in a 2000 calorie daily diet, 10 calories is 0.5% of the daily allotment, and even if we had the will, we do not have the skill to measure the total daily calories we eat to an accuracy of 0.5%.

     So how does one go about losing weight? The body has a fixed daily energy expenditure to keep your core temperature at 98.7 or whatever your normal temperature is. Then there is an additional energy expenditure, also gained by oxidizing food or flesh, for the motion of your muscles, both  involuntary (e.g. heart and diaphragm) and voluntary, as in your skeletal muscles. That's it. So if we ingest more calories than are needed to be oxidized to supply our daily energy requirements we will gain weight, and if we ingest less, we will lose weight. In other words, there are two types of foods: too much and too little. (And once we solve the weight problem we can proceed further as to food pyramids and the like.)

     At this point, I will give a small nod to the nutritionists, and add that the two most useless types of calories come in the form of white potatoes and white bread. Both have a high glycemic index, potato more than bread, and therefore stress your insulin-glucose system. No one on a diet should eat either of them, IMHO. The question of whether or not you should eat chocolate before your main meal so as to decrease your appetite and therefore eat less remains unanswered.

     Now for the hard part: actual weight loss. There are myriads of suggestions out there including drinking water before meals, leaving the table before you feel full, eating smaller portions, drinking more caffeinated beverages, eating more fiber, taking diet pills, exercising more, etc. But the advice begs the question of actually losing weight. Besides feeling your clothes become looser, the only way to know if you have lost weight is to step on a scale. And I mean an old-fashioned scale, not a digital one which can have errors.
Weigh yourself today and then re-weigh yourself tomorrow, or in two days, or at least in seven days. If you have gained weight then eat less, and keep on eating less between successive weighings until you start to lose weight. Then just continue. So long as you eat fewer calories than your body burns, you will lose weight. It all comes down to a fuel-energy balance, which is why your car weighs more when you fill it up with gas and then steadily loses weight as you burn the gas in the tank and it is used up. If you find as most people do that exercise both makes you feel better from the endorphins it generates and helps you to lose weight by suppressing your appetite and burning off calories, then do it.If it helps you to make a daily food/calorie list, then do it. If it helps you to omit lunch (I never have lunch when I am at home) then do so.
Everyone has a different pattern for weight loss, just as everyone has a different need for sleep. We are all wired differently, but the iron laws of physiology (physics as applied to the body) tell us that fuel is either oxidized or stored, and the amount of fuel ingested is the ultimate determinant. And yes, people do have different fundamental metabolic rates, so that a diet that works for one person may not work for another.

     And no one knows why everyone likes ice cream: I personally think that it is because it is similar in taste to frozen mother's milk: sugar and fat.


   

Tuesday, December 25, 2012

Tylenol/Acetaminophen/Paracetamol

     Shortly after I posted my blog on aspirin, several readers asked for similar information on Tylenol. Tylenol is the trade name for acetaminophen. Paracetamol is the chemical name throughout Europe. Phenacitin used to be marketed for the same purposes, since it is metabolized to acetaminophen in the body, but several studies suggested that phenacitin was carcinogenic, while paracetamol was not. The abbreviation for paracetamol is APAP.

     APAP is used for pain relief and to reduce fever, and its potency for both purposes is equivalent to aspirin. At high doses (1,000 mg) there is some evidence of an anti-inflammatory effect, but it is never marketed as such. Unlike aspirin, APAP as a fever reducer is safe for children of all ages, provided the dosage limits are observed. Traditionally the dose of APAP  for adults has been 2x325=650 mg or 2x500=1,000mg per dose. The suggested maximum dose used to be 4,000 mg/day. However, one very good article in NEJM showed that cirrhotics could suffer increased liver damage at total doses above 3,600 mg/day, and since APAP toxicity is the leading cause of acute liver failure in the world, the suggested maximum has been lowered to 3,000 mg/day by the FDA. The FDA can only suggest this maximum dose, and is not permitted to mandate it.

     APAP starts to work to relieve pain within 10 minutes of ingestion. It is metabolized by the liver, and its half-life varies between one and four hours. The liver's act of metabolizing it depletes the liver's store of glutathione, and this in turn makes APAP potentially toxic to the liver, an effect which is worsened by the simultaneous ingestion of alcohol. APAP is metabolized  by three different chemical processes in the liver; the one mediated by cytochrome P450 (a name familiar to doctors and pharmacists) produces the toxic metabolite.

     APAP will relieve the pain of osteoarthritis, but unlike aspirin and other NSAIDs does not affect the inflammation of the joint. Although APAP does not attach to platelets and is not a blood thinner or anti-coagulant, sustained daily use may increase the chance of gastric bleeding. The underlying process is poorly understood because we still do not know the full mechanism of action of APAP, although several suggestions have been advanced. One is that its pain-relieving action involves cannabinoid receptors in the brain(!). As a side note, APAP can relieve pain in dogs, but is toxic to cats through the formation of methemoglobin which inhibits the oxygen-carrying ability of the blood.

     And it is a tribute to the power of advertising that so many customers still will pay extra for the brand name Tylenol rather than the generic acetaminophen.

   

   

Sunday, December 23, 2012

Aspirin

     There have been many articles written about the uses and benefits of aspirin, and I thought I would review them here. Without clouding the discussion, it is important to understand the distinction between primary and secondary benefits from taking a drug. If the drug has a primary benefit, then it prevents the disease or condition from occurring, and everyone might benefit from taking it. If the drug has a secondary benefit, then it is given to patients who already have had an attack of the disease, to prevent a second attack. It is always easier to demonstrate the existence or non-existence of a secondary effect, because the greatest risk factor for an attack of any disease (especially a heart attack) is having had a previous attack of the disease. One example of primary benefit would be in taking medicine as malaria prophylaxis when traveling to a malarious region of the world. Another example would be yellow fever vaccine. One example of a secondary benefit is giving all survivors of a heart attack a daily dose of a statin, which decreases the chance  of having a second heart attack.

     Aspirin, abbreviated ASA, is acetylsalicylic acid. Hippocrates knew that the bark of the willow plant could reduce fever, reduce pain, and reduce inflammation. The active ingredient was salicylic acid, which is an extreme irritant to the stomach. Most people are unaware that not only do we ingest salicylic acid in our diets, but that our bodies synthesize it from benzoic acid.  In 1897 a German chemist working for Bayer, (Felix Hoffman) was able to synthesize ASA by acetylizing salicylic acid, thereby making it much less injurious to the mucosal lining of the human stomach. Although he was not the first to create ASA in the lab, Bayer successfully patented ASA and initially made it available only through a doctor's prescription. Interestingly enough, about the same time Bayer chemists synthesized heroin which is diacetyl morphine, and it was sold  over-the-counter as a non-addictive(!) form of morphine.

     The precise mechanism of the action of aspirin in inhibiting the formation of prostaglandins  (by inhibiting the action of cyclo-oxygenase enzymes) and thromboxanes  is unimportant for the purposes of our discussion, except to note that the inhibition is irreversible and the effects of a single dose of aspirin on the bleeding time can last for 10 days, unlike the other Non-Steroidal Anti-Inflammatory Drugs (NSAID's) such as Advil whose effect is reversible. Since aspirin binds irreversibly to platelets, patients about to undergo surgery are advised to avoid all aspirin and aspirin-containing products for 10 days before surgery, since that is the length of time for which an extension of the bleeding time due to aspirin can be measured. The aspirin achieves this effect through its binding to platelets, which normally can clump together to form a clot and stop bleeding, and platelets bound to aspirin do not clump together.

     Let me list a few known facts. Aspirin is 99% cleared by metabolism in the liver, but if too large a dose is taken the hepatic clearance mechanism is saturated, renal clearance is needed, and the clearance kinetics shift from first order to zero order.  Thus the half-life of a 325 mg pill is 3 hrs, but a 2000 mg dose has a half-life of 9 hours.
In the United states, the basic strength of an adult ASA tablet is 325 mg, and that of a children's tablet 81mg. In Europe the strengths are 300mg and 75 mg respectively, but it makes no apparent clinical difference. Adding caffeine to an aspirin pill increases its pain-reducing strength, hence the popularity of APC's or Excedrin migraine compounds (aspirin, phenaciten or Tylenol, and caffeine). ASA in an effervescent solution is absorbed faster, hence the popularity of Alka-Seltzer. The bleeding effect of aspirin on the stomach can be reduced by taking ASA along with 500 mg of Vitamin C, or 500 mg of SAMe, or 350 mg of deglycyrrhizinated licorice. Many  people who take aspirin on a daily basis develop an iron-deficiency anemia from microscopic bleeding somewhere in the GI tract, and buffering the aspirin seems to make no difference. But buffered ASA is absorbed more slowly, and some recent studies suggest that this is the cause of apparent "aspirin resistance". I should mention here that aspirin given intravenously causes absolutely no GI irritation.

     There are studies showing that taking a daily aspirin (check with your doctor for the suggested dose) can lower the risk of a second heart attack, a stroke following a TIA, a cardiac embolus if you have atrial fibrillation, and cancer of the colon; the first two are examples of secondary prevention, and the last two of primary prevention. It is extremely dangerous to give aspirin to febrile children up to the age of 16  because ASA in a febrile child can trigger a sometimes fatal condition known as Reye's syndrome, which is swelling of the brain compounded by liver failure. A few people develop an acute allergic reaction to aspirin with angioedema. Aspirin exposed to water decomposes back into acetic acid (vinegar) and salicylic acid, hence the vinegary smell when you open a large bottle of aspirin that you  have had for some time.

     There are many drug interactions with ASA; for instance Diamox (acetazolamide) enhances the likelihood of salicylate poisoning, and alcohol increases the risk of gastric bleeding, as does taking Advil or any other NSAID along with aspirin. Because aspirin is  bound to protein in the blood, it can displace other drugs that are bound to protein, thereby raising their plasma concentration to dangerous levels. Some of these drugs are tolbutamide, methotrexate, Dilantin, valproic acid, and probenecid. Taking ASA can  raise the blood level of uric acid. Very rarely through a kidney-based mechanism, aspirin can cause elevated potassium in your blood; this is especially true for diabetics (hyporenin hypoaldosteronism).Aspirin can also inhibit the renal clearance of penicillin G if either drug is given in very high dose. And paradoxically, very high doses of aspirin can cause fever rather than alleviate it.  So whenever you get a prescription for any drug, it would be wise to ask your doctor about possible interactions with ASA.

     And please never forget that unless your doctor gives you permission, never take aspirin with any drug that can cause bleeding, such as Advil, Alleve, Coumadin, Xarelto, and, sometimes, alcohol.

 

   

Wednesday, December 12, 2012

Rabies, Daytime Raccoons, and Bats

     There has been a significant increase in animal rabies in New Jersey this year, so it is prudent and also required by law to have your pet dogs and cats receive an annual rabies vaccine. When they do so, they get a color coded (all red, or all blue,etc. ) and shaped (fire hydrant, disk, sword) medallion for their collar so that at a glance you can determine if an unleashed pet who bit your child has been vaccinated against rabies this year. Rabies travels up from the site of the bite along the nerves to infect the brain, and then moves into the salivary glands of the animal. Raccoons are nocturnal animals by nature and instinct, so if you see a raccoon during the day, it is safest to assume that it is crazed from  rabies, and to call the local animal control office. Do not approach it or let your children or pets come near to it. A rabid raccoon may also become aggressive and charge at you, so it is safest to gather everyone into the house. The raccoon also may  bite other animals (skunks, horses, cows,  squirrels, and foxes and make them rabid as well.
     Bats are natural harborers of the rabies virus, which is a  harmless commensal for the bat. Therefore assume that ALL bats are rabid, and if one flies into your bedroom get out at once and call your doctor. They have small, sharp, needle-like teeth and you may not feel the bite.  If they fly around your campfire, get away from the campfire. And please don't make homes on poles  for bats in the hopes that they will keep your neighborhood free of mosquitoes  because they may  also bite and infect any raccoons, foxes and coyotes  in the neighborhood, as well as you and your loved ones. They also like to nest during the day under closed sun umbrellas by your pool.  (The recent epidemic of bat deaths due to the white-nosed fungus has nothing to do with their carrying rabies, and the most common place to encounter bats is in caves.)
     Three humans in the past 10 years have survived rabies attacks after the virus reached their brain, but they required prolonged stays in an ICU, and their survival was distinctly unusual.

Monday, December 10, 2012

Walking on Eggshells, Usually in the Presence of a SO with a Borderline Personality Disorder

     The information contained herein is taken from a site, http://bpd411.org, operated by the Turtle Island Center for Family Services. It deals with the trials, tribulations and stresses inflicted by BPD's on those around them, especially those who have a close emotional tie with them. It is not uncommon for BP's to exhibit strong narcissistic qualities, but this blog discusses the poor unfortunates who have to deal with them.
Patients with a Borderline Personality Disorder are literally incapable of seeing things from the other person's point of view and generally insist that any stresses in the relationship come from the actions of the other person, who is then forced to "walk on eggshells" to avoid provoking an outburst of emotional or physical aggressiveness. This becomes an impossible situation because any slight or mild criticism or disobedience is seen by the BP as an ego attack that has to be met with full fury.

     The victim in this situation has  to maintain an exceptionally high and excessive level of vigilance over both actions and words, as well as extreme caution in some situations and thus we are dealing with a relationship that is both tense and dysfunctional for the tiptoer. The SO of the BPD feels that if (s)he is  careful enough  then (s)he  will avoid provoking that craziness and rage of which the BP is capable of unleashing at the least perceived provocation. The SO feels that there must be some way (s)he can get it "right" so that the relationship  can be OK again. The SO is generally told by the BP over and over that any problems are all the SO's fault, and any negative issues in the relationship derive from the SO's behavior. And any self-blaming attitude the SO might have in always vigorously emphasized and reinforced by the BP. And the BP always holds him/herself blameless, and maintains that only the SO needs self-work and therapy.

     Vigilance can be a useful frame of mind when one is exposed to real danger (think Hurricane Sandy or jaywalking or being the goalie in soccer or hockey). But if you are forced to  maintain a hyper-vigilant state for too long a period of time, and are unable to take needed rest breaks for your psyche, then the perpetual stress will start to wear you down. Paying perpetual vigilance to everything around you leaves you no time to experience any joy or pleasure in your own life, and your own needs for nurturing and true companionship are incapable of being met. Just think of the spouses of alcoholics who end up going to Alanon because their spouses never quit drinking.

     We all occasionally walk on eggshells at various times in our life to preserve peace in the family, but that is quite different from being "on" 24/7. When you are always walking on eggshells, you have no time for self-development, receive no positive reinforcement, and your own emotions can be narrowed down. You may limit your choices severely in order to avoid "provoking" an outburst. You might even stop laughing, being playful and telling jokes about funny things in life because your entire vista with this person  is grey and black. Your own emotional needs of course are never attended to, so you never feel fulfilled. It is more like walking through a minefield, looking at your BP for any signs of disapproval or incipient hostility and criticism. You may even be fearful that in one of these temper outbursts real physical harm will come to you or the BP or someone else.

     You are entitled to peace in your own life. Your triggering his/her rage does not mean that you always make mistakes. Slowly your sense of self-worth becomes corroded and destroyed, and you lose the ability to think clearly for yourself. You start to wonder where your old self has gone, the happy, joyous, carefree self. Walking on eggshells also involves your excusing his behavior towards you because of his childhood trauma, or poor upbringing, etc, none of which you were responsible for. (S)he may also shrink and restrict your social circle, using various excuses. You may become totally subservient in an attempt to ward off further outbursts of rage. And finally you are usually forbidden to talk about this to your family and friends, or to seek out a therapist, because that would be seen by the BP  as a betrayal of the relationship.

     It is important  to understand that the raging is not controllable by you. It is not a response to what you do but to something inside the BP. You did not create his/her state of mind, you are not responsible for the outbursts of anger and rage from the BP, and you certainly can't cure him/her. His/her actions will continue towards you so long as you are there to receive them. And please, please, please never compromise your own safety. "The Devil made me do it" is not a valid excuse for emotional and physical abuse, and certainly has no place in a loving relationship, and in the long run you will be both frustrated and drained.

Mad Cow Disease

     The first case of mad cow disease (MCD) in six years was found in a dairy cow in California this past April. The cow showed no signs of infection with MCD (more properly called Bovine Spongiform Encephalopathy, or BSE). It had no weakness, altered gait, or decrease in milk production. This past year the U.S. Department of Agriculture tested 40,000 cows for BSE, down from the 380,000 they tested after  the MCD epidemic was noticed in England and attributed to eating meat or spinal cord tissues from infected cows. The disease in humans is progressive, 100% fatal, and has a lead time between infection and detection  in humans of years or decades. The curious fact to me is that one cow farmer (dairy or meat, I forget which) wanted to test ALL his cows for the disease, and the USDA refused him permission. I can think of no non-political reason for their denial, since he was willing to spend his own money on the testing so he could assure his customers that his animal products were disease-free. BTW I still continue to eat meat.

Friday, November 30, 2012

Do Statins Reduce Your Risk of Dying from Cancer?

    There was a very interesting article published in the November 8, 2012  issue of the New England Journal of Medicine (vol. 367, pp 1792-1802) as well as an excellent analysis of the study published as an editorial comment in the same volume (pp 1848-1850). One theory about cancer growth is that those cells need cholesterol for cellular reproduction, so that any drug that lowers cholesterol should provide a benefit. The study was done in Denmark, which has a remarkably homogeneous population and moreover, because of national health care, has excellent registries of cancer diagnosis and incidence, as well as deaths from cancer, all cause mortality, and the prescribing of drugs. (The availability of such statistical data is one side benefit of national health care if the computer programs are written properly.)
     The retrospective study reviewed data relating to medical care from 1995 to 2009, and encompassed almost 300,000 subjects. The hypothesis tested was that patients who were taking statins BEFORE the diagnosis of cancer would have a reduced cancer mortality. It was found that patients who were taking statins before the diagnosis of cancer had a reduction in  their probability of dying from cancer from 100% to 85 % and the same reduction was found in mortality from any cause after the diagnosis of cancer. (The actual number of 85% +/- 2% is the hazard ratio, which is a statistical concept.) One remarkable fact was that the 15% reduction in mortality risk was independent of the dose of the statin(!).
     Several clinical events and facts were not controlled for. No mention is made of cigarette smoking in the two groups, or if they had had cancer surgery. Also, no mention was made of OTC aspirin or NSAID use, and we know of several studies linking such use to a reduced incidence of colon cancer.
     It is naturally suggested that a clinical study be made to test the hypothesis that was generated by this retrospective study, i.e. the hypothesis that statin use has a positive effect on cancer mortality as well as on all-cause mortality. I want to re-emphasize that this was a statistical analysis, and not a forward double-blind study so it would be tempting but scientifically incorrect to draw a clinical conclusion from the results.  The problem I foresee is  that no one will want to be in the placebo arm of the study, and risk not lowering his/her chance of dying. (This is in fact what happened when St. Vincent's Hospital in NYC tried to test drugs for AIDS with a placebo arm in the study. The political pressure was so great that the FDA granted the researchers permission to omit the placebo arm.)   I predict that once the news of this study gets out to the general public, then millions of people will start taking statins of their own accord (probably from Mexico since almost every drug that is a prescription-only drug in the U.S. is sold OTC in Mexico).
     Isn't the motto of Dupont, the giant chemical company, "Better living through chemistry"?

Thursday, November 29, 2012

How to Interpret Medical Research Results

     As a former research physicist and editor and reviewer for physics journals, as well as  a reviewer for 10 years for the Annals of Internal Medicine, I feel compelled to comment on the plethora of clinical medical studies that are being released faster and more furiously. Research scientists understand the limitations inherent in clinical reports, whether published in a journal or presented verbally at a conference, but people who get their information by reading internet or newspaper summaries of the results do not. I will try to outline what to look for in these reports, and what level of trust should be placed in the reported results, without resorting to scientific and statistical jargon such as regression to the mean, Simpson's Paradox, and the Law of Large Numbers. Interested readers might want to read my two earlier blogs on the fallacies inherent in using meta-analyses to suggest valid clinical treatments.

     One problem in reading newspaper summaries of published articles is that in their efforts to simplify the results and conclusions for their readers, columnists have made interpretive errors. At the very least, the columnist should refer you to the National Library of Medicine's web page, www.PubMed.gov, where the abstract of the discussed article is contained. As a general rule, the abstract will contain the essential conclusions of the published journal article. There are a number of reputable newspaper columnists who are themselves practicing doctors, such as Danielle Ofri,  Perri Klass,  and Lisa Goldman, and I have always found their columns to be accurate. Without mentioning names, I have found errors in most articles written by science writers, especially when the interpretation of the published results is open to question, or ambiguous.

     You may take it as a general rule that if there is heated argument about the "correct" interpretation of a scientific result, then the clinical interpretation is not yet known with certainty. In physics we would say that if you have to argue about the interpretation of data points, then more data is needed.  And let us not forget the government's insidious modification of established facts, much as Stalin removed the faces of Politburo members from the Soviet Encyclopedia if they fell out of favor. The best example here in the U.S. deals with  the iconic picture of the abstract painter Jackson Pollock. This well-known photograph  showed him bent over his work with his ever-present cigarette dangling from his mouth. When the U.S. Postal Service reproduced this picture to use on a commemorative stamp, his cigarette was airbrushed out of the picture.

     For starters, please remember that the gold standard for the imprimatur of the probable accuracy of a scientific or clinical report is its publication in a journal article that has been reviewed by a scientist in the field. This has been shown to be the best way to make sure that there are no biases in the article, that the data is presented clearly and fairly, and that the conclusions follow from the data and are clinically significant.
Ideally, if any graphs are presented with data points, the data points should have error bars attached to them, showing the variation that could have been introduced by the imprecision of their measurement. Also,  the authors of the article should report who paid for the  research  and if  they have received speaking fees or consultation fees  from the government or drug companies, or any other sources (which of course newspaper reporters and TV news commentators almost never report about themselves).In addition, if the authors speculate about theoretical and possible future applications of their clinical results, the ideas should clearly be labeled as speculations and suggestions.

    From what I have said, it should be clear that a verbal report given at a medical conference should only be treated  as an interesting idea. All too often, initial verbal reports or announcements at news conference do not withstand the rigor of being reviewed for journal publication, let alone the test of time. I'm sure we all remember the foofraw connected with the report of table-top cold fusion. In fact, in this day and age of instant celebrity, I would expect any discoverer of an important clinical event to appear on the Oprah show (and this is meant as a compliment to Oprah, and not a denigration of her show). For this reason I take all medical news reports with a grain of salt until I can read about it in a refereed journal. In fact, The New England Journal of Medicine will often publish two similar studies in the same issue, and then have an editorial comment on why the two agree or disagree.

     And even reputable journal articles may not be correct. All too often one article is followed shortly (and sometimes in the same journal!) with a clinical research article coming to the opposite conclusion. To mention just a few: is lowering salt in the diet of an average person beneficial or harmful? do mammograms of women in their 40's save lives from breast cancer? does treating prostate cancer save lives? And then we come to the famous conflict in presenting data between relative risk and absolute risk. If the death rate from lightning strikes is 1/2,000,000 and I can reduce it to 1/1,000,000, I can present this result either by saying that I reduced your (relative) risk of lightning-stroke death by 50%, or I reduced your (absolute risk) by 1:1,000,000. Most journal articles and reports speak of the benefits of a new medical treatment in relative risk, because that number is always larger, and sounds much more impressive. A 35%  reduction in your change of getting leprosy would probably not be of much interest or medical importance to you because your absolute risk is so low. OTOH you might leap to take a new treatment that reduced your chance of getting a heart attack by 35%, but is it a 35 % reduction over the next  year, or is it a 35% reduction over the next 10 years, i.e. only a 3.5% reduction per year. In other words, how long do you have to live to reap the quoted benefit of the proposed treatment?

     Let me close with a statement attributed to Voltaire: No one argues over whether or not 7 x 8 = 56, but Giordano Bruno was burned at the stake for maintaining that the earth moved around the sun.

   

Wednesday, October 31, 2012

Alzheimer's Disease

     Alzheimer's Disease is a progressive dementia that causes a steady, virtually irreversible loss of social skills and intellectual skills, and eventually impairs the sufferer's ability to carry out the ordinary activities of daily living. There have been many studies purporting to show an external cause, or successful drug treatment or beneficial  interactive treatment, but no clinical intervention has been demonstrated to make a permanent difference in the course or incidence of the disease. Since the disease can only be definitely diagnosed by autopsy of the brain, it remains a diagnosis of exclusion, and since the diagnosis is a horrific one for the patient and his/her family, every effort should be made to look for a reversible cause of the person's dementia. The best book of which I know that discusses the stresses of being an Alzheimer's caregiver is "The 36 Hour Day", which describes what it is like to be the caregiver on a 24/7 basis of someone who's mind is being progressively ravaged. .

     It has been my experience that AD patients fall into one of two categories. Some (like my father who had it for five years) appear to be unaware of their condition. They slowly develop a childlike dependence on the caregivers, and cause little or no fuss as they regress to a point where they lie in bed all day and are unable to feed themselves. Others are aware that something is wrong and get frustrated, angry and paranoid and become hostile to caregivers. They are therefore much more difficult to nurse, because they are usually inaccessible to gentle reason.  Drug treatment of this latter  condition usually involves major tranquilizers, is seldom successful in the long run, and can have unacceptable side effects. On occasion physical restraints are necessary. Their caregivers are under major stress, and usually are mentally holding their breath, hoping that the latest outburst will be the last one. A special problem arises when the AD patient tells a relative that the aide has physically abused him/her, and the relative cannot tell if the patient is speaking the truth or succumbing to paranoid ideation. I know several families who have changed aides monthly.

     One problem that arises is guilt on the part of the immediate family members, especially a spouse or a child. They may feel that they have not done enough, or been sufficiently perceptive or supportive. They feel guilty if they cannot be with the AD patient 24/7, and I have to reassure them that caregivers need rest also, and that there is a reason that interns, truck drivers, and airline crews have strict limits on the number of consecutive hours that they are allowed to serve. An early point of stress is the family decision to remove driving privileges from the AD patient. The primary caregiver also often feels uncomfortable about  being more than one or two hours from the AD patient in case "something happens", let alone taking a weekend trip or an extended vacation.

     Then there are the well-meaning friends and relatives who bombard the caregiver with forceful suggestions about taking the AD patient to a special diagnostic or treatment center, or to a geriatric specialist. Again, the reversible causes of dementia are well-known to all competent internists, family doctors and neurologists, and are diligently looked for. One diagnosis that is occasionally overlooked is the pseudo-dementia of depression. And there is no good clinical evidence that intellectual interaction and stimulation affects the course of the disease. The main advantage of a day-care center for the AD patient is that it gives the caregiver a well-needed rest.

     All AD patients have some degree of memory loss and impairment, most commonly in short-term memory. As we get older, the transfer of information from short-term to long-term memory becomes less automatic and requires more effort,so that while in our 20's we remember our friends' phone numbers and addresses automatically, as we get older we write it down more and more often or log it into our smartphones. If you walk into a room in your 20's and say "where did I put my car keys", you curse yourself for being an idiot, but the same activity in your 60's immediately makes you concerned about AD, It has been my experience that a significant sign of serious memory loss is the inability to find one's way home after a walk or a drive, especially if the person  took an unfamiliar route to get someplace. And if you want to find something after you put it down, you will be most successful if you place it at eye level.


Thursday, October 18, 2012

Are Annual Physicals Beneficial?

     I have received a number of questions about the latest Cochrane report about the purported uselessness of annual physicals, so I thought I should analyze the report for my readers. (My earlier thoughts were posted in an earlier blog, entitled The Annual Physical.) For those of you who are not familiar with the Cochrane system, it is similar in concept to the group of French mathematicians who have published articles for over 50 years under the pen name Bourbaki. The Cochrane group is an international non-profit organization. It  has a fluid makeup and a number of different participants, and devotes itself to finding the best proven treatment or diagnostic process for a given disease or symptom, based on clinical studies. They publish a book each year under the auspices of the British Medical Journal, and when you read the book you are led to realize how few of our medical methods are well-grounded in clinical fact. As I have often mentioned before, what seems "obvious" often does not stand up under clinical studies, e.g. the proper treatment to reduce the number of calcium oxalate kidney stones you  produce is to INcrease the amount of calcium in your diet, not to decrease it. I should also mention that the calcification of your coronary arteries proceeds independently of the amount of calcium in your diet.

     A good summary of the Cochrane report to which I refer was published online by Med Page Today on October 16, 2012, at http://www.medpagetoday.com/PrimaryCare/GeneralPrimaryCare/35356. The study was a meta-analysis (and see my previous blog on that subject with an analysis of the weaknesses of such a study) of 16 clinical trials involving over 180,000 patients. The endpoint they looked at in 8 studies was cardiac mortality and in 8 studies was cancer mortality.  They found that patients who had regular health checkups died from both causes at the same rate as those who did not have an annual physical, and they also did not have less disability.

     There are several logical errors in this analysis. To begin with, since the mean time of the studies  was 9 years, they could not test for total mortality, i.e. extension of one's lifespan. Secondly, many patients go for  screening studies such as a pap smear and a mammogram without having an annual physical. Thirdly many patients take themselves to cardiologists of their own accord, and periodic cardiology visits were not counted as a regular health checkup any more than was a visit to one's gynecologist. The conceptual problem with all the studies is that no attention was paid as to how a potentially fatal disease or condition was discovered. We do know that certain interventions save lives, so that people who see a doctor, even aperiodically, live longer than people who never see a doctor. Therefore the questions devolves upon when and how often a patient should be examined by a doctor, and whether the schedule of the visits should be rigidly time-ordered, or one should wait for the patient to come in. At what time interval does a periodic physical exam of a patient with no complaints begin to save lives? This is the basic unanswered question.

Tuesday, October 16, 2012

West Nile Virus

     This has been an exceptional year for West Nile Virus infections in the U.S., especially in Texas where the majority of infections, permanent disability and death have been reported. As always, the most accurate and up-to-date information is available from the Center for Disease Control, whose website is www.cdc.gov. Since this RNA virus is spread almost exclusively by bites from infected mosquitoes, the best way to avoid infection is to minimize exposure to these insects, recalling that they are most likely to bite at dawn and at dusk. Some of the standard instructions include wearing long-sleeved shirts and pants, using mosquito repellent, and not venturing outside at times of maximum exposure. However the Asian tiger mosquito, which has also transmitted the infection in the United States, is a daytime feeder.

     The infection is now endemic in the United States in birds that perch. Most birds are just carriers, but crows and robins are often killed by the virus. In fact, the first case reported in the U.S. came from isolation of the virus from a dead crow in New York City, so it is advisable not to handle dead birds but rather to report them to your Board of Health.

     The virus was first reported along the Nile River in Uganda in 1937, but now has spread to all tropical and temperate climates throughout the world. It can infect mammals and reptiles, and most hosts show no signs of the disease. There is no vaccine against the disease, and no available anti-viral medicine for it,
so the only treatment for serious cases is support of vital signs in an ICU. It is diagnosed by tests of the blood or of CSF fluid from a spinal tap. It has been spread by blood transfusions, so banked blood is now tested for this disease. It can also be transmitted from pregnant women to the fetus,  from nursing women to their children, and by organ transplant. There has been no evidence of people-to-people direct infection.

     The majority of humans bitten by infected mosquitoes show no signs of the disease--- 80% have no symptoms at all. Of the remaining 20%, most just show mild symptoms of a viral infection, which can include fever, malaise, rash, swollen lymph nodes, muscle aches and lack of appetite. A few unlucky patients (about 1%) develop infections of the central nervous system, either meningitis or encephalitis, and these may be left with permanent disabilities or have a fatal outcome. The incubation period is 2 to 15 days.

     Those at highest risk for CNS infection are the very young, those over 50 years of age,  pregnant women, and patients with a weakened immune system, e.g. from cancer chemotherapy, AIDS, or immunosuppression after an organ transplant. Additional risk factors appear to be male sex, diabetes, and hypertension, and some patients may genetically be at higher risk for neurological complications. Some patients may have symptoms for 60 to 90 days, and there have been case reports of chronic fatigue persisting for one to two years after infection.

Sunday, October 14, 2012

Epidural (spinal) Injections and Fungal Meningitis

     There have been so many articles written recently about the outbreak of fungal meningitis secondary to spinal injections with a steroid that I thought I should make a few clarifying remarks. Most of what I say here is taken from the Morbidity and Mortality Weekly Report, or MMWR, published by the Center for Disease Control. Their statement is contained in their early release dated October 12, 2012, and their website is http://www.cdc.gov/mmwr.

     Steroids (in this case methylprednisolone) can be used to  relieve the inflammation of swollen nerves and joints, and are often given by injection epidurally (that is, near or into the spinal canal) to relieve the pain caused by sciatica or other neuritis. This can break the cycle of  pain causing  muscle spasm which in turn can pinch the nerve that travels through the muscle and perpetuate the pain. There have been various studies of the efficacy and permanence of the relief caused by this treatment, but a discussion of that is outside the scope of this blog.

     The potential problem with steroid injections lies in the fact that it suppresses inflammation in part by suppressing the local release and local action of white blood cells. So if the steroid solution itself is contaminated with bacteria or  fungi, you are not only inserting a pathogen into a very susceptible region of the body but you are also directly inhibiting the body's response to and elimination of the pathogen. In the recent epidemic, the contaminant was a fungus.

     Now fungi reproduce vary slowly, so it can take weeks for the implanted infection to manifest itself. (In the recent outbreak the time between injection and the development of symptoms ranged from 1 to 42 days.)  Because fungi reproduce slowly, the time necessary to treat fungal infections is measured in months, not in days or weeks, since  most antifungals work by attacking fungal DNA after it has uncoiled to reproduce. And because fungi have sterol compounds in their cell membranes, ordinary antibiotics cannot penetrate the cell and therefore do not work. In addition, because the two-drug combination suggested by the CDC to treat fungal meningitis has serious side-effects, one does not give prophylactic antifungals as a rule.

     Fungal meningitis is not contagious, and there has been no record of people-to-people spread. The contamination occurred at the factory where the steroid was compounded. For various legal reasons, such compounding facilities are NOT under FDA control, and therefore the production process is neither inspected nor sampled for absence of contamination by the federal government. A recall process has been instituted by the Massachusetts manufacturer under the auspices of the CDC, and over 90% of the patients who received injections from the contaminated lots have been reached and notified with the assistance of the local Boards of Health. IMHO, this does not mean that one should avoid epidural steroid injections, but it would be prudent to make sure that the supplier was  "reputable", i.e. the drug came from a drug company whose name you recognized, since they would have much more to lose if their product were found to be unsafe.

Wednesday, October 10, 2012

Diet, Health, and Longevity

     This blog was stimulated by a front page story in the New York Times of Saturday, October 6, 2012. It described the response of tens of thousands of high school students this fall to the new federal mandate that school cafeteria lunches be "healthy". The students are throwing the lunches away, or boycotting the cafeteria, or buying their food from vending machines. The same children who wouldn't eat their spinach as two year olds will not eat rice cakes and whole wheat pizza when they are sixteen. Come to think of it, neither would I (don't rice cakes really taste like styrofoam?). And the food pyramid that students are taught to guide their healthy eating habits in schools today is the inverse of what we were taught as students: What we were taught should be at the top of the food pyramid is now placed on the bottom, and our bottom is now their top.

     Do we really know what "healthy" food is? Do we really know which diet is "best" for us? What should be the nature of our diet to maximize our life span? Do we know if optimal health requires us to eat three meals a day rather than two meals or six meals? And at what time of the day should we eat our largest meal?  Is salt really bad for you, or sugar? How much or little fluid should we drink, and of what kind? Is it safe to fast for 24 hours?  What do we do with the fact that human skeletons from 9,000 B.C. when humans were hunter-gatherers and ate mostly meat  show no signs of tooth decay, while skeletons from 6,000 B.C. when humans began to cultivate grain and ate carbohydrates show extensive tooth decay and jaw abscesses? (saliva turns starch to sugar in your mouth, but only can break meat down into its proteins) What about the many benefits of coffee (described in an earlier blog), or the benefits of moderate alcohol consumption or dark chocolate? Should we eat until we are no longer hungry, or stop when we are only partially filled? Is the Japanese diet responsible for their high rate of stomach cancer or for their  longevity? or both? or neither? Isn't the reason that everyone likes ice cream due to the fact that it is really flavored frozen mother's milk, rich in sugar and fats?

     I will now list the top countries for life expectancy, first from birth, and then from age 40. There is a slight variation because infant mortality enters into the total life expectancy from birth: For instance the Unites States rates 49th in life expectancy from birth, but 33rd in life expectancy from age 40. If diet affects total health (as opposed to the amount of food or calories eaten at a single sitting) then we would expect a clustering of countries from the same area of the world who consume approximately the same diet, and we will see that this is not the case.
     Life expectancy from birth in descending order: Japan, Singapore, Australia, Canada, France, Sweden, Switzerland, Israel, Iceland, New Zealand, Italy.  Life expectancy from age 40: Japan, Switzerland, Australia, Italy, Israel, Iceland, Spain, France, Canada, Singapore, New Zealand . I have included 11 countries rather than 10, because I am not certain if Singapore should be classified as a city rather than as a nation.

     Japan and Australia rank #1 and #3 in both lists, and they have totally different diets and eating habits. The French paradox pops up, of course. Israel and Canada both rank high, and again they have radically different dietary habits. So if we look at total longevity, it is difficult to draw any conclusion about the benefit of any particular diet. I should also mention that the longest lived people born in America are Asians, so it would seem that genetic heritage might be more important than diet in determining longevity. As far as I am aware, no substantial research has been done on the country-wide genetic contribution to longevity, but we do know that there are many genetic factors which are common to people of a given country. As a trivial example, all 100% Inca indians from Peru have type O blood, but very little research has been done on the effect of a blood type on one's health. We know that almost every female Pima Indian from the American southwest has severe gall bladder disease and a cholecystectomy by age 18. The Parsees in India, who are descended from the Zoroastrians (who believe in a God of good and a God of evil) who were expelled from Iran and Iraq, have an exceptionally high rate of breast cancer. Much more research has been done on disease incidence and risk factors than on the incidence of health and longevity factors, for obvious reasons: Disease is immediately obvious, but the absence of disease is more difficult to measure, and longevity requires waiting for a life span to ensue.

     The problem in recommending a "healthy" diet is one of insufficient information. We only have biomarkers which are surrogates for health and longevity. A white laboratory rat reproduces every 30 days, so in six months I will have studied six generations of rats and have a fairly good idea of which diets are beneficial or harmful for them. Humans reproduce every 25 years (on the average) and the longest detailed interventional diet study was 5 years, with a few tracking studies of 10 years and the Framingham study also available. So we just don't have enough diet data to advise healthy people (except the trivial advice to not get fat, not to smoke, and to have a glass of wine three days a week). And we have gotten burned with misplaced advice: Vitamin E supplements were shown to increase the rate of heart disease, and  the anti-oxidant beta carotene was shown  to increase the incidence of lung cancer in smokers. Finally, there is absolutely no evidence that diet is more important than the genetic makeup in a country's overall longevity.

Thursday, September 27, 2012

Electronic Medical Records: A Solution or a Problem?

     There have been many articles written lately about the use of electronic medical records (EMRs)  in the hospitals, in the emergency rooms, and in doctors' offices. These articles have appeared in newspapers, in medical journals, and in statements from the government, from medical societies, and most recently from the office of the Medicare Inspector General. As one who used to always  use pen and paper and now still uses them in my office but not in the hospital, I would like to offer my perspective, which is in addition to my previous blog on this subject.

     Firstly, we have the Scylla of insurance companies saying that if you didn't write it down you didn't do it and can't bill for it, or the Charybdis of the same companies saying that just because you wrote it down it doesn't mean that you actually did it. In either case, you cannot prove a negative, and lack of evidence is not equivalent to evidence of a lack, as any first-year logic student could tell you. Doctors used to be told that they should document what they did very carefully in the chart because (a) other doctors would depend upon their notes, and (b) careful documentation was the best defense against malpractice. Now the same doctors are told that if they do not document their actions carefully, they cannot bill for what they did, so the incentive has changed from good (for the patient) medical practice to good (for the doctor and hospital) financial practice.

     Not to be a complete Devil's advocate, but we doctors are pretty savvy, and we have been gaming the system for our patients' benefit  for years: If the insurance company will not pay for a PPI drug unless the patient has GERD and not just a stomach ulcer, then presto---all of our ulcer patients for whom we wish to prescribe a PPI have GERD. Similarly, if I think a patient is anemic, Medicare will not pay for a CBC blood test to look for anemia, because "rule out" or "I think that"  is not a disease, but Medicare will pay for a CBC if the patient has fatigue (code 780.79) and every patient has been tired at least once since birth, so I can code "fatigue" with complete honesty, since no time frame is asked for in the diagnostic box. I even know doctors (not me) who code 799.99, "unknown disease", telling themselves that every patient has at least one unknown disease, which is ultimately known only to the pathologist. You note that in each of the above cases, our experience tells us that a patient needs a certain drug or test, and we have to adjust our codes and words so that it is paid for. One might argue that it is the patient's responsibility to pay, but if a doctor knows that then the test will not be taken or the drug not obtained, I feel that we are morally obliged to act in the patient's best interest to ensure the best possible result, because our implied contract is with the patient to see that he/she gets the best care possible.

     So the medical record now has a dual purpose: to document what the doctor sees and thinks as well as to record the results of tests, and to provide evidence for the doctor's and hospital's bill. Usually these two requirements are not at cross-purposes, but they do act to increase the amount of time a doctor spends recording data. Trivially, a doctor cannot write "cardiac exam unchanged" if he wishes to get credit for examining the heart, but  he must repeat his examination and notation of the PMI, murmurs, gallops, splits, clicks, etc. Of course with the right computer template he can just cut and paste to achieve this result, but this does take time, and time is a doctor's least fungible resource. There even are computer systems where if the doctor clicks "normal lungs" the template spits out words like "clear to percussion and auscultation, no vocal fremitus, no egophony, no post-tussive rales, diaphragms move well and equally", etc. I want to emphasize that the doctor did perform the complete pulmonary exam, but the use of the automatic printout saves him time in writing it all out. And the doctor is no more likely to click on the link without doing the actual exam than he would be to write "normal lungs" without doing the exam.

     Now what are the putative and actual results of electronic medical records aka computer printouts? In theory, there should be fewer errors and patients' care should improve, but I know of no studies demonstrating a decrease in morbidity and mortality. And the Johns Hopkins pediatric hospital where pharmacy errors were noted pre-computer orders was shown to have an increase in medication errors after the introduction of computer-only orders. At my own institution, the system was down for 36 hours due to some glitch (gremlins anyone?) and the residents were quite helpless. I do know that the housestaff have become technocrats: When I asked one resident what a patient's hematocrit was, I was told that it wasn't in the computer yet, and when I suggested calling the hematology lab for the result, I was met with an incredulous stare, as if it never occurred to the resident that somewhere a human had to generate the test result before it was logged into the computer.

     Then we have the question of the security of medical records. We are always reading about CD's being left in taxicabs with thousands of patients' records, or a computer billing service accidentally releasing patients' information. I doubt that any of you would trust the security of a computer to keep secret the fact that you are an adulterous, bisexual,  cocaine-using, HIV-positive patient with a gambling and an  alcohol problem. All of us have patients that ask us not to write down certain embarrassing facts, but if the ER doctor thinks that the electronic record is complete, they will never call the family doctor to find out those key additional facts. My main responsibility is always to the patient, and I keep a problem list of embarrassing facts separate from the office chart, with the understanding that I will forward a complete problem list to any doctor to whom I refer the patient. I also should mention that when a patient comes to the ER, where one would think an accurate record would be of vital importance, his/her life is generally saved without reference to any written past medical history. The complete medical  history is of most value to the next office doctor, who needs the total story to be digested at leisure.

     One last concern: I know that I have trouble finding a place to view my VCR tapes, I've given up on my 8-track musical tapes, and my new car won't accept cassettes, but only plays CD's. What happens when an old computer record cannot be accessed by the new computer system? Yet I have pen and ink notes in the chart of 80 year old patients that are perfectly legible 50 years after they were written by my predecessor. Does anyone have a timeless electronic version of the Rosetta Stone?

   

   

   

   

   

   

   

   

Tuesday, September 18, 2012

Fingerprints and Fingerprint Identification

     I had been reading articles about how "incontrovertible" eyewitness identification and/or fingerprint identification led to the conviction of indicted persons, only to have the conviction legally overturned when DNA evidence showed scientifically that the person so identified was not the person who committed the crime. I began to investigate the use of fingerprints, looking for the basic science involved in saying that a fingerprint found at the scene of a crime matched that of a suspect, and I was surprised and shocked at what passed for "scientific evidence". As you will see below, any fingerprint identification is purely a judgment call, and the only basic science is that no two individuals have been shown to have the same ten fingerprints, much as no two individuals have exactly the same face (and both statements do apply to identical twins). The only distinction between the two is that some people are born without fingerprints and never develop them, while everyone has a face.

     The fingerprint found at the scene of a crime is called a latent fingerprint. It typically is only a portion of a fingerprint, and is usually smudged and distorted. The job of the fingerprint expert (with or without the help of a computer) is to make the final decision as to whether or not this partial fingerprint can be reliably and validly said to have come from a person whose fingerprints are on file. The decision is a judgment call, based on the expert's experience and visual intuition, and the fact that no two people have the same set of fingerprints is not the same as saying that no two people could leave the same latent fingerprint.

     The examiner looks for points of agreement, called Galton points, between the partial ridges of the latent fingerprint and the fingerprints on file, and no one knows the error rate for fingerprint identification. How many points of agreement are needed to call it a match (assuming the determination of a point of agreement is made without error)? New York, California, and London all have different numbers. In Italy, 16 points of agreement are needed to declare a match, while France and Australia require 12, and our own FBI has no minimum number of matching points to declare an ID. In America the number of points of agreement required varies from state to state, and even within a state.

     No pair of latent and rolled (recorded) fingerprints are ever 100% identical, so the question is: how much agreement is enough? There is no available evidence to answer the question as to how much correspondence between two fingerprints is needed to say that they were made by the same person. The examiner decides how much is enough, and there are no universally agreed upon standards as to what constitutes a match, nor are there any published studies of the ability of experts to match one fingerprint to another.

     I could find mention of only two tests given nationwide to fingerprint experts. In one case, the FBI sent two fingerprints from a robbery (where the identity was known) to 50 state fingerprint laboratories, and 10 failed to identify them correctly. In 1995 the Collaborative Testing Service, in a test okayed by the International Association for Identification sent 156 experts 4 suspect cards with all 10 prints along with 7 latents for identification. Only 66 of the 156 correctly identified all 7 latents, a success rate of less than 50%, and there were 44 incorrect identifications.

     Lest my readers think that this is all theoretical, and I am exaggerating the room for error, let me close by citing two internationally known cases of fingerprint error, one by the FBI and one by Scotland Yard, which led to the arrest of innocent people (one of them a policewoman), and then payment of monetary damages ($2M to the American) to both individuals because of the harm done to them.

     In 1998 the fingerprint of Policewoman McKie was found in the room of a murdered man in Scotland. The police had arrested a man for the murder, and asked her to account for the presence of her fingerprint. She swore that she had never been in the room, but even her father, a former policeman, believed the evidence. On the basis of the one fingerprint, she was indicted and put on trial for perjury. Her expert (who was later hounded out of his job at Scotland Yard and shunned by his co-workers) testified that not only wasn't it her fingerprint, but they police had  claimed that the partial had matched her left thumb, while he clearly demonstrated that the latent was of a right forefinger. She was acquitted but left the force.

     In 2004 a bombing in Madrid, Spain killed over 100 people. The Spaniards found one latent print, and circulated it around the world. The FBI claimed that it was the print of an Arab in the U.S.  named Mayfield, and arrested him as a material witness. They said they had 15 points of agreement, and that this was verified by three different FBI fingerprint experts. The Spanish police said that there were only 7 points of agreement, and that he couldn't have been the man (plus he had never left the country), and that the FBI had misidentified him. The Spaniards later found a man whose fingerprint they said was a match, and they then connected him with the presence of explosives, arrested him and convicted him.

     Until I began my reading, I did not realize how subjective the "science" of fingerprint-matching really was. There are no hard and fast standards, and the match is really in the eye of the beholder, much as is facial identification. The fact that fingerprints are almost certainly unique does not in and of itself make fingerprint ID valid and correct, any more than the uniqueness of our face makes witness ID 100% accurate.

Sunday, September 9, 2012

Untreated Hypertension (High Blood Pressure)

     One of the latest pieces to hit the news is that there are 32 million patients with hypertension (high blood pressure), 30 million of whom have medical insurance, who are not properly treated. By this the report means that their blood pressure is still at 140/90 or higher after being seen by a doctor (how many visits is unclear). Then the report calls for a massive effort to treat 10 million of these people to goal blood pressure in the next five or ten years.

     The problem with the emphasis on this statistic is that it completely ignores the patients, and focuses on the health profession instead. This is not dissimilar to the problem with getting patients to stop smoking, to exercise more, and to lose weight. The patients know what has to be done, but choose not to do it.

     The treatment models for smoking and obesity do not work for hypertension. Firstly, there is no moral obloquy in having high blood pressure, because the general public has no way of knowing that you are an untreated hypertensive. Secondly, until the first stroke, the patient feels no ill effects from the high blood pressure, much in the same way that diabetics feel no effect that they can ascribe to a high blood sugar. Thirdly, because of #2, it is difficult to convince most patients that they have a medical problem that requires pharmacological and/or lifestyle intervention.

     The easiest person to fool is yourself, as Richard Feynman famously remarked. When I encourage my hypertensive patients to take their blood pressure at home, close questioning reveals that most of them duplicate the behavior of my diabetics who measure their blood sugar by fingerstick at home. Both groups usually repeat the measurement several times until they get a number that satisfies them and then they record that number. With diabetics, I can use the glycohemoglobin to demonstrate this, but with hypertensives there is no way to verify their home numbers.

     What I am saying is that there has to be a massive propaganda effort to convince patients that untreated hypertension is a time bomb waiting to explode in their brain, to discuss the debilitating effects of a stroke, and to quote from the studies that have demonstrated that lowering high blood pressure significantly reduces the risk of a stroke. We still would then be left with a subset of patient who insist that lifestyle modification alone can control their blood pressure, while I try to explain that blood pressure, blood sugar and blood cholesterol all usually increase with age and that once they have hypertension the number rarely decreases of its own accord. In other words, the problem is not a lack of information transfer from the medical staff to the patient, but a lack of belief on the part of the patient that intervention is necessary.

Thursday, September 6, 2012

The Art (i.e. Human Side) of Medicine

     It has often been said that medicine is an art in addition to being a science, in that it is based, in part, on human-to-human interaction, with all the dynamics and pitfalls inherent in this process. There are qualities that  make a warm, interactive, "human" doctor, and we try to instill them in our medical students and residents both by lecture and by example. Below I will try to list some of the qualities and actions of which we try to make the students aware; some are actions to imitate and assimilate and some to avoid. This list is by no means complete, and the order in which it is presented does not correspond to the relative importance of the topics.
 
     Try to maintain eye contact. Patients complain that many of their doctors, especially referred-to specialists, spend most of their time entering data and looking at their computer screens.

     Always touch the patient at every visit, even if it is only to feel the pulse.

     Always sit down when you talk to the patient, so the patient doesn't feel hurried.

     Remember that ALL patients are anxious when in the presence of a doctor, and their anxiety increases sharply as the physical exam commences.

     If the patient has a chronic disease, there is probably also an element of depression.

     One of the most challenging problems in medicine is to help a patient with irritable bowel syndrome to realize that the symptoms and complaints are functional in nature.

     If the patient comes in with a cough, and you diagnose diabetes, the patient will feel untreated because you didn't "solve" the presenting problem.

     Always ask the patient what he/she thinks is wrong.

     Remember that the patient does not see and interact with you per se, but with Doctor You, so you are being viewed through colored glasses.

     Try to understand the patient's mental model of disease and acceptable treatment, or else your advice will not be fully followed, and possibly not followed at all.

     Roughly speaking, 25% of patients never fill the doctor's prescription, of those who fill it 25% never take it at all,  and of those who take it only 25% take it as frequently as prescribed.

     Always ask the patient which medicines their friends and relatives have given them to try.

     All patients have unspoken assumptions about their doctors, based in part on their prior interaction with authority figures as well as  with adults of the doctor's age and sex, and they will ascribe qualities to you that you do not possess.

     Please remember that no matter how intelligent your patient is, almost no patient has an accurate idea of how the body works, and is woefully ignorant of basic human physiology. (If I had my way, a year course of human physiology would be mandatory in every high school in the United States----I think that this would produce healthier patients.)

     Part of a doctor's responsibility is to define "normalcy" for the patient. Remember the old saying that an alcoholic is a patient who drinks more than his/her doctor does.

     Patients will emphasize and de-emphasize if not totally omit or forget parts of their medical history, in part due to the stress of seeing a doctor,  so I find it useful to repeat some questions during the patient's examination. In the hospital it is very common that the history I obtain from the patient on my morning rounds is different from the history the intern recorded in the medical chart the previous evening.

     In general, only a fraction of what you tell the patient will be remembered, and only some of your advice will be acted on.

     If the patient has a chronic illness, then the spouse is also under stress, and this stress is often ignored or not thought about by the patient's physician.

     I often call the patient the next day to see if further thoughts have occurred to the patient, or if any other questions have occurred to him/her, as well as just to "touch base", and I invite the patient to call me if new symptoms or questions occur.

     All my patients were told that if they called my office with a problem before 10 AM then I would fit them in that same day.

     If I had important instructions for the patient, I would type them out on carbonless carbon paper, with the note mailed to the patient and the copy placed in the chart, so that we each knew what the plan was.

   

   

   



   
   

Wednesday, September 5, 2012

Swine Flu Variant Outbreak

     The flu vaccine immunizes you against the swine flu, H3N2, but there has been a recent outbreak of a variant of this virus, called H3N2v, which variant has extra genetic material. It is associated with being in close proximity to live pigs, and so far there has been one death. It probably behooves us to get the flu shot early this year, and to avoid live pigs if you have any immune deficiencies or suffer from a chronic disease. The link to the article posted by the cdc is http://www.cdc.gov/flu/swineflu/h3n2v-outbreak.htm.

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.