This month, Dr. Sydney Spiesel discusses the latest in fat-fighting drugs, why bubble bath gets a bad rap, the likely merits of over-the-counter cough remedies, and the solved mystery of the 1977 red flu. (Click here and here for the last two roundups.)
Fighting fat: Still no magic bullet (sigh).
The problem: Excessive weight is harmful in many ways; it is also very hard to take off. The essential problem is this: The psychological rewards that we gain from weight loss—improved health and mobility, approval and admiration, perhaps increased attractiveness—are more than balanced by the physical rewards of eating. The succulence of a roast goose, the delicately spiced aroma of bhagan bartha, the rich sweetness of a shaving of chocolate melting on the tongue, the … well, you get the idea. It is not unusual for the best specialists to fail even when they are treating patients who seem strongly motivated, and sometimes in life-or-death situations. That is why we are searching for new and better methods (and medications) to approach this problem.
The old treatment: Many weight-loss medications have been tried over time, sometimes with lethal results. One, banned since 1938, uncoupled the body’s mechanism for “burning” (oxidizing) fat and making use of the energy produced. The released energy was lost as heat, which resulted in both weight loss and (oops!) death. Other old drugs that dulled appetite are no longer used because of side effects like sleep disturbance and addiction.
The new treatment: Now in the news is orlistat (Xenical), which an FDA committee has recommended may be sold over the counter. (No final decision has been made yet.)
Does orlistat work? Yes, especially if given in the context of a weight-loss program that includes exercise and dietary control—the sort of program that people may be less likely to embark on if they take the drug over the counter. Orlistat may be particularly useful to children and adults heading toward Type 2 diabetes. It works by inhibiting an enzyme produced by the pancreas that is necessary for the absorption of dietary fat. Block the enzyme, and ingested fat passes right through you.
Caveat: Which brings us to the side effects. The unabsorbed fat often leads to flatulence, diarrhea, increased bowel movements, and even anal leakage. These are undesirable for many reasons; they also have medical consequences. For instance, poor fat absorption leads to poor absorption of fat-soluble vitamins, like vitamin A and vitamin D. So, patients taking orlistat must take extra doses of these nutritional elements. It may be that orlistat’s side effects (“anal leakage,” for goodness sake) account for some of its moderate effectiveness—they are so unpleasant that patients learn to avoid eating fatty foods. There is plenty of medical precedent for that. For example, the drug disulfiram (Antabuse) negatively conditions alcoholics by making the physical effects of drinking quite horrible. Unfortunately, with orlistat as with Antabuse, the conditioning quickly fades when the medication is stopped. Patients generally regain the weight they’ve lost.
The future: Orlistat may offer some benefit but certainly is not an ideal medication. What’s next? Remember the munchies that you got when you were, umm, exploring the chemosphere in your college dorm room? In development are “anti-munchie” pills: medications that block the receptors in the brain for endocannabinoids, naturally produced materials with marijuanalike properties that make you want to eat. One of these experimental products, rimonabant (Acomplia), is undergoing clinical testing as an appetite-control agent. We’ll see if it is effective and safe.
Bubble bath: Not guilty.
The mystery: Recently, I saw a youngster with all the symptoms of a urinary tract infection. She was in pain when voiding, frequently needed to pee, and had difficulty in starting a stream. As usual, I took a history. She obliged me with a report of a recent bubble bath—on every pediatrician’s list of risk factors for a UTI. I congratulated myself on asking the right question. Then I thought about the answer. How is it that bubble bath causes urinary tract infections? Is bubble bath exceptionally acid or alkaline and thus irritating when it washes into the urethra? Does it roughen the lining of the urethra, enhancing the attachment of bacteria to the urinary tract? Does it cause real urinary infections or merely irritations? I decided I’d better go look up the answer.
Clue: I found only two papers in the medical literature that spoke to the question of UTIs and bubble bath, both published before 1970. One mentioned a total of three cases of irritation, not infection. The other described four cases—also of irritation rather than infection. Interestingly, five of the patients in the two reports were boys and only two were girls.
Resolution: The absence of other reports suggests that bubble bath probably doesn’t do anything bad, except in what must be vanishingly rare circumstances. Everything I (and most of my colleagues) believe about its role in generating UTIs is almost certainly wrong.
Lesson: So, what about the history I obtained from the girl with the UTI? I asked a question prompted by my preconception and, sure enough, I got the answer I expected. But if I’d asked the same question of the many youngsters I see who don’t have UTIs, I might have heard about a lot more bubble baths. Too much of what we “know” in medicine is like what I knew about UTIs and bubble bath—stories based on a few case studies, presented uncritically, which are handed down from generation to generation. You can’t understand the epidemiology of an illness unless you can compare affected patients with patients who are free of the disease or condition in question.
Cough medicine: Does it work?
The problem: Coughing makes patients crazy. It cuts into sleep, interferes with school and work, and often drags on and on and on, adding to general anxieties about the state of people’s health. Coughing also makes doctors crazy because it is often hard to pinpoint the cause of a cough—and because every once in a while the cause is a serious and dangerous illness we dare not miss. The consequence of this mutually high level of anxiety is a strong inclination to treat a cough. Remedies merit a good hard look, to avoid wasting money and harming patients with useless or inappropriate treatments.
State of the science: This month, the American College of Chest Physicians, an umbrella organization of doctors with special interest in respiratory medicine, published a comprehensive paper devoted to the cough in the journal Chest. The paper recommended against using over-the-counter cough medicine for patients sick with the common cold. Written by a committee chaired by Dr. Richard Irwin of the University of Massachusetts Medical School, the article did not report new research. Instead it examined 239 questions or assertions (if I counted correctly) about the cough and its management. Throughout, Irwin’s committee set the worthy goal of examining critically the scientific basis for the underlying evidence in support of each of its recommendations.
Caveat No. 1: Cold medicines perfectly fit my First Law of Pediatrics: If there are 100 treatments for an illness, none of them works. Still, do the recommendations in the Chest paper stand up to scrutiny? From my standpoint, that’s a little hard to say. One of the two components that the authors used to grade treatments is “benefit,” a value judgment that seems pretty subjective. What I consider beneficial another doctor might think trivial. I’ve noticed that before they have children, the pediatric residents I train are unyielding rocks when parents request cough medicine; afterward they often tout the medicines they previously disdained. This doesn’t mean that cough syrup actually works, but it says something about the role of desperation in evaluating a remedy.
Caveat No. 2: I’m also a bit suspicious of the scientific evidence the committee drew from the research literature. I’ve gone back to the original papers on which some of the recommendations are based, and sometimes I would have rated them more poorly for quality of evidence than Irwin’s committee did. The gold standard in medicine is the “randomized controlled trial,” in which patients are assigned randomly to receive a real treatment or a sham treatment and neither the patient nor the doctor knows which is which until the results are in. But the trial isn’t worth much if the investigator doesn’t ask the right question. For example, one common cough-medicine ingredient is dextromethorphan, or DM. It’s similar to codeine (though not addictive and not a pain reliever). Like codeine, DM decreases cough. Also like codeine, it lasts only a very short time in the body before it is eliminated. So, if you give a dose of cough medicine containing DM at bedtime and ask patients how well it worked the next morning, you likely won’t get a very positive response.
Conclusion: That’s how the studies behind the Chest paper’s negative recommendations were done. If, however, you could slowly dribble in the medication all night (and there are cough medications that do just that), your patients might give a different answer. I want to stress that while slow-release might seem great, we won’t know if it is until a careful study has been done. But by the same token, it seems premature to recommend against the use of all cough medicines.
Bonus: I never take cough medicine myself. I don’t think that anything works unless you believe in it and I’m a skeptic about most of these sorts of remedies. I remember my mom giving me honey and butter for a cough when I was young. But I noticed that when she had a cold, her choice was whiskey and lemon juice.
The red flu of 1977: A whodunit.
The mystery: As I don’t need to tell anyone, a new form of avian flu (or H5N1) is traveling the planet. So far, few humans have caught the disease—about 150 confirmed cases in the last three years. But other forms of influenza have caused 21 pandemics in the past 250 years. Now scientists are paying close attention to these previous pandemics in order to understand the factors that cause—or at least foretell—the emergence of a huge outbreak. As a result, we understand much more about how the unique biological characteristics of the influenza virus can lead to an epidemic. The recent research has had an unexpected consequence: It pretty much confirms an old suspicion that one influenza outbreak—the “red flu” of 1977—was man-made.
History: The 1977 outbreak began in northern China and adjacent regions of Russia. “Red” flu (named for its Communist country origins) represented a reappearance of the H1N1 flu type, which first appeared in the 1918 Spanish flu pandemic. H1N1 flu fortunately lost much of its human virulence as time passed after that disaster. It flared again in about 1950 but by about 1957 appeared to die out. After that, H1N1 was not found anywhere in humans with the flu for two decades. Then suddenly, there it was again in 1977.
Resolution: The tools of molecular biology rule out the theory that H1N1 was carried for 20 years as a mild, unnoticed, human-to-human infection, or an animal infection that again became infectious for humans. The 1977 red flu turns out to be virtually identical to the H1N1 flu of the 1950 epidemic. Given the mutation rate inherent in the genes of influenza virus, H1N1 couldn’t have passed unchanged for 20 years from person to person or from animal to animal. New research also rules out the return of H1N1 via the corpse of a 1950s flu victim, buried in frozen ground and then exhumed and thawed. This virus can remain stable and contagious in the supercold conditions of a laboratory freezer, but it falls apart in the much warmer natural temperature of permafrost. We can deduce, then, that the 1977 pandemic flu could only have come from the release of a specimen from a laboratory freezer.
Culprit: So, whodunit and why? We’ll almost certainly never know the answer. Probably the release was simply a mistake. But it’s also possible that it resulted from an experiment in live-virus vaccine-making gone horribly wrong.
The future: Could this kind of accident happen again? Sure, but it is far, far less likely than it used to be, precisely because we have become aware of the risks. A more limited accident in England caused a few cases of smallpox in 1978, after the worldwide elimination of the disease as a natural infection. And at least 68 people died of anthrax in 1979 after an accident caused a widespread release of this germ from a Russian biological-warfare plant. These days, work with dangerous pathogens is conducted in specialized labs designed to prevent the accidental release of these materials. In 1977, however, we dodged a bullet when the effects of the release of the 1950 H1N1 influenza turned out to be relatively mild.