This month, Sydney Spiesel discusses heartening research about statins, disheartening research about vaccinating the elderly for the flu, inhaled insulin, the word from doctors treating Katrina victims, and the plague. (Click here for the August and July roundups.)
Statins revisited: They help after heart attacks, too.
State of the science: Statins, the medications that block the body's production of cholesterol, seem to have no end of valuable properties. Besides their usual job—cutting down coronary artery disease and heart attacks—they also appear to decrease the chance of getting certain kinds of cancer and strokes. Recent research, which examined more than 90,000 U.S. veterans, suggests that elderly patients taking statins are at decreased risk for broken bones. An even more striking finding emerged this month from research involving over 170,000 patients studied immediately after a heart attack. Conducted by Gregg C. Fonarow of UCLA's Division of Cardiology and his colleagues, the study makes a strong case that early use of statins following a heart attack substantially decreases the risk of death or serious complications.
Question: Interestingly, we really have no idea why these beneficial effects occur. The studies that uncovered them were following up on incidental observations in other studies or on rabbit and rat experiments that showed similar protections for animals at risk for heart attacks.
The flu vaccine: Not so good for the elderly.
State of the Science: The most recent outbreak of the avian flu (H5N1) in Indonesia has probably involved over 40 people, of whom six have died. Out of the six, perhaps two or three acquired the disease from infected people rather than birds. Sooner or later, it is likely that this virus will acquire the ability to infect human beings more efficiently. We need a vaccine. There's a problem, though: Recent research by Lone Simonsen and his colleagues at the National Institute of Allergy and Infectious Diseases casts some doubt on the protection that the current influenza vaccine gives to the elderly, who are most at risk of a bad outcome from flu.
Simonsen's group looked at mortality trends that could be attributed to an exceptionally virulent strain of human flu (H3N2) that emerged in 1968. If immunization helps prevent serious disease in elderly people infected with influenza, then the flu death rate should fall as the percentage of older people who are immunized rises. Simonsen's complex statistical modeling boils down to this finding: Even though immunization rates increased from 15 percent to 65 percent during the period under study, there was no substantial effect on influenza-related mortality.
Caveat: The authors of this study are careful to point out that their results are somewhat at odds with some earlier studies, which suggested greater value for elderly people who are immunized. As a doctor, I don't want to risk carrying flu to my patients, and I'm in the age range for which this shot has traditionally been recommended. So despite the serious questions raised by this study, I'm sure I will yet again take my flu shot this year. But it will not surprise me if future research shows that older people need a different vaccine than young adults—perhaps a more concentrated one.
Inhaled insulin: No more shots?
State of the Science: As all science-minded schoolchildren should know, in 1921 the Canadian scientists Frederick Banting, Charles Best, J.J.R. MacLeod, and J.B. Collip developed insulin, the first treatment for diabetes. Insulin was a miracle drug, capable of transforming an almost uniformly fatal disease into a survivable illness with good quality of life. But as any diabetic will tell you, its failing is that it must be injected. Other methods of giving insulin—oral administration, nasal sprays, others—have been tried, but none have worked.
Now, for the first time, an insulin inhaler (which carries the drug into the body via the lungs) is close to FDA approval. Exubera, as the product will be called, is the first of five similar products in development. The manufacturer, Pfizer, submitted data to the FDA that suggests that the insulin inhaled through Exubera is approximately comparable in performance to injected insulin (though not better). A majority of the FDA advisory panel that examined the data recommended approval, and such recommendations are usually accepted.
Ancient History: It is not easy to deliver a medication to the place in the body where it is needed. In the olden days (but, alas, in my memory) there were basically three ways to administer one. If you wanted topical effects, you could apply creams or ointments to the skin. If you wanted to administer a medication to the entire body, you could take a drug orally or by injection. Medicines taken either way are usually absorbed rapidly and eliminated by the kidneys or liver equally rapidly. A few tricks were available to slow down the absorption. Injection could be packaged in a slowly dissolving goo and the whole mess deposited as a glob in a muscle, from which the active ingredient would be released slowly over a period of time. In a hospital, intravenous medications could be set to gush or to drip slowly. Oral medications could be placed in the center of many small beads, each covered with coatings that dissolve at different rates (remember those "tiny time pills"?).
Modern History: The first big improvement in drug delivery was the introduction of inhaled drugs for lung diseases like asthma. Once perfected, this method allowed high concentrations of active medications to be delivered deep in the lung. The next stride forward was the tiny portable pump. It permitted the long, slow injection of medications, which proved to be of enormous benefit to many diabetic patients, as well as sufferers from other diseases. Next came patches held to the skin by adhesives. These dispense drugs that pass through the skin slowly. They're used for everything from motion sickness treatments to contraceptives.
Other new technologies are stunningly clever. Concerta, a medication used to treat attention deficit disorder, consists of a capsule with a tiny laser-drilled hole in one end. The drilled end is packed with the active drug, which passes out into the intestine through the hole. The other end of the capsule holds a material that swells as it absorbs water. As the material swells, it pushes the active ingredient out through the tiny hole. So, Concerta capsules are really tiny pumps that release their active ingredient at a precisely controlled rate over a very long period of time.
Caveat: Exubera is a tremendously attractive product, both for diabetics and for Pfizer stockholders. It's important, though, to point out that not all the members of the FDA panel (the vote was 7 to 2) agreed that it was the right time to release inhaled insulin for general use. The dissenting panelists raised significant, if theoretical, safety concerns about this medication. They were concerned about possible long-term side effects from extended chronic use. For example, in some tissues insulin acts as a kind of growth hormone, stimulating cells to proliferate. What if this effect were to take place in the lungs? These organs need to be mostly hollow to function and excess cell proliferation might fill them up—with ill consequences.
Inhaling insulin could also produce antibodies that could either inactivate the inhaled drug, or cause serious allergy and inflammation in the lungs—as asthma does. For some reason, this method of giving insulin stimulates considerably more antibody production than the old-fashioned method of injection. Still, so far we have not seen any of the predicted negative effects. The two dissenters on the FDA panel to release the medication point out, however, that the product has only been in testing for four years, perhaps not long enough for serious side effects to emerge.
Katrina: Report from Slidell.
FEMA on the Ground: I just spoke with Dr. Jim Morgan, a friend and local pediatrician who joined a group of other doctors from Connecticut who traveled to Slidell, La., to help out in the wake of Katrina's devastation. He adds to the reports that the professionals sent by disaster relief agencies like FEMA and the Red Cross were often hampered by the bureaucratic nature of their agencies. For example, unlike the mobile New Haven doctors who arrived with stocks of medications, the FEMA staffers had no medications to give out and weren't organized to travel to patients in need of care. Confined to a fixed location in the middle of the destruction, they could only pass out prescriptions to people who had little or no money and in places without open pharmacies.
The victims: Dishearteningly, Dr. Morgan and his colleagues found that most of the medical problems of the Katrina victims were not the result of the hurricane, but rather poverty and scarce health care. The patients they saw suffered from obesity, high blood pressure, the form of diabetes associated with a poor diet, and the consequences of a lifetime of little or no dental care. These are not the medical problems of a natural disaster; they are the problems of going without health insurance.
The plague: A camel's tale.
Outbreak: Bizarre medical report of the month: Abdulaziz Bin Saeed of the King Saud University College of Medicine in Saudi Arabia, joined by Nasser Al-Hamdan and Robert Fontaine of the U.S. Centers for Disease Control and Prevention, describe a cluster of five plague cases in a remote desert town in Saudi Arabia. Investigation of this outbreak revealed that most of the victims suffered from an exceedingly rare form of plague (sometimes called the Black Death), the devastating illness that wiped out perhaps one-fourth of the population of Europe and Asia in the 14th century.
Usually, people get the plague when they are bitten by fleas that previously feasted on plague-infected rodents. In this case, plague-infected Libyan jirds (essentially rat-sized gerbils) and their fleas were found near the camel corrals. But there is substantial evidence that neither the jirds nor the fleas caused the human cases. The patients were all related to each other. The four with bubonic plague shared another thing in common: They had all eaten raw camel liver from a sick camel. The fifth patient, who developed bubonic plague, was the man who had slaughtered the camel. Two of the five patients died. The others were hospitalized.
Lesson: One might think that a case this exotic would be unlikely to yield much of a take-home lesson. But this rare manifestation of the plague was quickly diagnosed because the local preventive medicine specialist who called for assistance remembered seeing similar cases 10 years earlier. This sort of memory bank is invaluable. Every doctor cherishes a remembrance of hospital rounds with an experienced physician who pulled just this kind of rabbit out of his or her hat.