Wednesday, May 27, 2009

Online Docs Give Advice About...Generics?!?


I am minding my own business, trying to keep up with my general infectious disease knowledge by following a link to a brief 15-minute video lecture on Clostridium difficile infection (subscription required) at the website Medscape. For those unacquainted, Medscape is a website designed to provide information for physicians about recent studies, with expert commentary, internet roundtables, and chat rooms for docs to anonymously cross-talk about a variety of professional topics. It's got a nice layout, the links are good, I'm a fan. A similar website that is also extremely popular among the medicine crowd is Up To Date, though its layout has a slightly different purpose, being more of an online textbook rather than a sort-of internet physician magazine as Medscape is modeled.

One of the critical and important differences between the two is that Up To Date generates its revenue by selling subscriptions, likely making the bulk of its money by package subscriptions to hospitals and medical schools. No commercial advertising can be found at the website. By contrast, Medscape's business model relies on commercial sponsors to generate revenue, and while I have no doubt that the editorial policies of the company are designed to create a firewall between pharmaceutical manufacturers and the physicians providing expert commentary, from my standpoint their corporate organization is inherently more prone to commercial influence than that of Up To Date. I don't consider Medscape out-of-bounds as a consequence--and I don't necessarily mean to imply that the creeping influence of drug companies is absent at Up To Date, but I do view the Medscape commentaries, particularly when it involves discussions of newer, patented drugs, with particular skepticism.

Which was why I was surprised to hear some refreshing commentary from Dr. David Johnson of the Eastern Virginia School of Medicine as he weighed in on the treatment of Clostridium difficile. Only a little tedious detail is needed here to explain matters. "C diff" infection is one of the most common causes of diarrhea in the US; standard treatment involves using a drug called metronidazole, but relapses in this disease are common, and the gold-standard medication for relapse is oral vancomycin. Vanco is an old-time drug, still incredibly useful, used most commonly in IV form. In that IV form it's pretty cheap. However, the pill form of it--and only the pill, not the IV, form of vanco is effective against C diff--is very expensive: a two-week course can run anywhere from just under $650 to more than $1700 depending on the dose. And oral vanco has but one manufacturer, ViroPharma Inc (annual sales approx $232 million in 2008, which makes it a small player by industry standards).

Given that, Dr. Johnson's advice perked up an otherwise thorough-but-staid academic discussion:

For oral vancomycin, I'm going to give you a tip: When you send the patient to the pharmacy for vancomycin, 125 mg every 6 hours for 14 days, that's about a $1200 ticket for that oral therapy. That pill or capsule is actually a nongeneric and it is something that's extremely expensive. It's anywhere from $15 and upwards per capsule. Now, the tip is to work with your pharmacy. Get them to compound this. Take the IV vancomycin -- take a gram. Have them compound that in a liquid formulation. It doesn't taste very good, but they can put some sweetener in this. They can then take a gram and make 8 doses of this in a liquid formulation. The half-life or shelf life of this you'll have to work with your pharmacy in compounding, but that dose now costs approximately a dollar.

If you're not doing this, you really need to be. Think about the cost savings. We have about a 15-fold-plus cost reduction per dose. Patients now take this incredibly cheap medication, oral vancomycin, as an IV formulation compounded, delivered over the course of the same timeframe. If you're not doing this, you really should be. It's a tremendous savings and certainly of equal efficacy. [my emphasis]

I am not trying to pick on ViroPharma, which for all I know is a perfectly respectable corporation trying to bring useful drugs to the marketplace. But I am saying that vanco has been around for a long time as a drug, well past the expiration of its patent, so there is no reason why a doc shouldn't be proud of pushing a cheaper form of the medication and doing so in the patient's best interest. For we are in theory supposed to act solely on their behalf and not on those of a multimillion dollar corporation. If both interests can be dovetailed, that's fine, but I am now a fan of Dr. Johnson because his little digression makes it entirely clear where he places his loyalties.

Saturday, May 23, 2009

The Difference Between HIV and AIDS

President Obama gave his commencement address at Notre Dame last week, and not surprisingly the mainstream media used it as an opportunity to focus on the topic of abortion, with the usual suspects touting their usual views. None of which is my concern here. Instead, I was caught by surprise by a quick reference the president made about the different assumptions that create the framework by which people understand today's political issues. He noted:

The soldier and the lawyer may both love this country with equal passion, and yet reach very different conclusions on the specific steps needed to protect us from harm. The gay activist and the evangelical pastor may both deplore the ravages of HIV/AIDS, but find themselves unable to bridge the cultural divide that might unite their efforts. Those who speak out against stem cell research may be rooted in an admirable conviction about the sacredness of life, but so are the parents of a child with juvenile diabetes who are convinced that their son's or daughter's hardships can be relieved.

I have no quibbles with anything he said, but I was curious as to who was advising the president about using the phrase "HIV/AIDS" rather than either "HIV" or "AIDS." Why both?

To understand what's at stake here we need a little history lesson. In the spring of 1981, gay men in Los Angeles and New York City began falling ill with what at the time were genuinely weird diseases--lung infections from a fungus called pneumocystis carinii and a skin cancer known as Kaposi's Sarcoma which had previously been seen almost exclusively in elderly men from the Mediterranean. Nobody knew what it was, nobody knew how it worked, nobody understood why just gay men in the biggest cities would be coming down with two highly unusual diseases. Lots of very smart people from several institutions like the CDC and the NIH had good ideas about it, but nobody knew for certain.

When a situation in medicine like this occurs--that is, when a patient has a constellation of signs or symptoms but there is no clear-cut explanation for why the patient is ill--we use the nomenclature of syndromes. As I sometimes tell my patients, calling something a "syndrome" is a way for a doctor to say, "we don't really know what's going on, but we do know something's wrong, and we want to sound smart about it." Whence the "Chronic Fatigue Syndrome" or "Chronic Pain Syndrome." In truth, for most medical conditions that bear the label "syndrome" today we do know the underlying cause. Down Syndrome, for instance is caused by the fetus carrying an extra 21st chromosome in all of its cells; but when Dr. Down was doing his seminal work in the 1860's describing the syndrome, he had no idea about how the syndrome occurred. It wasn't until nearly a century later, in 1959, when the chromosomal abnormality that causes Down Syndrome was identified.

So in late 1981 and early 1982, docs were getting a pretty good idea about the features of the syndrome causing mostly gay men and hemophiliacs to die, but nobody knew what the causative agent was (although several scientists such as Don Francis were already reasonably confident that it was a sexually-transmitted virus). An early clinical description that won out was the unfortunate term "GRID," for Gay-Related Immune Deficiency, but by September 1982 the current term Acquired Immune Deficiency Syndrome gained official recognition by the CDC, and it has been called such ever since.

The causative agent of AIDS was discovered the following year by Luc Montangier of the Pasteur Institute and Robert Gallo of the NIH. Montangier's group referred to the virus as the Lymphotrophic Adenovirus, or LAV, while Gallo called the virus HTLV-III, for Human T Lymphotrophic Virus (the "T" standing for "T-cell"). Immediately it became clear that both viruses could be the same (they were), and a heated scientific dispute broke out over who would receive credit for the discovery. (This remains something of a controversial topic, covered for instance in Randy Shilts's great book And The Band Played On.) The dispute was essentially resolved in 1986 when the virus was dubbed the Human Immunodeficiency Virus. But by that point there had been five years of extensive, fear-mongering press coverage even by the most well-meaning outlets, and the default term during that time was AIDS.

It is hard in the post-Magic Johnson era to recall how much fear surrounded the diagnosis of AIDS between 1981 and 1991 (almost exactly ten years separated the initial reports of the disease with Johnson's announcement that he would withdraw from playing basketball), and while that term does not quite possess the same ability to engender fear in people, it still has the power to stigmatize. And it does so in ways that "HIV" hasn't quite managed to. I was not fully aware of this until I started my HIV clinic during fellowship, and discovered that my patients weren't terrified by having "HIV infection", but they didn't want the word AIDS used around them and they would avoid hearing it at all costs--all this due to the power that the word has in the various communities from which many of these people come.

We could simply do away with the word, fully replacing the concept of "AIDS" with "HIV infection," were it not for a little quirk of CDC and why Obama's use of the term "HIV/AIDS" was technically correct, though unfortunate. AIDS is now considered to be a special subset of people with HIV infection, which the CDC defines as people who have a T-cell count below 200 (the range for people without infection is between roughly 500 and 1500) or those who have developed opportunistic infections like the pneumocystis carinii mentioned above.

I myself have decided in my professional life to call patients who fit that description those who suffer from "advanced HIV," and to eschew using the term AIDS altogether. The disease has enough stigma attached to it; I see no reason for adding to the potential for shame, and the use of the term "AIDS" appears to do just that.

Thursday, May 14, 2009

Influenza as Metaphor

Two examples, one from the right and one from the left:

Jay Severin of WTKK-FM in Boston is typical of the class of overheated right-wing nativists that populate talk radio. During the height of the H1N1 panic a few weeks ago, Severin used his radio platform to describe Mexicans as, among other things, "primitives," "leeches," and a personal favorite, "exporters of women with mustaches and VD, [...and] swine flu." Severin was suspended for his remarks, which as the saying goes, is saying something. Severin was hardly the only right-winger that waxed disgustic on the nativist theme, using the virus as a shorthand to talk about how "pure," "real" America is being polluted by its southern neighbor. He was simply the most outrageous, which again is saying something.

A different take on the flu epidemic can be found here (the animal-rights organization PETA), or here (a columnist of an English-language newspaper in Pakistan), or here (generic blog entry) where the theme of "Mother Nature's Revenge" was sketched out. Of these three, columnist Irfan Husain has the most lucid observations:

"In a sense, this latest epidemic is an example of nature striking back. As in avian flu and mad cow disease, the close proximity of animals and birds due to industrial farming, as well as the feeding and breeding of these unfortunates creatures, is causing diseases to mutate very rapidly. As soon as one antidote is discovered, the virus mutates. Rats in Britain are now resistant to virtually every kind of poison used to reduce their numbers, and there is a growing concern that they might cause a plague."

But both these political "readings" of the flu are inherently flawed. The virus is not an immigration problem, nor is it a symbol of an immigration problem. American press coverage of lethal viruses have a tendency to emphasize the foreign-ness of certain viruses (e.g. Ebola and Marburg) while de-emphasizing the fact that we harbor such viruses or bacteria within our own borders (Sin Nombre, plague). The notion that scary and dangerous threats to our civilization come from the outside, and at that typically from third-world countries, is easily understood. If you don't believe me, watch the Dustin Hoffman movie Outbreak again.

Nor is this influenza episode an example of "nature's revenge." It may yet prove true that some of the industrialized agricultural conditions (see here for a good outline of the problem) might have laid the groundwork for a fast-moving and potentially dangerous pandemic; but that is not mother nature trying to "teach" us a lesson. Nature is neither something for which we are specially-appointed caretakers, nor is it (like the metaphor of God) a parental figure there to bring us sustenance or punishment depending on our behavior. Nature is complicated, messy, fascinating, teeming. But it is not moral.

I don't mean to imply that this right/left misreading of the outbreak has an equivalent impact on political dialogue. While both ways of interpreting the recent events may have their problems, it is the right-wing (at least in this country) that has the power of many mass media outlets behind it. That a maniac like Jay Severin has the ability to have a show on a major commerical radio--keeping in mind that Severin is just a small cog in this media machine, small fry compared to the likes of Limbaugh, Michael Savage, Ann Coulter, Sean Hannity, and Bill O'Reilly--while the voices of the far-left are by-and-large confined to certain corners of the internet and some very local AM radio, says a lot about the disproportionate influence of far-right thinking on national political dialogue. Just because they both be wrong don't mean they's the same.