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Monthly Archives: August 2007

Today we had our first onslaught of Medical Microbiology, a course that I already find quite interesting: if not for the subject itself, at least I know that my future pursuits will require that I have a very solid knowledge of infectious diseases (especially nosocomial, or hospital-acquired, infections). After today’s introduction and overview of the course, we launched into the two large Gram-positive bacteria families: the Staphylococcus and Streptococcus species, together accounting for large proportion of morbidity and mortality due to infectious diseases directly or indirectly as complications of other diseases (i.e. chronic, autoimmune, etc.).

The Staph family is responsible for a wide variety of diseases from skin infections to fatal conditions such as endocarditis (inflammation of the inner walls of the heart), septic shock, toxic shock syndromes, and pneumonias. The most famous Staph is MRSA, or Methicillin-resistant Staphylococcus aureus, a strain resistant to many antibiotics that is frequently found in cases of both community-acquired infections and hospital-acquired infections. Meanwhile, the Strep family is similarly responsible for a broad spectrum ranging from impetigo (a skin infection involving “honey-crusted” lesions) to pharyngitis (strep throat) to pneumonia to scarlet fever, rheumatic fever, and acute glomerulonephritis. Lastly, but most interestingly, the Strep family includes Streptococcus pyogenes, the bacterium most infamously known as the flesh-eating bacteria that causes a most terrifying disease known as necrotizing fasciitis.

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What I find most remarkable, though, is the surprise with which we meet the discovery that this horrifying microbe is not an exotic, tropical disease agent, but rather, it lives in our own backyards: on our skin. It’s not a swarm of migrating killer bees, or a particularly nasty species of fire ant stowing aboard a ship from the South Pacific. It’s just an everyday, common, garden-variety bacteria. My colleagues who have not read Atul Gawanade’s Complications or watched that episode of House, M.D. featuring what my girlfriend’s classmates affectionately call “nec fasc” (pronounced “neck-fash”) seemed alarmed by the notion that such a common bacterium could cause a disease that sounds like it came from a 1950’s horror film. Similarly, when cases of necrotizing fasciitis appear in hospitals, the popular media is often quick to jump on the latest scare with the same, strange avidity with which Hollywood has produced sequels to I Know What You Did Last Summer (I Still Know What You Did Last Summer,I’ll Always Know What You Did Last Summer…).

Now, we can be repeatedly suckered into the popular media’s (at best, ignorant) scare tactics every time a case of necrotizing fasciitis shows up, or we can actually learn something about this disease. A few pointers:

1. In NF, the bacteria infect the “fascia” or connective tissue beneath the skin, causing damage and the closure of blood vessels. The muscles and other tissue supplied by those blood vessels become ischemic (lose their oxygen and nutrient supply) and necrotic (cells start dying). While the bacteria spread through the connective tissue under the skin, certain components of the multi-faceted immune system are triggered by the infection and cause further damage to the surrounding tissue while the bacteria manage survive the attack with special protective mechanisms that inhibit the immune system components that might otherwise defeat the bacteria. The severe, sometimes fatal infection can spread quickly, within hours or days, and may have a mortality of rate of between 25-30%. NF may begin with any breakage of the skin (cut, scrape, surgical procedure, etc.) or through other unknown mechanisms.

2. Necrotizing fasciitis is a rare disease according to the Office of Rare Diseases at the NIH (National Institutes of Health), meaning it affects less than 1 in 200,000 individuals in the U.S.

3. Necrotizing fasciitis is usually caused by S. pyogenes, but may be caused by other bacteria or combinations of bacteria. These bacteria are often normal inhabitants on or in our bodies. It’s speculated that NF cases tend to occur when either:

(a) the patient is immunocompromised, such as with glucocorticoid treatments, immune deficiency diseases, immunosuppressant treatments, prior infections, or chronic diseases such as diabetes mellitus.

(b) or the bacteria on the skin interact with anaerobic (non-oxygen-requiring) bacteria, possibly swapping traits that allow one or the other bacteria to spread more readily and escape the immune defenses.

4. Again, necroticizing fasciitis is a RARE disease. However, if you or someone else is having a fever, chills, and a rapidly spreading, red swelling (aka erythema) (and/or other symptoms), it’s worth having it checked immediately by a physician. Catching and treating the infection early is very important for improving the patient’s prognosis.

This makes me wonder why there seems to be no such thing as “urgent” or “emergency care” in dermatology (though I suppose these extreme skin infections are thus treated in Emergency Departments, Medicine wards, and Operating Rooms). Which reminds me of an episode of Scrubs:

J.D.: “You see a lot of sad things in a hospital, but nothing’s quite as sad as a dermatologist that’s just been paged, milking it for all it’s worth.”

Dermatologist: “Alright everybody! Watch your backs! Skin doctor coming through! I gotta get somewhere! STAT!”

References:

1. MedlinePlus Medical Encyclopedia: Necrotizing soft tissue infection

My third week of my second year of medical school is coming to a close, marked by the first block exam: Inflammation. As one of our Mechanisms of Disease (Pathology and Pathophysiology) professors gleefully sang to us in his song “-Itis, -Oma, -Emia, the Big Three in Path-ol-og-y,” inflammatory diseases (”-itis”) are integrally involved in 80% of total morbidity of all diseases (including trauma), while vascular diseases (”-emia”) account for 60% of total mortality attributable to disease and neoplasias/cancers (”-oma”) account for 20% of total mortality attributable to disease. On that opening note, the second year represents a shift from the normal to the abnormal, the exploration of function to the identification of dysfunction, the passivity of being a bystander to the activity of being an intervener. Although we’re not responsible for patients yet, there is a subtle change underlying our shift in focus: just as Harry Potter finally learned after several books that he had no choice but to fight Lord Voldemort in mortal combat, we are beginning to learn the faces and MOs of our enemies, the diseases that we all must face at some point in our lives, whether in our own bodies or by the bedsides of our loved ones or our patients. (I couldn’t help but throw in an HP reference there.) Each year marks a significant step in our professional progression, and each change is arguably many fold greater in magnitude than the previous one. However, the feeling of “extended premed” education from the first year is gone: now, we are beginning to acknowledge our future opponents.

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But enough of the overly dramatic prelude! Here are some impressions so far:

Courses

Pharmacology has been very appealing and interesting so far: instead of being intellectually passive observers in Problem-Based Learning sessions or in the clinic with only the power of detection, we are now learning the tools of the trade. That is, we are learning the thought processes by which to treat and manage the maladies of our patients, and also learning the ins and outs of the treatments themselves. The emphasis then is more on problem-solving than on discovery: we’re medical students because we want to solve problems, not just point them out.

Clinical Diagnosis provides the other half of the equation: the skills of identifying and differentiating between disease states. This course, taught by the Chief of Medicine, was described by him as being a “meta-course,” a course that helps us use all of the information we learn in the other courses. Knowing something is one thing, being able to use it is another. This course, with its excellent lecture sessions and hopefully useful and carefully tailored preceptorships, is definitely going to be this year’s gem.

Pathology is the monster course of the second year: that is, it is the course with the most information, and it may not always be presented in the most effective or engaging ways. I’m very thankful that my Gross Anatomy instruction was top-notch and enjoyable as it can be a miserable experience for many medical students, but I’m worried that Pathology might be less cohesive. Although an inherently interesting topic (i.e. these are the diseases we will be fighting), I’m bothered that the course is explicitly and repeatedly described as being “not a lecture course.” This makes some sense in that there is a lot of material and limited time to convey all of the information, but without strong course leadership and direction, there is substantially less incentive for professors to teach comprehensively. It seems that the course policy should be “This course requires out-of-class study, but in lecture, we will help you learn the methods and core principles of pathology.” Either way, it seems that I will be spending quality time with outside resources.

Clinical Work

The Clinical Diagnosis course involves a preceptorship, not with a community preceptor (outside of the jurisdication of the university), but rather, with a preceptor at our medical school. Our Chief of Medicine seems to work closely with the preceptors, many of whom are his residents, and we’re supposed to have the opportunity to work by the bedside with the residents and clinical faculty in an academic hospital setting. Last year, my clinical experiences were almost “third world” in some respects, since I was often working with minimal equipment in free clinics and ERs. However, this year is likely to provide a much more solid and uniform clinical training on which we will tested during the spring semester with standardized patient examinations (focusing on both the patient-doctor interaction and clinical skills). It also will be nice working in a real academic hospital, rather than only being allowed to observe in community hospitals.

Despite having a heavy courseload this year, I also hope to spend some time at one of the free clinics that runs on a “medical home” model, and which received a multimillion dollar grant from Congress based on its success (one of a handful of clinics to be awarded such, and one of the few local institutions that has received any post-Katrina federal funding).

USMLE Step One

This test will certainly be the culmination of this year’s hard work and have an underlying influence on all of my activities this year, whether as a motivator or detractor. However, in some ways, I’m actually looking forward to it. It certainly won’t be fun studying all of the time, but herein lies an opportunity to prove my mettle and wrap up the first two years of my medical education with a significant challenge.

General Impressions

I think this is going to be a good year, albeit a challenging one. While the first year’s challenge was primarily one of transitioning to a new school setting and mode of learning, this year’s challenge will mainly be one of withstanding the mental duress. If no one was depressed last year, there certainly will be many signs of depression among my classmates and all second year students around the country this year. I’m bound to write about this topic with some frequency this year: I’ve managed to maintain composure and calm in light of the panic and stress of my classmates these past two weeks, but I plan to continue finding new ways and reinforcing old ways of keeping myself energetic and in high spirits. And yet, despite this, I think we’ll all make it through, perhaps not unscathed, but wiser and stronger.

Reference:
1. NEJM – “White Coat, Mood Indigo – Depression in Medical School”

There are many things I dislike about many medical blogs (and blogs in general): the term “medical blogosphere” sounds silly and full of self-aggrandizement, posts are usually too short or superficial to reveal any insight or critical thought, and many bloggers tend to be too lazy to include references where needed (including myself, but I try). Most of all, though, it disappoints me how one-sided the most popular blogs tend to be: many writers express a single viewpoint or emotion, appealing to a niche audience (however wide). Life is never so simple, though, and so the same debates repeat in an endless, 250-word cycle, across days, months, and years as new readers discover blogs and new writers emerge to express the same thoughts. I suppose this is a condensed, proliferative phenomena reflecting the slower growth cycles of popular media prior to the emergency of the Internet: with each generation comes new voices with old stories. Old wisdom with new packaging. Like the popular media, bloggers thrive on negativity: complaints and exposés provide a powerful catharsis for themselves and for their readers. Blog writers often criticize the popular media and try their best to uproot the establishment, but they themselves are prone to mimickry of that which they dislike: using sound bytes and sensationalism to prove a point. Blog writers, of course, are not unique in their approach; the same can be said about all people in the ways they express their thoughts and emotions. However, is this all there is to say and share about medicine, or about anything in life?

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There certainly is much to be frustrated and angry about in health care and medicine today, and it’s no surprise that many choose to vent this through public writing. It’s also no wonder, however, that even the most negative of blog writers find themselves periodically answering to their readers who question their continued participation in the practice of medicine: why keep practicing if medicine is really that awful a field to work in?

From what I have seen so far, it’s really not as bad as many make it seem (judging from my experiences, my interactions with physicians at all levels and stages of their careers and in different work environments, and from a broader perspective of the directions toward which medicine and health care are headed). The people who really can’t find reward, personal worth, and meaning in their professional work fall by the wayside: they drop out of medical school, they don’t continue on to residency, they choose not to engage in clinical practice, and sometimes they even try to justify their choice to end it by bestowing unsolicited advice and foreboding warnings upon others. If anything, I hope that medical school admissions committees improve their screening methods to weed out these individuals before any financial and time investment is made. Yes, the financial investment belongs to the student, but the time investment belongs to the school and our society: there are limited number of spots in each medical school class, and there is no room to waste on individuals who aren’t willing to make the commitment, be team players, and be nonjudgmental and compassionate healers.

Medical school candidates can’t just be smart: they also need to have some strength of character, willingness to grow, and capacity to be humble in the face of death and disease. It is this last characteristic that I believe is in short supply among physicians and physicians-in-training who are most vocal in their disdain for patients, in their contempt for difference and change, and in their self-aggrandizement. These individuals are a minority, but a loud and obnoxious one. Yes, there are many frustrations and problems with health care and its impositions on the good intentions and practice of physicians, but these frustrations should never alter the way we treat or view our patients. I believe the words of my Chief of Medicine: that you cannot believe one thing and act in a different way, you cannot have a certain attitude in private life and hide it completely in one’s professional work.

There’s an easy test to diagnose one’s own humility (as it is hard to detect in another person): have someone you respect tell you, “It is a privilege to be a physician.” There are definitely people who clearly demonstrate that they don’t believe this at all: perhaps they have lived in privilege all their lives and have never known hardship or suffering. For them, medical school and becoming a physician is just a matter of going through the motions to assert their social and financial status in a society that emphasizes accomplishment. And then there are those of us who are quietly tempted to believe that we have worked hard to earn a right to something: we’re placing ourselves in massive debt, we are (or will be) working ridiculous hours for minimum monetary compensation, we’ve worked hard in school for years, and we’re sacrificing the best years of our lives to work and training.

And yet, there is another, less tangible force pulling us in the opposite direction. For those of us who have seen or experienced true suffering and pain, whether just recently or early in life, there is something incredibly humbling in the exchange of glances, the hearing of cries, the feel of a painful twitch, the smell of death. There you are, in a room with someone who is sick or dying, and some part of you feels another presence, something wrong. Would you really stand around and do nothing, or even leave, if you had the capacity to do something? Whether for a loved one or a complete stranger, all of us feel (to some degree or another), a feeling more powerful than the fear and disgust: love. It’s you and another person against something inhuman, and the bond between you is more than a desire for survival; to survive, all you would have to do is run away. But we’re better than that: we don’t leave a man behind, we don’t leave our sick and wounded to die with fear in their eyes. There is no more humbling experience than to love, because in loving truly, one gives up one’s ego and pride to share an experience with another.

I am not an explicitly religious person, but I do believe in a greater order, a reason for life and a purpose for reason. I believe that there is no greater purpose in life than to express the best part of our humanity, and in doing so, reflect and express the divine origins and reasons for our existence. A couple of weeks ago, I had a friendly conversation with a complete stranger in front of my apartment. She, a member of the church next door, asked me not long after our greeting, “Do you believe in God?”, and I had no reservations or discomfort in saying, “Yes, I do.” That is, in fact, why I chose to pursue medicine in the first place: because there is no greater expression of humanity than love, and I can think of no other profession that can most benefit from an abundance of love for humanity. No other profession involves the same expression of humanity every day: in each moment we hold a patient’s hand, or deliver news, or work hard to find the answer, or offer strength to another in need. We’re not training to be doctors so that we can be weak, malcontent, and impotent: we’re here to offer our strength and hope to others, and there is no strength offered in contempt, disdain, and negativity.

“To love another is to see the face of God.”Les Miserables

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I’ve never been a stickler for political-correctness, but I’ve also had enough common sense to avoid needlessly offending others. I’m not offended by much, but it feels quite odd when I hear something and I know I should be offended but I can’t quite place my finger on why I should be. Recently, one of our otherwise charismatic and effective lecturers continuously referred to Asians as “Orientals,” clearly with no intention of offending but still lacking any clue that the term might be offensive to some people. While I was mostly amused (since my dad, an Asian and a first generation immigrant, occasionally used the term when I was growing up), there were scoffs and looks of surprise and disdain in the lecture hall. And then she showed this figure on a slide -

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And I laughed out loud. It was just too much. I’m surprised that the lecturer herself was a relatively young woman, maybe in her early forties, as opposed to the expected crotchety old male doctor.

I wouldn’t be surprised if many people are offended by the use of terms to which they are conditioned to be offended to (rather than know the specific reasons why), so I decided to find out why “Oriental” can be offensive. It turns out that the term is not considered offensive in most of Europe, in the United Kingdom, and in former United Kingdom territories (such as Hong Kong, where my parents grew up, thus explaining why my dad used to use the term before he became an American). However, it is considered offensive in the United States, primarily because it is an outdated term originating in a period of history when Asia was considered exotic and difficult to comprehend. In other words, young Asian-Americans are much more aware of non-Eurocentric views of history, and may be offended just as others might be offended by “Negro,” “colored,” or perhaps referring to all Hispanics as “Mexican.” The problem is not with the term itself: it’s with the clear-as-day, public declaration that it is acceptable to be ignorant.

On another note, I find myself not surprised but disappointed in the lack of foresight of some of my classmates who are completely turned off by the idea of researching and writing a paper on Complementary and Alternative Medicine therapies. While this year (the second year of medical school) will undoubtedly be intense and time-limited, it’s almost impressive how little understanding of the world around them people can demonstrate on a whim. While I am neither a supporter nor detractor of CAM therapies in general, it is clear to me that it is very important to understand them: they are either friends or enemies to our mission of helping our patients recover from disease and injury, and can we be so arrogant as to ignore them or write them off outright? No, we can’t: anyone with half a mind for strategy should realize that you have a very low probability of success of beating an enemy without knowing your enemy (especially one for which approximately $36-47 billion was spent in 1997, and for which approximately 36% of the American adult population used in 2004, not including prayer or megavitamins, which raises the number to 62%).

In stark contrast, it warmed my heart at this past Friday’s activities fair to see the many student groups dedicated to improving medicine, and in particular, those dedicated to enhancing the social awareness and responsibility of young doctors. Yet again, I’m proud of many of my classmates.

In some ways, this is a reminder to myself of the education I’ve sought: after four years at Harvard, in the highly progressive and insulated Boston, I now return to a world more representative of America: a mixture of liberal and conservative thought, a celebration of discovery but also of the weak comforts of ignorance, a wider spectrum of talent, interest, and passion. I’m in a world without larger-than-life heroes, for here, the names Paul Farmer and Atul Gawande and Jeffrey Drazen mean nothing to most people, including my classmates. Comparing notes with my girlfriend, I sometimes wonder if I’m missing much: there’s no telling where I’ll be in the future, but I do know that I’m exactly where I should be at this time. I need to know how (different types of) people think. I need to see how they grow during these four years in perspective and conviction. I need to see what it takes to make people the best they can be, and that might give me an idea of where I will focus my efforts to make a difference in the future.

I’m already in my second week of my second year of medical school, but I realize that I didn’t get the chance to properly bid farewell to my summer home: Washington, D.C. Although I worked harder than I would have liked or intended, these past two months have been very important to my career and personal development.

First and foremost, the bond between myself and a fellow physician-in-training has grown stronger and even more profound than before, leaving me excited to continue along this medical journey side-by-side with a kindred spirit. Though we have differences in interests, approaches, and educational styles, there is much we can learn from one another and much that we can share, and I feel very grateful that I can share this challenge with someone close to me rather than feel that the duress is driving us apart. When you’re too tired for self-reflection, it always helps to have someone else hold the mirror in front of you so that you can see who you are, how far you’ve come, and where you’re headed.

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Secondly, I’m grateful to my lab group and PI (principal investigator) at the NIH, where I spent the summer with a research fellowship. Nowhere else have I ever felt as welcome and as much a part of the group in a working environment as I did in this lab. My PI would check in on everyone each day, allowing thoughtful discussions to continue across the course of experiments rather than simply intersecting at the conclusion of experiments or the beginnings of new ones. (At no point did it feel like he was looking over my shoulder, either!) The other members of the lab were very friendly and welcoming, and they always seemed genuinely interested to know what I was working on even though the lab was very diverse in its lines of investigation. Lastly, despite some (government-style, administrative) mishaps, the overall atmosphere of the NIH seemed to encourage cooperation, professionalism, and productivity. In some ways, I feel bad that the experience didn’t inspire me to incorporate lab research into my vision of my future career; it certainly wasn’t because of the people or the place! At this fork in the road, I do feel that I am more drawn to clinical research (drug trials, treatment protocol development, etc.) as it more directly draws from the source of my inspirations to enter medicine: to improve health care, and to relieve suffering and the burden of disease to the best of my ability. To that end, research as a means of improvement will inevitably be an integral part of my career, though I hope my career will always keep me at the interface of individual experiences and disease rather than at a computer in an office – by choice, rather than by necessity.

Lastly, thanks to my wonderful, old friends and new friends in D.C. who made the city feel like a second home: I may come back someday to stay, if my pathway through medicine leads me back there.

Though never a panacea for the original problems, it is always nice to hear about companies (or people associated with them) working to ameliorate the negative side effects of product production and research. I recently visited the National Botanical Garden and was pleasantly surprised to find a room dedicated to herbal medicines: not “alternative medicines,” but rather, medicines that have been derived from plants throughout human history. It was impressive to see the wide variety of plants that people have used throughout the years, and also learn more about the historical context through which herbal medications were shelved upon the introduction of techniques to allow the production of isolated, purified chemical compounds. The benefits of this change are apparent: chemical compounds are much more uniform in efficacy and effectiveness, easier to store, have longer shelf lives, are easier to regulate and standardize, and are harder to produce (and thus bring their producers lots of money and market share). Many drugs, though, have their origins in nature, and there are substantial government, commercial, and NGO movements aimed at preserving biodiversity, natural habitats, and cultural knowledge of herbal medications that might otherwise be erased by modernization and globalization.

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There were two particularly interesting examples of plants being converted into drugs: the Pacific Yew tree producing the cancer drug Taxol/paclitaxel, and star anise providing the key ingredient in Tamiflu/oseltamivir. Interestingly, when paclitaxel was first made, the ingredients had to be isolated from the actual trees: a single tree might provide enough for one gram of the drug. The tree nearly became extinct as people rushed to cut them down and sell them to the pharmaceutical company (Bristol-Myers Squib). Fortunately, chemist Robert Holton was able to synthesize the drug in the lab, thus removing the need to harvest more of the slow-growing trees. (It’s not clear to me whether or not Holton was working with funding from BMS, but I suspect that the company would have seen incentive in developing a method of chemically synthesizing the drug’s main ingredient.) The synthesis for the key ingredient in star anise has not been devised yet (as far as I know), but hopefully Roche (or someone else) is working on that.

It’s important to know the repercussions and unexpected side effects of our actions, and it’s part of our responsibility as human beings to solve the problems we cause.

(aka “A Bad Day for GSK”)

Such is an original idiom from one of my college roommates, good friends, and one of a select few individuals for whom I would ever consider working for as a government official. Like many young government reformers, he is idealistic, hopeful, and believing in our generation as being the one that will restore credibility to federal authority. As much as I would like to share his optimism, I am more guarded in my faith in the ability to enact change through legislation and regulation: knowing what it means to spend years in the process of seeking citizenship and witnessing the combined effects of a presidential administration’s reluctance to provide meaningful, timely aid to a largely poor, Democratic city and the painful lack of coordination between federal, state, and local governments in the revitalization of the city of New Orleans have tempered my positive outlook on government as a medium for positive change. Nonetheless, I do believe that the government can be an incredibly positive force, perhaps the only sufficiently large, funded, and organized force, that can counteract large scale abuse and unseemly manifestations of human nature – when it functions properly and with the right tools.

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Last Monday, I attended the morning session of the FDA advisory committee meeting on the safety of thiazolidinediones (Avandia/rosiglitazone and Actos/pioglitazone). Of all of my experiences while working at the National Institutes of Health this summer, this was the most eye-opening and revealing. I took from the meeting this one insight:

The protection of the freedom of speech, above all things, is the most powerful tool against tyranny and the worst parts of our nature.

Repression comes in many forms, but most notably in these cases in the form of job security. The “hero” of the hour was Dr. David Graham, a drug safety and public health expert at the FDA who thoroughly (and objectively) skewered Avandia, despite the weak arguments in favor of its safety by the GSK scientists/vice-presidents. Tying together the data provided by the other FDA presenters, Dr. Graham asked the important question: If Avandia/rosiglitazone offers no benefit over a safer alternative in the same class of drugs, why should anyone take Avandia/rosiglitazone? Although the data on Actos/pioglitazone still needs to be as rigorously reviewed as that on Avandia/rosiglitazone, all of the studies on the pioglitazone “compass” point towards it being neutral towards coronary heart disease risk (though both drugs increase risk of non-lethal heart failure, which is a different disease) while all of the studies on the rosiglitazone “compass” point towards an increased risk of acute myocardial infarctions (heart attacks). Graham furthermore concluded with this point: Not only is there a projected multimillion dollar public health cost in the form of cardiovascular disease treatment if we keep Avandia/rosiglitazone on the market, but there is also an additional (up to one-third or so) opportunity cost if Actos/pioglitazone truly has a “protective” effect against acute MIs. His presentation, which unfortunately would take me forever to report in full here, was extremely solid.

Interestingly, after Graham’s presentation (the last of the presentations before the concluding statements of the morning sessions), the FDA department director who approved Avandia/rosiglitazone didn’t disagree with most of Graham’s presentation, but he did disagree as to the utility of glycemic control as an important objective in the treatment and management of diabetes (Graham argued that Avandia has no proven clinical benefit for the complications of diabetes mellitus, and it is the complications of diabetes mellitus that are directly linked to morbidity and mortality in the disease, not hyperglycemia/high glucose by itself. However, it is thought that hyperglycemia is the origin of the complications. Nonetheless, if that is so, one would expect that Avandia would decrease heart attacks, not increase them, since it reduces blood glucose by increasing insulin sensitivity, suggesting that the drug has specific negative effects.). Graham’s department head agreed with the presentation, indicating some of the fundamental disagreements within the FDA as to how to handle the regulation of Avandia. Nonetheless, before his presentation, Graham gave a verbal disclaimer that his boss fully endorsed his presentation but that it wasn’t the official stance of the department as his boss has to show it to the rest of the department, and that he (Graham) wasn’t presenting as an “FDA whistleblower.” (Graham, as muckrakingly noted by some popular news sources, has been involved in several previous drug safety disputes as a behind-the-scences champion for public health safety.) I was later told that Graham’s job security is under the protection of Congress: apparently, it has not been unknown for drug safety experts working for the FDA to be silenced and retired shortly after they exposed drug safety issues. This seems to correspond with the reports that there was an FDA safety official reviewing Avandia at its introduction to the market whose responsibility was removed after she expressed concerns on the drug.

Unfortunately, the suppression of honesty is not just within the government. As objective and open-minded as I was when I entered the room, I couldn’t help but feeling both very sad for the GlaxoSmithKline representatives and disgusted by them. The two physician-scientists who presented for GSK spoke very differently from the FDA presenters: they were monotone, they spoke slowly, and they repeated themselves frequently. However, it was painfully clear that the FDA officials and the invited committee members (physicians, scientists, patient advocates, etc.) were not at all convinced by the “new” data or the GSK meta-analysis provided by the GSK representatives, and it almost seemed like watching a cat-and-mouse game when questions were asked after the GSK presentations: they simply couldn’t answer many of them (effectively, if at all), such as why they chose an integrated rather than stratified stastical approach to their meta-analysis (which was an objection that spawned an FDA analysis which confirmed the Nissen and Wolski findings and provided further, more nuanced conclusions) which would “clearly favor rosiglitazone’s safety” and whether or not they were aware of a recently published study suggesting that pioglitazone reduces the risk of heart attacks as compared to active comparators (metformin and sulfonylureas) (despite GSK’s claims that “rosiglitazone and pioglitazone are exactly the same with respect to cardiovascular health”). While the two GSK representatives gave the impression of being sleazy and dishonest, another interpretation was suggested to me: they don’t have the freedom of speech. When things go well, it is great to be an industry scientist, but as soon as there is question as to the safety of a drug, the scientists have to toe the party line or they suddenly find themselves unemployed. I found this notion to be incredibly sad: I would hate to be in that position. Although Dr. Graham’s job is undoubtedly difficult and stressful, at least he can feel justified and have a clear conscience about his work; not so with the GSK scientists, or so it seems.

I think my friend described his saying to me as meaning this: “If you’re a barnacle on a whale, you have a pretty good life. You don’t need to expend any energy moving around, and the food comes to you. However, if the whale is beached or is killed, that’s a bad day to be a barnacle.” That must be what the GSK physician-scientists feel (to some degree, if we give them credit): despite their very hard work to produce an excellent product to save lives and treat disease, they have been put in a terrible position of suppressing their knowledge and the truth in order to preserve their livelihoods. Self-preservation over the lives of others.

It reminds me of this quote I recently rediscovered upon my adventures in our nation’s capital:

“I have sworn upon the altar of God eternal hostility against every form of tyranny over the mind of man.” – Thomas Jefferson (inscription at the Jefferson Memorial in Washington, D.C.)

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