02/03/10 1:16 PM
It's the Phenome and Not the Genome: Put Your Money on Mortal Flesh
Strong is your hold O mortal flesh . . .From The Last Invocation, Walt Whitman
Is it just me, or are you also getting a bit tired of all the hype about the genome? Don't get me wrong-- it's pretty incredible that in my lifetime we have mapped out the 25,000 plus genes in our DNA. What's even more amazing is that the price for that chart of the human genome has gone from millions to less than $50,000 and now it takes only a few weeks. I bet by next year it might be a few hundred dollars and take a day! Companies like 23andMe (an innovative venture with a great marketing plan) offer to check you for genetic markers that predict your risk for certain diseases for just a few hundred dollars.
But the fact remains that for most of us, the genotype is much less relevant than the phenotype. What is phenotype? It is the things we can see, the outward or observable physical or biochemical characteristics and they are determined by both your genetic makeup and environmental influences. Your blond hair, your weight, your strange nose, green eyes and that funky shaped little toe of yours --all examples of phenotype.
So what do I mean when I say phenotype is more relevant than genotype? Well, let's say a new patient, a male, walks into my office and he is in his fifties. Let's say he happens to have the outline of a pack of cigarettes showing in his front pocket. As a male he already has one risk factor for coronary artery disease--just being male, alas. The cigarettes tell me that he is four times more likely to have a heart attack than his peers who don't smoke. His risk of sudden death is at least doubled. Let's say I notice he happens to be carrying more than 30 pounds of extra poundage above the belt line: that allows me to predict he has a higher chance of being at risk for diabetes, if he is not already frankly diabetic. Let's say that I notice too the pale outline of a recently-removed wedding ring (I can't help it, my eyes are always looking at the body as text--even when I am out of the hospital), then I know that his risk of death as a recently divorced man can be double that of his married peers.
At this point, before he has even said a word or before I have examined him, I already know so much about his risk of death and disease. Once we talk and I learn more about his job, his stress, his heredity, his habits, his past illnesses, then my predictions get more accurate. Once he disrobes and I examine him, I might find other phenotypic markers that predict risk (such as yellow plaques related to high cholesterol on his eyelids or elbows; high blood pressure; skin tags and velvety darkened areas of skin that predict diabetes; narrowed blood vessels when I look into the back of his eye . . . the list could go on for pages). In short, I'll have an excellent sense of my patient's risk for death or disease. At that point, mapping his whole genome, sexy as it might seem, won't tell me much more than I know and will probably matter much less than getting him to quit smoking, exercise and lose weight.
The famous Whitehall Study of British Civil Servants ranging in ages from 20 to 64 found that the lower grades of civil service had higher mortality rates from heart disease and from all causes than did people in higher grades, even after accounting for risk factors like obesity and smoking. (Yes, it was counterintuitive and that is why we do studies). Stress was thought to be the factor responsible for this disparity.
The Whitehall studies are ongoing and one of the latest reports from that study made me think of Walt Whitman and reminded me that the phenotype is so relevant. In their report (titled, "Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study" and appearing in the British Medical Journal, 2010 Jan 14;340:b4838), the scientists compared a panel of genetic tests for diabetes (common single nucleotide polymorphisms) with non-genetic or phenotypic findings like age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status, HDL, triglycerides, fasting glucose.
What they found was that the phenotypic tests did better. Indeed the gene tests added little to the risk already determined by phenotypes. In their own words, "the addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation . . ." Translation: use your eyes, take a good history, weigh the patient and get a few simple blood tests, and you can predict risk far better than a panel of genetic tests.
I am not a Luddite (I find I say that a lot) and indeed, I do think the genome studies will help us eventually understand more about causes of disease, and perhaps even point to particular treatments. But until then the message for us in the trenches is: Strong is your hold O mortal flesh and that's where the money (speaking diagnostically) is.
Photo credit: David McNew/Getty Images
For one who has an interest in the body as text, airports are treasure troves of information. It seems almost un-American to enjoy delays, and perhaps enjoy is not the best word, but certainly a delayed flight, if it does nothing else, allows one the opportunity to make prolonged observations about one's fellow travelers.
"Why airports?" you might ask. Well, for one thing there is the lighting--the big picture windows that allow you to see planes taking off are marvelous at lighting skin, muscle. A turn of a woman's neck, an elegant profile, but also an enlarged thyroid, perhaps not pathologically enlarged, and yet readily seen, an entity that is more common in young women and in pregnancy.
But here is the real asset: airports offer long corridors, miles really, and the leisure of observing a gait as it plays out coming or going or both. The features of an old stroke, the so called "hemiplegic" gait, are readily seen (the arm flexed, the lower limb stiff and extended, the leg making a little outward semicircle as it moves forward --this is the circumducting gait). But at times the only vestige of the stroke is none of these things because there has been an almost full recovery, all but for the fact that the arm on the affected side does not swing easily as the person walks. This last, the arm swing, is an "associated" movement and is the last to come back. It is a rule in neurology, I am told, that the most recently learned functions are the first to go and the last to come back, and so it is with the arm swing.
Other common gaits? The shuffling gait of Parkinson's; the antalgic gait of someone with a bad knee; the occasional foot drop on both sides of a patient with neuropathy producing a decided lift of each leg with every step.
What else does one notice commonly? The furry brown darkened skin at neck creases in those who are overweight--it is a skin condition is called acanthosis nigricans and it suggests insulin resistance, potential diabetes. One also sees cafe-au-lait spots, cherry angiomas, tremors....
I could be here all day.
P.S. If you are wondering what I am doing in airports, I am on a book tour. Details here. I am trying to blog here, and make notes from the road on Twitter (@cuttingforstone) and on Random House's Facebook page for me, but really it is so tempting to just sit here and stare....
Photo credit: joiseyshowaa/flickr
In 1996 a surgeon was operating on a rare malignant tumor when he accidentally cut himself. Some months later he developed an identical tumor at the very spot he had injured. Fortunately, this new cancer responded to treatment. Still, the idea of this means of cancer genesis--a "catching cancer" if you will--was mind boggling at the time. Mind you, this was the height of the HIV era and we were seeing a lot of patients with Kaposi's sarcoma (another cancer) and we were performing biopsies and bronchoscopies on patients with these malignancies, so the idea of a "catching cancer" was alarming. Could tumors accidentally be aerosolized and inhaled in the course of such a procedure?
Of course, the notion of cancers spreading from one person to another is not new, but it always involves a virus. An example would be papilloma virus which causes venereal warts and which can predispose to cervical cancer. Kaposi's sarcoma (which is now rare for me to see in North America) proved to be related to sexual transmission of HHV-8, a human herpes virus. But for a cancer to spread from one person to another in the absence of a virus would be remarkable, which is why the report of the surgeon getting inoculated with a cancer through a skin cut was memorable.
There is, however, one animal species at least where such "catching cancer" occurs commonly. Tasmanian devils are prone to something called Tasmanian Devil Facial Tumor. Tasmanian devils, in keeping with their cartoon reputation and their colorful name, are ornery, combative creatures, prone to biting each other. But it's not the internecine warfare that's threatening the existence of the species, but instead a peculiar cancer of the face and jaws, a cancer that seems to sprout from the very spot where one devil was bitten by another.
Careful research by Elizabeth Murchinson and a group of scientists, reporting in the journal Science, suggests that Tasmanian Devil Facial Tumor is truly unique in that it is not a virus causing the transmission. Instead, the work of these scientists suggests that one day, perhaps two decades ago, a cell became cancerous in one Tasmanian devil. The cancer grew and probably killed the original animal but not before that devil had bitten another devil and allowed the cancer to graft on to the new host.
In that sense, the Devil Facial Tumor is truly like a transplant of an organ. But most transplants of organs are rejected by the immune system unless the host is a twin; it is possible that Tasmanian devils are pretty inbred and therefore genetically very much alike so that the cancer cells are not rejected the way a transplant from an unrelated donor would be rejected.
The only comparable "catching cancer" is one in dogs that is sexually transmitted; this is an ancient cancer and it does not always result in death; it can even regress. Sadly for the Tasmanian devils, the Devil Facial Tumor might be cause for the eventual extinction of the species. The population is already down by 70%.
I found the Tasmanian Devil Facial Tumor story to be a fascinating piece of research, a good explanation of a novel means of cancer development. Often, in isolated case reports--such as that of the surgeon who nicked himself and developed the very tumor he had cut out from a patient-- we get an insight into a previously unknown mechanism of disease.
Of course, a behavioral change could prevent further spread: no bite, no cancer. Alas, for all the potential life saving benefits, behavior change is so hard. And that's true of both humans and Tasmanian devils.
I watched an extraordinary documentary last night, right on my computer. A Walk To Beautiful, set in Ethiopia, has special meaning for me because it tells the story of childbirth injury and the resultant fistula, and because the Hamlins--pioneers of the surgical repair of fistula--were my professors in medical school. You could hardly live in Addis Ababa and not be moved by the suffering of women with fistula, or not know of the Hamlins' legacy. Not surprisingly, the story of fistula is very much at the center of my novel, Cutting for Stone (Knopf) which takes place in Ethiopia and America.
Reginald Hamlin passed away some years back but Catherine Hamlin is very much a presence, The two of them built the Addis Ababa Fistula Hospital in 1974. Catherine Hamlin tells the story of their lives together and their legacy in a wonderful memoir called The Hospital by the River: A Story of Hope. On my last visit to Ethiopia in 2004, I got to visit the hospital (which was built after I left). Alas, I didn't get to meet Dr. Hamlin, who was away, but we corresponded. In her last letter she said she was halfway through Cutting for Stone and enjoying it. I am waiting the final verdict.
The incredible cinematography makes A Walk to Beautiful almost like a poem; there is a tenderness on display that seems to emanate from the camera. There is also great sensitivity to the women whose stories are being told--never did I have a sense of the subjects being exploited. This is particularly important because the story of fistula repair dates to Marion Sims in 1845 (even though women have suffered with fistula since recorded history); Marion Sims's story is heroic, at least by his account, and yet shameful when we look at it now. His surgical success occurred on the backs of patients who were slaves, cast out by their owners because of the incontinence caused by the fistula. Sims operated on the same three slave women multiple times, until he perfected a technique which is similar to what is used today. His accounts imply the three women consented to his surgery, but how can anyone in bondage truly give informed consent? We have little record of the women's account of the experience.
Ultimately, fistula is a reflection of a failed infrastructure and societal failure; the medical disaster is a side effect. It is largely a rural story. It begins with child marriage--girls who are not fully grown being given to grown men. Rickets and malnutrition contribute to a narrow pelvis and when pregnancy occurs, the baby often cannot come out--its head is bigger than the pelvic circumference. The prolonged trauma --days of futile labor--results in death to the baby and often to the mother. If she survives, her bladder and bowel, which were pinned between the bony baby's skull and the bony pelvis are scarred and sometimes torn so that the contents are continuously dribbling into the vagina. The resources to do a Cesarean sections quickly would avert this catastrophe. And that requires good roads, transportation,and health clinics where obstetrical problems can be managed.
It is striking to me that in south India, where I also trained in medicine, fistula which was once common is now rare--the infrastructure--roads and clinics--allows quicker access to medical care and extraction of the baby.
I hope you'll click the link and watch A Walk To Beautiful. In these times when we are wrestling with healthcare reform, this documentary is a breath of fresh air. It reminds us how much we take for granted.
Reginald Hamlin passed away some years back but Catherine Hamlin is very much a presence, The two of them built the Addis Ababa Fistula Hospital in 1974. Catherine Hamlin tells the story of their lives together and their legacy in a wonderful memoir called The Hospital by the River: A Story of Hope. On my last visit to Ethiopia in 2004, I got to visit the hospital (which was built after I left). Alas, I didn't get to meet Dr. Hamlin, who was away, but we corresponded. In her last letter she said she was halfway through Cutting for Stone and enjoying it. I am waiting the final verdict.
The incredible cinematography makes A Walk to Beautiful almost like a poem; there is a tenderness on display that seems to emanate from the camera. There is also great sensitivity to the women whose stories are being told--never did I have a sense of the subjects being exploited. This is particularly important because the story of fistula repair dates to Marion Sims in 1845 (even though women have suffered with fistula since recorded history); Marion Sims's story is heroic, at least by his account, and yet shameful when we look at it now. His surgical success occurred on the backs of patients who were slaves, cast out by their owners because of the incontinence caused by the fistula. Sims operated on the same three slave women multiple times, until he perfected a technique which is similar to what is used today. His accounts imply the three women consented to his surgery, but how can anyone in bondage truly give informed consent? We have little record of the women's account of the experience.
Ultimately, fistula is a reflection of a failed infrastructure and societal failure; the medical disaster is a side effect. It is largely a rural story. It begins with child marriage--girls who are not fully grown being given to grown men. Rickets and malnutrition contribute to a narrow pelvis and when pregnancy occurs, the baby often cannot come out--its head is bigger than the pelvic circumference. The prolonged trauma --days of futile labor--results in death to the baby and often to the mother. If she survives, her bladder and bowel, which were pinned between the bony baby's skull and the bony pelvis are scarred and sometimes torn so that the contents are continuously dribbling into the vagina. The resources to do a Cesarean sections quickly would avert this catastrophe. And that requires good roads, transportation,and health clinics where obstetrical problems can be managed.
It is striking to me that in south India, where I also trained in medicine, fistula which was once common is now rare--the infrastructure--roads and clinics--allows quicker access to medical care and extraction of the baby.
I hope you'll click the link and watch A Walk To Beautiful. In these times when we are wrestling with healthcare reform, this documentary is a breath of fresh air. It reminds us how much we take for granted.
Of late we Americans have discovered Yemen, thanks to a foiled terrorist and the recognition of a burgeoning Al Qaeda camp in that country. The front page of the New York Times today has a story about Yemen, complete with map. But it fails to mention the one thing that will most impress you if you visit Yemen and it's a plant called qat. You can't fathom Yemen (or Somalia for that matter) if you don't understand qat--no map can quite explain its influence on politics, culture and the economy.
If you land in Aden or Sanaa, you will notice people with a chipmunk like bulge in their cheek and the unique slewing movement of the jaw that characterizes the qat user. By chewing lots and lots of the tender leaves of this nondescript plant, one experiences a very mild amphetamine-like high. Alas, this does not translate into a super-industrious nation with a tremendous work ethic and high productivity. It translates instead into a nation where 80% of people spend many hours a day chewing qat and a nation whose ground water is rapidly drying up because 80% of water by some estimates is being used for qat cultivation. A Yemeni friend I grew up with once explained to me that mornings in Yemen are spent planning and day-dreaming about the afternoon qat session (and good luck to you in transacting serious business after one), and the actual session takes care of the rest of the day. Qat sessions are intensely social: men sitting on mattresses, bolsters for their backs and knees, a big pile of leaves in front of them, hot tea and cold water being served, and animated discussions taking place. The world's problems are soon solved in that room. After several hours, things turn quiet and contemplative (the Hour of Solomon, as it is known) and at last the session is over. Alas, no brilliant solutions actually emerge; nothing but hot air comes out of the room.
Qat is grown in Ethiopia (where I spent my years until early adulthood--my parents were schoolteachers from India hired to work there), Yemen and other highland areas and is popular all over East Africa. As children, our trips back to India during the holidays involved a stop in Aden, a fascinating city best described as an oven carved out of volcanic rock, albeit an oven that was a duty-free haven. My novel, CUTTING FOR STONE (Knopf), has my protagonist, Sister Mary Joseph Praise saying the following about Aden when she finally disembarks after a terrible sea voyage from India and after a prolonged quarantine of her ship anchored outside Aden (an experience which no doubt colors her perception):
My own memory, I must say before I get angry letters, is more charitable to Aden than hers. I recall as a child landing with my parents, emerging from a DC3 into the stifling heat, and eventually finding shade in a cool and sophisticated hotel. I recall too that from the hotel there was a tiled walkway, with a Rolex watch symbol embedded in the tile, and if you followed this trail it led you to a duty-free shop. My father bought a Rolex there in 1957 or so, an entry level model (and yet an expensive purchase for him), with a face so small that these days it looks more like a woman's watch. The dial is now yellowed but it still runs and ever since he gave the watch to me, I wear it proudly. In a world of glittering, diamond-studded Rolexes and other such timepieces, this humble watch generates attention from the cognoscenti-- I have been stopped more than once and given a short treatise on the provenance of this watch. I know nothing about watches except how to tell time, and I am proud to be one of the few analog people left in a digital world; but it does allow me to tell the the story of my father, Aden and the duty-free store. (N.B.: Rolex, if you read this, you can send me a free diamond-crusted one but please don't mind if I continue to wear the old one--it is truly priceless.)
Sadly, despite oil and other resources, Yemen seems stuck. I recall being told by a Yemeni shopkeeper in Addis Ababa that but for qat, Aden could have been a great cosmopolitan city, another Paris or Beirut, to use his words. I don't know about that. But I do know that what Yemen has become now in the eyes of the world--a country in the news for the worst possible reasons-- has to have some connection with qat, which is the economy and yet which hamstrings the economy, a plant that energizes while paradoxically producing societal apathy.
So if we are trying to understand how former Guantanamo Bay prisoners sent to Yemen managed to escape from a 'high-security' prison to now lead a newly vitalized Al Qaeda cell in Yemen, I don't doubt that money and qat opened some doors.
If you land in Aden or Sanaa, you will notice people with a chipmunk like bulge in their cheek and the unique slewing movement of the jaw that characterizes the qat user. By chewing lots and lots of the tender leaves of this nondescript plant, one experiences a very mild amphetamine-like high. Alas, this does not translate into a super-industrious nation with a tremendous work ethic and high productivity. It translates instead into a nation where 80% of people spend many hours a day chewing qat and a nation whose ground water is rapidly drying up because 80% of water by some estimates is being used for qat cultivation. A Yemeni friend I grew up with once explained to me that mornings in Yemen are spent planning and day-dreaming about the afternoon qat session (and good luck to you in transacting serious business after one), and the actual session takes care of the rest of the day. Qat sessions are intensely social: men sitting on mattresses, bolsters for their backs and knees, a big pile of leaves in front of them, hot tea and cold water being served, and animated discussions taking place. The world's problems are soon solved in that room. After several hours, things turn quiet and contemplative (the Hour of Solomon, as it is known) and at last the session is over. Alas, no brilliant solutions actually emerge; nothing but hot air comes out of the room.
Qat is grown in Ethiopia (where I spent my years until early adulthood--my parents were schoolteachers from India hired to work there), Yemen and other highland areas and is popular all over East Africa. As children, our trips back to India during the holidays involved a stop in Aden, a fascinating city best described as an oven carved out of volcanic rock, albeit an oven that was a duty-free haven. My novel, CUTTING FOR STONE (Knopf), has my protagonist, Sister Mary Joseph Praise saying the following about Aden when she finally disembarks after a terrible sea voyage from India and after a prolonged quarantine of her ship anchored outside Aden (an experience which no doubt colors her perception):
" . . . from the sailors on the Calangute she had gathered one could hardly go anywhere in the world without stopping in Aden.The port's strategic location has served the British military. Now its duty-free status made it the place to both shop and find one's next ship. Aden was gateway to Africa; from Africa it was gateway to Europe. To Sister Mary Joseph Praise it looked like the gateway to hell. The city was at once dead and yet in continuous motion, like a blanket of maggots animating a rotting corpse. . . "
My own memory, I must say before I get angry letters, is more charitable to Aden than hers. I recall as a child landing with my parents, emerging from a DC3 into the stifling heat, and eventually finding shade in a cool and sophisticated hotel. I recall too that from the hotel there was a tiled walkway, with a Rolex watch symbol embedded in the tile, and if you followed this trail it led you to a duty-free shop. My father bought a Rolex there in 1957 or so, an entry level model (and yet an expensive purchase for him), with a face so small that these days it looks more like a woman's watch. The dial is now yellowed but it still runs and ever since he gave the watch to me, I wear it proudly. In a world of glittering, diamond-studded Rolexes and other such timepieces, this humble watch generates attention from the cognoscenti-- I have been stopped more than once and given a short treatise on the provenance of this watch. I know nothing about watches except how to tell time, and I am proud to be one of the few analog people left in a digital world; but it does allow me to tell the the story of my father, Aden and the duty-free store. (N.B.: Rolex, if you read this, you can send me a free diamond-crusted one but please don't mind if I continue to wear the old one--it is truly priceless.)
Sadly, despite oil and other resources, Yemen seems stuck. I recall being told by a Yemeni shopkeeper in Addis Ababa that but for qat, Aden could have been a great cosmopolitan city, another Paris or Beirut, to use his words. I don't know about that. But I do know that what Yemen has become now in the eyes of the world--a country in the news for the worst possible reasons-- has to have some connection with qat, which is the economy and yet which hamstrings the economy, a plant that energizes while paradoxically producing societal apathy.
So if we are trying to understand how former Guantanamo Bay prisoners sent to Yemen managed to escape from a 'high-security' prison to now lead a newly vitalized Al Qaeda cell in Yemen, I don't doubt that money and qat opened some doors.
By New Year's Eve I will have finished another spell on the wards as
attending physician overseeing a wonderful team of interns, residents
and students; our team has been admitting patients every fourth night.
The experience always leaves me in awe and reaffirms my faith in
internal medicine.
I've become better at the EMR--electronic medical record--and grateful that the days of hunting all over the hospital floor for the missing patient chart are over. So also with trooping down to radiology and trying to get a file clerk to find a particular x-ray, which too often had been checked out by another team. I'm so glad we don't do that anymore. Now, from any computer, including my home computer, I can call up CAT scans, MRIs, lab results for my patients. The only thing I resent about the EMR is that it is a time sink and it's in direct competition with time we should spend with patients.
I so appreciate these advances. The other day I felt compelled to describe to a student how "in the old days" (and at another institution) we would go down to medical records in a basement dungeon and hunt down the old charts, which might run to several volumes. Those thick stacks of paper held together by rubber-bands were dust laden, often fenestrated with book worm tracks, and sure to trigger some wheezing if you were predisposed. (I was.) My student listened to me with fascination, almost as if I were describing something romantic and desirable. I hastened to say it wasn't something I'd want to do again.
Two days ago a Stanford colleague in anthropology introduced me to the term, "imperialist nostalgia": romanticizing the past while choosing not to remember the particular injustices of that period. An example might be a colonialist recalling the wonderful days in a hill-station bungalow, while forgetting the slavery or apartheid that might have made that possible.
"Imperialist nostalgia" is a great term, and for me its a cautionary one. I 'm keeping it in mind as I make this very short list of things I like about the way we practice medicine now:
The analogy for me would be skills for which boy scouts earn badges; those skills hardly equip you for all the exigencies of life. But they do make you appreciate that technique is important, as is repetition. It's not enough to read about a slip knot or a bow line or an anchor bend (and by the way, check out "Animated Knots by Grog"-- a lovely site ); you still have to pull that rope out and practice, practice, practice.
That's no nostalgia, that's a fact.
I've become better at the EMR--electronic medical record--and grateful that the days of hunting all over the hospital floor for the missing patient chart are over. So also with trooping down to radiology and trying to get a file clerk to find a particular x-ray, which too often had been checked out by another team. I'm so glad we don't do that anymore. Now, from any computer, including my home computer, I can call up CAT scans, MRIs, lab results for my patients. The only thing I resent about the EMR is that it is a time sink and it's in direct competition with time we should spend with patients.
I so appreciate these advances. The other day I felt compelled to describe to a student how "in the old days" (and at another institution) we would go down to medical records in a basement dungeon and hunt down the old charts, which might run to several volumes. Those thick stacks of paper held together by rubber-bands were dust laden, often fenestrated with book worm tracks, and sure to trigger some wheezing if you were predisposed. (I was.) My student listened to me with fascination, almost as if I were describing something romantic and desirable. I hastened to say it wasn't something I'd want to do again.
Two days ago a Stanford colleague in anthropology introduced me to the term, "imperialist nostalgia": romanticizing the past while choosing not to remember the particular injustices of that period. An example might be a colonialist recalling the wonderful days in a hill-station bungalow, while forgetting the slavery or apartheid that might have made that possible.
"Imperialist nostalgia" is a great term, and for me its a cautionary one. I 'm keeping it in mind as I make this very short list of things I like about the way we practice medicine now:
- terrific ability to look inside the body, to probe, see, reconstruct
- incredibly efficient ways that we can store and access data
- much less shuttling between the radiology file room, the medical records room and the patient room
- quick access to information about disease--everyone seems to carry a peripheral brain (a PDA loaded with ePocrates or Skyscape or the like) so knowledge has become democratic and instantly available at the point of care
- great choices in therapy for the treatment of so many diseases that just twenty years ago would have had a different outcome (rheumatoid arthritis is a great example).
- pretty good data to tell us what works best - "evidence-based medicine" (I can't believe I am touting the term, having railed against its zealots for some time. The fact is that I am all for evidence as long as its well applied and applied to the right patient.)
- I regret that more and more we seem to distrust our eyes (and almost all of dermatology for example relies on observation, as do a myriad of other diagnoses); we distrust our ears (and the tale the patient might tell us if we only listen long enough) and we distrust our senses. We are putting far too much emphasis on "test results" to tell us what to do next.
- We see too little of our radiology colleagues because we don't go down there as much as we used to. It's a loss--it was great to show them a CAT scan or MRI and give them the clinical context, and then hear their opinion.
- I miss the nurses' station with the chart racks which used to be the social center of each floor of the hospital. Since you can write your note from anywhere (including from Starbucks), we we wind up "talking" to each other through the medical record. We don't develop relationships that are good for coordinated patient care.
- I bemoan the fact that the art of bedside diagnosis is in danger of extinction. The people who invented these skills (beginning a hundred and fifty or more years ago) had to wait for an autopsy to reconcile what they saw or felt or heard on the outside of the body with what was actually going on inside. Now, we can make those correlations in real time; it should have made us superb at the bedside. Instead I worry we will get to a point where if you are missing a finger and show up in a hospital, no one will believe you till they get an MRI, CAT scan and an orthopedic consult.
- Technique at the bedside is rarely emphasized, never really tested in board-certifying exams (at least in my field of internal medicine), and there are a diminishing number of people who will be able to teach it as time goes on.
The analogy for me would be skills for which boy scouts earn badges; those skills hardly equip you for all the exigencies of life. But they do make you appreciate that technique is important, as is repetition. It's not enough to read about a slip knot or a bow line or an anchor bend (and by the way, check out "Animated Knots by Grog"-- a lovely site ); you still have to pull that rope out and practice, practice, practice.
That's no nostalgia, that's a fact.
12/25/09 2:35 AM
Health Reform: Magnificent Xmas Present But Needs Assembly
So it's done. The health care legislation has passed and that makes this a special Xmas. Despite its flaws, it is a milestone for a nation that could be so generous with its aid abroad, yet stymied in caring for its own. I clearly could not have been a politician--I would not have the patience of the president to tirelessly campaign for this and to see it through; nor would I have the tenacity of the opponents to the legislation who opposed it to the end.
This morning I will drive in for my rounds at the hospital (my team is on call, bless their hearts,and will stay all day and night, while I get to come home well before nightfall) and I am already trying to digest what this Xmas present means for my patients and for my house staff. In the last few days we pulled out all stops to get patients home. The ones who can't go home are too ill, and going home may not be an option; instead it might be a specialized nursing facility or rehabilitation place. One or two of these patients have been very much on my mind, long after I leave the hospital, their suffering both palpable and difficult to forget, and making me conscious of the blessings of just walking outside, stepping into a car and going somewhere.
Watching the health care reform process from a relative distance, from the front line so to speak, as opposed to being in the generals' tents (though I did get invited to the White House to watch the president on ABC's "Prescription for America" months ago in the summer), here is what I note:
Recently an infectious disease colleague mentioned on a listserve that after a high altitude trip he developed a 'splinter hemorrhage' on one nail (a red vertical streak, looking like a splinter). These are not very specific and can happen from trauma; but they can also come about from heart valve infection. The finding would be ominous in someone who is an intravenous drug addict and presents with fever and other signs pointing to heart valve infection. I got a kick out of the tongue-in-cheek response from Victor Yu (a visionary infectious diseases physician) to his colleague, which was Victor's way of bemoaning the spiraling empiricism (a term that he coined) and the utter lack of worry about how much things really cost:
"I think you should get empiric antibiotic therapy for endocarditis (heart valve infection)--might as well add caspofungin plus voriconazole (two expensive anti-fungal drugs) for Candida endocarditis. Take these antimicrobial agents for 6 weeks and get a cardiac CT scan. And if that doesn't work, how about some empiric corticosteroids (steroids or prednisone) for SLE (lupus)? That's what House would do."
Not just House, but in too many hospitals this won't be far from the truth; Victor does not mention all the consultants who would be called in, and the many more blood and imaging tests that would be ordered, all of which would add up to a huge bill for a heart valve infection that may or may not be there. It doesn't matter if the patient is insured or not--it's a huge waste of money. Diagnosis matters; and if costs truly matter, then accurate diagnosis will matter even more.
All said, this is still a historic day. Whichever side you are on, this is a milestone, a real surprise that Santa has brought. We will spend the next few weeks and months and years assembling it for use. Today let's make merry. Joy to the world!
This morning I will drive in for my rounds at the hospital (my team is on call, bless their hearts,and will stay all day and night, while I get to come home well before nightfall) and I am already trying to digest what this Xmas present means for my patients and for my house staff. In the last few days we pulled out all stops to get patients home. The ones who can't go home are too ill, and going home may not be an option; instead it might be a specialized nursing facility or rehabilitation place. One or two of these patients have been very much on my mind, long after I leave the hospital, their suffering both palpable and difficult to forget, and making me conscious of the blessings of just walking outside, stepping into a car and going somewhere.
Watching the health care reform process from a relative distance, from the front line so to speak, as opposed to being in the generals' tents (though I did get invited to the White House to watch the president on ABC's "Prescription for America" months ago in the summer), here is what I note:
- If you passed out mint and chocolate cookies in the Senate, you would get takers for both, a mix of Republicans and Democrats. Taste is individual after all. Given all the verbiage, the millions of articles, blogs and the like around health care, is it really possible that the only views one could have on health reform align so perfectly with politics? That tells me it was all about the money, all about lobbies and special interests, much more than it was truly about health or the suffering of the needy.
- Speaking of money, the AMA (and I am not a member) had much to do with opposing the expansion of Medicare, because of the low rates Medicare pays. It says something about the AMA and its now unblemished record of putting its members' income first.
- The disappearance of the public option says that the private insurance companies won. Yes, I know they will be forced to rein in costs, to not deny coverage and so on. But a public option would have put the real squeeze on them. The lobbyists and Lieberman did a good job on killing the public option. The drug companies ... they made an early concession that now looks like a real sweet deal, too good to be true.
- The increase in the number of people who will now be insured is fantastic and laudable; that is what it was all about and we should not lose sight of this.
- Finding the money to pay for all these newly insured is still an issue and finding the projected savings by cutting Medicare and Medicaid expenses seems very optimistic.
- The issue of costs, which is at the heart of what is wrong with health care, has yet to be addressed directly, I believe. In fact we have done a good job of skirting around some of the low hanging fruit, low hanging but protected by powerful lobbyists. An axiom in this debate has always been that every dollar spent on health care is a dollar of income for someone and any attempt to rein in costs will bring vitriolic responses and dedicated opposition. Well, we saw that.
That's the kind of cost overrun that I worry we won't address as well as we should.As the emphasis moves from quickly establishing the correct diagnosis to efficiently moving down a selected pathway, it is sometimes difficult to see the damage done. One illustration: after thorough investigation of a severe outbreak of Clostridium difficile (a diarrheal disease that follows use of an antibiotic and which can spread in a hospital) we discovered it was likely associated with overzealous application of a pneumonia care plan. Many of the patients treated for bacterial pneumonia never had that infection, but the one they acquired as a result of their antibiotic exposure did far more harm.....the report of that outbreak is here:
Recently an infectious disease colleague mentioned on a listserve that after a high altitude trip he developed a 'splinter hemorrhage' on one nail (a red vertical streak, looking like a splinter). These are not very specific and can happen from trauma; but they can also come about from heart valve infection. The finding would be ominous in someone who is an intravenous drug addict and presents with fever and other signs pointing to heart valve infection. I got a kick out of the tongue-in-cheek response from Victor Yu (a visionary infectious diseases physician) to his colleague, which was Victor's way of bemoaning the spiraling empiricism (a term that he coined) and the utter lack of worry about how much things really cost:
"I think you should get empiric antibiotic therapy for endocarditis (heart valve infection)--might as well add caspofungin plus voriconazole (two expensive anti-fungal drugs) for Candida endocarditis. Take these antimicrobial agents for 6 weeks and get a cardiac CT scan. And if that doesn't work, how about some empiric corticosteroids (steroids or prednisone) for SLE (lupus)? That's what House would do."
Not just House, but in too many hospitals this won't be far from the truth; Victor does not mention all the consultants who would be called in, and the many more blood and imaging tests that would be ordered, all of which would add up to a huge bill for a heart valve infection that may or may not be there. It doesn't matter if the patient is insured or not--it's a huge waste of money. Diagnosis matters; and if costs truly matter, then accurate diagnosis will matter even more.
All said, this is still a historic day. Whichever side you are on, this is a milestone, a real surprise that Santa has brought. We will spend the next few weeks and months and years assembling it for use. Today let's make merry. Joy to the world!
One of the reasons I went into infectious diseases as a sub-specialty of medicine was that I enjoyed the notion of being a sleuth at the bedside, of seeing someone with pneumonia and examining their sputum by personally carting it to the "wet lab" adjacent to the hospital ward, then smearing a tiny sample on a slide and then, using a time-honored method of staining bacteria called the Gram stain, coming up with the exact cause of the pneumonia and thereby beginning appropriate treatment. A better example, and a memorable one from my training days, was seeing a patient with HIV (in the first days of AIDS when we did not know the viral cause) and watching as his fever raged on despite our efforts. One morning, I spotted some unusual skin lesions on his forehead. I scraped one with a needle and put the material on a slide. In the wet lab under the microscope, I saw tons of small budding yeast: this was cryptococcus, a fungus that affects persons with HIV.
There are so many instances in infectious diseases where a rapid and precise diagnosis can be made by directly examining sputum, wound drainage, blood smears, skin lesions and the like. Over two decades I can still remember those "Eureka" moments; it made all the difference in the care of the patient by finding precisely what was causing the problem, short circuiting what was otherwise blind therapy with many drugs, hoping one was treating the cause of the infection. Diagnosis matters--surely that's something we can all agree on.
Perhaps not. Some years ago, OSHA closed down our wet labs."These historic rooms--where interns and residents in the night or at any time could look at urine, use a Gram stain to look for bacteria in various specimens, and do other simple tests--were gone. Admittedly, they were messy rooms, and I suppose there was some potential for exposure to unsafe pathogens. But it was also the place where a generation of interns and residents learned bread and butter tricks that made them better diagnosticians. We lost that battle.
Once the wet labs closed, the choice was then to walk over to the microbiology department. Well, I got used to that, and in many ways this worked well, as the lab had more resources, better microscopes, and you could also look at the culture plates with the microbiologist and see what was brewing. Though I was willing to make the walk--microbiology is integral to my specialty-- for busy interns and residents, the walk made it less likely they would drop by the lab.
But then, many hospitals (including some where I see patients) went one further and have farmed or moved their microbiology labs off site, miles away! (I kid you not.) Say I happen to see a patient without a spleen who has come in with fever and shock, someone in whom I might make a diagnosis in minutes by quickly examining the buffy coat of blood (because such patients are prone to overwhelming infection so that their body fluids will be teeming with organisms); now all I can do is helplessly watch as the specimen is transported away, with inevitable delay. And what is worse, more and more, no one seems to be too bothered. No one seems too worried about what exactly is causing the infection, but rather people are content instead to empirically add antibiotic after antibiotic, to "cover" the patient. And if the fever persists and the patient is worse, well then the answer is to keep "broadening" the antibiotic coverage. It's kind of like flushing out a sniper who is terrorizing your own city by bombing the city to rubble in the hopes of silencing the sniper. Diagnosis matters.
My friend, Victor Yu who is a wonderful clinician and Legionnaire's disease expert, has called this phenomenon "spiraling empiricism" in an editorial he wrote for the journal Chest this year. It is a wonderful term to describe the illusion that you can treat infection by just shooting in the dark. The consequences of such blind empiricism (and I see this all the time) is not just cost, but bacterial resistance, diarrhea and severe colitis related to antibiotics, not to mention the direct side effects of the drugs themselves. Indeed, as an infectious disease specialist, the number one thing I seem to be doing on hospitalized patients is stopping the cornucopia of antibiotics they seem to be on. We are great at starting empiric therapy, but terrible about stopping. And in a health care system that my colleague Alan Garber describes as a menu without prices, it is all too easy to tick off more items on the menu. That's not patient care. That's not diagnosis. As Congress wrestles with cost (and that is really the crux of health care reform: paying too much for things we don't need, and having perverse financial incentives to make us do things to patients that they do not need), this is the sort of nuance that does not get discussed. Indeed, the push for efficiency and "quality" has every hospital touting "pathways" and "algorithms" for the treatment of pneumonia. And with the focus on "outcomes" research we will probably be saddled with more pathways and algorithms. It is commonplace to see patients being wheeled down the "pneumonia" pathway and meeting all the quality and other metrics that measure a hospital's efficiency, only for me to disagree with the label of pneumonia. Diagnosis matters. Patients would concur, even if we seem to have forgotten.
We have overvalued the electronic medical record and its hypothetical cost savings (except that it might keep doctors and nurses so glued to the monitor that the patient will get bored and check out from the hospital) and we have underestimated the sheer waste, cost and danger of clinical error that have come about from the "business" decision to locate diagnostic microbiology labs somewhere so far away that the clinician has little chance to look at the specimen on their own patient. That is just dandy if we don't care about diagnosis.
Let's give ourselves a chance at precise diagnosis before we treat. That means good specimens, hand carried, examined by the people who care for the patient. Proxy wars never seem to work. "Find the enemy and win the firefight" is a good philosophy for infectious diseases as it is for war. Diagnosis matters.
The time of year has come when we interview final year medical students from across the country applying for internships. I experience deja vu when I see the candidates appear in their suits, because we have been doing these interviews twice a week for some weeks. And also because I feel kinship with them, as if I have just been in their shoes, although (I am shocked to realize) it has actually been 25 years. I try to imagine what these interns-to-be will experience when they start in the wards in six months. I suspect it will be much like what I felt: exciting, overwhelming, scary. What hasn't changed that much is the kinds of problems their patients will present with--the common conditions that manifest with regularity on an internal medicine service: pneumonia, heart failure, cirrhosis and stroke to name a few.
What has changed dramatically is the fact that the charts (now largely electronic) have tons of information in them, and they mushroom every hour that a patient is in the hospital. The electronic medical record (EMR) contains blood tests of every kind, problem-lists that scroll off the page, medication lists that fill several screens, and notes from an army of people. The great challenge is figuring out what is critical, what is of current importance, and what isn't. (It's very much like the cancer screening problem I wrote about in my last post: so many tests coming back with information that we don't always know what to do with.)
I finished a stint on the wards two weeks ago, and I start again in a day. I still find the best way to understand a hospitalized patient whose care I am taking over is not by staring at the computer screen (or not by that alone) but by going to see the patient; it's only at the bedside that I can figure out what is important. When I know the patient well, I become aware of how much detritus has accumulated in the chart obscuring the data that does need our attention. (In the health care reform debate, proponents of the EMR don't talk too much about this, implying instead that EMR is a panacea for what ails us.)
David Orr makes a wonderful distinction between "slow" knowledge and "fast" knowledge, which he explains in his book, The Nature of Design.
In brief, fast knowledge (and I am interpreting Orr's work to the medical setting):
- Celebrates lab tests, imaging, consultations and the more the merrier--you can never have too many tests or images.
- It suggests that what counts are only the things one can measure (and counts more than the patient's or the family's subjective observations and their verbal reports).
- It presumes that an error made from misinterpreting the existing data can be overcome with even more data. (More tests can help you claw your way out of a clinical impasse, in other words.)
- It celebrates wisdom more than cleverness, a sense of the individuality of the patient and the need for a tailored treatment, rather than one-size-fits-all algorithms.
- It recognizes that the volume of tests ordered and the results that come back can compound mistakes.
- It suggests that mistakes are often generated in part by the fact that there is no filtering function to the data.
Photo Credit: Flickr User The National Guard
I can't get over the incredible images generated by our latest CT scans and MRI's. The details of organ anatomy and the 3D reconstructions they can do are just amazing. One side effect of getting such fine resolution, is that more and more we are stumbling onto abnormalities that we were not necessarily looking for--incidentalomas, we call them.
Sometimes the discovery is fortuitous and lifesaving. But often what ensues is worry at the very least, or at the other extreme, painful and expensive tests and procedures which can wind up showing that the incidentaloma could well have been left alone. Read More
Sometimes the discovery is fortuitous and lifesaving. But often what ensues is worry at the very least, or at the other extreme, painful and expensive tests and procedures which can wind up showing that the incidentaloma could well have been left alone. Read More
Abraham Verghese
