Seminal Work

The Worcester area continues to be a hotbed for scientists looking to redefine sex and human reproduction. In the 1950's, female oral contraceptives were developed there. A few years ago, Advanced Cell Technologies cloned the first human embryo. And today, Dr. George Witman announced plans
for the male birth control pill:

The approach by the UMass Medical School scientists involves turning off the tiny tails that allow sperm to swim to the female egg for fertilization. If their theory is right -- and animal studies suggest it is -- the method could result in a male contraceptive that is easy to take, free of side effects, and reversible.

UMass has forged a licensing deal with a Norwegian biotech company called SpermaTech to use this pioneering approach to develop a male pill, a process that could require a decade of lab work and human testing.

Yep, they're definitely swimming against the tide with this. Be still my beating... heart. Alright, ok, I'll stop. But this stuff is so ripe for humor, I think even reporter Stephen Smith got into the act:

When researchers at the foundation wanted to better understand how they might be able to prevent men from reproducing, they decided to look at pond scum.

Of course! This is why previous attempts failed -- none took the appropriate perspective on male behavior. Either that, or there's just something about being in Worcester that inspires thoughts of stopping sexual reproduction.

Age of Maturity

A friend read this this Onion blurb and said he thought of me immediately:

ROCHESTER, MN—Dr. Erich Stellbrach, a general practitioner at the Mayo Clinic, could barely contain his exhilaration Monday upon discovering that patient Oliver Patterson, 54, has the extremely rare degenerative nerve disease Gertsmann-Straussler-Scheinker syndrome. "Mr. Patterson, I'm so sorry to tell you this, but you have—you're not going to believe it—spinocerebellar ataxia!"

It gets drummed into our heads in medical school that, when you hear hoofbeats, think of horses, and not zebras. And so, in my limited experience, it's hard to get "exhilarated" by the prospect of a rare disease in front of a patient. Usually the thought of zebra first occurs during the history and physical, it prompts a lab test, and any "gee whiz" moment is experienced safely away from patients in the charting room, when the lab results come back.

The disease described above is real -- prior guru Stanley Prusiner described it in this 1991 paper:

Gerstmann-Straussler-Scheinker disease (GSS) is a rare, dominantly inherited neurodegenerative disease that can sometimes be transmitted to experimental animals through intracerebral inoculation of brain homogenates from patients.

If I saw a patient with a prion disease, well, um, my friend knows me pretty well.

But, as a counterpoint, there's a powerful story in this week's New York Times Magazine about a physician-scientist who finds a patient with progeria. This extremely rare genetic defect gives the appearance of rapid aging, and is usually fatal by the time the wizened child reaches the teens. It's a fascinating disease that could potentially tell us how we all age. The patient is, sadly, the doctor's son -- and she's changed the course of her career to try to cure him in time.

Selection Dysfunction

Medical students don't just apply for residency positions at graduation -- they "match" into them. The students rank their favorite programs, the hospitals rank their favorite students, and everyone hopes for the best as an algorithm puts them together. This process, more or less unchanged for decades, across many specialties, went terribly wrong last week during the urology match ...

I still haven't seen any coverage of this in the mainstream media -- I only heard about it on the interview trail, and there are some discussion boards talking about it.

As far as I can tell: the original Urology match on January 24th left several prominent hospitals with unfilled positions. The odds are strongly against places like Hopkins and Baylor having unfilled spots, when so many excellent applicants rank them highly. It became clear that something went wrong.

A re-match was run on the 27th. I don't know if this kind of error, and solution, has ever happened before. A medical student on a discussion board posted part of this email from the AUA:

After hearing concerns about this year's results, it came to our attention that there may have been a problem with our automated match process and that a manual audit was necessary. Upon careful review, we found that one of the criteria in the match was not applied correctly, causing some outcomes to be skewed. With this evidence, it is important for us to perform the match again so that all involved are given the opportunity to be treated fairly...

...We know that this will change some results, but by applying the criteria appropriately, we are confident that the results will align with what you have come to expect from the AUA Residency Match.

We're all told how the match algorithm works, but the actual computer decisions made each year are essentially a black box -- to applicants and institutions. As far as I know, everyone operates on good faith that the computer is working properly. It takes a monumental glitch like this one to trigger a re-evaluation. I can't help but wonder if smaller glitches, maybe affecting fewer programs or individuals, go uncorrected each year.

If you doubt the inconvenience of this, listen to some discussion participants, from the period before the re-match:

...I cancelled 7 general surgery interviews today and told programs to withdraw me from consideration as I matched in Urology. If the AUA match were rerun, damages for those who have made plans based on its results are quite significant (housing commitments, decline of other opportunities, etc.). Damages to those who did not match due to the "errors" are significant as well.

and:

...I had expected to match at my home institution who are completely surprised I did not match with them since they matched someone way down their list. The PD almost called me a liar for telling them that I ranked them 1 when in fact I did. Please help fix this, how can I contact you or give my contact info anonymously. I would like to take action and bring it to the AUA's attention. Something just isn't right here...

This is like those Diebold electronic voting results -- with no paper trail, you just have to hope it's correct. Unless the system is transparent, it will always be vulnerable to head-scratching and conspiracy theories.

New Options

Reflecting on my pediatrics rotation, I must say: Kids are not so bad.

My rapport with patients had always been based on language -- information, verbal persuasion, and examples. On peds, I was forced to add to the repertoire, because language isn't an option with 18 month olds. But shiny stethoscopes are! And the Bert puppet. And if you want a kid to exhale, you can't beat giving them a pinwheel.

The children, for their part, were more reasonable than I expected. And they have flashes of insight that are simply stunning.

I recall a talk from a pedi neurologist, who was treating a 9 year old boy with cerebral palsy and a growing depression. The kid once remarked:

If I was for sale, I'd be free.

Damned if everyone in the audience didn't gasp.

Going Dutch

The speaker also had a new wrinkle on how to approach raising a child with significant deficits. I must admit, this is something my mind returns to from time to time, especially as I watch my friends start families. I simply don't know how I'd respond to

The old outlook, which I had heard many years ago, was to "mourn for the child you lost, before you start to accept and appreciate the child you have." Meaning, you may not get to cheer for your kid at the soccer game, or watch her win the science fair, so don't foist those expectations on your child.

That phrasing always left me a little cold. The speaker's new interpretation, in addition to making me smile, is more illuminating (apologies if any European readers take offense):

"Welcome to Holland! All your friends have gone to Italy and taken these glamorous pictures, told these great stories about Rome and the countryside... You've always dreamed about going there, too. But you've found yourself in Holland, instead. It's not as flashy or fast-paced, but if you look around, you know, there are a lot of worthwhile things about it."

Smile

Gladwell's Blink summarizes the work of Paul Ekman and Wallace Friesen and their Facial Action Coding System -- a 500 page catalog of muscle movements that signify emotional states. He also recounts the story of how, in compiling this compendium, they were forced to make a lot of expression of anger and distress.

"It was weeks before one of us finally admitted feeling terrible after one of those sessions," Friesen says. "Then the other realized that he'd been feeling poorly, too, so we began to keep track." (p206)

Hooked up to monitors, they found that pursing the lips, narrowing eyelids, and lowering brows is enough to generate an autonomic response similar to anger. The heart rate rises, the extremities get hot. And the subject feels something.

When studied further, psychologists found that viewers forced into a smile enjoyed comedy more than viewers physicially prevented from smiling. I'm not sure if it's relevant, but the study was German. Also, the smiles were generated by clenching a pen between the subject's teeth (and smiles were prevented by gripping a pen with the lips).

I bring this up in the context of Moebius Syndrome, though it's easily relevant in Parkinson's patients or stroke victims, or general old age.

Moebius Syndrome is sad and interesting: the patients are born with facial nerve paralysis. They can crudely chew and phonate (mediated by other cranial nerves) but can't smile or frown or otherwise express emotion. Patients report frustration at not being able to smile at a friend's joke.

A muscle transplant (gracilis to masseter) lets patients retract the corners of their mouth when they send the impulse to clench their jaw. In addition to improving speech, a rudimentary smile is made possible, on command.

I wonder: does it become natural to clench when a Moebius patient wants to smile? Does it become second nature? Obviously such patients would get more out of human interactions, but, say, if I were a German psychologist, would I find that they suddenly enjoyed watching comedies more?

Precipitous

I remember discussing the state of emergency medicine research at a program with a burgeoning basic science lab. My interviewer, too, was pleased with new developments, and dismissed a huge chunk of older EM publications as "cocktail party research" -- quick and easy to analyze, interesting to talk about, but ultimately nothing that will change the way medicine is conducted. He cited one of his own efforts as an example:

A retrospective review was conducted of cardiac arrest patients presenting to a New England ED during the months of October through May, from 1991 to 1994. Comparing daily frequency of cardiac arrest patients with climactic data, a 27% increase was observed in the frequency of cardiac arrest presentation to the ED on days with snowfall (P = .0004). ED physicians and staff should anticipate an increased frequency of cardiac arrest patients on days with snowfall.

I thought of his paper today with the news that David Nyhan has died.

David Nyhan, whose fiercely liberal columns for The Boston Globe made him a force in local and national politics even as his generous nature won him a legion of friends, died early yesterday at his home in Brookline, apparently of a heart attack. He was 64.

Mr. Nyhan was stricken yesterday after coming in from shoveling snow and was rushed by his wife, Olivia, to Beth Israel Deaconess Medical Center in Boston, where he was pronounced dead...

...He was scheduled to leave this week for a month-long trip to Sri Lanka to accompany and write about a group of about 50 nurses and doctors taking part in tsunami relief efforts.

If you read the opinions page of the Boston Globe in the late eighties or early nineties, you couldn't miss his presence. I was in high school then, and Nyhan's accessible, passionate columns introduced me to politics -- and addicted me to newspapers.

Every year he'd write a poignant open letter to graduating high school seniors, about not getting into one's top choice for college. I still think about his essay every few years, with each cycle of applications.

I only wish his world intersected more closely with ours. Maybe then what we refer to as cocktail party banter, what we see as obvious and unchangable, would be more widely understood and appreciated.

The Clear-eyed View

I've been meaning to blog about Blink, Malcolm Gladwell's new book. In the author's words:

When you meet someone for the first time, or walk into a house you are thinking of buying, or read the first few sentences of a book, your mind takes about two seconds to jump to a series of conclusions. Well, "Blink" is a book about those two seconds, because I think those instant conclusions that we reach are really powerful and really important and, occasionally, really good.

You could also say that it's a book about intuition, except that I don't like that word. In fact it never appears in "Blink." Intuition strikes me as a concept we use to describe emotional reactions, gut feelings--thoughts and impressions that don't' seem entirely rational. But I think that what goes on in that first two seconds is perfectly rational. It's thinking--its just thinking that moves a little faster and operates a little more mysteriously than the kind of deliberate, conscious decision-making that we usually associate with "thinking." In "Blink" I'm trying to understand those two seconds. What is going on in inside our heads when we engage in rapid cognition? When are snap judgments good and when are they not? What kinds of things can we do to make our powers of rapid cognition better?

Gladwell cites study after pop-culture study to answer these questions. It's fascinating reading about taste-tests, gamblers' sweat, the Implicit Association Test, and anecdotes from various experts (art, food, marriage, and more) about their honed first impressions.

For instance, Gladwell recounts Gawande's story of the experienced firefighter who "sensed" a floor was about to collapsed (previously blogged about last March -- his intuition was actually guided by subtle clues from the fire that he processed subconsciously).

Then there's the marriage researcher who's watched so many videos of couples, and studied outcomes for so long, that he can process tiny details of intonation and body language and predict which couples will last, after just a few seconds of watching.

One study of interest to doctors: a group of psychologists were able to predict which surgeons would be sued for malpractice, not by looking at hospital citations, or training sites, or previous suits. Rather, they make predictions based on snippets of patient-doctor dialogue, with the voices stripped of high-pitched frequencies (so as to make the actual content unintelligible). In other words:

The judges knew nothing about the skill levels of the surgeons... They didn't even know what the doctors were saying to their patients. All they were using for prediction was their analysis of the surgeon's tone of voice... Malpractice sounds like one of those infinitely complicated and multidimensional problems. But in the end it comes down to a matter of respect, and the simplest way respect is communicated is through tone of voice... (page 43)

The trouble is, my first impression of this study, blogged about in May, was that it was bunk. Shazaam agreed! Maybe I'm not enough of an expert to trust my formative impressions, but there still seem to be many potential confounders -- is a dominant tone from the surgeon related to a patient's belligerent body language? Or to the degree of bad outcome? The paper (reg req'd) is doesn't delve into these externalities. Also, the stats don't seem that impressive. Or maybe malpractice is complicated and multidimensional.

A more appropriate medical application of the Blink thesis is made regarding Goldman's Chest Pain algorithm (free registration necessary). Gladwell cites Goldman's conclusion -- that the likelihood of chest pain being due to heart attack is largely dependent on just three pieces of data -- as an example of "less is more" -- it turns out that Goldman's criteria can ferret out MIs better than docs with tons of data on patient age, heart rate, appearance, etc.

I'm all for data mining to determine which test results are truly diagnostic. And I'm always impressed with seeming mind-readers (Blink goes into detail about what should be called face-reading) who can divine useful information from flickers of facial muscle contractions. As far as medicolegal studies are concerned, I don't think we're at the point where expressions and intonations can coexist alongside assays and echocardiograms as actionable data, subject to statistical interpretation. That's just my snap judgment.

Escape from Philadelphia

Nothing quite unites and preoccupies people like a snowstorm. Especially at an airport. Especially on a boarded plane that can't take off until the "indeterminate number" of planes in front of it have de-iced, as the snow starts accumulating on the wings. You could almost hear a collective buzz of nervousness amongst the passengers. Then the crew started passing out beverages, and our mood improved.

One thing that's different about this blizzard, compared to the last record-breaking snowfall (waaay back 23 months ago), is the appearance of weather blogs. I wish my area had something like Capital Weather, because it's easy to grow tired of TV correspondents reporting live from a parking lot. I've been waiting to see a snowfall probability chart on TV ever since I learned about school cancellations. And whatever's missing in the posts is made up in the active, erudite comments section.

Still, I'll always be partial to the Forecast Discussion folks at the National Weather Service (page frequently updated):

Record setting snowfall progged for Boston in a storm that will fall short of the bliz of 78 in the severity and duration of coastal flooding but overall we have just reviewed kocin uccellini vol ii p495 snowfall graphic and only somewhat less extensive 2-3 foot siege but this is dangerous and close to bliz of 78 snowfall!!!

Short term (today through tonight): 06Z eta has the better handle.

Ku storm, comparing favorably aerial coverage 2 Ft plus, wait for final. And all in 24 hours!!!!!

I wish my profession condoned the use of exclamation points in our notes to colleagues. But I'm glad that meteorologists are starting to share their insights with a public that wants a little more depth to their snow forecasts.

Unmistakable

This week's Grand Rounds is being hosted at Waking Up Costs. The theme is medical errors, but the formatting is organized and efficient. Also, Dr. Venable's added aggregator buttons for the blogs you like best. Enjoy!

Next week's host is Dr. Bard-Parker at A Chance to Cut is a Chance to Cure.

One of a Kind

I hate hyperbole, but it's something one must accept when reading about sports. Players, fans, and even writers just get swept up in the moment and say things that give reasonable people pause. So when an athlete, minutes after an emotional playoff win, makes an effort to avoid over-the-top exaggerations, it's a special occasion:

"I've never seen anything like it," Steelers linebacker Larry Foote said. "I'm not going to say it was a miracle, because that's crippled people getting up and walking, the blind seeing. But that's the closest thing to it I've ever seen."

Hey, he's honest, reasonable, and yet still unmistakably affected. Maybe he's related to this Foote, who also sought precision in language.

Ticking away

I woke up today with some confusion -- my alarm clock said 2:55 PM. Could I have really slept for thirteen hours?

No. My watch was set to ten. I looked closer at the alarm clock and noticed the blinky colon was blinking too fast. Further measurements revealed that it was blinking twice as fast as normal: instead of once per second, it was blinking every half-second. The clock was advancing one minute for every thirty seconds that passed. Apparently, at seven-thirty this morning, the clock up and decided to race through the day.

I'm going to need more coffee if I'm going to try to catch up.

The English Way

Speaking of time, now it seems appropriate to take up my former roommate's suggestion to blog about The Long Now, an organization of forward-thinking individuals including Stewart Brand, Esther Dyson, and of course, Brian Eno. I've blogged about one of their projects involving long-term betting and predictions. But their plans for a 10,000 year clock deserve mention, as well.

In 01995 (they use the extra digit to protect against the deca-millennium bug), the clock's creator, Daniel Hillis, wrote:

I think of the oak beams in the ceiling of College Hall at New College, Oxford. Last century, when the beams needed replacing, carpenters used oak trees that had been planted in 1386 when the dining hall was first built. The 14th-century builder had planted the trees in anticipation of the time, hundreds of years in the future, when the beams would need replacing. Did the carpenters plant new trees to replace the beams again a few hundred years from now?

I want to build a clock that ticks once a year. The century hand advances once every one hundred years, and the cuckoo comes out on the millennium. I want the cuckoo to come out every millennium for the next 10,000 years. If I hurry I should finish the clock in time to see the cuckoo come out for the first time.

The first prototype was indeed ready on December 31, 1999. Since then, the Long Now organization has purchased some land in Nevada for the site of the final, larger version of the 10,000 year clock. Design principles (transparency, durability, low-tech) and schematics are available on their web page.

What's the motivation? Jonas Salk, right before he died, challenged the clock builder to figure out what, exactly, he was trying to preserve. In response, he wrote:

I know I am a part of a story that starts long before I can remember and continues long beyond when anyone will remember me. I sense that I am alive at a time of important change, and I feel a responsibility to make sure that the change comes out well. I plant my acorns knowing that I will never live to harvest the oaks.

I guess, ultimately, it's awe-inspiring, but not moving. I'm reminded of Ypres, where, every evening, the Fire Brigade has been sounding The Last Post in honor of a solider who died on that Great War battleground. They've been at it since 1928, and, since about 90,000 died at Ypres, the brigade will keep playing, daily, well into the 22nd century.

Their acts may not generate the mind-blowing plans for the 10,000 Year Clock, but the Ypres brigade moves me in a way the Clock fails to. Even the Oxford tree-planting is more striking, because it's long-term planning with purpose. However, the Long Now's Rosetta project and library perservation goals may yet give future Clock visitors a reason to care about the culture that built it.

Air travel

Frequent flying and snowy weather have conspired to give me some free reading time. Gladwell's Blink just arrived from Amazon, even before I finished The Youngest Science.

I also received Kundera's The Unbearable Lightness of Being for Christmas. The book is about a doctor who writes a newspaper article. Also, there's some sex. And a discourse on whether Jesus had functional intestines (it's a "novel of ideas"). Anyway, here's the excerpt I thought medibloggers might want to mull, after the main character publishes his political article:

"Perhaps his deep-seated mistrust of people (his doubts as to their right to decide his destiny and to judge him) had played in part in his choice of profession, a profession that excluded him from public display. A man who chooses to be a politician, say, voluntarily makes the public his judge, with the naive assurance that he will gain its favor. And if the crowd does express its disapproval, it merely goads him on to bigger and better things, much in the way Tomas was spurred on by the difficulty of a diagnosis.
A doctor (unlike a politician or an actor) is judged only by his patients and immediate colleagues, that is, behind closed doors, man to man. Confronted by the looks of those who judge him, he can respond at once with his own look, to explain or defend himself. Now (for the first time in his life) Tomas found himself in a situation where the looks fixed on him were so numerous that he was unable to register them. He could answer them neither with his own look nor with words. He was at everyone's mercy..."

Tomas, of course, did not have Haloscan comments enabled, nor could he peruse his readers's details with Sitemeter. The relationship between reader and writer is approaching that the give-and-take seen with patient and doctor.

Thin line

Finding a narrative where others see randomness: It's either a sign of genius, or the mark of madness. Madman is hosting this week's Grand Rounds.

Next week's host is Waking Up Costs -- please direct your submissions there. Future hosts are noted below, and previous editions of Grand Rounds are archived at an undisclosed location.

Swan Song

The Swan-Ganz catheter is an ingenious device that gives clinicians information on the status of heart chambers and the lung. Is this information valuable? Probably, but it comes at a price -- studies have shown that mortality is actually higher in patients randomized to receive Swans (also known as pulmonary artery catheters).

It might be that the information on left ventricular end-diastolic pressure doesn't help clinicians after all. Or it might be that the side effects narrowly outweigh the benefits.

A recent conversation with an intensivist illustrated the point:

Fellow: "What's the #1 complication due to Swans?"
Me: "Arrhythmias!"
Fellow: "That happens, but it's not #1."
Me: "Piercing the heart and causing tamponade!"
Fellow: "That happens, but not #1."
Me: "Infection! Thrombus formation!"
Fellow: "No, no."
Me: "ummmm...."
Fellow: "It's actually misinterpretation of the data. Overwedging, or mistaking PAP for LVEDP. It leads to errors in fluid management."

Which made this exchange on rounds, few days later, that much more clear to me:

Intensivist: "Why haven't we pulled the Swan from this patient? It's not telling us anything anymore, and it's just going to lead to problems. We need it out."
Resident: "But the surgeons want it in."
Intensivist: "OK, fine. It's their patient. But we can still protect against complications."
Resident: "How?"
Intensivist: "Turn of the monitor readings from the Swan. This way, it stays in the patient, but can't cause misinterpretations and bad management."

Everybody was happy, and we moved on to the next bed.

Testimonial

Part of the interview day for these emergency residency positions involves a tour of the department. One day, on tour at a particularly endowed emergency room, the attending was showing the applicants his department's various assets: a paperless ordering and patient tracking system, the PACS radiology computers, and a pair of new ultrasound machines.

"Profiency in reading ultrasound, as you know, will be increasingly important as you advance in your training," the attending intoned.

I had a great case during my first ED month where we used ultrasound to rule out testicular torsion in a guy with... a lot of pain. And I had just been hearing about new uses of ultrasound. I thought I could make an impression during the tour, so I interjected, "You know, just recently, it was shown that ultrasound is superior to X-ray for pleural effusion."


"That's right," the attending agreed. "Ultrasound is quickly proving its worth for rapid imaging of lungs, hearts, galbladders..."

I thought back to my torsion case. Should I mention it? Or just echo his sentiments? Or say nothing and let the tour continue?

I said, "Scrotums."

Everyone was quiet. Maybe my timing was off, and I spoke a few moments too late. But the seconds ticked by and still, no one spoke.

"Um..." I continued. "See, we had this neat case where doppler ultrasound ruled out testicular torsion... Yeah."

"Oh, good," the attending smiled. "I just thought you might have Tourette's."

Administrivia

Here's the upcoming schedule for Grand Rounds hosts (UPDATED 1/10/05)

1/11/05 Chronicles of a Medical Madhouse
1/18/05 Waking Up Costs
1/25/05 A Chance to Cut is a Chance to Cure
2/01/05 Daily Capsules
2/08/05 Enoch Choi's Medmusings
2/15/05 Sumer's Radiology Site
2/22/05 Catallarchy

As you can see, we're diversifying here. Waking Up Costs is an anesthesiologist's perspective on medical advances and health care delivery. Daily Capsules are notes from the field of continuing medical education. Sumer uses more exclamation points than any radiologist I've known. And the resident behind medical madhouse might, in fact, be mad.

I'm trying to mix some familiar and accomplished bloggers (Medmusings, Cut-to-Cure) with some new voices. And there are many more bloggers who've contacted me, and I plan to schedule them in the coming weeks. But all this interviewing and international travel is really cutting into my blogging admin time! Just keep tuning in, and we'll keep delivering the goods.

A shot in the arm

USAToday is reporting that the much ballyhooed flu vaccine shortage will end up as a surplus in some areas. Though I did my share of ballyhooing back in October, in recent weeks I had a feeling this reversal might occur. Look at how the hard line from our student health administrators reflects the change in supply over the past few months:

10/15/04 Influenza Vaccine Shortage; medical students will not receive vaccination.

11/15/04 Clinical medical students with documented lung disease working with high-risk populations may recieve vaccination.

12/01/04 Clinical medical students may receive flu vaccine between 7 and 7:15 AM.

12/15/04 All medical students may receive flu vaccine, whenever.

01/05/05 We'll give you a dollar if you get the flu shot. We'll vaccinate your pet, as well.

I think I can get a better offer if I hold out another few weeks.