Dr. Andy

Reflections on medicine and biology among other things

Saturday, April 30, 2005

Bad news about Marburg

Just when it seemed they were getting things under control:
Dangerous mistakes at a hospital in Angola in recent days could undo the work of medical teams who have been battling an epidemic of the deadly Marburg virus
Apparently a series of mistakes have led to unnecessary exposures in the hospital which is the focus of the outbreak
Two other mishaps threatened patients. In one, the report said, "the body of a deceased patient was left, uncleaned and uncollected, on an open ward for more than eight hours, placing hospital staff and other patients at risk."

In another case, staff members put a baby into the cot of a child who had just died of Marburg virus, without first disinfecting the cot.

Based on this, I'd have to agree with those who suggest closing the hospital would be for the best.

Friday, April 29, 2005

Biotech food- danger or not?

I just finished an interesting article in the Annals of Allergy, Asthma and Immunology (not available except to subscribers) about the risks (or lack thereof) of genetically engineered crops.

One of the authors works for Monsanto, so keep that in mind.

Genetically modified crops are those where specific changes to the DNA are made using recombinant DNA technology, rather than the old-fashioned method of breeding plants and selecting for desired characteristics. The article points out that making the specific changes you want results in much less DNA shuffling, than breeding where large piecess of chromosome are shuffled

The article notes there are 3 ways biotech crops could be harmful

1. Addition of known allergenic proteins to existing crops. This would be bad and there was a transgenic soybean in development which expressed a Brazil nut protein. Luckily, the potential danger was detected and development halted.

2. Increasing expression of allergenic proteins. This could potentially increase severity of reaction in already allergic patients. It turns out that for foods like wheat and soy there are a lot of people who make IgE antibodies to antigens and may even have minor reactions to ingestion of large amounts but can take small amounts without problem. If all of a sudden, there was a lot more of the protein they are allergic to in the wheat, that could be bad. Studies so far have been reassuring.

3. Creation of new allergens. The idea is changing the proteins in a plant could create new allergies. The authors think this is unlikely and point out that several kinds of testing are done on bioengineered crops to make sure they are safe:
all genes introduced into food crops undergo a series of tests designed to determine if the biotech protein exhibits properties of known food allergens. All biotech proteins are assessed as to their source (allergenic or nonallergenic), any amino acid sequence similarity to known allergens, and their stability to digestion with proteases from the GI tract
I didn't know that did all that testing.

Finally the authors point out the potential exists to create HYPOallergenic foods by modifying particularly allergic proteins.

As background, if you are allergic to a food you don't react to every protein, but to one or more specific ones. Different people allergic to a food react to a similar but not identical subset of proteins. In other words, only a few proteins cause allergies.

The proteins that cause allergy share certain characterisitics like being resistant to digestion in the stomach.

I have long felt that bioengineered foods were likely to be safe, probably somewhat safer than crops derived from breeding and I am even more reassured about that safety after reading this article, primarily because of the testing the new crops undergo

Thursday, April 28, 2005

Great Medical Writing

From an article in the April issue of Annals of Allergy, Asthma and Immunology
The panel recommended that instead of asking questions that elicit yes or no responses (eg, “How’s your asthma?”), HCPs use specific questions related to QoL to get a more complete picture of a patient’s control.
HCPs are health care providers and QoL is quality of life. Even better, the article is about IMPROVING COMMUNICATION between patients and health care providers

Summers, Sexism and Free Discussion

The brouhaha over Harvard president Larry Summers speculating that men had a biological advantage towards excelling in math and the hard sciences is dying down, but I couldn't resist commenting on this editorial by Andrew Marks, editor of the Journal of Clinical Investigation.

My basic feeling on Summers' remarks can be summarized as

1. There may be some truth in his hypothesis

2. A larger factor currently is cultural. To reach the upper echelons in science requires a tremendous amount of time and dedication, in addition to talent. Many more men are willing to make the sacrafices required, not least because it is much easier for a man to focus on his work and still have some semblence of a "normal" personal life (spouse, children) than it is for a women
Whether this is inevitable and how much if any effort society should put into changing the dynamic is not clear to me, but it's existence is impossible to deny.

3. The outrage over Summers' comments shows just how smothering the blanket of political correctness has become in much of academia.

So what is Dr. Mark's take?
The current system for recruitment and career development in the sciences is biased toward the success of white males, hence the lack of women and minorities in the system (1). To suggest otherwise is to turn a blind eye to the gross inequities that are pervasive throughout academia with regard to providing opportunities for women
Got it? Dr. Marks makes no attempt to refute Summers' hypothesis. The lack of women and minorities at upper levels of science is, IN AND OF ITSELF proof of bias against them. No need for discussion or evidence.

He goes on to recite the usual statistics about the decreasing % of women at each step up the ladder (grad student, asst professor and so on) and cites that as proof that discrimination is the only possible culprit.

But wouldn't Summers' hypothesis predict the same thing? Since we are talking about the extreme right end of a distribution with progressively higher standards, any less able group would be increasingly underrepresented with each step.
Perhaps Dr. Summers thinks there could be a gene on the Y chromosome that is activated during the assistant-to-associate professor transition. Otherwise, the argument that there are innate differences underlying the paucity of women in more advanced positions in the sciences and medicine does not hold water.
The only thing that doesn't hold water here is Dr. Marks logic.

His solution is even better:
Given that there is a simple explanation for the lack of diversity in science and engineering, i.e., the lack of effort to diversify, there should also be a simple solution. . . . Academic leaders simply need to raise awareness about the lack of diversity and then set about to correct it.
See? it is that easy. Just a little bit of consciousness raising and the problem goes away. I find it hard to believe Marks seriously thinks that simply raising awareness of diversity will make a big difference. Whatever factors cause the imbalance of sexes at the upper levels of the sciences, lack of awareness of diversity is not among them. Academia is obsessed with diversity.

Look I agree with a lot of what Marks says: that cultural factors are important and that we need to make accomodation for women (and I'd add men) who want to take time off for their family. I disagree with his belief that equality of outcome, not just equality of opportunity needs to be enforced, but that is a legitimate difference of opinion.

But it is asinine to suggest that there could be no validity to Summers' suggestion and that we should just dismiss it out of hand.

Not the brightest patients (or parents)

These posts by Dr. Tony and Gruntdoc got me to thinking about some of the funniest/silliest patients I've seen/heard/been involved with.

My all time favorite presented to a colleague who was finishing up an overnight pedi ED shift. It was a 1 month old whose parents brought him in because the dad had mistakenly mixed up a bottle of formula double strength.

The solution: give a bottle of water and mix by gently inverting baby several times

Remember, NEVER shake a baby (this part is serious).

Another was the parent who brought a child in to the ED with fever:

Doc: How high has the fever been
Mom: about 350 degrees
Doc: 350 degrees, did you measure that?
Mom: No, but we were baking some cookies and he felt about the same temperature as the cookies.

Wednesday, April 27, 2005


is increasingly a problem in kids.

This month's Journal of Clinical Investigation (JCI) has a good review of melanoma (free to all), most of which is pretty accesible to non-experts (the part on genetic lesions in melanoma was tough for me to follow). Amy Adams, the senior author was an intern I worked with when I was a 3rd year resident, before she went on to do derm.

I hadn't realized how much worse melanoma is getting:
Recognized as the most common fatal skin cancer, melanoma incidence has increased 15-fold in the past 40 years in the United States
The increased risk seems to be related to increased sun exposure. I would have thought if anything, sun exposure has decreased (more people working inside, kids playing outside less) but apparently people wear a lot less clothing now:
In the 1920s, women’s fashions became more revealing, and French fashion designer Coco Chanel, who developed a suntan when cruising from Paris to Cannes, is credited with initiating the modern sunbathing trend (10). As our social dress has moved from petticoat and parasol or topcoat and hat to tank top and sunglasses, the incidence of skin cancers, including melanoma, has increased significantly.
Unlike basal and squamous cell carcinomas (which develop from skin epithelial cells, not pigment producing melanocytes) in which cumulative skin exposure is most important, melanoma risk is increased with history of bad sunburns.

Unlike many other cancers, the only effective treatment for melanoma is excision, once it has spread there are no established therapies:
Numerous agents have been used in the treatment of late-stage melanoma, but to date no single agent has significantly changed survival rates.
The article does a good job reviewing various promising, but experimental modalities, but unfortunately neglects "cancer vaccines" where attempts are made to harness the bodies own immune system to fight the cancer, which, I think, have shown particular promise against this cancer

Shaken Baby Syndrome

is about the most tragic think I've dealth with.

People make fun of pediatricians sometimes because generally kids do well, but stories like Isabella's just tear you apart:
The 3 1/2-month-old baby spent her days with her father while her mother went to work. He liked to play video games and watch TV, and became disturbed when the baby started crying. So he shook her until she stopped
When I did general peds, I told my parents that if kids were crying loud, they were probably okay. If you were getting frustrated, put them in the crib and let them cry for awhile.

I think the lack of respect our society shows for infant's lives is shown by the total of 22 months Isabella's father got. 22 months for trying to kill your own daughter.

Tuesday, April 26, 2005


An excellent article in today's New York Times about the recent outbreak of Marburg virus in Angola.

Among the interesting tidbits:
Traditional healers here say their grandmothers knew of a bleeding disease similar to the current epidemic of hemorrhagic fever that has killed 244 of the 266 people who have contracted it. The grandmothers even had a treatment for the sickness, the healers told Dr. Boris I. Pavlin of the Centers for Disease Control and Prevention. But the remedy has been lost. The old disease was called kifumbe, the word in the Kikongo language for murder.

But kifumbe did not seem to be contagious. And so, Dr. Pavlin said, though he did not doubt it was real, it was probably not the same as the disease in Uíge today.
It is interesting to speculate that various hemorrhagic fevers exist in non-human primates and occassionally jump to the human population. What exactly kifumbe was we can only guess, but a non-contagious disease that kills a few people in an underdeveloped country probably won't get much attention.

The paradox of the high mortality rate is also explained, colorfully
"It is easier to count the dead people," said Dr. Pierre Rollin, a physician in the special pathogens branch of the C.D.C. "The numbers in the beginning don't mean anything."
The article also gives us some useful information about the animal reservoir:
It must have a natural host in some animal, but one that is not known for Marburg or Ebola. The host would have to be a species that is not wiped out by the virus. That requirement would rule out monkeys and apes, because when they catch Marburg or Ebola, they have even higher death rates than people do. Health authorities in Africa warn people to stay far away from the corpses of dead primates, because they may have died of Ebola.
There is some indication bats may be the primary carrier, then spread them either directly to humans or to non-human primates.

Finally, this article and another one from the day before suggest that what they call traditional healers may have helped spread the virus:
The experts suggest that the healers, who lack medical training and supplies but are a substitute for doctors in many rural African communities, are administering injections in homes or in makeshift clinics with reused needles or syringes.
Someow it doesn't seem like injections with reued needle or syringes qualify as traditional healing, but clearly these kind of practices are a disaster waiting to happy.

Full props to the New York Times for their coverage of this story. They have one reporter actually in Angola where the outbreak is going on and seem to have by far the best reporting on this from both a news and a science perspective.

Be sure to check out the cool multimedia features with the original article

Grand Round XXXI

is here. Many interesting posts.

I suppose this was inevitable:

A group backed by the U.S. food and restaurant industries on Monday launched an advertising campaign aimed at dismissing as hype concerns about the large number of obese Americans.

Another piece of cake, take two

A recent study suggests that the lowest mortality in the US is found among those categorized as "overweight" by national guidelines and that body mass index has a much smaller influence on mortality than had been commonly believed and that being thin causes as many or more deaths than being too fat. This is obviously a major change in the way we think about obesity and health, so I've blogged a lot about it.

In part I, I reveiw the study itself
in part II, I ponder the question of what thin people die from
in part III, I criticize BMI as a measure of obesity and the current categories (normal, obese, etc.)
in part IV, I try to illustrate what I see as the most important implications of the study

(Boy this post adds a lot -ed; I wanted to organize it for Carnival of the Vanities; you'd better hope vanity doesn't increase mortality; guilty as charged)

Weight and Mortality IV: this changes everything

Having reviewed the JAMA study itself, considered the question of what might account for increased mortality in the thin, and criticized BMI as a measurement of obesity and the arbitrary categories used to pigeonhole people, I now want to consider the implications of the study for public health.

Basically, it boils down to me being extremely healthy. I eat an okay diet (too much junk, but lots of good stuff, too), exerciese pretty regularly, have good cholesterol numbers and drink alcohol in moderation. My blood pressure is normal. Until now I'd have said I'd be really healthy if i could just lose 10 or 15 lbs and keep it off. Turns out I'm fine where I am (BMI 27 or so).

My mom is pretty thin and my dad has always struggled with his weight. Until now. Now my dad is in good shape and my mom needs to put on a few lbs, especially as they head up in years. Well, maybe not. The study showed an association not causality, which is always an issue in epidemiologic studies.

All that stuff you read about calorie restriction extending lifespan. Probably crap. Wouldn't it suck to restrict starve yourself for twenty years and then figure out you had SHORTENED your life? But since the thin (and BMI<18.5 is really thin) die younger, it is hard to imagine drastically reducing calories would decrease mortality.

And how would you feel if you'd just published an article in the New England Journal of Medicine arguing that increases in life expectancy were threatened by increasing obesity (my criticism is here)? Pretty foolish, huh? Maybe life expectancy would increase if we could get thin folks to eat some more

Most of all I think this means people can relax. Eat an okay diet, get some exercise, have a glass of wine or beer a couple times a week (or day) and don't worry so much about your weight.

It seems every week we read about some public health initiative designed to decrease obesity in one group or another. But maybe that's the wrong focus. Probably we should focus on encouraging healthy behaviors rather than the Sisiphyean task of encourage weight loss.

Sunday, April 24, 2005

Marburg Outbreak

is apparently coming under control as I predicted, with new cases dropping rapidly and better cooperation from people in the most afflicted areas.

While I remain skeptical of the potential for hemorrhagic viruses to cause world-wide epidemics, this is certainly good news.

Lacking the common sense God gave a brussel sprout

is how a high school friend used to desribe people who were academically smart, but lacking common sense. This describes a lot of physicians.

3 months ago the NEJM had a study demonstrating a greatly increased risk of MVCs (motor vehicle collisions, they are no longer accidents) in post-call interns.

So some geniuses at my med/grad school alma mater, the University of Chicago, write a letter about their brillant solution of paying for cab rides home for those too tired to drive, as if driving is the only bad thing about exhausted doctors. To quote the next letter:
I find it shocking that one of the proposals mentioned in the article is to supply taxicab vouchers to residents after extended shifts. If these interns and residents are exhausted enough to have an accident while driving, what does this say about their ability to make life-saving (or life threatening) decisions with their patients? This is the real issue that must be addressed

Indeed. I remember from my residency days that the post-call surgical intern got the priveledge of going to the OR. Just who I want operating on me.

Weight and Mortality III: BMI and "normal weight"

I know I'm blogging a lot about a single study that isn't even in an area of my expertise, but I think this a huge deal whose import has yet to be recognized.

I think both BMI and the definition of "normal weight" as a BMI of 18.5-25 need to be revisited.

BMI (weight in kg/ height in m^2) is a rather crude measure of obesity. I'm 6'2" and 210 right now, and while I'd like to lose 10 or 15 lbs, I don't think many people would say I'm fat. Someone else might be significantly overweight with the same statistics. On the other hand, there are professional athletes who are 6'2" 225 and have 4% body fat.

BMI may be a useful crude measure for epidemiologic studies, but I don't think it really captures how fat someone is. I speculate that people have gotten more muscular over the last 30 years as weight work and strength training have come into vogue for everyone, not just football players and weight lifters, but I have exactly zero data to back that up.

At this point I think it is past time to readjust what is considered "normal weight." According to the discussion in the JAMA study:
In many studies, a plot of the relative risk of mortality against BMI follows a U-shaped curve, with the minimum mortality close to a BMI of 25; mortality increases both as BMI increases above 25 and as BMI decreases below 25,
While, I don't agree with those who think this has all been a big conspiracy, you have to wonder why the "normal weight" category starts at the low point of mortality and goes down, not both ways.

I'd suggest the categories be recalibrated as follows:

<18.5 severely underweight
18.5-22 underweight
23-28 normal
28-33 overweight
>34 obese

Even better would be to go back and use actual data to draw lines, but these categories would probably correspond much better to actual mortality risk. And actual size as well. 57% of the population in the most recent survey were above average weight.

UPDATED reformatted new categories

Saturday, April 23, 2005

Weight and Mortality II: what do thin people die of?

Now that we know that being a bit overweight is good and being too thin is roughly as bad as being merely obese (except for the elderly, for whom it is worse), I was wondering: what are all those thin people dying of? And how about the "regular" weight ones? It seems like for the big killers the obese are at higher (cardiovasclar disease, diabetes) or equal risk (cancer) compared to others.

According to the CDC, the 5 biggest killers are (along with deaths and % of deaths):

Diseases of the heart 725,192 30.3%
All cancers 549,838 23.0%
Stroke 167,366 7.0%
Chronic obstructive pulmonary disease 124,181 5.2%
Diabetes 68,399 2.9%

Well, COPD is almost entirely a disease of smokers. The study corrected for smoking, so we'll assume that has no effect. Whether obesity is an independent risk factor for heart disease and stroke is unclear, but 2 factors not accounted for in the study, high fat diet and lack of physical activity clearly are risk factors and also lead to obesity. Diabetes is also clearly worse in the obese (at least type 2 which makes up the majority of the cases).

So I'm still not clear exactly what thin (and regular weight people) are dying of.

One explanation is that there are very few underweight people. In the survey data sets, only 2-3% of the sample qualify as underweight while 16-23% are obese and 34-36% overweight, so the increased deaths in the underweight don't make a big impact in overall mortality numbers.

The paradox of increased deaths among the normal weight (versus the overweight) remains. One possibility is that the data are wrong (after all the differences didn't make statistical significance). Another is that there is a group of individuals suffering from chronic diseases who are both think and likely to die. These could include those with type 1 diabetes, arthritis, lupus, etc. Follow up in the study was long enough it is unlikely that undiagnosed cancer or HIV plays a huge role, but maybe cancer and HIV treatments are good enough now that the two lower weight groups contains a subset of people who will eventually die of those illnesses but not for many years. Finally, other causes of deaths such as accidents may be higher in the relatively thin.

Note that increased rates of smoking in the thin should have been accounted for by the multivariate analysis.

The article suggest that part of the explanation is improved prevention and treatment of heart disease and hypertension (which predisposes to strokes) but that can't be the whole story or they wouldn't be such important causes of death.

I remain at a loss as to what causes of death are so increased among the "regular" weight that they outweight presumed increased rates of more common diseases in the overweight and obese.

UPDATE: more recent statistics from the CDC suggest accidents have overtaken diabetes for the #5 spot.

Weight and Mortality I - the study

First the study that everyone is talking about, is available free online at the JAMA site.

I think it has yet to sink in what a big deal this is. It is almost as if all of a sudden smoking wasn't bad for you.

I want to explain what the article shows and then discuss a bit.

The study looks at mortality in 3 cohorts of US citizens designed to represent the population at large. The cohorts are part of a longitudinal (basically following people over time) study funded by the NIH called the National Health and NutritionExamination Survey (NHANES) for which various information like height,weight, smoking status.

The study looks at 3 NHANES cohorts recrutied in 1971-1975, 1976-1980 and 1988-1994. Mortality was followed until 1992 for the first 2 and until 2000 for the 3rd group. They divided their cohorts into groups based on Body Mass Index (BMI) which is defined as weight in kg divided by height in meters squared (kg/m^2). Based on federal guidelines they defines a BMI of <18.5 as underweight, 18.5 to 25 as normal, 25-30 as overweight and >30 as obese. They further subdivided the obese group into classes with BMI of 30-35 and those >35

To give you an idea of about what these mean, I'm 6'2" and I'd be underweight at 144.5 lbs or less, regular weight from 145 to 194.5, overweight from 195 to 234.5, obese I from 235-273.5, obese 2 from 274 up.

They then looked at mortality based on weight using a statistical technique called multivariate analysis to control for things like age (older people die more) and smoking. This is important because it allows the true effect of weight itself to come out.

Surprisingly they find much less of an effect of increase BMI than had been previously believed. In patients <60, the lowest level of death was seen in the "overweight" category, but this was NOT statistically signficiant. Underweight and obese with BMI <35 individuals seemed to have higher death rates, but again this didn't reach statistical significance. Those with BMI >35 did have a statistically significant increased mortality. For older patients the data looked the same, but there were some minor differences in what did and did not reach statistical significance.

They go on to calculate the excess (or decreased) deaths attributable to people not being in the "regular" category, based on the US population as a whole. They find 110,000 excess deaths in the obese and 34,000 excess deaths in the underweight (there are a lot more obese people than underweight). The overweight group has 86,000 fewer deaths. Most of the increased deaths in the underweight occurred in people >70 suggesting being young and thin is probably okay.

For reasons that I can't explain clearly but have to do with statistics, the changes in estimated deaths were statistically significant, even thought the mortality rates in the first part of the study were not.

Finally, they show that the increased risk associated with obesity seems to have declined from the first cohort to the second and third, suggesting fat people are healthier than they used to be.

So to summarize the results

1. BMI<35 seems to play a small role in determining overall mortality.
2. The lowest mortality is seen in the BMI range of 25-30.
3. Underweight is associated with increase mortality, but the majority of this risk is in the elderly
4. Over time, the US population is getting fatter, but the negative health effects of obesity are diminishing.

Remember this is only one study, but a big one with roughly 36,000 people and 9,000 deaths. There may be criticisms raised about the methods or analysis and there is always a chance the sample, although large, is anomalous.

Remember that differences in mortality in the underweight (higher) and overweight (lower) were NOT statistically significant.

Nonetheless, the results challenge the idea that carrying a few excess pounds is unhealthy, despite the clear association of obesity with cardiovascular disease and diabetes.

My #1 takehome message for now would be not to worry so much about one's weight but focus on healthy behaviors like good diet, regular exercise, not smoking and moderate alcohol consumption.

Thursday, April 21, 2005

Processed meats and pancreatic cancer

Just when you thought it was safe to indulge, comes word that heavy consumption of processed meats like hot dogs and sausages is linked to increased risk of pancreatic cancer.

Of course the American Meat Institute isn't buying it:
The American Meat Institute disputed the study's claims in a statement Thursday, saying "processed meats are safe and wholesome foods that can be part of a healthy, balanced diet."
Honestly, do you think this is really going to dissuade people from eating hot dogs and sausages? Do people really think eating a lot of this stuff is good for them?

Other foods didn't have the same effect:
The study showed no heightened pancreatic cancer risk with eating poultry, fish, dairy products or eggs nor did overall intake of total fat, saturated fat or cholesterol cause additional risk.

Another piece of cake, please

So now being overweight is good for you.

It has long been known that mortality follows a J shaped relation to weight. Very thin people are at increased risk for death, as are the obese. In the past some, if not all of the mortality in the thin was thought to be from people losing weight when they are sick. For example, many people with cancer lose a lot of weight, but the cancer causes the weight loss, not the other way around.

In this study, they made sure the "thin" people were persistently thin, presumably removing this bias, and still found increase mortality.

This confirms my overall belief that things like good diet and exercise are more important than weight itself. In addition, classification as thin, normal, overweight, obese, etc is based soley on body mass index, which is a simple mathematical relation of height and weight (kg/m^2). But two people the same height and weight can have vastly different body compositons. Alex Rodriguez makes $10 million dollars a year, but has a BMI of 26, making him overweight.

UPDATE: fixed BMI formula which is kg/m^2

"Jimmies" Etymology

Several weeks ago, while we were on vacation in D.C. my kids were excited to get "jimmies" or sprinkles on their cones.

We wondered where this term came from. A woman next to us explained that for years in New England, ice cream shops would donate the 10 cents charged for sprinkles to the Jimmy Fund, a charity for children's cancer care at the Dana-Farber Cancer Institute in Boston. Over time, she went on, people began calling the "small particles of chocolate or flavored candy sprinkled on ice cream as a topping." jimmies.

A wonderful story, but is it true? Unfortunately the answer seems to be no.

Dictionary.com notes the origins are unknown. This column at www.word-detective.com makes no mention of such an origin, suggesting instead "jimmies" comes from the word "jim-jam" meaning:

"Jim-jam," in turn, has since the 16th century meant "a trivial article or knick-knack,"
An article in the Philly Inquirer (free registration required) confirms that at one time "jimmies" was a regsitered trade-mark and gives this explanation for their name:

Back in the 1930s, the Just Born candy company of Bethlehem produced a topping called chocolate grains. The man who ran the machine that made these chocolate grains was named Jimmy Bartholomew

"Thus, his product became known as jimmies," said Ross Born, the chief executive officer. He was told this story by his grandfather and company founder, Sam Born. Just Born registered jimmies as its trademark, and continued producing jimmies until the mid-1960s - which is why the name was so popular here.

But it also notes a 1986 NPR commentary by poet John Ciardi which dates "jimmies" to about 1922, suggesting the term was in popular use well before it was trademarked.

"From the time I was able to run to the local ice cream store clutching my first nickel, which must have been around 1922, no ice cream cone was worth having unless it was liberally sprinkled with jimmies."

The only online reference to the Jimmy Fund story I can find on-line is in the comments to this guide to "Boston English." This blog refers to a "jimmie fund" in Western Mass today, but the proceeds go to Big Brother/Big Sister.

Another comment in the Boston English entry raises the question of timing. If the use of "jimmies" predates the Jimmy Fund, that would be rule out Jimmy Fund as the origin.

Indeed, the Jimmy Fund Website dates the Jimmy Fund from 1948, almost certainly after the term "jimmies" was in common use.

So the origin of "jimmies" is not related to the Jimmy Fund. I do think it's possible that at some point one or more ice cream stores in New England did have "jimmie funds" where money from purchase of sprinkles was donated to the Jimmy Fund. In retrospect, it seems like that might be an obvious idea, and once it happened it would be easy to conflate the fund-raiser with the origin of the name.

The also circulating on the internet story that "jimmies" is short for "Jim Crows" and applies only to chocolate, not multi-colored sprinkles, is also, in this case thankfully, without basis.

Tuesday, April 19, 2005


Contrary to earlier reports, there are now 3 countries with unaccounted for H2N2 influenza virus, the strain that caused the 1957 pandemic.

I don't know which is more troubling. That they sent out this virus in the first place or that they cannot keep straight what happened to all the shipments.

I'll say again how much more attractive bioterrorism must look to our enemies when you consider that 1-4 million people died in that pandemic.

Oversize caskets

the perfect business for an aging and enlarging population

Living pancreatic islet cell donation

A fascinating article and associated commentary posted today at Lancet (only for subscribers but see press account here). A Japanese woman with severe, brittle type I (insulin dependent) diabetes was treated by transplantation of pancreatic isletes (which contain the insulin producing beta-cells) harvested from her mother.

For non-experts, Type 1 diabetes (sometimes called insulin dependent) is due to inability to produce insulin, usually because the body's immune system has destroyed most or all of the beta cells in the pancreas whose job is insulin production. There are a few other rare causes, like recurrent pancreatitis (basicially, inflammation of the pancreas) that can cause it as well, as in this case (which is important as we'll see in a minute). Patients with Type 1 diabetes tend to be young and thin.

Type 2 diabetes is because of inability to produce enough insulin. It often happens in older, often obese patients. Some of these patients require insulin, but they can still make some insulin themselves. The insulin also doesn't seem to work as well as in other people, so it is said they are insulin resistant.

Treatment of Type 1 diabetes involves frequent measurements of blood sugars and injections of insulin several times per day. Even then patients are prone to complications from chronically elevated blood sugars such as kidney and heart problems, loss of vision and poor wound healing. Overagressive use of insulin can lead to episodes of hypoglycemia (low blood sugar) which can be fatal. Obviously better treatments are needed. Insulin pumps which are planted in the body can help some, but have some problems of their own.

The holy grail of Type I diabetes would be to give patients back pancreatic beta cells and therfore the ability to produce insulin. Beta cells have a complex sensing mechanism which integrates information such as blood sugar level, nutritional status etc and secretes just enough insulin. That is why most of us (w/o diabetes) never think twice about our blood sugar. Even checking blood sugar 4x/day and guessing about what one is going to eat is nowhere near as good as the beta-cell at optimizing insulin secretion. Not even close

Various methods of restoring beta-cell function have been tried including transplant of a pancreas from an organ donor (or part of a pancreas from a living donor) and infusing the insulin producing islet cells back into the body. More speculative at this point are using stem cells to grow new islet cells and put them back in.

One problem with these strategies is that the recipients immune system can destroy the new beta-cells as efficiently and ruthlessly as it did the original ones. In addition, with transplant of islets or the (islet containing) pancreas itself the immune system will recognize the tranplanted tissue as foreign and attack it. Therefore with all of these strategies, patients need to remain on powerful immune suppressive mechanisms with many side effects.

A group in Edmonton has recently had good success isolation islet cells (which include beta-cells) from cadavers and reinfusing them into the portal vein. The islets then lodge in the liver and start to function, excreting insulin when the blood sugar gets high. The results and their importance is controversial (not in a bad way). Multiple pancreases from different donors are required because the yield of islet cells is low, making widespread use impractical, at least for now. Because islets are harvested from dead people, a lot of them die before they can be harvested. In addition, processing to isolate the islet cells and keep the volume of cells lows leads to further loss of cells. Patients have become insulin independent (although now immune suppressive dependent) and how long the new islet cells will survive is unclear.

Now a Japanese group has reported successful islet transplantation using a living donor. The patient had difficult to control diabetes for a number of years from chronic pancreatitis. Her mother served as donor and had about 1/2 her pancreas removed. The donated pancrease was broken down into small chunks using enzymes, but because the volume was already low, complicated purification of islets was avoided. The patient did well after tranplantation and became insulin independent pretty quickly.

I think this is very cool, but am not sure how useful it will be.

Remember this patient did NOT have autoimmune destruction of islets, so survival of transplanted islets in her may be better than in typical type 1 diabetes patients. Also, it is unclear what the risk to the donor is. Earlier reports have shown increased risk of diabetes in pancreas donors, so only non-obese patients with no evidence of glucose intolerance (basically pre-diabetes type 2) and no evidence of islet cell immunity are considered potential donors (the donor in this case met all these criteria).

Eventually, I think stem cells will be the source of islet cells, hopefully stem cells derived from the patient themselves, but that is a ways off. For now, I think this is a big advance, but the whole field is really awaiting safer immunosuppressive drugs (or alternative methods of preventing immune destruction of transplanted beta-cells) so both cadaveric and live donation of islets can be used more widely. As the authors of the assoicated commentary note:
Recent publicity about the UK’s nascent programme of islet transplantation resulted in a stream of inquiries from parents and grandparents of children with
diabetes, desperate to offer their children relief from the urgent needs of living with insulin-deficient diabetes.
I know if my child had diabetes, I'd be happy to give part of my pancreas to cure them.

Primary vs. Tertiary care

Medpundit addresses the fall-out when all the high-tech treatments at a famous referral center is for naught and the patient ends up. Often these patients end up dying at community hospitals nearer to home:
But even worse, is the tendency of the tertiary care centers to leave their failures on the doorsteps of others....

But, I do know that all too often, when the treatment has been exhausted and the patient ends up in the closer hospital in extremis, the miracle-working specialists are nowhere to be found.

I'm sure this is frustrating from the local doctors perspective, but I'm not so sure it serves the patient poorly. If I found out I had pancreatic cancer, say, I'd want to go see the best surgeon to have a Whipple (surgery to try to excise the cancer) and even go wherever they had a new chemotherapy trial; basically do everything I could to maximize my chance of cure.

But if the surgery wasn't curative and the chemo didn't work, I'd want to die (and get palliative care) close to home. For me that might be a tertiary care center, but if I lived out in the burbs or a rural area it would be a community hospital. This paradigm may suck for the community docs, but it does a pretty good job of satisfying the patients desires.

Monday, April 18, 2005

Is this the best idea?

Actor James Garner, whose daughter has lupus, is alerting women to the risks and dangers of this common but poorly understood illness in a new campaign.

Wasn't Garner's last stint as spokesman for the Beef Board unhappily ended when he required quintiple bypass surgery? Yes it was.

A whole blog

devoted to avian flu.

I guess I have to learn blogrolling this week so I can add it.

Sunday, April 17, 2005

Always Look on the Bright Side of Life

and you won't go senile, at least according to a recent study that examined scores on a personality test (the Minnesota Multiphasic Personality Inventory) then looked for evidence of demential 40 years later.

This is interesting but I'd urge several cautions
1. Diagnosis of dementia was based on interviews of patients and/or families. Maybe people are more likely to label cranky old relatives as demented than optimistic ones
2. Maybe the pessimism seen earlier in life is a manifestation of underlying factors that also cause early dementia (i.e. the study shows correlation not causation).

I think this quote, by the leader of the research, gets it wrong:
"Certainly the last thing you want to do is to say, 'Well, I am a pessimist; thus, I am doomed to develop dementia 20 or 30 years later,’ because this may end up becoming a self-fulfilling prophecy.”
I think the study would tend to reinforce pessimism, not necessarily drive dementia.


An article about the outbreak of Marburgh virus in Angola that is actually bylined from Uige, Anola, where the outbreak is taking place. Despite 4 (internet) pages, the story really doesn't tell us much new.

Given the death toll is only 230 now, I suspect it is starting to burn itself out.

The story of Maria Bonino, the Italian doc who ran the pediatric clinic at the hospital and picked up first on the outbreak is touching, as she died of the virus along with another doctor and a number of nurses. It certainly puts into perspective all the whining among US MD's about Medicaid reimbursement rates and malpractice premiums.

Somewhat disconcerting is the idea that epidemiologists are simply ignoring certain areas when tracking the virus since they are mistrusted there:
A van had been attacked by an angry crowd armed with sticks. The day before, rocks were thrown at a surveillance vehicle. The week before, all trips had been suspended for two days because of rock-throwing.

Reluctantly, the health organization crossed three bairros off the list that surveillance teams could visit. Now, if anyone died or got sick there, health officials might not know - a breach of the defenses they were trying to build.

This is a bit reminiscent of the drunk looking for his keys near the lightpost; if you can't contain the virus everywhere, how useful is it to do so some places?

Friday, April 15, 2005

Missing Flu Vials

So two shipments of the H2N2 influenza virus that caused a pandemic in 1957 are missing. Great. And unlike avian flu, this one already spreads efficiently human to human. Except maybe they were never sent out at all:
“We are worried, but CAP (College of American Pathologists-ed) said there is a possibility they were never sent. (Otherwise), I cannot say at this stage what we would possibly do,” Stohr said. “The carrier, the transporter and packager would have to be questioned particularly about these packages."
Great. This quote doesn't give one a great deal of faith in pathologists. You think they could at least keep straight who they sent the stuff out too.

This strain killed between 1 and 4 million in that pandemic.

I think that statistic shows why bioterrorism is so scary. It took nearly 19 people willing to committ suicide to kill 3000 people in the WTC attacks. Think how many more would die if this virus were released. Even assuming better supportive care, antivirals, etch. you'd have to guess at least 10% of the deaths in the original pandemic, which would be 100,000 to 400,000 people.

Not so fast

Turns out there is a Pittsburgh city income tax as well. Who knew? So I spent the afternoon frantically trying to fill in the forms. Turned out I was underwithheld because one of my two paychecks (I get paid partially by the University of Pittsburgh and partially by the hospital) thought I wasn't a Pittsburgh resident, despite the fact they have my address as in Pittsburgh.

Oh well, what can you do.,

Thursday, April 14, 2005


are done!

This is our worst year ever with income in both Massachussets, buying a house, selling off investments to pay for the downpayment, etc. On the bright side we did get to itemize deductions for the first time with all the interest, points and property taxes.

Ugggh. I don't know how I did this before Turbotax.

Hyponatremia II

Or what is an ultrarunner to do?

The NEJM article I discuss in the previous post deals with hyponatremia in runners in the Boston Marathon. Risk was increased with longer finishing times, presumably because it gave more time to get into trouble. The highest risk group was runners who took more than 4 hours to finish.

How much higher is the risk in an 100 mile run where the winner might take 16 hours (and the conditions generally more extreme)? One would guess higher, but it might not be so bad. In an ultra, the pace is slower, and the races last long enough that taking a break to urinate is no big deal (some runner try to go without stopping, the "Western States Wiggle"). The participants are generally better trained as well.

As the old saying goes "the dumbest kidney is smarter than the smartest nephrologist." This is why we don't have to worry about our fluid and sodium intake all the time. We take in whatever we feel like and our kidney secretes more or less sodium (and other electorlytes) to keep us in balance. Pretty nifty (and nephrologist are mostly really smart).

Hopefully in an ultra, you take in enough salt and water and go slow enough that your kidney sorts it out. But not always.

I've had two experiences in ultras that suggest hyponatremia, both 100 milers. At Vermont in 2002, the day after the race (I ran fast enough to finish in the early morning hours) I had pitting edema in my lower legs (pitting means you push your finger in and it makes a dent that stays there for a few minutes). At Western States in 2003, by the 20 mile point or so my hands were very swollen and I hadn't urinated at all (4+ hours). I also gained about 5 lbs. I was also having trouble breathing, but that might just be the altitude. As I went on, and lost altitude, I started urinating and felt better, but kept most of the weight until the end.

I do regularly take Suceed caps, which are modified salt pills during both races, and all my ultras for that matter. I think they help by replacing sodium you lose sweating, but at this point is it a bitconfusing what the best hydration/electrolyte strategy is (except to make sure you pee!)

Hyponatremia I

is a word that strikes fear into sports-medicine docs and medically aware long-distance runners. It just means low blood levels of sodium.

For reasons that are not clear, some runners retain water which dilutes out the sodium in their blood. Basically, runners drink a lot while they run, but don't urinate, losing water and sodium only by sweating. Most drinks, even sport drinks, have low sodium contents relative to blood, so runners can end up taking in too much water and not enough salt.

This can go unnoticed or can progress to big-time problems like seizures, confusion (mental status changes) and, worst, swelling of the brain (cerebral edema) that can cause death (never a good outcome in a healthy runner).

This issue jumbed into the public spotlight in 2002, when a previously healthy young women died during the Boston Marathon.

Despite being an MD and an ultrarunner, I don't really know much about this issue. What studies have been done have been mostly small and retrospective (looking back at patients after they got hyponatremia).

This weeks, New England Journal of Medicine (NEJM) has an excellent prospective article of more than 400 runners in the 2003 Boston Marathon. Most of the authors were a year behind me in residency, and they did the study as sort of a "class project." (ed: NEJM article, quite a class project; indeed).

They signed up runners before the marathon, then drew blood samples after and measured sodium levels. Concerningly, they found that 13% of runners had low sodium (<135)>4 hours, which is not that slow), gaining weigth during the marathon and being either thin or fat were the primary factors associated with increased risk. Females were at increased risk but this seemed more related to slower times and weight gain than to sex itself.

One weakness of the study is they don't provide follow up on those runners (did they go to the hospital, feel bad, or never notice anything).

In an accompanying commentary, Drs Benjamin Levine and Paul Thompson point out that overall marathon running is pretty safe:
In actuality, marathoning is a reasonably safe sport, with less than one death per 50,000 participants. Deaths that occur during less extreme physical activity and in previously healthy persons are usually caused by cardiac disease — predominantly, congenital problems such as hypertrophic cardiomyopathy or coronary anomalies in young athletes and atherosclerotic coronary artery disease in persons older than 35 years of age

but point out the paradox of hydration. Copious water intake during strenuous exercise, especially in hot weather, helps prevent problems like heat stroke, kidney failure and dehydration (obviously) but may lead to hyponatremia. So what should runners do?

One problem is that fluid requirements probably differ markedly among runners, summed up nicely in the original article:
Because runners vary considerably in size and in rates of perspiration, general recommendations regarding specific volumes of fluids and frequencies of intake are probably unsafe and have been superseded by recommendations favoring thirst or individual perspiration rates as a primary guide.
They note periodic weighing may also help. Interestingly, may ultras, especially 100 milers, periodically weigh runners, but usually looking for weight loss, not weight gain.

So I think runners need to drink to thirst, not excessively, but that is not much to go on.

Use of sodium containing drinks (such as Gatorade) would intuitively seem a good idea, but didn't seem to protect against hyponatremia in this study.

Not addressed in this study is use of sodium supplement (salt pills) which are widely but not universally used by ultramarathon runners.

Shameless self-promotion

is here.

The reporter did a good job, but these articles always strike me as funny, as peoples allergies get worse every year when the weather warms up, so it isn't really "news," but I'm sure most readers find it useful.

Did you ever wonder how reporters find people, like allergy sufferers to quote. Well Marianne Stefanik, quoted in this article, conveniently works as an administrator in the allergy/immunology section at Children's Hospital of Pittsburgh.

Wednesday, April 13, 2005

Avian Flu Vaccine

Earlier, someone asked why they couldn't just make next year (or this year's) influenza vaccine include H5N1, the avian flu

As this article explains:
The H5N1 bug first emerged in Hong Kong in 1997, but early efforts to make a vaccine against it didn't work well. Researchers concluded they had used the wrong strains of the virus, partly because they couldn't get more dangerous varieties to grow in the laboratory.

To get around this problem, vaccine makers use vaccines that do grow well in the lab and use genetic engineering to replace the most important genes of the virus (from a vaccine standpoint) with their avian flu counterparts.

This is a bit risky, since you can't be as sure the vaccine will work, but even more importantly, takes time.

News Flash

Lovers of dim sum, beware.

A study in Hong Kong has found the tiny, mouthwatering Chinese snacks are high in fat and sodium and excessive consumption will increase the risk of obesity.

In other news today, mathematicians announced that two plus two equals four.

Seriously, did anyone think all that fried food was healthy?

Einstein's at work

Countries around the world were destroying vials of a nearly 50-year-old killer flu virus Wednesday that were sent to thousands of labs as part of a routine test kit, raising fears of a global pandemic.

Unlike the avian flu, which doesn't effectively infect humans (yet), this is the exact strain that caused a worldwide pandemic in 1957. So if it got out, it could spread rapidly between humans, an ability the avian flu has yet to acquire. Of course, this report notes that 70% of poultry in Vietnam are infected with the H5N1 virus, suggesting it is just a matter of time before it jumps to the human population

This will most likely occur when someone is simultaneously infected with the avian variant and more mundane flu. The viral genes can then recombine to form a hybrid strain. This strain will infect humans efficiently, but not be recognized by the immune system because it doesn't resemble previous influenze strains that infected humans.

Elidel and Protopic manufacturers fund "yes groups"

which defend their products.

I decided to check the Elidel and Protopic web sites to see what their manufacturers response to the recent FDA advisory about a possible link to cancer was. Needless to say I'm a bit disappointed.

Neither site's main page directly mentions the link between the medicine and cancer. The Protpic site has a small box entitled "Recent FDA Advisory" with links to the American Academy of Dermatology (ADA) and the National Eczema Association for Science and Education (NEASE), whic have come out against the black box warning

The Elidel site has an inconspicuous link labelled "Recent FDA statement" which leads to statements downplaying the link from the AAD, NEASE and the Inflammatory Skin Disease Institute (ISDI). Here is the AAD statement:
"The American Academy of Dermatology is disappointed that the FDA has taken this action, despite the fact that there is no data that proves proper topical use of pimecrolimus and tacrolimus is dangerous in people. Because these medications are applied to the skin, virtually none of it gets inside the body. It's not the same as taking a pill. These are valuable medications...if used properly..."
I am familiar with the ADA, but have never heard of NEASE or ISDI, despite the fact I treat a fair amount of eczema.

The NEASE website allows you to download the annual report for the year ended 2003. Guess who the major contributors to NEASE are? If you guessed patients with eczema and their parents you would be wrong.

Fujisawa and Novartis each gave >$50,000 to NEASE in the 18 months ended 12/31/2003, with no other donors giving >$10,000 and only 2 giving more than $5000. So when NEASE downplays the risk of cancer with these medications, remeber they get a substantial proportion of their funding, perhaps the majority form their manufactueres.

How about the ISDI. I couldn't find the annual report or a donor list online, but this page on the ISDI site, conveniently displays the Elidel logo.

So when you here ISDI executive director LaDonna Williams testify:
"These medications have been the only treatments that have given my children anything resembling a normal quality of life,"
remember who pays her salary.

What about
The American Academy of Dermatology (Academy), founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. With a membership of more than 14,000 physicians worldwide
Surely they are free of conflict. Nope.

Fujisawa is a "Diamond" level corporate donor, meaning they gave >$500,000 to the AAD in 2004. Novartis "only" made "Sapphire" level ($250,000-500,000). The AAD does have a wider range of pharma donors compared to the others.

So if you think these organizations press releases read like they could have been writting by Fujisawa and Novartis publicists, now you know why

Tuesday, April 12, 2005

Grand Round XXVII

is up here


Monday, April 11, 2005

Progress on Marburg outbreak

This article says yes:
Dr. Nestor Ndayimirije, an epidemiologist and leader of the World Health Organization's efforts in Uíge, said he that believed headway was being made."If we compare with previous weeks, when we had 10 to 15 cases a day, now we have 4 to 5 cases a day," he said. "I am certain we will control this epidemic if we work more with the communities."
but this article suggests otherwise:
Doctors Without Borders and WHO medical workers were attacked on Thursday by residents who feared the teams had brought the virus with them and were responsible for spreading it. The emergency coordinator for Doctors Without Borders, Monica de Castellarnau, said the attacks stemmed from lack of information and that education campaigns were being launched.
The first article gives some interesting insight into the situation on the ground in Angola and how the WHO teams operate

Placebo effect

Do placebos work and if so is there in routine practice ethical?

The answer to the first question is still not clear. It is clear that in many placebo controlled trials patients given placebo improve. Whether this is just regression to the mean or a true effect of the placebo is unclear.

I see enough patients in whom treatments haven't worked to have much faith in the placebo effect for most illnesses. What I do wonder about is chronic illnesses with poorly defined biological basis like chronic pain syndromes, fibromyalgia, chronic fatigue syndrome, irritable bowel, etc. These patients clearly experience discomfort, but without a real biological basis there isn't much to go on for treatment. In these cases I suspect a placebo might help.

What I can't see is actually incorporating them into practice. How could I make a patient believe I was giving them a real treatment and then give them a placebo? What would I write on the prescription? I think if I lied to them (which is what I'd be doing) and they found out, they wouldn't trust me anymore, and I'm pretty sure I couldn't lie to them in good faith in the first place.

Sunday, April 10, 2005

More Marburg

In general, I think the risk of a worldwide epidemic with a hemorrhagic fever is low, but his oubtbreak is starting to get scary:

An international medical charity battling a hemorrhagic fever that so far has killed 181 Angolans has urged the government to close the regional hospital here, at the center of the outbreak, saying the medical center itself is a source of the deadly infection.

In general when you are closing hospitals, it means that things are no where near in control. While it may well be the right move now, it means new sufferers will have to be quarantined at home in their villages or elsewhere. Of course, the supplies to effectively quarentine highly infectious patients are likely lacking in Angola.

Keep in mind that so far this has killed just over 200 people, which while the largest Marburg outbreak ever, is about 1/5 the number of US citizens killed in traffic accidents each month

I think I'll be avoiding New York State venison

Through unlucky circumstance, tissue samples from a deer that one farmer donated for the banquet tested positive for chronic wasting disease, and the results were discovered after the meat had been eaten at the banquet. It is the deer version of mad cow disease, and the first documented case in New York.

Though people have become ill with mad cow disease from eating infected beef, no human is known to have become ill by eating infected venison.

Not yet anyway. Prion diseases are extremely odd in that they are spread by proteins with no nucleic acid (DNA or RNA) component. This makes them completely unlike any other infectious illness. They seem to work by causing misfolding of homologous human proteins and may be one reason cannibalism is nearly universally frowned upon.

As of now, there is no treatment for prion diseases.

Misconduct at NIH

is rampant according to this article. While I have no idea how much of a problem it is, I always think it is a bad sign for someone when they don't deny the actual accusations:
Alyza Lewin, Kagan's lawyer, said her client occasionally hugged or kissed female subordinates, and used "earthy language" in some e-mails to workers. Lewin also said Kagan once had retrieved a red bra that had been a gag gift among women in the office and sent it to a woman who had been a subordinate and who had transferred from his office after a falling out with him.
When the best your lawyer can do is admit to grossly inappropriate behavior and claim it doesn't rise to the level of sexual harassment, you are not in great shape.

"I think we (safety officials) got in the way, and that we were an impediment to the science," Luzar testified.
is true in every research institution.

Saturday, April 09, 2005


Coroner Dr. Cyril H. Wecht yesterday changed his ruling in the deaths last month of inmates Amy Sartori, 31, of Mount Washington, and Valeria Whetsell, 51, of Wilkinsburg. He initially ruled they died after mixing cleaning products that formed deadly fumes, but additional tests showed the women had the flu and then developed an infection caused by methicillin resistant Staphylococcus Aureus, which caused their deaths
I'm not a pathologist, but it seems like it should be relatively easy to tell the differnce on autopys between inhalation of toxic chemicals and infection.

Wonder if there is any relation to this headline, also on the front page of the Pittsburgh Post Gazette today:
Wecht's offices raided by FBI

New Driver's License

Wife of Dr. Andy and I both got Pennsylvania Driver's licenses today. The process was about as painless as possible. Upon arrival at the center, you took a number. By the time we finished filling out the form (which was not obviously available on the web site) our numbers had been called. Forms were filled out, we sat for another 2 or 3 minutes and then were called back up to have our pictures taken, and a few minutes later our licenses were ready.

Much more pleasand than I had anticipated.

They do have a more sophisticated vision screeing, as they picked up that I have horrible vision out of my left eye, even corrected. I've always been able to pass the vision tests (with glasses or contacts) before. So now I have a restriction on my license that not only do I have to wear corrective lenses (duh) but can only drive vehicles with mirrors on both sides. No biggie.

I went to an opthamologist last summer and he told me the vision in that eye was so bad, I never used it much growing up so my brain learned to ignore it. I only really miss it biking, since it is hard to look back over your shoulder when you can't see out of that eye. Luckily, I don't bike much lately.

Patients rights

An argument, from a libertarian perspective, that "morning-after" contraception should be available over the counter (OTC):

Something is off when access to contraception depends on who is working the late shift at Walgreen's. The real scandal is not that women are being denied birth control, but that they have to ask for it. There is no reason why a woman's access to contraception should depend on a single Roman Catholic with a conscience, or why a pharmacist should have to weigh the decision between denying a woman her prescription and violating deeply held moral beliefs.

Contraception doesn't belong behind the counter; it belongs over-the-counter. A woman's access shouldn't hinge on whether she has health insurance, whether she has a doctor she can call at 5 a.m., or how her neighbors feel about the culture of life. Women should be able to order stacks of the stuff off of the internet to keep in their medicine cabinets

In my limited experience, I just called in the prescription after talking to the patient on the phone, so I don't really see why not.

In a similar vein, many patients are apparently willing to bear the risk of increased cardiovascular disease to keep taking Vioxx or Bextra.

I suspect this is the triumph of marketing over science. I am unaware of any data showing the Cox-2 inhibitors are more effective than traditional NSAIDS (which inhibit both forms of cycoloxygenase --abbreviated COX), and none of the people in the article were reported to have had GI issues with NSAIDS, which is the one advantage the COX-2 inhibitors have.

The article comically degenerates in the second half into the idiosyncratic comments of patients with minimal, if any, medical knowledge. We learn that naproxen (Aleve) makes Yankee outfielder Garry Sheffield drowsy and that Denver golfer Robert Arnold felt anixous after taking Vioxx and Bextra. No word if this only started after he learned of the cardiovascular risk. Neither of these are common side-effects of these medicines.

Elidel, SAM, and Cancer

Imagine your child had eczema. It was not too bad, certainly not disfiguring. It got better with topical steroid cream, but the word steroid made you nervous. Your doctor told you kids with eczema were at increased risk of going on to develop asthma and that made you nervous as well.

When your doctor told you about a study to prevent your child from going on to get asthma you were enthusiastic, especially when you heard that it involved using a cream that would treat the eczema and that wasn't a steroid. In fact the nice adds on TV kept talking about how safe it was.

The study involved putting this new medicine or placebo, you weren't sure which, on your young child for long periods. Since everyone told you how safe the medicine was you figured it couldn't hurt.

But imagine it turned out the medicine might not be so safe. Imagine it turns out the medicine might cause cancer, and that the FDA is particularly concerned about long term use and use in young children. What would you expect the study investigators to do? Cancel the study or at least stop it until the safety of the medicine is clear? Inform the parents of patients enrolled in the study of the new warning, go over the risks and benefits of the study in light of the new information and reobtain consent? Or do nothing?

Incredibly, the answer to the question is do nothing. I have talked to 2 parents this week with children in the study WHO HAD NO IDEA ABOUT THE ELIDEL/CANCER LINK, and others who had only found about it on their own. So the investigators are sitting on this informationm, potentially increasing the risk of more than 1000 kids of getting cancer, and not even waring their parents.

I first blogged about the link at the end of February in one of my first posts, when the FDA issued it's warning to health care providers.

Six weeks later, parents of children in the study have not been informed of the new warnings! No one has called them, no one has sent them a letter, nothing.

Pretty outrageous, huh.

Even worse the study violates several of the specific warnings in the FDA alert:

From a Novartis press release:
a clinical trial called SAM (Study of the Atopic March), involving 1,100 infants aged 3-18 months who are currently being recruited at 20 centers in the US.

For the first 36 months of treatment in this study, investigators will assess the effect of long-term treatment with Elidel on the natural course of atopic eczema

From the FDA alert:
#Avoid use of Elidel and Protopic in children younger than 2 years of age. The effect of Elidel and Protopic on the developing immune system in infants and children is not known. In clinical studies, infants and children younger than 2 years old treated with Elidel had a higher rate of upper respiratory infections than did those treated with placebo cream.

#Use Elidel and Protopic only for short periods of time, not continuously. The long term safety of Elidel and Protopic are unknown.
Of course, unless you found it on your own, you'd have no way of knowing the risk you were exposing your child to.

Friday, April 08, 2005

More dueling headlines

New aggregation services (I use Excite) just make this too easy:
Former smokers should rest easy
from USA Today and
Jennings' Case Highlights Risk to Ex-Smokers
from Excite

So which is right? Probably both. As the first article puts it:

Research shows that former smokers reduce their risk of developing heart disease and stroke to the risk level of non-smokers within a few years after quitting. It takes about 10 years to reduce the risk for lung cancer and other cancers, but risk never drops to the level of someone who has never smoked, says physician Michael Thun, head of epidemiological research at the American Cancer Society.

Recall that the devlopment of cancer requires multiple genetic changes in a single cell that leads it to proliferate uncontrollably. These build up over time, abetted by smoking, and never really go away. On the other hand, it is never to soon (or to late) to quit:
A landmark study published last year in the British Medical Journal found that cigarette smokers die an average of 10 years sooner than nonsmokers. At least half, and possibly up to two-thirds, of people who smoke from youth on are eventually killed by their habit, a quarter of them in middle age, the study reported.

Outsourcing Medical Care

Foreigners are increasingly travelling to India for first class medical care at bargain prices, at least according to this article.

Europeans and Americans, looking for world-class treatments at prices a fourth or fifth of what they would be at home, are traveling to India. Modern hospitals, skilled doctors and advanced treatments are helping foreigners overcome some of their qualms about getting medical treatments in India.

I can't say I am too surprised, but I doubt this will turn in to any sort of significant trend. First, the cost of travel will likely more than offset the savings for all but big-time operations. However much cheaper an allergist in India is, the cost of flying there is much more than it costs to see me. Plus you presumably need to stick around for a while. You can't just have hip replacement and hop on a plane back to San Francisco the next day.

Second, follow-up is problematic. If you get, say angioplasty, in India who follows you for your heart disease when you get home? For stand-alone surgeries like joint replacement, this is probably okay, but for chronic conditions this sort of outsourcing won't work too well.

Finally, what if something goes wrong? While the individual surgeons in this article are well-trained, do the hospitals have the depth of infectious disease and critical care specialists to take care of infections and other adverse events. Even if they do, if you end up with an infected joint requiring prolonged IV therapy or on a ventilator with a pulmonary embolus, wouldn't you like to be close to home.

One other tidbit from the article about the miracle of socialized medicine:

For some foreigners, like George Marshall, a 73-year-old violin restorer from Yorkshire, England, India's hospitals also offer speedier treatments. Last year, Mr. Marshall said that he started having trouble finishing a round of golf. An angiogram showed two blocked arteries in his heart. With the British National Health Service, Mr. Marshall would have had to wait three weeks to see a specialist, and six more months for coronary bypass surgery. "At 73, I don't have the time to wait," Mr. Marshall said. "Six months could be the rest of my life." Nor could he afford the £20,000 ($38,000) for surgery at a private hospital.

Six months for bypass? And people wonder why Americans aren't in favor of single payer health care.

Thursday, April 07, 2005

On the other hand

Dueling headlines:

Experts inject reality into cervical cancer prevention schemes

in Nature Medicine versus

Vaccine appears to pre-empt cervical cancer

in USA Today. Normally I'd view Nature Medicine as more sober and reliable, but lately I'm not so sure.

In fairness, the Nature Medicine article deals largely with problems in using cervical cancer vaccines in under-developed countries.

Two inspiring stories of

overcoming adversity to achieve the goal of being a doctor here and here

Both are inspiring stories. I think the partially paralyzed rehab doctor must be particularly inspiring to his patients.

Wednesday, April 06, 2005

The Economic Impact of Avian Flu

is discussed here.

CLSA Asia-Pacific Markets, the Asian investment banking arm of Crédit Agricole of France, estimated in a report on Monday that the disease had already cost Asian nations $8 billion to $12 billion, mostly from the deaths or destruction of 140 million chickens and other poultry. But the cost would be greater if the disease gained the ability to spread easily from person to person, a possibility that is not factored into current stock and other asset prices, said Christopher Wood, CLSA's chief equity strategist.
"the cost would be greater" may qualify as understatement of the year.

While I don't think this will be as bad in the US as some are predicting, it could be bad in Asia where there is less capacity for sophisticated medical care. Or it might just die out with a couple hundered human cases.

Pedometers and walking

A good example of the aphorism "You manage what you measure"

Women who try to walk 30 minutes a day walk a lot less than those who actually wear pedometers.

Great medical reporting

Doctors didn't give Clanton Crumbley much chance of surviving. One suggested an abortion when a serious problem with the fetus was detected. Others suggested his parents leave the newborn baby at the hospital until he passed away....
Kim Crumbley said a test 19 weeks into her pregnancy showed that Clanton had a genetic abnormality so rare it doesn't even have a name
Apparently, the disorder is so rare, the AP can't even tell us what it is.

From the fact it was picked up at 19 weeks gestation, I think we can assume it is some sort of gross chromosomal abnormality, not a subtle defect. Trisomy 21 is not rare, and trisomy 13 (Patau Syndrome) and 18 (Edwards syndrome) are rare and usually fatal soon after birth, but have well-known eponyms and even share a support organization.

So what defect does the delightfully named Clanton Crumbley have? Could mosaicism (having a mix of cells with normal chromosomes and cells containing the genetic defect) explain his course? Has this unique case been reported in the medical literature? We will apparently never know.

Since the AP article references The Cullman Times ("Serving all of Cullman County") but a search revealed no article about Clanton Crumbley.

What to do with the FDA

is the subject of a good perspective piece in the NEJM several weeks past (I'm behind in my reading, so shoot me), which is probablly only available to subscribers (for academics, most medical schools give you on-line acess).

Several interesting points, including that unlike previously, most new drugs are now approved first in the US.

Two good criticisms of the curent process are that

1. Once a drug is approved, the FDA has no authority to order more safety trials

2. Long term studies are not required, even for drugs that will be used long term:
Bruce M. Psaty, a professor of medicine, epidemiology, and health services at the University of Washington in Seattle, believes that for drugs that patients are likely to take for years, companies should be required to initiate long-term trials before approval and to continue them after the drugs are marketed. "For drugs that are going to be used by millions of people for many years, six-week studies are not adequate to assess the trade-off between risks and benefits," he said.
The article goes on to point out that for statins, there are actually additional benefits to long term use not seen in shorter trials

The article goes on to give a balanced discussion over whether safety oversight of approved drugs should be done inside or outside the FDA, with the Alastair Wood of the outside camp getting the best line:
"When a plane crashes, we don't turn over the investigation to [the airline] and the air-traffic controllers," Wood said. "We get someone else to do it."
Finally, the article makes the point I (and many others) have made previously, that going from approval to mass marketing is a disaster waiting to happen. The disaster with Vioxx is not that it was approved. For patients with arthritis and history of gastric ulcers it is a good medicine. The disaster is it was successfully marketed to everyone with a backache or sore knee.

More criticism of the HOTHEAD paper

is here.

Via the newest Tangled Bank

Tuesday, April 05, 2005

The race is on

to get enough antiviral drugs stockpiled in time
So far, the United States has just 2.3 million treatment courses of Tamiflu on hand; discussions are under way about how much more might be needed and who would get them first. According to a Roche spokesman, Terence Hurley, among the other countries that have placed firm orders, Britain will buy 14.6 million courses of the drug; France wants 13 million; and Canada, 5.4 million. The orders are to be filled over the next several years.

Roche, too, has scrambled to increase production to meet the increased demand, doubling its production capacity for Tamiflu from 2003 to 2004, with another doubling expected by the end of 2005. The plan, Mr. Hurley said, is to bring additional manufacturing to the United States in the fall, with the first pills from those plants reaching the market 10 or 12 months late

I've said before, that the risk of a bird flu pandemic may be a bit overstated, but it could definitely happen

Evolution of Snake Venom

This is cool. Imagine your job was working out how snake venoms evolved. This is not only neat itself but may have important medical applications in that harnessing some of the venoms components may be beneficial. For example, one component of venom from the inland taipan is related to atrial natiuretic pepetides which are important in relaxing blood vessels and may be a good treatment for heart failure.

You also get to use cool technology developed (mostly) as offshoots of the human genome project:
Dr. Fry is able to identify all of the genes that are active in venom gland cells, and then read their DNA sequence. About half of the genes that are active in a venom-gland cell produce well-known "housekeeping" proteins that are essential to any animal cell. Most of the others are venoms.

He's also made other cool discoveries like the fact that most pathogenic venom molecules are evolved from gene duplications of proteins expressed in other organs. The duplications are then duplicated, expressed in venom cells and evolve for increased toxicity.

All in all a very cool job.

Ionic Cleaners

are not only bad for you, but they are ineffective. I knew from the first time that a parent brought the flyer for one of those in. Ozone is known to decrease lung function and trigger asthma, so producing it in your own home can't be a good idea, but they don't work very well either:

The magazine found that five of the six ionizing cleaners don't clean
very well. "They were all ineffective in removing pollen, dust and smoke from
air," says Jeff Asher, the magazine's technical director.

In general, the data on any type of air purifier having a signficant effect on allergies is low. Individual studies have generally shown no signficant effect, but a metaanalysis did show some benefit.

Overall, I don't generally recommend them, but I am not against them either, if the family wants to spend the money. I do think money and effort are better directed at specific allergens such as dust mites or pollens.

Monday, April 04, 2005

Medical Economics

for beginners in this Atul Gawande New Yorker piece. It does a good job of showing how medical care is payed for and some of the problems. He doesn't have the solution, but eithe does anyone else.

I would say the pay set-up for attendings at the Brigham is pretty free enterprise (they get paid for surgery and are charged for expenses, at least after a few years of straight salary support). I (and I think many academic physicians) am paid a salary with a small (10-15% of salary) incentive payment depending on productivity and academic achievement. I don't know which is best, but the piecework system clearly creates incentive to increase the amount of medical care provided.

The hassles with insurance are unbelievable. One advantage of practicing at an academic institution is that there is a huge bureacracy to deal with these issues.

The downside is it is done less well than I'd do it if my pay depended on it (our incentive is based on RVUs billed not collection) and all those people are expensive so I make less than I would in private practice. I recently found out that I was not accepting patients with several different insurance plans because my credentialling hadn't gone through. I found out by accident (I had spoken with a pediatrician about a patient and asked the schedulers to add him on, but they told me they couldn't because of his insurance) and started asking around. I found out I was indeed accepted by those plans but for some reason the scheduling program wouldn't accept me as a provdier, so the schedulers were just booking those patients with other physicians. Apparently, no one thought to look into fixing thisAaargh. Of course if I was running my own practice I'd have been more on top of this (or fired the people who didn't do anyting about it).