Shut up

Sen. Arlen Specter yesterday backed off a threat to have a Senate subcommittee investigate whether the NFL and the Philadelphia Eagles violated antitrust laws in their handling of Terrell Owens. Specter, chairman of the Senate Judiciary Committee, said he talked to lawyers in the Department of Justice about the issue.

"I think it's more a matter for them than us because we've got ... a lot of matters which take precedence over this for our own time," said Specter, R-Pa.

On Monday, Specter said it was "vindictive and inappropriate" for the league and the Eagles to prohibit Owens from playing and prevent other teams from talking to him, and he might refer the matter to the subcommittee.

Like the Justice Deparment doesn't also have better things to spend it's time on. What did Mark Twain say? "It is better to keep your mouth shut and have people think you a fool, than open it and remove all doubt?"

Doctors behaving badly

Now this is inappropriate

Patients say the problems come in many guises. The arrogant or dismissive doctor. The impatient doctor with his hand on the doorknob. The patronizing doctor. Or, as one young woman experienced, the doctor who is callous and judgmental.

The woman, who lives in Washington, asked not to be identified because she did not want her mother to know about her sex life. Her problem doctor was a new gynecologist she saw for a routine checkup. The doctor began the examination, inserting a speculum into the young woman's vagina.

"She asked if I was sexually active," the woman said. "I said I was. She asked if I was sexually active at this moment. I said yes."

Leaving the speculum in, and the woman with her feet in the stirrups, legs spread, the gynecologist walked to the head of the exam table and proceeded to lecture her on the perils of sexual activity outside of marriage. "I was so humiliated and so scared," the woman said. "And so embarrassed."

I agree that certain fraction of doctors have horrible bedside manner (in addition the general inappropriateness in this case) and for the most part no one does anything about it. I agree with the article that many don't even know.

We get very detailed feedback on how our patients rate us, almost to the point ridiculousness. Patients are asked to rate us on a five point scale encompassing poor, fair, good, very good and excellent. The ratings are then transformed to a 100 point scale (Children's Hosptial of Pittsburgh motto: even our worst doctor gets a 20!). They then report our ratings on a variety of factors to a decimal place! Like 93.7 means something different than 93.5 on this scale. My ratings are generally good, with the exception of parking, which I do poorly on.

Anyway, I am always mystified by patients reluctance to switch doctors. If you go to a restaurant with bad food and lousy service, do you go back? Of course not, you try somewhere else. So if you get a doctor you don't like, why do you keep going back? I think this has something to do with power dynamics; people somehow fear that doctors will find out they went somewhere else and be mad, although what exactly they'd do is not clear. I can tell you patients switch doctors all the time. Being in a small specialty I often see patients who want a second opinion or new allergist and know my patients leave me to go elsewhere. It is no big deal.

Vaccine safety and the internet

This article concisely summarizes why vaccines are overwhelmingly safe and life-saving:

At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine “scares” continue to have an international impact on immunization coverage.

It goes on to point out the communication difficulties vaccine advocates (such as myself) face given the emotional appeals and pseudoscience used by those who oppose vaccination, recognizing the internet as a powerful force in today's world:

The Internet has increasingly become a powerful means of international communication and an almost inexhaustible source of information, capable of playing an influential role in both the positive and the negative sense

The article itself is not available except to subscribers to the Journal. Sometimes I feel like we are fighting with one hand tied behind our back.

To torture or not

This excellent column by Charles Krauthammer makes the case for torture, in certain, limited situations:

Ethics 101: A terrorist has planted a nuclear bomb in New York City. It will go off in one hour. A million people will die. You capture the terrorist. He knows where it is. He's not talking.

Question: If you have the slightest belief that hanging this man by his thumbs will get you the information to save a million people, are you permitted to do it?

Now, on most issues regarding torture, I confess tentativeness and uncertainty. But on this issue, there can be no uncertainty: Not only is it permissible to hang this miscreant by his thumbs. It is a moral duty.

I have to say, troubled as I am by the whole concept, I agree. And once you agree that torture is sometimes justified, the whole Pandora's box is open. Krauthammer makes what I think is a good argument, that torture should be limited to specific cases: the "ticking time bomb" situation as above, and analagous situations where terrorists have important information, but the time urgency is less (e.g. an attack is being planned and the detainee knows the identity of the planners but not the details themselves). Obviously, the second exception could vary in scope enormously depending on the definition of important information.

He goes on to suggest that the military be banned from using torture and only specific, specialized intelligence agents be allowed to use these techniques. This would certainly help cut down on the Lyndie England type abuses.

I can't say I can personally see a way around the "ticking time bomb" problem. The two most appealing arguments for an absolute ban on torture are that it damages us as a country and that it doesn't work.

I do see how the abuses at Abu Ghraib, for example, have really hurt the U.S. position as promoter of freedom and democracy, which I don't think I fully understood at the time. I suspect that is why the CIA apparently operates secret prisons for high-level terrorists.

The second argument, that torture doesn't work is appealing primarily because it gives us such an easy solution to the problem: torture is ineffective, therefore we are absolutely against it. Unfortunately, I think much of the basis for torture's ineffectiveness is wishing it to be so. A priori, I just can't imagine torture wouldn't work. Sure, there are problems, like people tell you what you want to hear, but I have to believe torture to be effective in certain cases.

To sum up, I suspect everyone is troubled by the idea of torture. But if you oppose torture absolutely, you are saying you'd let the bomb in Krauthammer's scenario blow up, killing all those thousands for the sake of your principle.

Tangled Bank

a science themed blog carnival is here

Grand Rounds 2:10

is up at Over My Med Body. I like this name, but I'm still waiting for someone to use the name of my med school softball team, Grateful Med.

Avian flu hype

This article, by Michael Fumento, effectively makes the case that an avian flu pandemic may never come and, if it does, it is unlikely to be as bad as we've been led to believe. While I overall liked the article, there are some things I disagree with. Fumento, although not a scientist or physician that I know of, obviously knows much more than most science writers about biology, virology, etc.

The one thing Fumento doesn't seem to appreciate is the power of evolution. He notes that H5N1 has been around for some time and doesn't yet effectively infect humans or spread from human to human. What he doens't discuss is that the more birds are infected the more virus there is replicating and the more chance of the emergence of a strain that is tropic for humans.

He also states

With all flu viruses, to paraphrase a bumpersticker, mutation happens. Avian flu could randomly mutate to be transmissible between humans. But it would indeed be random, since the virus is doing just fine in the bird population, thank you very much. There is no evolutionary pressure for it to reach out and infect other species. Such mutations nonetheless come along now and then. The infamous Spanish flu, for example, appears to have started as an avian flu.

This belies a fundamental misunderstanding of evolution. For any individual virus particle, it either infects another cell or it doesn't. Every avian flu viral particle in the world today is the progeny of a previous virus that managed to infect another cell. While the avian flu virus in aggregate is "doing just fine," imagine how many descendants the viral strain that infects a human and then spreads effectively to other humans will have. Of course evolution isn't anticipatory; that is, the virus can't somehow "know" what mutations are likely to be beneficial in the future. Mutations accumulate and then natural selection acts, not vice versa. So Fumento may be right that it is unlikely the requisite mutations for effective infection of humans will occur, but how well or poorly H5N1 is faring in birds isn't relevant (except that the more infected birds, the more virus replicating and the more mutations out there).

Also, despite the hype this article has generated, Fumento seems to agree we should keep working to mitigate the impacts of a pandemic, in case it does come.

Mutating flu virus

I'm not sure this really even qualifies as news

The H5N1 strain of bird flu seen in human cases in China has mutated as compared with strains found in human cases in Vietnam.

Chinese labs have found that the genetic order of the H5N1 virus seen in humans infected in China is different from that found in humans in Vietnam, Xinhua news agency reported Monday.

In China's human cases, the virus has mutated "to a certain degree," health ministry spokesman Mao Qun'an was quoted as saying.

"But the mutation cannot cause human-to-human transmission of the avian flu," he noted.

Viruses which use RNA as their genetic material have high mutation rates. The differences aren't necessarily important as one would expect some random accumulation of mutations. There is nothing to suggest the virus is increasingly able to infect humans or be transmitted from human to human. That would be big news.

Recruiting drug reps

This is too funny

Anyone who has seen the parade of sales representatives through a doctor's waiting room has probably noticed that they are frequently female and invariably good looking. Less recognized is the fact that a good many are recruited from the cheerleading ranks.

Known for their athleticism, postage-stamp skirts and persuasive enthusiasm, cheerleaders have many qualities the drug industry looks for in its sales force.

I don't want to minimize the problems with drug reps, free gifts, etc. but I'd say the reps I deal with don't necessarily fit this stereotype. Roughly half of our reps are men and they range from attractive to regular guys. Of the women, many are married with kids (many of the men are too) and while not unattractive I don't think they were selected on looks alone (with possibly one exceptinon). Without exception, however, the good reps do have a cheerleader's personality. They are persistent, enthusiastic, and always upbeat, which I find unbearable.

Also note that the article is pretty light on actual data. They talk about several individual cheerleaders who've gone on to be drug reps, then quote someone who started a company to match cheerleaders with drug rep jobs saying he knows of hundreds of examples. Of course, he is not exactly neutral on the issue

Peanut allergy death

A Quebec teenager with a peanut allergy has died after kissing her boyfriend who had eaten a peanut butter sandwich hours earlier.

Fifteen-year-old Christina Desforges died Monday. She went into anaphylactic shock and in spite of being given an adrenalin shot, could not be revived.

She obviously had a very severe allergy given the small amount of peanut that must have remained on her boyfriends lips and face. Still this reminds all of us who have or take care of people with food allergies how vigilant we must be.

This letter to the NEJM (requires free registration) reports that exposure via kissing is not rare, but this is the first death I'm aware of.

Stem cell ethics

This is not what the field needs:

Hwang Woo-suk, one of the world's leading stem cell experts whose South Korean team cloned the first human embryo and created the first cloned dog, publicly apologized yesterday for ethical breaches at his lab and said he would resign from all his official posts.

Apparently, he lied about the source of some of the embryos his lab worked on: some came from women paid for donating and some from members of his research team. He had previously denied that either of these things had happened.

I have no inside information, but I suspect there are some other problems with the work of this team. Their results have been controversial and hard to replicate, now the group's leader is stepping down over what might be considered signficiant but not overwhelming ethical issues. Apparently, neither paying women nor researchers themselves donating were clearly proscribed at the time of the donations.

Reading between the lines of this

But earlier this month, Pitt researcher Gerald Schatten said he was pulling out of his association with Dr. Hwang, citing concerns about the way the group had obtained human eggs -- whose difficult procurement is typically one of the most vexing obstacles to large-scale stem cell research. Mr. Schatten, a medical school professor, had been for more than a year the prime American stem cell scientist working with Dr. Hwang

I would not be surprised to learn soon that there are significant questons about the accuracy of the South Koreans data.

Counting my blessings

Why me Lord, what have I ever done
To deserve even one of the pleasures I've known
-Johnny Cash

Yesterday, I had 3 new consults and a follow-up to see. Two of the consults were complex and the fellow had clinic in the morning, so she didn't finish them until nearly 5PM. I was beginning to feel a bit crabby, having to stay late the day before Thanksgiving and all.

I got over that real quick. One infant has a life-threatening immune deficiency that will require a bone-marrow transplant, another young child is permanently neurologically devastated from an event where breathing stopped, cutting off oxygen to the brain. The third a preteen with enough psych issues to be on a long list of meds, one of which was causing an allergic reaction. The lucky one was a boy with asthma waiting to go home. Despite what must seem horrific luck, none of the parents were bitter or angry. All went out of their way to wish us a happy holiday. Taking care of sick children truly is an honor and a priviledg
I got home to a hot dinner and two healthy, happy kids demanding to help me shovel snow. I hope we all count our blessing today.

Happy Thanksgiving

and peaceful travels to all Dr. Andy readers.

May your journey be restful and without complications. We will be staying in Pittsburgh and driving just 20 minutes or so for dinner

UPDATE: this doesn't sound encouraging

Breast feeding cuts risk of diabetes

according to this article, summarized here:

Longer duration of breastfeeding was associated with reduced incidence of type 2 diabetes in 2 large US cohorts of women. Lactation may reduce risk of type 2 diabetes in young and middle-aged women by improving glucose homeostasis.

The weakness of the study is it is observational. In other words they just followed women who did or didn't breastfeed and then observed who developed diabetes. Ideally, you'd randomize women to breastfeed or not, but this is not really ethical. One has to watch out for the "healthy lifestyle" effect in which women who breastfeed also exercise, watch what they eat, don't smoke, etc. Perhaps it is one or more of those things, not breastfeeding itself that provides the protection. The authors try to control for this, but you never know for sure if you are missing something.

I'd say the results are intuitive since it an article of faith that women who breastfeed lose weight quicker after delivery than those who don't and obesity is definitely a major risk factor for type II (adult onset) diabetes.

Gifted children

Last Sunday's NYTimes Magazine features an article on gifted children. Although not the angle I would have taken (I'd have focused on the pushy moms), it is very interesting.

One exasperating thing about the article, and the field in general, is that no one defines what gifted is: is it the merely smart (say the top 1%, a group I'd consider myself a member of) or the truly gifted (say IQ>180, which I'm not even close to). This makes a big difference in the number of folks you are talking about. There are approximately 4 million births in the US each year. The top 1% represents ~40,000 kids/year. According to this site only 1/3.5 million people have an IQ > 180, about 1 per year. Obviously this makes a difference when you are talking about public policy.

To illustrate, at one point the article talks about Lewis Terman's studies of those with IQs greater than 135, which is about the top 1% of the population, actually a few more. Later the article talks about "the more mundane variety of Ivy League-aspiring kids". But given 8 Ivys with say 1500 students/class, we get 12,000 kids/year. Making some assumptions about the number of similar schools (Stanford, MIT, etc) and how well Ivies and similar schools attract the most talented students, I'd say the Ivy League does represents about this top 1%. Maybe not exactly, but pretty close.

So point one is that you have to define who you are talking about. One thing you find if you look into gifted programs (which I've done as the father of a child who'd meet at least some definitions of gifted) is the idea that gifted kids aren't just smart, they are somehow different. That is, they don't just represent the extreme right end of a normal distribution, but they are truly distinct. This idea makes no intuitive sense and while the article doesn't directly address it, it's overall take is that this is not the case. I suspect that this idea is mostly put forth by pushy moms demanding special services for THEIR child (I think of these moms as the equivalent of dads who are obsessed with their son's sports careers).

The focus of the article is questioning how useful programs to identify and provide services for the gifted are. Do such efforts help or would the kids do fine on their own? The data on this is at best mixed and in some ways suggest no benefit.

Lewis Terman tried to collect the brightest school children in Northern California:

Terman emerged with an overwhelmingly white and middle-class sample of roughly 1,500 students whose average age was 11 and whose I.Q.'s ranged between 135 and 200, about the top 1 percent.

Not surprisingly, Terman's group didn't yield any Nobel Prize winners. But incredibly it missed two Nobel Laureates in physics: William Shockley and Luis Alvarez! Not only did his screen fail to pick up two Laureates, both might be considered unique even among the select company of physics Nobel winners. Shockley helped develop the transistor, an incredibly important advance, and went on to make a name for himself (unfortunately a bad one) in an unrelated field, eugenics. Alvarez not only won the prize for insights on particle physics, but went on to theorize that the impact of a large asteroid killed off the dinosaurs, a theory that seemed crazy at the time but is now widely accepted. Aren't these exactly the kind of creative geniuses a gifted program would be looking for? Of course, at least these two did alright, even without whatever help Terman's programs might have given them.

One thing I find incredible is that neither Shockley or Alvarez had an IQ high enough to gain entry into Terman's program. The story say Shockley has an IQ of 129, but doesn't mention any score for Shockley. If true Schockley's score would undercut the value of IQ in predicting achievement. I mean The Bell Curve (which I actually liked) told us how important general intelligence is in predicting success in life, and one of the most important physicists of the last 50 years (look at this list of Nobel Laureates in physics and see how many since 1950 you recognize) has an IQ that puts him all the way into the top 3% of the population. That says to me IQ may be necessary and useful (there aren't a lot of laureates with IQs in the 80s) but luck, hard work, and determination are much more important.

Going back to the usefulness of programs to identify and provide services to the gifted, no one has every done a controlled study to show the programs help. I don't find in at all suprising that kids selected for high intelligence are succesful. Check the IQs of succesful people and you'll find they high. But I see no evidence that early identification and providing special services contributes to this. One could certainly imagine ways in which it might even hurt: too much pressure early, discouraging hard work by making them feel above it, etc.

The one exception to this would probably be gifted kids from disadvantaged environments. Middle class kids with smart parents in good schools are probably going to do fine; poor kids in bad schools and tough social situations might benefit from extra stimulation and from being among a group of similarly bright peers. Unfortunatley, all the "gifted" kids profiled in the article (and my guess is the kids in most gifted programs) seem to come from the former group

Well, this is a long post, but my take home from the story is that lots of people worry about what we do for our smartest kids, but there is little evidence that early identification makes any difference. In fact, early programs seem to have missed some of the kids with the most potential.

UPDATE: I've gotten a lot of good responses to this post, most of them emailed to me, not posted as comments. I think people are hesitant to admit they were "gifted" even anonymously. I wonder if they feel bad they haven't achieved as much as they think they should.

The concensus is that hard work is equally important as a determinant of success.

One more point I wanted to make was about pushing kids ahead. I am ambivalent about this in any case since it puts a kid's intellectual needs ahead of social and emotional needs. I think in many cases trying to work out an enrichment program would be much better

What drives me nuts is when kids are pushed ahead when they aren't even ready. If you can enter Harvard at 14 and get A's I can see the argument for doing so. But if you are getting Bs and Cs at a community college at 14, that is child abuse. What is the point of pushing someone ahead so they can struggle?

There was a kid when I was in grad school who had graduated from college (University of Chicago) at 17. His options at that point were limited, since professional schools are unlikely to take someone so young and not many employers are likely to hire someone that age for a typical entry level position for college grads.

So he enrolled in graduate school in biology and failed all his classes the first year due to some personal issues. So now he is a 17 year old college grad who failed out of grad school. What exactly is he supposed to do next?

UPDATE 2: I highly recommend this book

Grand Rounds 2:09

is here

Natural selection at work

A French woman who is terrified of flying admitted in an Australian court Monday that she drunkenly tried to open an airplane door mid-flight to smoke a cigarette.

Sadrine Helene Sellies, 34, was placed on a good behavior bond after pleading guilty in Brisbane Magistrates Court to endangering the safety of an aircraft. . . .

She walked toward one of the aircraft's emergency exits with an unlit cigarette and a lighter in her hand and began tampering with the door, prosecutors said. But a flight attendant intervened and took Sellies back to her seat

via Drudge, who also alerted me to this gem:

A teenager has been charged with indecent exposure after he was caught trying to have sex with a female mannequin on display at an arts centre.

Security guards found Michael Plentyhorse, 18, sprawled with the dummy on the floor with his trousers and pants down.

Police spokesman Loren McManus said: "There was inappropriate activity between him and the mannequin

"That's theonly way I know how to put it.".

Sounds like there is little chance of his DNA making it into future generations.

Psychotherapist spat

I have no real interest in this, but you would think a bunch of psychotherapists could get along, or at least disagree a bit more privately:

The executive director of a renowned Upper East Side psychotherapy institute said yesterday that he was resigning amid a bitter and increasingly personal feud with the institute's founder, Dr. Albert Ellis, considered by many to be one of the most provocative and influential figures in modern psychology. . . .

Dr. Broder's resignation, reported yesterday in The New York Post , follows weeks of personal attacks, in news articles and Web logs, in which Dr. Ellis and other psychologists have accused Dr. Broder of a power grab to promote his own career

Bad idea

This sounds like a really bad idea:

Bird vaccination campaigns involve a huge amount of labor because the animals must be injected one by one. China's Agriculture Ministry said last Tuesday that it would inject all of the nation's 5.2 billion chickens, geese and ducks with a vaccine.

While wildly impractical, the big problem is all those people tramping around from farm to farm to do the actual vaccinations could spread the disease:

Vaccination teams can easily carry the virus from farm to farm on their shoes, clothes and equipment unless they change or sterilize them each time, the experts said. That could be particularly difficult in a country like China, where the veterinary care system is underfinanced and millions of birds are kept in small flocks by families.

This would be problematic enough in, say, the US or Western Europe, but might be surmountable; in China it is almost certain to cause more harm than good.

Finally, unlike humans, birds turn over rapidly (turkeys particularly so at this time of year in the US), so this scheme will require multiple rounds of vaccination.

More Tamiflu deaths

I posted a few days ago about 2 deaths of Japanese teenagers on olsetamivir (Tamiflu) and was skeptical of the connection.

There are now additional cases with 12 total suspected deaths in addition to instances of non-fatal behavioral changes (the first two deaths were trauma suspected to be secondary to unusual behavior brought on by use of the medicine):

An update by FDA staff also includes reports of 32 “neuropsychiatric events” associated with Tamiflu, all but one experienced by Japanese patients. Those cases included delirium, hallucinations, convulsions and encephalitis.

High fever from influenza can cause delirium, convulsions and viral infections cause many cases of encephalitis, so most or all of these events may well be unrelated to Tamiflu.

In addition, the drug is most widely used in Japan, so it's not surprising possible side effects are emerging there:

Of 32 million people treated with Tamiflu since its approval in 1999, 24 million were in Japan.

The additional cases, both deaths and non-fatal cases of unusual neurologic events and strange behavior certainly raise my concern. However, overall safety data remain reassuring:

Roche said that several studies in the United States and Canada had shown that the death incidence rate of influenza patients who took Tamiflu was far below those who did not.

So far, these reports wouldn't change my view that olsetamivir is safe and effective, especially in the case of a pandemic.

Malaria vaccine

This sounds good

A malaria vaccine has been found to protect children in Africa from serious disease for at least 18 months.

Researchers working in Mozambique found the jab cut the risk of clinical malaria by 35% and nearly halved the risk of serious malaria.

It turns out malaria is a devastating disease in much of Africa, with most of the morbidity and mortality concentrated among the young:

Malaria kills over a million people world-wide each year, and one African child every 30 seconds.

so this is potentially a huge step forward.

I always wonder about the relationship between health and economic development in poor countries. I suspect that primarily as countries become richer they get healthier, both because of improved living conditions and more money for health care, rather than vice-versa (spending more on health care leads to greater productivity), but in cases of specific severe diseases like malaria, I don't doubt the relationship goes the other way.

At least it has better odds than Powerball

13 days until the lottery for Western States. Normal people (i.e. non-ultra runners) may find it suprising that so many people want to run a difficult 100 miles that there has to be a lottery, but WS was the first trail 100 and one many ultrarunners want to do. It is big (~350 starters) and has great support.

Here is part of the release I signed

I am also aware that I may be exposed to physical injury from a number of natural factors including snow, hazards on the trail, lack of water, communicable diseases, wildlife, hazards of vehicular traffic and other hazards attendant to running along or across roadways during the day or night. I understand and accept that the risks include the fact I may become injured or incapacitated in a location where it is difficult or impossible for the Run’s management to get required medical aid to me in time to avoid additional physical injury or death.

The odds of getting in (winning the lottery) are typically about 50%. Of course you have to qualify to enter, so that keeps the number of entrants down. To help make it fair, if you lose twice you are automatically in the 3rd year (you still have to qualify). I lost last year, so if I don't make it this year I'll be guaranteed entry for 2007, as I've already qualified (the qualifying period started 10/1/05, the day I ran Arkansas).

Grand Rounds 2:08

is here.

Avian flu and cytokine storm

This article (via Instapundit) describes the effects of the H5N1 avian flu virus on lung tissue in culture

Reporting in the Nov. 11 online edition of Respiratory Research, Michael Chan from the University of Hong Kong and his collaborators in Vietnam looked at the levels of cytokines and chemokines in human lung tissue exposed to the H5N1 virus.

They compared protein levels induced by strains of the H5N1 virus with levels induced by a more common, less virulent human flu virus, called H1N1.

Chan's team found that H5N1 induces more pro-inflammatory proteins than H1N1. After infection with H5N1, levels of the chemokine IP-10 in bronchial epithelial cells reach 2200 picograms per milliliter, compared with only 200 picograms per milliliter in cells infected with H1N1. Similar results were found for levels of other chemokines and cytokines.

The original article, in PDF form is here.

As advertised, the report does show an increase in some cytokines and chemokines (cytokines are small soluble signaling molecules that carry messages from one cell to another and chemokines are similar molecules that help direct the migration of inflammatory cells to where they are needed). Basically what they did is infect cultures of cells from human lung with different strains of influenza and then measure production of various chemokines and cytokines. They performed the important control of showing that both avian and "regular" influenza virus replicated similarly in the cells. How important the differences in these signaling molecuse are is not clear. I wouldn't worry much about it except that it seems to replicate the clinical experience seen with H5N1 infection of humans.

The clinical experience with H5N1 is that it does generate severe lung pathology with an overexuberant amount of inflammation. This leads to the lung filling with fluid and debris which makes it increasingly hard to breathe. Most deaths from avian flu have been from respiratory failure. What you want with any infection is a medium amount of inflammation to recruit inflammatory cells to fight it off, but not so much that it starts being detrimental to normal organ function.

As to Glenn's idea of using inhaled steroids, I'd say it is not bad for a law professor. Definitely better than I could do in, say, discussing the establishment clause and prayers at high school football games. Steroids will fight inflammation and may decrease morbidity in conditions with overwhelming inflammation. They've been tried empirically in patients with avian flu with mixed success.

Corticosteroids have been used frequently in treating patients with influenza A (H5N1), with uncertain effects. Among five patients given corticosteroids in 1997, two treated later in their course for the fibroproliferative phase of ARDS survived. In a randomized trial in Vietnam, all four patients given dexamethasone died

They were also used empirically in SARS, again with uncertain benefit (when a doctor says he wants to try something "empirically" it basically means he/she ha no idea if it will work or not). Empiric use of steroids in critically ill patients is common, an onc fellow once noted "nobody goes down without steroids," but studies have suggested they are only beneficial in the general population of critically ill patients in low doses and to the extent that the patient's production of endogenous steroids is compromised, with no additional benefit from higher, anti-inflammatory doses.

The benefit of inhaled steroids in asthma is not that they work better, they don't, but that it decreases the side effects (decreased growth, decreased bone density, etc) that occur with prolonged use of steroids. When patients with asthma have acute exacerbations and go to the ED, they get systemic steroids. In an acute infection like influenza I'd want to maximize efficacy by giving the steroids systemically (oral or via IV) and wouldn't worry much about the side effects since they'd only be used for a short time (and because the patient is presumably so sick).

Tamiflu danger

Thanks to an anonymous commentator who pointed me to this story:

Two teenage boys who took the antiviral drug Tamiflu exhibited abnormal behavior that lead to their deaths -- one jumped in front of an oncoming truck and the other apparently fell from a building, the Mainichi Shimbun reported Saturday.

I would be a bit skepitical about cause and effect here. Roche is making ~55 million doses of the medicine this year and two teenagers have died, both of deaths that could have been accidental or suicide. It is unfortunately not rare for teenagers to commit suicide (or have fatal accidents) even without a known history of depression or other illness.

I think we'll have to wait and see if more cases are reported now that the possible association has been raised. If a flood of similar cases emerges, I'd be more convinced. I can't offhand think what the mechanism linking the medicine and erratic behavior or suicide

UPDATE: changes in behavior are NOT a recognized side effect of olsetamivir (Tamiflu) according to this review:

Oseltamivir has few adverse effects when administered for either treatment or prophylaxis. The most frequent side effects are transient nausea, vomiting, and abdominal pain, which occur in approximately 5 to 10 percent of patients.

UPDATE 2: More possible deaths and non-fatal cases of neurological and psychiatric disturbances, all from Japan here. My comments here

HDTV

My wife decided we absolutely could not live witout a new high-definition television. I was against it since we don't watch much TV and Ididn't think it would be any better than the picture we get over-the-air now (we don't have cable).

Boy was I wrong. The picture is incredible, better than cable. The technology gets rid of all the snow and picture wobble and locks in a perfect picture. Of course, only some stations currently broadcast digitally.

Now I'm thinking we need a second one.

We got a Sony KD-30XS955, althoug for several hundred less that the price at the Sony website

A real doctor

Today I got to play a real doctor.

I was doing some laundry when by wife pointed out a bunch of smoke outside our window. I ran out and saw that someone had driven their car straight into a light pole. Smoke seemed to be pouring out of the engine and some landscapers who were working at our neighbors were trying to get the driver out.

My initial reaction was just to watch, but once I realized the driver was still in the car, which could burst into flames any minute, I ran over to help. One of the landscapers had managed to cut the seat belt and he and I pulled the driver out. Luckily, he had been wearing a seat belt and his airbag had deployed.

It turned out the engine wasn't smoking at all. Rather the drivers foot was stuck on the gas and the right rear tire was spinning against the curb, generating all the soke. Once the tire had fully worn down, someone realized this and turned off the ignition. Once we realized there was no imminent danger of fire or explosion we stopped moving the driver and laid him down with his feet still in the car.

It took me a second to remember what to do (I hadn't been in a similar situation since I was a senior resident nearly 5 years ago). ABC: airway, breathing, circulation. He had a bit of mucous at his mouth, but was breathing well and had strong carotid and radial pulses. Now there was nothing to do but wait until help came.

One thing I've read about emergencies is that people tend to stand around thinking everyone else will do something. If you order someone to do something they will but if you just ask for someone to do it, everyone will think someone else will do it. So I pointed at my wife and said "Call 911 now!" Too late, she and several others already had. So I told her to get a blanket, but our neighbor had already gone to get one.

The driver was not responding, but at least he was breathing. Incredibly, a tow truck driver made it first, followed by a fire truck and then an ambulance. The landscapers taunted the tow truck driver as a "vulture." The firemen asked if he had a pulse, which he still did. When the EMTs got there they put him on a board and in a collar.

He was moving his legs and fighting a bit when the strapped him down, which I took as a good sign. I had been worried when we moved him that he might have had a spinal injury although the fact he was wearing a seat belt and had an airbag were in his favor. Of course, worried the car would catch on fire, I would move him again.

Later, I talked to the women who had been behind him. She said she saw him jerk around BEFORE the crash, suggesting he had a seizure. He had hit a car in front of him before smashing into the light pole

Whew. I was glad to get through that without everything going well. It is hard to be sure, but I assume the driver will do well. The crash was bad, but not horrendous and he had no obvious orthopedic injuries.

I am not a natural at these situations. My inclination is to stand and watch, and as a resident I was never comfortable in code situations. I had trouble taking charge. But today I did okay. It took me a few seconds, but I got in there, took action and followed the algorithms. Realistically, it didn't make much of a difference as if noone had done anything the guy would have been okay, but I was glad I did my best

First 50 miler

Congrats to my friend Tom Watson on his first 50 mile run!

His report is here and some pictures here. Nice job Tom on a hot day and very rocky course

Life is good

and it is only getting better:

Sacks of coal ash, a widely available waste product, promise to make arsenic-contaminated water safe to drink and provide relief to millions in South Asia.

A new filter dubbed ARUBA—for Arsenic Removal Using Bottom Ash—uses fine ash particles from coal-burning power plants in India. Coating the microscopic ash particles with a thin layer of ferric hydroxide and exposing them to air changes the fine gray dust into a rust-colored powder that traps arsenic on its surface

Arsenic contaminated water is a huge problem in South Asia, particularly Bangladesh, and this filter, while not quite ready for wide spread deployment seems like a big step forward:

In the lab, ARUBA has been shown to reduce arsenic concentrations of 2,400 parts per billion (p.p.b.), more than twice the highest levels found in Bangladesh, to below the World Health Organization guideline of 10 p.p.b. and five times lower then the Bangladeshi standard of 50 p.p.b. Only 2 of 18 arsenic removal plants have consistently met the 50 p.p.b. standard, and none have met the World Health Organization guideline

So you want to be an allergist

I am wading through the folders of applicants for our Allergy/Immunology fellowship program, and have come up with a list of hints for preparing your CV and personal statement. These are based on our fellowship but many will apply more generally. (For non-docs, allergy/immunology is a fellowship, meaning applicants have finished medical school and are roughly midway through either pediatric or internal medicine residencies at the time they are applying for fellowship.)

1. Blah, blah, blah. Most personal statements are boring and formulaic. They are generally based along one of two themes: the applicant's (or their relative's) experience with allergic disease or a patient with allergic or immunologic disease they cared for. These are not original, but they are low risk. I think about 80% of personal statements are neutral, 10% hurt and 10% help signficantly. Unusual statements (such as not writing one but instead giving a list of favorite quotes, which I did when applying for medical school) increase the chances of both helping and hurting. If you are an otherwise strong applicant consider a low-risk strategy.

2. Microsoft Word has a grammar and spell check function. Use it. Misspellings, subject-verb disagreement, etc. look bad. If you are not a native English speaker it would be a good idea to have someone who is look over your CV and personal statement

3. I do not care that you can program in FORTRAN and BASIC.

4. Sell yourself. If you are fluent in Spanish, made AOA (a national medical honor society) or won an award as most caring intern let me know. Don't hide these things on the third page of your resume.

5. Don't try to hide things. If there are several unexplained time gaps on your CV and your program director's letter states "Steven was never proven to be under the influence of alcohol or drugs while conducting patient care duties" I can read between the lines. If you took 6 months off medical school because you weren't sure you wanted to be a doctor or were going through a tough divorce, it is no big deal. But be upfront about it, otherwise I'll think the worst.

6. High school was forever ago and college is fading. Medical school admissions comittees don't put much weight on high school honors and awards and I don't care at all. On the other awards from medical school and residency, particularly being elected to AOA, can help alot.

7. Letters count a lot, and don't stop at 3. Any good letter will probably help and certain ones can help a lot. For instance, if you have 3 very good letters from non-allergists, even a perfunctory one from an allergist (Candidate X did a good job on our rotation and is easy to get along with) can help us feel better about you. Likewise, 3 letters from an outpatient month in allergy don't tell us how you did on your tougher rotations. Letters from other specialties stating they tried to recruit you into their specialty make you seem desirable and well-rounded.

On the other hand, avoid bad letters like the plague. We have more than enough good candidates and faint praise or criticism usually moves you to the reject pile.

Letters from fellow residents or friends don't count.

8. I'm glad you love your family and new kid, but this is an application for fellowship, not father of the year. Many men seem to go on and on about how important their families are to them. I'm glad and a discrete mention makes you seem well-grounded, but ultimately we need fellows who are ready to be good doctors. Women are more aware of the home/work tension so don't make this mistake.

Likewise, I know the lifestyle as an allergist is good, but don't go overboard about this. I don't want someone lazy.

9. Flattery/schmattery. I use Word so I know how easy it is to "find" and "replace," so the fact that your personal statement refers to Pittsburgh by name does not impress me. If you really have a reason to want to come here (family here, spouse has job, etc.) let us know. If you either mispell it (it is not Pittgsburgh) or call it Pittsburgh University Health Center (because you are from Arizona University Health Center and that is your first choice) I will think you are a phony.

10. Be honest about your research. Saying you have a manuscript in preparation for the New England Journal of Medicine when you are thinking of writing up a case report is borderline dishonest and I don't believe it anyway. Unless you've published, which is rare for candidates without a Ph.D., it is hard to tell how serious your research is and how much you are actually putting into it. A letter from a research mentor describing how reliable you are, how much you are actually contributing intellectually, and, if appropriate, that he/she expects eventual publication goes a long way to demonstrating you are actually accomplishing something. So does submitting an abstract to a meeting.

More Tamiflu

This sounds good:

"There's a shortage right now," said William M. Burns, head of Roche's pharmaceutical division. But he quickly added that the company plans to raise annual production capacity to 300 million courses of treatment by this time next year: a drastic increase from 55 million this year and more than 10 times the output capacity in 2003.

Hopefully this will be fast enough.

Apparently, the big holdup is something called shikimic acid:

Analysts also say that ramping up production of shikimic acid, a basic material in the making of Tamiflu, presents a potential bottleneck. Roche relies on a relatively rare Chinese spice, star anise, to make around two-thirds of the acid. The spice, grown in the mountains of southern China, is in increasingly short supply. . . .

Roche produces a third of the acid by fermenting E. coli bacteria. Jan Van Koeveringe, head of global technical operations at Roche, said the company hoped to reverse that proportion, but gave no timeline.

Recovery from spinal cord injury

An injury to the spinal cord, once considered a lost cause, may no longer mean an inevitable slide into chronic illness and physical decline. Studies are increasingly supporting the once-controversial idea that exercise can improve sensory and motor function long after the initial injury.

according to a news article in this month's Nature Medicine.

A recent trial showed that exercise training several years after injury using electrical stimulation of muscles (which are no longer effectively controlled by nerves) led to signficant gains in motor control, muscle mass and decreases in uncontolled jerking. These results suggest, but don't prove, that even well after the injury signficant regeneration of nerve-muscle connections are possible. Studies in animals also suggest nerve regeneration can occur, although some are skeptical.

The article also notes the impressive progress Christopher Reeve made before his death:

Before he died in 2004, Reeve had regained sensation in 98% of his body and some motor function, McDonald says.

Reeve could, for example, stand unassisted in a swimming pool, breathe on his own for several hours without the aid of a respirator, and hold a glass. His recovery was especially remarkable because he began to improve after five years of exercise therapy, hinting that some nerves had regenerated.

Optimism about avian flu

The optimistic alternative to this apocalyptic viewpoint is that the appearance of a modified avian virus capable of triggering a human pandemic is unlikely: there have been more than 3300 flu outbreaks in birds with 150 million killed and only 118 human cases, and the disease in birds is proving containable with good surveillance and prompt action.

Of course past performance is not a guarantee of future results. Nonetheless, this might mean we have some time before the pandemic comes. From BMJ but no free, full text. Glad to see the British Medical Association, which spares no opportunity to lambast pharmaceutical companies for their greed, thinks getting people to subscribe is more important than disseminating iformation on avian flu.

Growth Hormone as an anti-aging treatment

is apparently not a good idea

Recombinant growth hormone (GH) is being inappropriately marketed as an anti-aging treatment, something I’d been previously unaware of. While it is true that growth hormone levels fall as you age, it is not clear that GH supplementation would prevent or reverse other manifestations of aging (e.g. your hair turns grey as you get older, but coloring it doesn’t help your knees any).

This article talks warns doctors against getting involved in this, for a variety of reasons

First, it apparently doesn’t work and may even hurt:

Transgenic mice that produce supraphysiological levels of GH for their age have markedly reduced life spans and experience premature onset of age-related cognitive changes….Growth hormone–resistant and GH-deficient mutant mice experience substantially increased life spans.

Of course theses studies aren’t exactly analogous to use in aging humans; we really need a study of Gh replacement in older mice, but these data certainly don’t support use of GH for aging.

In addition, off-label use of GH is illegal. For most medications, once they are approved licensed physicians can prescribe them as they see fit (which is not an ideal system), but not so for GH:

off-label distribution or marketingof GH to treat aging or aging-related conditions is illegal. Unlike most FDA-approved medications, GH can only be distributed for indications specifically authorized by the Secretary of Health and Human Services—aging and its related disorders are not among such indications.

Apparently penalties can be quite stiff, $250,000 fine per incident, although the article doesn't note any physician who has actually been charged, and I'd be surprised if they go after anyone. I also think the GH manufacturers have some responsibility to ensure their product is being used appropriately, although all their incentives are to have it used as widely (and inappropriately) as possible. Of course one $100 million judgement for someone who took it inappropriately and had a heart attack could wipe out all those profits (ed- are you defending all those malpractice lawyers? Just saying, incentives are incentives)

The article is a bit one-sided and I knew nothing about the issue coming in, but it does sound like a bit of a scam. For an example of misleading claims see here:

Dr. Di Pasquali's work is . . . often referenced by Exercise & Nutrition periodicals

Wow, it must be true if it is Exercise and Nutrition periodicals.

I would say if I wanted to make easy money, going after the vanity of aging baby boomers would be a good strategy, they aren't going to go gracefully.

UPDATE: this article also contains the weirdest disclosure I've ever seen:

Drs Perls and Olshansky report that they are defendants in a lawsuit brought against them by the American Academy of Anti-Aging Medicine and others.

More details are here and it sounds like an attempt to intimidate criticism of GH use. When what is at heart a scientific dispute gets dragged into court, I'd bet against the party who initiated the lawsuit.

The cost of medicines

An interesting article (probably not free full text) in the October 26th JAMA about why medicines cost so much. It is a good introduction for those who haven't thought much about the problem including my colleagues who drive around in Mercedes thinking the pharmaceutical companies should just lower their prices.

It does a good job pointing out many of the problems with the current system:

Six major problems with the patent system are (1) recovery of research costs by patent monopoly reduces access to drugs; (2) market demand rather than health needs determines research priorities; (3) resources between research and marketing are misallocated; (4) the market for drugs has inherent market failures; (5) overall investment in drug research and development is too low, compared with profits; and (6) the existing system discriminates against US patients. Potential solutions fall into 3 categories: change in drug pricing through either price controls or tiered pricing; change in drug industry structure through a "buy-out" pricing system or with the public sector acting as exclusive research funder; and change in development incentives through a disease burden incentive system, orphan drug approaches, or requiring new drugs to demonstrate improvement over existing products prior to US Food and Drug Administration approval

but finds many suggested solutions are equally problematic.

For example, one commonly suggested remedy is too require new drugs to demonstrate improved efficacy compared to currently available medicines not just to placebo. The idea being that many new meds are very similar to existing ones (think beta-blockers or statins). The authors point out that having several medicines in the same class may decrease costs by allowing insurance companies to bargain for good prices. In addition, there may be significant medical differences among medicines in the same class.

They have some good suggestions, including requiring post-approval comparison studies of the new medicine vs. established treatment, public funding for study of rare illnesses and something called patent "buy-out" in which the government pays off an inventor for the value of his invention (in this case a medicine) for the amount he/she could have expected to make in monopoly profits and then puts it in the public domain. In this case, the government would pay a pharmaceutical company what it would make from selling a given medicine and then allow generic manufacturers to make it and sell it near the marginal cost of production. This would have the benefit of making the medicine cheaper but still encouraging innovation. Of course how to determine the profit the company would make would be hard and the government would spend a lot of money (not to mention problems of international access).

Nonetheless, there could be significant benefits. For example Omalizumab (Xolair), an anti-IgE antibody for the treatment of asthma, is very effective but very expensive. Only a few asthmatics qualify for it. On the other hand the companies profits are limited because althought very expensive only a few patients use it. If the government paid Genentech/Novartis their expected profits from charging $15-20,000/year for 5% of asthmatics, they'd get the same amount of money. But if the cost came way down, a much larger number of patients could benefit. It seems like a win-win situation. The article notes downsides including difficulty in establish which drugs deserve buyout and calculating a fair price and the difficulty generating enthusiasm to pay a huge amount upfront. In addition, GlaxoSmithKline would be justifiably upset having to Xolair priced cheaper than Advair thanks to a huge government subsidy.

Apparently, the only time this has actually been done is in the case of the dagguerotype patent in France in the 1800s. This may be an example of something that makes sense to economists but is hard to put into practice.

Read the whole article if you are interested, it does a good job addressing the issue of drug costs in an even-handed way.

There were also a couple of interesting statistics in the article. In 2002 drugs accounted for just over 10% of health care spending, up from 5.8% in 1992 but similar to the proportion in the middle 1960s. Also, the average cost of brining a new medication to market is $800 million.

My own sense is that there needs to be effective price competition among medicines. Either consumers (maybe with health savings accounts) have to pay for a lot of the cost themselves so they make tradeoffs like "is $20 more a month worth it for once daily dosing?" or HMOs/insurers have to negotiate prices for specific meds in a class and charge more for patients who use other ones (I know they do this to some degree and it is pretty effective, since almost none of my patients is willing to pay a higher copay than necessary).

Voting

Voting in 2005 was a lot different from voting in 2004. Last year I arrived about 10 minutes before the polls opened and there were already 10 or 15 people waiting.

Today I forgot to go on the way to work so stopped on the way home (I walk) and was the only one there. I chatted up the poll workers and they told me I was the 98th voter today, compared ot more than 600 last year. When I left, a couple with their kids had just arrived, but with poll closing only an hour away I doubt they'll get much over one hundred.

Grand Rounds 2.07

is here.

My running is mentioned for the first time.

Andy

Treating the Amish

A good article in the NYTimes magazine about Holmes Morton, a graduate of the same residency as me.

Morton has set up a clinic in Lancaster, PA, home to many Amish, where he treats primarily Amish and Mennonite kids, focusing on the many genetic diseases present in these communities.

Morton made the simple observation that at least one common disease, glutaric aciduria type I, is easily treatable if diagnosed early, but if untreated, it leads to irreversible mental retardation. Treatment basically involves supplementation of sugar by IV during illnesses (e.g. gastroenteritis). Unfortunately, the Amish kids were often not diagnosed until they were neurologically devastated. The families, who don't have insurance, run up huge medical bills.

He started the Clinic for Special Children which helps make diagnoses BEFORE the kids get really sick. The kids do remarkably better, don't need outrageously expensive care and everyone is happy.

Read the whole thing, he is an inspirational guy.

My residency classmate, Kevin Strauss, is mentioned. He is the second full-time pediatricain at the clinic. Kevin is the smartes physician I've encountered, by a very wide margin and his strength is genetics and metabolism, so I'm sure he is a huge asset to the clinic and the kids.

The Clinic is also a resource for all of us who take care of Amish kids. A year or so ago, we had an Amish boy with severe combined immunodeficiency (SCID) a disease in which the immune system is largely absent. There are many causes, but I contaced Kevin who knew of several cases in the Amish and correctly predicted the defect would be in the enzyme adenosine deaminase (ADA). Interestingly, a different defect (IL-7 receptor) predominates in Mennonites.

The story tries to make the case that Morton is the exemplar of what all physicians will soon be: geneticist-clinicians. Given that Morton works entirely on single gene defects in a population where these are particularly prevalent, this seems quite a stretch. Medicine is good at dealing with single gene disorders. The problem is all the big killer (cancer, heart disease, diabetes, etc) are not caused by a single gene, but by an interaction of multiple genes with the environment. While some progress has been made in identifying these genes, integrating this knowledge into clincal practice has not happened.

Don't retire

A study in the BMJ shows that those who retire at age 55 have an almost 2 fold increased risk of dying in the subsequent 5 years relative to those who kept working. However, retiring at 60 neither increases nor decreases mortality compared to those who kept working until the mandatory retirment age of 65.

The study utilized records from Shell Oil about its employees. One could imagine some jobs at an oil company are bad for health due to exposure to various toxins, but if anything early retirment seemed to be the most detrimental for those classified as having low socioeconomic status.

Of course, the big confounder, acknowledged in the article, is that those in poor health probably retire early.

Th article claims:

there is a widespread perception that early retirement is associated with longer life expectancy and that retiring later leads to early death.

but this seems contrary to what most people I know believe, which is that many people who retire early just sit around waiting to die.

Personally, I hope to never retire, but am lucky in that I enjoy what I do.

Arkansas Traveller redux

Just over a month ago I finished my 4th 100 mile run (ever) at the Arkansas Traveller run in the Ouachita National Forest outside Little Rock (you can read my race report here).

The race is incredibly runner friendly with 2 free meals (dinner the night before and breakfast the next morning), great aid stations, a nice shirt, etc.

Then today in the mail I got a nice "update" newsletter telling how the race had played out and a print out of a detailed spread sheet showing all my splits, and some nice pictures of me running



I continue to be a bit disappointed about my run, feeling I could have done better, particularly in the last 1/3 of the race, however....

It was pretty hot. Only 18/120 starters broke 24 hours (which is sort of an unoffical standard of excellence in a 100 mile race, and I did that, plus finished 9th overall, well inside the top 10%. Of course, I was in 5th place at mile 95. Looking at the splits, I think I passed 5 people in the last 42 miles from the turn around (the course is an 16 mile loop followed by and out and back) and 3 people passed me. They all happened to pass me in the last 5 miles, but that's just how it went.

Kudos to overall winner Tracy Thomas on an incredible race. She was 1 minute ahead of me at 48 miles and beat me by 3 hours. Ouch

And yes, I have sent in my Western States application
I particularly like this last picture where I'm looking down at my watch like a true runner. As if I didn't know my finish time within a minute or 2!

Bush's avian flu plan

President Bush announced Tuesday that he would ask Congress for $7.1 billion to prepare the nation for the possibility of a worldwide outbreak of deadly flu. Most of the money would be spent on research and a national stockpile of vaccines and antiviral drugs

"Our country has been given fair warning of this danger to our homeland and time to prepare," Mr. Bush said. "It's my responsibility as the president to take measures now to protect the American people."

I'm glad to see the government taking it seriously. I'm also glad to see that Democratic critics of Bush are criticizing him for doing too little:

But in the Senate, where a measure to spend $8 billion on pandemic flu preparations passed on a vote of 94 to 3 last week, Democrats immediately criticized the president's plan Tuesday as inadequate. One of them, Senator Edward M. Kennedy of Massachusetts, said Mr. Bush's proposal "needs to be stronger," and called for more spending to ensure that hospitals and other health care facilities have the capacity to handle a flood of patient

Bush is so hated by some, that I've seen suggestions that the avian flu is just a conspiracy to allow him to consolidate power, declare martial law, cancel the 2006 elections, etc. Love him or hate him, the avian flu is real. I've long felt that the biggest danger was inaction when the threat wasn't imminent. I don't know enough to comment on the specifics of Bush's plan, but I think a major effort now to develop a vaccine and stockpile anti-virals (which will mean increasing production capacity for olsetamivir aka Tamiflu) may well make all the difference.

Also, I noted this article in which scientists have made the process of vaccine engineering a bit easier. It doesn't sound like a lot, but what we need know is not huge breakthroughs but an accumulation of small advancements.

Bad consults

Barbados Butterfly has a great story about incompetence in the ER causing her much uneccesary pain:

Bleeding into the brain is to be considered a more significant health problem than an eyebrow laceration. Patients who have "an eyebrow laceration" require significantly different management to patients who have "an eyebrow laceration and an intracerebral bleed and a maxillary fracture following blunt head trauma". It's important to distinguish between the two if you want your patients to live.

It reminded me of one of my worst consults as a fellow, which I'll try to present in the same style. Briefly, as a fellow covering the pediatric rheumatology service I got called to see a 15 year old girl with Kawasaki disease (KD), which is basically a systemic inflammatory illness of unclear cause that occurs mostly in young kids. After seeing the young women I made the following points to the peds resident who saw the patient in the ED.

1. I am happy to come into the ED from home on a Friday evening to see patients who need my help. I am less happy to come in because of your incompetence.
2. Fever and rash are not always Kawasaki disease
3. KD is unusual, but not unheard of, in an adolescent. It is advisable to consider other illnesses in the differential diagnosis
4. Toxic shock syndrome shares many features with Kawasaki's, but, unlike KD, often presents in adolescent females. It is associated with tampon use and particularly retained tampons. A pediatric resident is perfectly capable of obtaining a menstrual history and obtaining the information that the patient put a tampon in >24 hours ago and hasn't removed it.
5. A second year resident may not be aware that hypotension is common in toxic shock but rare at best in KD. However, if you need the rheumatology fellow to point out that a patient who has recieved 5 liters of normal saline and not achieved a measurable diastolic blood pressure is in need of more intervention than a "rheum consult" you might consider another line of work.

The patient eventually was transferred to the ICU, got appropriate therapy and did well.

Fatal reactions to food

Fatal and near-fatal reactions in food allergic patients are the one thing that really makes allergists nervous. Having food allergy, or being the parent of a food allergic child is a bit like being an anesthesiologist or airplane pilot: 99% calm punctuated by 1% sheer terror. Asthma, in contrast, is much more up and down, with less explosive onset of symptoms.

A new study from England looks at the number and characterisitics of severe reactions to food in pediatric allergic patients. The authors used database searches and letters to pediatricians to try and find every case resulting in admission to the hospital. Any such search is likely to miss some cases, although one would expect they would be the less severe ones.

They divided reactions into fatal, near fatal, severe, and non-severe. The definition of fatal is obvious. Near fatal reactions were those requiring intubation, which is a pretty high standard. Severe reactions met one of the following criteria:
1. Cardiorespiratory arrest (patient stopped breathing, heart stopped beating or both)
2. Need for inotropic support (special meds had to be given to keep blood pressure up or heart beating effectively)
3. Fluid bolus of 20mg/kg or more (usually a sign of hypotension aka low blood pressure)
4. More than one dose of epinephrine
5. More than one treatment with bronchodilator (usually albuterol or salbumatol as they call it in the UK. This indicates ongoing wheezing).
Non-severe reactions were ones that didn't meet the severe criteria.

These criteria are okay, but the definition of "severe" is quite broad. I'd argue that cardiorespiratory arrest is "near fatal" because without intervention they would likely have died. On the other hand getting 2 doses of epinephrine or 2 albuterol treatments is not that remarkable. Many patients with asthma seen in the emergency department get a standard regimen of 3 albuterol treatments and are then discharged home. I suspect some kids who would meet their standards for severe reactions were not admitted.

Using their criteria they identified 3 fatal, 6 near-fatal, 58 severe and 171 non-severe reactions. Their data covers aobut 13 million kids (<16) over 3 years for 50 million kid-years. So death from food allergy was about a 1 in 1.7 million event. Obviously, the risk is much higher among kids with known food allergy.

Although peanut causes the most consternation among parents and allergists, only 1/3 fatal reactions was to peanut, the other two being milk. In the 9 combined fatal and near-fatal cases 3 were due to milk, only one clearly to peanuts although another was to walnuts and 2 were likely peanut (one kid with known peanut allergy ate a chocolate bar with nuts and another kid wiht no history of allergies ate at a Chinese restaurant). Unfortunately they didn't follow up on the kids without a clear cause to see what testing showed (i.e. if the kid who reacted at a Chinese restaraunt was peanut allergic on testing in follow up that would be the presumed trigger).

Their data contrast a bit with a famous series from the US where peanut and tree nuts were responsible for 10/13 reactions. In the US series, delay to giving epinephrine seemed to be an important risk factor for fatal reactions (vs. near-fatal) whereas in the present study it didn't seem to matter. Only 1/3 fatal reactions got epinephrine at home, one died en route to the hospital and never got it and one got it only on arrival to the hospital after arresting in the hospital. Likewise, only 2 of the 6 near fatal reactions had epi at home and those didn't have it with them when they had their reaction. To an allergist who diligently prescribes Epi-pens and teaches families/patients how to use them, this is more than a little disheartening. Both studies found pre-existing asthma to be a signficant risk factor for severe or worse reactions.

So what can we take from these 2 studies.
1. Milk, peanut and tree nut allergy seem to lead to most severe, near-fatal and fatal reactions
2. Avoidance is the best strategy
3. Patients should have Epi-pen available, carry it with them ALWAYS and use it! It does no good if it is sitting at home

There is some contoversy about who exactly needs to carry an Epi-pen, with US docs prescribing them more widely than those in Europe. This study would indicate they are underprescribed there.

Tangled Bank #40

is here. Tangled Bank is a science/evolution blog carnival, although there is lots of medical blogging as well.

Grand Round 2:06

is here