Archive for: November, 2010

Book Review: Written in Stone

Nov 26 2010 Published by under Book reviews

Brian Switek has been one of my favorite science writers for years.  His blog Laelaps is a consistently informative and enjoyable read.  It exists in a realm that is more in depth and interesting than a typical newspaper piece, but more readable than formal scientific literature.  His ability to read that literature (and he has seemingly read it all) and synthesize it for the rest of us, without dumbing it down, is rare (this he shares with blogger Ed Yong, although with a different style and voice).

A few months ago, I received the proofs of his new book Written in Stone.  I wasn't sure what to expect.  It's subtitle, Evolution, the Fossil Record, and Our Place in Nature, sounded rather ambitious.  And the book is ambitious.  Switek once again takes an enormous amount of literature (essentially, most of what has been written on evolution and paleontology, with an emphasis on primary sources) and tells us a story.  His story begins in the 16th century with the first writings on fossils, through the discoveries of evolution and deep time, right through to discoveries so recent that I'd imagine his publisher might have lost a bit of sleep.

After an initial section that brilliantly describes the discovery of evolution, natural selection, and paleontology, he gives us chapters detailing the evolution of various familiar species, including our own.  While reading, I discovered a new reading technique: I found myself reading by the computer, pulling up images and looking up some of the many animals Switek discusses, either in passing or in great detail.  For all the readability of Written in Stone, it is at times a bit of work, but that work is well-rewarded (and made easier by access to the internet to help with the avalanche of fossil names).

Switek's book doesn't just answer the question of how evolution occurs, but more important explains how we know what we know.  His choice of megafauna such as whales, horses and elephants was sharp---I love Stephen Jay Gould, but snails?  No snails for Switek.  Sea monsters---factitious and otherwise---emerge from the soil, travel the globe, and set off religious, cultural, and scientific firestorms.  Tetrapods emerge from the seas, evolve into a diverse set of mammals familiar yet alien, and return to the sea to become whales.  And elephants---did you know that elephant molars slowly erupt throughout their lives so that these long-lived animals always have teeth capable of chewing the tough plants that they have to eat by the ton?  I didn't either, but I do now.  The book is full of surprising facts about familiar animals, and how they became what they are.

Most important, though, is Brian's ability to give us a sense of what life really is---a contingent, stochastic, well-pruned bush of relationships.  All of we living things are related, but our relationship is complex and beautiful.  So is Brian's book, and it's well-worth the read.

A pre-publication copy of Written in Stone was given to me at no charge by the publisher.  --PalMD

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Thanksgiving

Nov 26 2010 Published by under Uncategorized

I realize that it makes me sound a bit old when I say that I can't believe it's Thanksgiving....2010!, but I can't believe it.  When I stayed with my sister in Chicago while interviewing for medical school, my niece was a cute little toddler.  I have a picture of her sitting on my lap, laughing.  This week she turned eighteen, and knows a Homo ergaster from an Autralopithecus.

A couple of years ago, my father-in-law sat at Thanksgiving dinner tired and weak.  A few days later he went to the hospital and never came home.

Families change.   Ours has shrunk considerably in the last few years, giving a bit of a melancholy cast to Thanksgiving. Still, I'm thankful for the family I have, and to the career I love.  I'm thankful that my daughter goes out to breakfast with me and is too busy doing math problems to remember to eat her bagel.  I'm thankful for a wife with more common sense in her great toe on a bad day than I've ever had at my sharpest.  Despite the ups and downs of any normal life, I'm quite lucky.

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Omega-3's and heart disease: where's the evidence?

Nov 22 2010 Published by under Medicine

Omega-3 fatty acids (more properly called "n-3 fatty acids") are a group of naturally occurring fat molecules.  They are found mainly in fish and other marine-derived oils, but some can also be extracted from plants.  Omega-3's are currently very popular, but the evidence for their usefulness isn't so clear.   A recent study failed to show any benefit in preventing dementia.   A new study out of the Netherlands looked at omega-3's in heart disease.  In order to understand the study, we need to back up for a moment.

We already know that some dietary fats have a strong effect on heart disease: certain types of cholesterol are elevated in heart disease, and altering the levels of these fats reduces the risk of heart disease.  The treatment of cholesterol problems is a mainstay of heart disease treatment and prevention.   The idea that omega-3-fatty acids may help prevent heart disease is a few decades old.  Like many interesting hypotheses, it was based on observations.  In this case, investigators noted that Greenland Inuit had a much lower rate of heart attack than "Westerners".  Researches posited that it was the high levels of dietary fish oils that protected Inuit from heart disease.

We've already discussed some of the ways scientists evaluate risk and benefit; in this case, much of the evidence for the benefit of fish oil in heart disease is based on observational studies rather than randomized controlled trials.   Many of these studies looked at the dietary choices of subjects to assess their omega-3 consumption.  There is evidence for a role for omega-3's in the primary prevention of heart disease, that is, preventing someone who doesn't have heart disease from getting it, but the evidence isn't terribly strong.  The evidence for secondary prevention is a bit meatier.  One large Italian study gave omega-3 supplements (rather than guessing at dietary consumption) to people who had had a recent heart attack.  The results were very encouraging, with a large reduction in the risk of death from another heart attack.  But---there's always a 'but'--the study was done at a time when many of the effective medications (such as statins) weren't yet in wide use, so it's unclear what effect there would be in a more modern context.

A newer study out of the Netherlands took an interesting approach.  Rather than simply guessing at diet or giving a pill, the researchers developed margarines supplemented with omega-3's.  They gave the margarines to people who already had heart disease and observed them for a period of time.  The doses of omega-3's were relatively low, but when they compared the regular margarine group to the omega-3 margarine group, there were no significant differences in the rates of major heart attacks.

This isn't the final word on omega-3's for heart disease-prevention.  Part of the problem in studying the question is that the current treatment of heart disease is impressively effective.  Any intervention that doesn't have a dramatic effect is going to be hard to evaluate.  Given the epidemiologic evidence, and the questions still out there, this study isn't going to end the question of omega-3's in heart disease.

References

Kromhout, D., Giltay, E., & Geleijnse, J. (2010). n–3 Fatty Acids and Cardiovascular Events after Myocardial Infarction New England Journal of Medicine, 363 (21), 2015-2026 DOI: 10.1056/NEJMoa1003603

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Stroke prevention: a less bitter pill?

Nov 20 2010 Published by under Medicine

Stroke is one of the three most common causes of death in North America.   A while back, we briefly discussed some of the causes of stroke, including a heart rhythm problem called atrial fibrillation (afib).  Afib is a very common problem, affecting over 2 million North Americans.  It becomes more common with age.  In afib, the normal flow of electricity through the heart is disturbed.  Before we discuss it  in a little more detail, we'd better take a look at how the heart's electrical system works.

Normally, a pacemaker near the top of the heart called the sinoatrial (SA) node sets the rhythm for each heartbeat.  It sends an electrical signal through the top chambers to a choke point between the top and bottom chambers called the atrio-ventricular (AV) node.  From there, the electrical signal spreads through the main pumping chambers of the heart, causing the muscles to contract.

1) SA node; 2) AV node

On an EKG, like the one below, the bump at the purple arrow (the p-wave) represents the discharge of the SA node.  The larger blip (the QRS complex) represents the electricity flowing through the ventricles.

What would happen if the the SA node decided not to fire?  Each point in the conduction system has its own pacemaker which can serve as a backup.  The SA node generally fires at about 60-90 beats per minute.  If it fails to fire, the AV node can kick in at about 40-60 beats per minute.  If the AV node fails, the ventricles can fire at about 20-40 beats per minute.  These low heart rates can usually keep you alive, but not much else.

In atrial fibrillation, the SA node stops firing regularly and instead, electrical signals discharge chaotically.  Some of the signals make it to the AV node, and some don't, so instead of a nice, regular rhythm, the heart often beats in an "irregularly irregular" rhythm.  Since the SA node isn't working properly, the top chamber (the atrium) flops around instead of pumping cleanly, and the relatively stagnant blood in the fibrillating atrium can form clots.  The top tracing in the EKG above is typical for atrial fibrillation: the p-waves are rapid and varied, and the QRS's don't march out regularly.

Which brings us back to strokes, and preventing them.  Afib is a major cause of stroke.  As clots form in the floppy atrium, they can shoot into the main chamber of the heart, and then to the brain.  Depending on a number of factors, the risk of stroke in people with afib is about 5% per year.  This risk is cut significantly with drugs that prevent blood clotting.  The classic drug is warfarin (Coumadin).  Warfarin interferes with vitamin K, preventing blood from clotting normally.  Even when used properly, warfarin increases the risk of bleeding, for example from a stomach ulcer or from a burst blood vessel in the brain, but this risk is usually balanced by the stroke-preventing effect.

Warfarin is a pain to use.  A dose takes 2-3 days to kick in, and the only way to measure the effect is with frequent blood testing.  Foods containing vitamin K interfere with it, as do many different medications.  If levels are too low, the stroke risk goes up, and if they are too high, the bleeding risk goes up.  It is a "messy" drug.

For a number of years, an alternative has been available in Europe.  Under the generic name Dabigatran, it is dosed twice daily and requires none of the blood monitoring needed for warfarin.  It also has fewer drug and food interactions.  It is also horribly expensive.  Warfarin generally costs under $15 per month, while Dabigatran can cost that much per day.

These costs are tricky, though.  The overall cost of warfarin is more than just the pill; it is the care for patients who have complications, and the frequent blood testing.  A recent study in the Annals of Internal Medicine examined the cost-effectiveness of warfarin and Dabigatran and found that depending on pricing (of course), the two treatments can be equally cost-effective.  But not to the consumer, at least not yet.

Unless insurance companies are willing to price dabigatran based on money they will save on complications and blood testing, few patients will be willing to pay for the drug.  As it stands, the consumer sees the price of the drug at the pharmacy checkout line, and there is one clear winner.  Many insurance companies farm out their prescription coverage; the prescription company won't save money from fewer tests and has no reason to lower the drug price.

If our health care system continues a shift toward outcomes-based pay, this will change.  Until then, it may be a while before Dabigatran makes it big in the U.S.

References

Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation (2006). ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Circulation, 114 (7) DOI: 10.1161/CIRCULATIONAHA.106.177292

Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, Wang PJ, & Turakhia MP (2010). Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation. Annals of internal medicine PMID: 21041570

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Listening

Nov 12 2010 Published by under Medical Musings, Medicine

The exam room is a sacred space, one in which people  bare themselves both emotionally and sartorially.  It is a secular confessional, a chapel for the examination of sinew and sin, pain and disbelief, intimate failings and mortal fears.  Sometimes it is a place to share joy, but more often it is a place to explain one's physical and emotional imperfections in hope that someone will hear and understand in a concrete way.

The interaction between patient and doctor isn't that well-studied.  There are strong suggestions in the literature that the more we allow our patients to set their own agendas and to answer open-ended questions completely, the more likely the patient's problems are to be addressed.   But what takes place in the exam room?  What is it that allows a patient to bare soul and body and allows a physician to really understand what a patient is saying and feeling?

One popular notion is that empathy, like good looks, is something some people just happen to have. I perceive myself as being an empathic physician (which of course may not be entirely true) and I'm curious what makes me so.  When I think of my own interactions with patients  I notice a few things.  In addition to standard listening techniques, I try to imagine how a patient feels---viscerally, literally, physically.  If a patient describes chest pain, I try to imagine what it feels like as described.  I try to imagine the emotions they felt when they had it, the fear, the uncertainty.  And I try to gauge the patient's reactions to my reactions.  My facial expressions and posture can promote fear or give comfort.  If I want the patient to continue to be concerned, my words and actions can purposely fail to give them complete reassurance (always telling them, though, that we will do whatever we must to get to the bottom of things).

I don't presume that this always works out for me and my patients---this is necessarily an empiric exercise, a muddy one that goes on from minute to minute and is measured in subtleties.  I'm also not sure how deeply this should be studied formally.  While I'm certain that empathy can be taught (or at least a reasonable facsimile of empathy), I'm also certain that there is not one sort of "empathy" that works for all doctors and patients.  There will always be some mystery in the exam room, and that is what makes it sacred.

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Keeping 'em alive

Nov 12 2010 Published by under Medicine

As I prepare to emerge from my self-imposed hiatus, I've decided to share some classic posts.  Thanks for reading.  --PalMD

One of the frequent complaints I hear about real medicine is that it is dangerous. Of course, it's true---so is riding in a train, but it sure beats walking. And that's the danger of this particular fallacy---yes, medicine is a sharp tool, but it's also an effective tool, so we must use it properly. And this is where the tools of evidence- and science-based medicine can give us a hand.
The potential harms of modern medicine must be approached carefully. If they are ignored or approached in an ineffective way, we'll miss an opportunity to save lives. This comment is typical of the type of thinking that gets one in trouble:

You asked if so-called traditional Chinese medicine has ever eradicated any diseases. Well, yes. It pretty much eradicated one that is in epidemic numbers in the U.S. and most of the developed world: Iatrogenic disease.

This is wrong is so many ways. The definition of "iatrogenic" is difficult. The traditional definition is "adverse effects of medical treatment or advice," and that's probably the one he's using. One could broaden this to include failure to give proper advice, as inaction by a physician has similar consequences to action, so negligence is also a form of iatrogenesis. The physician has the tools, but doesn't use them, and the patient suffers. But let's examine the original meaning.

The way in which our commenter is wrong is the "false dichotomy". Yes, medical errors would be reduced to zero if we didn't treat people, but the consequences would be rather dramatic. Our goal should not be to abandon modern medicine because it sometimes causes harm. Our goal is to reduce iatrogenic illness in a science-based way.

Continue Reading »

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Hiatus

Nov 09 2010 Published by under Uncategorized

Hey, folks, I have a bunch of great posts sitting in the hopper, almost done, but I have a ton of stuff to get done in meatspace that require me to enforce my first-ever blog hiatus since WCU began in May 2007.  If it looks like I will need more that a brief period of time, I may end up closing up blog commenting to avoid getting clogged with spam.  Thank you in advance for your patience, your reading, and your conversation.

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Donors Choose: "that doesn't make sense!" (#donorschoose)

Nov 04 2010 Published by under Donors Choose

A few evenings ago PalKid surprised me with the fact that MrsPal was born very close to the time Dr. Martin Luther King, Jr. was killed (I wasn't surprised by the fact, but by her knowledge of it).  I asked her if she knew who MLK was, and she said, "Not really."  I started to sketch it out in terms a first grader might understand, telling her the story of Rosa Parks, a woman I was fortunate enough to have met.  As I explained to her that Ms Parks would not give up her seat to a white passenger and was arrested, PalKid said, "That doesn't make sense!"  I explained it in a few more ways but she couldn't understand such insanity.

A free society remains free only if its populace is educated.  When education is tied to wealth, democracy becomes plutocracy.  Segregation doesn't make sense if you favor freedom over servitude. That public schools, the base of our democracy, must rely on charities for essential supplies just doesn't make sense if you favor democracy over plutocracy.  But until we can fix the our schools, we must help them, and that's what Donors Choose does so effectively.  It allows teachers to identify pressing needs and donors to pick projects that they agree are worthy.

The yearly Donors Choose challenge is drawing to a close.  Hewlett-Packard is going to match donations, so every dollar you give makes a difference.  Our current 29 donors have reached nearly 900 kids.  While the total amount we raise is important, participation is as well.  I'd love to see that 29 grow to 50, even through 1-5 dollar donations.  There are several worthy projects in impoverished Michigan schools.  Please help.

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My daughter the writer

Nov 04 2010 Published by under Fatherhood

OK, PalKid is only in first grade, but her new school insists that she write regularly, a practice I strongly endorse.  For those of you who don't have little kids, the current practice is to let kids spell however they wish when they are free-writing.  Because I love my readers, I will share with you some of the earliest works of the soon-to-be famous PalKid.

Moday

My Weekend

I plad a socr gaem.  it rand. it was fun. I went to pik up my cussin for a move. it was fun.

Tuesday

If i was a fair fitr for a day. I wud put out the fire. i wud be fun and i wud slid down the poll vere sopr dopr fast

Wednesday
If an alien landed in scool. I wuod giv it loss ov fod. and I giv it a bubule bath.

Friday
I went to the appal orchrd I had cidr and donas i pikd like 80 appals. i went an a hae rid. i went with my Daddy and Granp and my Grama. it as all fun.

If trick-or-treating was cancelled my Mommy and daddy would put candy in a estr eggs. it wuld be cool.

She also sent me her first text message today: "it is [PalKid's full name]    i love you very much daddy            a lot"

All that's left to do is set her up on WordPress and twitter.

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Why science reporters should do their homework

Nov 04 2010 Published by under Journalism, Medicine

One of the most significant medical advancements of the last few decades has been the use of cholesterol-lowering medications called statins.  These drugs, when used properly, have been shown over and over to lower the risk of heart attacks, strokes, and death.  But like all drugs, they have many effects, both those we like (preventing heart attacks) and those we don't (in this case, rare liver and muscle problems); the latter we call "side-effects".  Studies done on drugs before they hit the market can identify common side-effects, but it's not until many more people are exposed for a long period of time that rare side-effects show up.

A recent Scientific American article wondered if one of these rare side-effects could be memory problems.  At first glance, the idea seems pretty improbable, but the SI article takes some sketchy anecdotes and runs with the idea, managing to cobble together an interesting hypothesis:

It is not crazy to connect cholesterol-modifying drugs with cognition; after all, one quarter of the body’s cholesterol is found in the brain. Cholesterol is a waxy substance that, among other things, provides structure to the body’s cell membranes. High levels of cholesterol in the blood create a risk for heart disease, because the molecules that transport cholesterol can damage arteries and cause blockages. In the brain, however, cholesterol plays a crucial role in the formation of neuronal connections—the vital links that underlie memory and learning. Quick thinking and rapid reaction times depend on cholesterol, too, because the waxy molecules are the building blocks of the sheaths that insulate neurons and speed up electrical transmissions.

It's not crazy to connect cholesterol-modifying drugs with cognition, but it's quite a stretch.  We do know that statins affect the central nervous system.  They've been proven to reduce the risk of stroke, a devastating central nervous system disease.  If they can prevent brain disease, might they also cause it?  We have some ideas about why statins prevent strokes: they lower cholesterol and stabilize arterial plaques, perhaps by reducing inflammation in these plaques.  They can even cause plaques in some arteries to shrink.  Is there a plausible hypothesis as to why statins might cause memory problems?  What is being posited is that statins actually reduce cholesterol levels so much that cell membranes are damaged and neuronal saltatory conduction* is impaired.  If this were the case, we might also expect to find cognitive differences  when comparing people with high and low cholesterol levels, or to see cognition affected by cholesterol-lowering diets.  This is not the case.

Still, dementia---the most common and severe form of memory loss--- is a devastating disease, so if there is even a chance, maybe we should ask the question.   A large  cohort study published in Archives of Neurology in 2005 looked into whether statins might actually help prevent dementia.  They groups of elderly patient who took statins, and those who did not and compared the incidence of dementia in each group. There found neither a protective effect nor a harmful effect.

The idea that lipids (fat molecules) can affect brain function has been supported by certain epidemiologic studies and some animal models.  Omega-3-fatty acids have been touted for possible use in preventing and treating dementia.  Last week, a randomized controlled trial of a particular omega-3-fatty acid was published in JAMA.  The study design was strong, and the study found no evidence that this particular molecule helped dementia patients.

The two most common types of dementia are vascular dementia and Alzheimer's disease.  The cause of Alzheimer's disease isn't known, making prevention difficult.  Vascular dementia, however,  is to a certain extent preventable.  It is caused by a variety of factors that affect blood vessels such as hypertension, and studies have shown that many of the same interventions that prevent stroke can help prevent vascular dementia.  One of the most potent risks for vascular disease is cigarette smoking, so it would make sense that smoking would be a risk factor for vascular dementia.  A surprising result of a study recently published in Archives of Internal Medicine was that smoking is a risk factor not only for vascular dementia but also for Alzheimer's dementia.

The story of dementia risk is complex, and there is a rich vein of literature to mine.   I was disappointed that the SI article presented anecdotes rather than data, case-reports rather than good studies, and highlighted "experts" who presented fear-mongering testimony rather than the measured caution that we can expect from real experts.

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*"Saltatory conduction" describes a way that nerve signals travel quickly.  Nerve cells can function as a sort of wire for electrical signals, and the myelin sheath allows electrical signals to jump from node to node, increasing the speed of conduction when compared to an un-myelinated neuron.  Certain diseases, such as multiple sclerosis, involve destruction of the myelin sheath, decreasing nerve conduction velocity, leading to weakness and other symptoms.    Myelin contains cholesterol, among other things.

References

Rusanen, M., Kivipelto, M., Quesenberry, C., Zhou, J., & Whitmer, R. (2010). Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia Archives of Internal Medicine DOI: 10.1001/archinternmed.2010.393

Quinn, J., Raman, R., Thomas, R., Yurko-Mauro, K., Nelson, E., Van Dyck, C., Galvin, J., Emond, J., Jack, C., Weiner, M., Shinto, L., & Aisen, P. (2010). Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial JAMA: The Journal of the American Medical Association, 304 (17), 1903-1911 DOI: 10.1001/jama.2010.1510

Rea, T. (2005). Statin Use and the Risk of Incident Dementia: The Cardiovascular Health Study Archives of Neurology, 62 (7), 1047-1051 DOI: 10.1001/archneur.62.7.1047

Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, & Fagard R (1998). Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet, 352 (9137), 1347-51 PMID: 9802273

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