Year: 2011

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Dogs, squirrels and evolution

This is my dog Bo.
Bo is a Woodle. I wanted to name him Chewbacca.


He loves to chase squirrels.
On google image search the top suggested related-search for squirrels is squirrels with guns

He was chasing squirrels all over my neighbor’s lawn, much to the delight of the 6-year old twins that live there. I proceeded to tell them the story of the only time Bo caught a squirrel.

I was jogging with Bo and he saw a squirrel. He chased the rodent for 10 feet until the squirrel climbed a tree. Bo looked up the tree and tried to jump a few times but the squirrel was too high. I told Bo that maybe he’d catch the next squirrel and we started to run down the block. Then the squirrel fell out of the tree and landed right in front of Bo. Well, Bo grabbed that Squirrel in his jaws and killed it faster than you could say “rabies shot.” It happened so fast all I could remember was the sound of his little lungs being punctured by Bo’s teeth. (Six year olds love the gory details. Bilateral pneumothorax, gotta be a quick way to die.)

Then I asked the twins, do you think that squirrel was a good climber?

They answered, “No.”

Do you think that squirrel’s babies would be good climbers?

They answered, “No.”

Do you think that squirrel is going to have any more babies?

They answered, “No.”

That’s why squirrels are so good at climbing trees. The ones that are bad at climbing, die and can’t have babies. We call that evolution.

And I call that a teachable moment.

Come on America, Its not that hard.

Gallup Poll Feb 2009

Level of support for evolution from wikipedia

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Doctors are like the pyromaniac fireman

A patient, on Friday, explained that doctors are like the pyromaniac fireman who when he’s not putting out fires is secretly setting them so he can fight them.

Ridiculous?

Well, on that same day I saw a patient who previously had uncontrolled blood pressure. I had gotten her blood pressure under control with a combination of torsemide, spironolactone, carvedilol and amlodipine. Her office blood pressure  was 123/72 with a heart rate 86. During the visit she told me that she had fallen three times in the last few weeks. Her standing blood pressure was 96/53 with a heart rate of 96. On her previous visit I had extinguished and set a new fire at the same time. Her previous blood pressure had been in the 150s. Controlling her blood pressure was the right thing to do medically but undoubtably it was the cause of her recent falls and my attempt to trim long term morbidity resulted in her being exposed to increased short term morbidity.

Pyro fireman.

Another patient I saw has advanced diabetic nephropathy, CKD stage 4. He needs an ACE inhibitor or an angiotensin receptor blocker to stave off dialysis, unfortunately he cannot tolerate them because of recurrent of hyperkalemia. A few months ago I added a loop diuretic to control edema and hypertension and a couple of weeks ago he returned for a follow-up. His potassium was 4.6 mmol/L. The loop diuretic had increased kaluresis enough that I felt that I had some room to give another trial of renin-angiotensin blockade. Yesterday I received a call informing me of a critically high potassium in this patient.

Pyro fireman

These cases are not limited to clinical medicine, the ACCORD trial tried to determine if normalizing the Hgb a1c in diabetics reduced cardiovascular mortality. Better diabetic control caused increased total mortality.

In OnTarget the combination of an ACE inhibitor and an angiotensin receptor blocker was tested to see if it could reduce cardiovascular events. The  combination was a favorite among nephrologists as a way to stave off dialysis in patients with persistant proteinruia despite single drug renin-angiotensin blockade. Dual blockade was the fashion mostly in response to the subsequently retracted COOPERATE trial. In OnTarget there was significant increase in renal dysfunction with dual ACEi/ARB and a trend toward increased dialysis:

“…whereas the rate was increased in the combination-therapy group, with 65 patients (0.8%) undergoing dialysis”

Pyro fireman, academic style. 
It’s what makes medicine so difficult, the more you try to help your patients the more you expose them to unintended, adverse reactions. I feel that so little of medical education prepares us to balance these competing end-points, how do you judge what is an acceptable risk of hyperkalemia, how do you balance the risk of hypertension versus the risk of orthostatic hypotension?
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Fellow-level lecture on urea kinetics

I reworked an old lecture from ’05 on urea kinetics. The old lecture had a hideous purple background, so changing that to black would have been enough but I added a number of cool touches to fully update it. It worked pretty well, though the end’s pacing is off.

PowerPoint | PDF

I especially like the sequence walking through using the iPhone to calculate the simplified single pool Kt/V. Its amazing how many people don’t realize that turning the calculator sideways brings up scientific functions. I love watching their faces light up when I say, “Now turn it sideways.”

The lecture uses the three randomized controlled trials on dialysis to introduce and explain the three varieties of Kt/V:
  1. NCDS: to discuss single pool Kt/V
  2. HEMO: to discuss equilibrated Kt/V
  3. Frequent Hemodialysis Network in center study: to discuss standard Kt/V
I have another hour long time slot in December to talk about dialysis prescription. I’m going to discuss the recent data on dialysis interval and mortality. 
What else should I talk about?

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Steve, you put a dent in the universe

The link is to  Apple.com
Google, keeping it classy
jonathon mak

Brian Lam on Steve Jobs during the lost iPhone 4 story
Flags at 1 Infinite Loop
Steve and wife, Laurene, after his last product introduction, WWDC 2011 iCloud 

John Siracusa’s touching remembrance


In the official version Richard Dreyfus is the narrator. I had never heard this version with Steve at the mike.

Egg Freckles is a Apple website, the term is from a Doonesbury comic poking fun at the Newton’s terrible handwriting recognition.

Gruber, always subtle, changes the background of Daring Fireball to a darker, almost black, grey.

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The agony and ecstasy of of secondary hyperparathyroidism

Managing secondary hyperparathyroidism in dialysis patients should be a rewarding aspect of nephrology. I thrive on complex management that involves balancing various numbers with clever treatment strategies. It is exactly what I find so exhilarating about a juicy electrolyte case in the ICU.

The principle variables in secondary hyperparathyroidism are:

  • PTH
  • Phosphorous
  • Calcium
And I use one additional lab that is generally ignored in the guidelines, alkaline phosphatase.
To bend these numbers we have a variety of tools with interesting effects, mechanisms of action and side-effects. The principle therapeutics:
  • low phosphorous diet
  • calcium containing binders
  • non-calcium binders
  • calcitriol
  • paricalcitol and doxercalciferol
  • cinacalcet
And additional therapeutics that can be brought to bear in difficult cases or in unusual circumstances
  • dialysate calcium concentration
  • parathyroidectomy

And K/DOQI provided cleanly laid out treatment goals:

  • PTH 150-300
  • Caclium 8.4-9.5
  • Phosphorous 3.5-5.5
  • Calcium x phosphorous product < 55
Patients that achieve those targets have a lower mortality risk than patients that miss these targets:

The numbers (0 of 3, 1 of 3, etc) refer to the number of months a patient is at the K/DOQI target in the quarter, PTH was measured only once a quarter

The problem is that no one has performed a prospective randomized controlled trial showing these targets improve outcomes. We want to believe that the retrospective data showing a survival advantage with cinacalcet and paricalcitol are real and that the observational data showing better calcium and phosphorous (and to a smaller degree, PTH) results in better patient outcomes.

Teng et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med (2003) vol. 349 (5) pp. 446-56

Block et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol (2004) vol. 15 (8) pp. 2208-18
But given nephrology’s previous relationships with retrospective data (see anemia, Kt/V, and statins, and homocysteine) I can’t accept that data. I can’t take these treatment goals seriously. I appreciate that the fresh KDIGO guidelines readily admit that the emperor has no clothes and that the best they can recommend is to generally keep the calcium and phosphorous close to normal (evidence level 2D) and the PTH anywhere from 150 to 600 (evidence level 2c) or roughly wherever the hell you want it.

I love this figure from KDIGO, essentially once the PTH rises over 150 it provides no information. PTH > 300 has a positive predictive value of only 65% for high turnover disease. And don’t miss the laughably small numbers. We are basing global guidelines off of a study of less than 100 patients. From Barreto and Barreto.

It is shameful that Abbott has not done an RCT with survival as an endpoint on Zemplar or Calcijex. They have had 20+ years to do this. Both of the other players in CKD-MBD have taken a chance at building RCT data to support there products:

  • Genzyme took a poke with DCOR (RCT of sevelamer versus calcium based binders) 
  • Amgen is in the final countdown of EVOLVE (RCT of sensipar + usual care vs usual care)
Abbott the oldest player is sitting on the sidelines.
The lack of data, the lack of clarity, and the reliance on observational data muddles the issue enough that I don’t enjoy taking care of secondary hyperparathyroidism. But recently I had a great case, a situation where treating secondary hyperparathyroidism did more than loaded the dice in my patients favor but actually really made a difference.
I have a young dialysis patient who suffers from a horrific trauma a number of years ago. As a result he has profound chronic pain. Much of the pain is back pain but he also complained of diffuse body aches. Earlier this year his PTHs were consistently over a thousand with some over two thousand.
We added 90 mg of cinacalcet daily and the the PTH plummeted to goal. This was in a patient who had not responded to doxercalciferol 10 mcg three times a week. It was nice to see the PTH come down but what made this case standout was that his body aches melted away. We had been sending him to pain clinics and switching narcotics trying to get his pain tolerable and all of a sudden, done. Pain dramatically improved with a log reduction in PTH. 
Sometimes I get so carried away worrying about total mortality that I forget about the direct toxicity of high PTH. 
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Warhol, Coca-Cola and the iPhone

What’s great about this country is that America started the tradition where the richest consumers buy essentially the same things as the poorest. You can be watching TV and see Coca-Cola, and you know that the President drinks Coke, Liz Taylor drinks Coke, and just think, you can drink Coke, too. A Coke is a Coke and no amount of money can get you a better Coke than the one the bum on the corner is drinking. All the Cokes are the same and all the Cokes are good. Liz Taylor knows it, the President knows it, the bum knows it, and you know it.

–Andy Warhol

Replace Coke with iPhone and that is what I think is so cool about the pocket computer revolution. No matter how rich or how powerful you are, the best phone you can get is the same one you see high-school kids using.
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Intriguing thoughts on pulmonary embolism

The blog post claims that the data on treating pulmonary embolism is shaky, a randomized study from 1960 with a few handfuls of patients that was terminated early after 6 end-points.

The author then goes on to point out that since our methods of diagnosis are so much more sensitive than they were in the 1960s we should be skeptical of using old treatments for this modern concept of pulmonary embolism.

Read it. What do you think?

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Medical school humor

I am knee deep studying for my internal medicine recertification, so my sense of humor maybe a bit warped, but I found this to be a scream: