Friday, November 29, 2013

The Cholesterol Conundrum

Originally published in The Vault Magazine, November 22, 2013.

On November 12, the American College of Cardiology and the American Heart Association released an update to their clinical guidelines for the management of high cholesterol.  Amid all the ensuing controversy and debate, the most remarkable facet of the guidelines was forgotten.

Previous guidelines promoted measurement of cholesterol and frequent monitoring for the purposes of “getting to target”.  Start treatment, measure cholesterol, adjust treatment if it needs to go lower, and repeat.  

The new guidelines suggest these numbers be almost entirely abandoned in clinical practice.  If a patient has excessive heart disease risk and it has not been ameliorated by lifestyle changes, they suggest you take a statin (eg. LipitorTM and CrestorTM) and be done with it.  The cholesterol measurement only remains important for determining risk. 

It’s about time.  These targets were always arbitrary.  They have no scientific underpinning and led to excessive treatment including unnecessarily high doses and use of drugs that have no proven benefits beyond lowering cholesterol.  

Wait a minute.  If a drug lowers cholesterol, isn’t that good for you?  

Not exactly.  And herein lies the public interest in this issue.  

Cholesterol is a “surrogate marker”.  If studies show lower cholesterol correlates with lower heart disease risk, then a drug developer might look at the impact of their treatment on cholesterol and assume any reductions in this number translate into reductions in heart disease.  Measuring heart attacks, strokes, and deaths in your research takes time and money.  Measuring cholesterol does not.

If A=B and B=C, in medicine at least, A does not always equal C.  

For example, many cholesterol drugs on the market reduce bad cholesterol but only statins are known to reduce heart disease.  

Not convinced?

Torcetrapib was a drug being developed by Pfizer which showed great promise as the next “blockbuster drug”.  Early small studies showed the drug raised good cholesterol by 60-100%.  This should, by extension, mean it reduces heart disease.

Shortly after, Pfizer’s large clinical trials were stopped early because the drug increased risk of death by 60%.  

Why should you care?  

Because the media, TV doctors, and internet snake oil marketers LOVE surrogate markers.

Dr. Oz’s most popular recommendation of the year has undoubtedly been raspberry ketones for weight loss.

Too bad they’re useless.

His website quotes all sorts of research on the topic to lend it credibility but it is useless for everything but hypothesis generation.  All the studies he quotes were done on animals or in test tubes and they studied things like markers of metabolic rate and fat metabolism.  

Not a SINGLE piece of research shows raspberry ketones do ANYTHING useful in humans, let alone cause them to lose body weight or body fat.  

THAT is why you need to know about surrogate markers and why from now on, you will know to ignore practically everything Dr. Oz says.  

Unless by some miracle he starts promoting products based on high quality medical research conducted on humans.


I can dream.

Next time: Why some would argue that ice cream causes swimming pool drownings.

Other Resources
A hilarious video on surrogate markers from my friend and colleague, James McCormack, PharmD.

References
1.  http://newsroom.heart.org/news/acc-aha-publish-new-guideline-for-management-of-blood-cholesterol
2.  http://www.theglobeandmail.com/life/health-and-fitness/health/us-heart-guidelines-may-threaten-new-class-of-cholesterol-drugs/article15413756/
3.  http://en.wikipedia.org/wiki/Torcetrapib
4.  http://www.nejm.org/doi/full/10.1056/NEJMp078020
5.  http://www.ncbi.nlm.nih.gov/pubmed/15071125
6.  http://www.ncbi.nlm.nih.gov/pubmed/16326978
7.  http://www.doctoroz.com/videos/rasberry-ketone-what-science-says

Wednesday, November 20, 2013

The Problem with Origins


I was directed to this "enlightening" image by a Facebook friend.  I don't take umbrage with her sharing it with me.  I believe she only meant to guide me toward the origin of the word Pharmakeia.  However, after looking at the link, I have to take umbrage with the suggestion inherent in the text of the image.

Instead of writing a giant tirade of a comment on Facebook, I thought I would post it here.

The origin of the word pharmakis in Ancient Greek did indeed mean "witch".  This makes sense as much of the origin of pharmacy came from experts in botany and translating that into medicinal uses.  Many early chemists were considered "witches" by the medical establishment at the time, which is funny given that the docs thought disease was caused by unbalanced humours in the body and treated everything under the sun with blood letting.

And yes, they were seen as potions and witchcraft, but only because the science hadn't caught up to their use.  Use of pharmacologic substances was much more advanced in the Arabic world early on than it was in Europe.  It is there that pharmacology as a science originated.  Meanwhile in the "modern" world of Europe, because the drugs they used were not understood, those making them were considered witches, sorcerers, and poisoners.  All drugs are really just poisons brought to a dose tolerable by the human body.  Anyone suggesting that this means pharmacists are poisoning everyone doesn't understand science.

As the science of pharmacy evolved, it always remained connected to medicine.  It is only recently that it evolved into an independent profession, and, in turn, it evolved into a more clinical profession than one focussed solely on drugs.  The word "pharmacy" today means something very different than it did even 25 years ago, let alone in the Middle Ages or Ancient Greece.

If we are going to take the word literally, the original practitioners that were labelled this way practiced something more similar to modern herbalists and "natural" practitioners.  If homeopathy, for example, actually worked, it would only be through witchcraft, given that there is no detectable active compound in homeopathic substances.

As well, the word "physician" comes from "healer", "sage" and even "physicist".  "Doctor" comes from the word meaning "teacher".  That doesn't mean they teach kids in classrooms about how to prove String Theory.

More etymology fun.  "Sycophant" originates from "showing the fig".  Figure that out.  Or "clue".  Originates from "ball of thread".

The point is that the origins of words are meaningless without historical context and evolution.

The poster of the image above sells essential oils for a living.  She actually promotes essential oils for weight loss.  Essential oils have absolutely no scientific evidence whatsoever of effectiveness, no less for weight loss.

I'm not going to comment on her use of Bible quotes to deride and debase modern medical science.  If she wants to believe that using products that have no scientific evidence to support their use means she has "knowledge", she can go on thinking that.

Or MAYBE, just MAYBE, she is making those arguments because, gee, I don't know, she sells essential oils through her website?  And yes, I know I'm a pharmacist, before someone points out the obvious and says I also have a financial interest in promoting drugs as safe.

Too bad I spend more time talking people OUT of taking drugs (which, no matter what way you slice it, "natural" products are also considered; as a dietitian once said "If you get it from food, it is a vitamin.  If you get it in a bottle, it's a drug.").

And that the majority of problems associated with medication use are due to inappropriate use or prescribing.  Roughly 7.5% of hospital admissions in Canada are due to adverse drug reactions.  Roughly 40% of those adverse drug reactions are considered preventable.

But none were likely due to natural products, right?  Wrong.  Natural products cause serious reactions too.  Unless you think that hepatotoxicity leading to market withdrawal is not serious.  Sadly, many of them go unnoticed because, despite appearances, they are poorly regulated and there is very little in the way of formal pharmacovigilance monitoring programs.

If someone wants to go back to the time before modern medicine, they can be my guest.  But I'd rather revel in the advances of modern medicine that have expanded the human lifespan.  It has not been universal by any means, but we are getting somewhere.  Estimates range from roughly half of the 7.5 years gained in life expectancy since 1950 being due to medical care to 25 of the 30 years gained since the early 1900s being due to public health measures (vaccines, improvements in sanitation, etc.).  And yes, some of these things, like pasteurization (this is a really good article; check it out), were discovered by scientists and not necessarily "medical" practitioners, but the scientific method underpins the discovery, as it does medicine, so the argument still stands.

Natural does not mean safe.  Synthetic does not mean dangerous.  I wonder if proponents of this notion would be willing to part with all of the other synthetic products in their lives?  Or if they knew some essential oils were extracted with solvents like methanol and hexane? Or if they knew stevia is manufactured using a chemical extraction process and marketed by such major players as Cargill?

If worshiping modern technology means that I adhere to the scientific method and refuse to condone anything that has yet to be proven effective or has actually been proven completely useless, than a witch I am.  Or warlock I guess.

Friday, November 15, 2013

The Cause and Effects of Health and Disease

First published in The Vault Magazine, November 15, 2013

This is the first in a series of articles that will run in The Vault.  As part of the agreement with the editors, I will not publish the article on my blog until 1 week after publication in The Vault.  Feel free to comment on the blog or send comments to the e-mail below.  Enjoy!

In 1853, a cholera outbreak struck a neighbourhood in London.  A bright physician named Dr. John Snow questioned the prevailing wisdom and was certain the disease spread through some mechanism other than “foul air.”

Through a meticulous and systematic investigation, he traced the source of the outbreak to the Broad Street water pump, into which had been leaking human excrement.  The pump handle was removed and, shortly thereafter, the local outbreak ended.

This proved Snow’s theory.

After Snow’s death, Louis Pasteur demonstrated the germ theory of disease and Robert Koch isolatedVibrio cholerae, the responsible bacteria.

For his methodology in isolating the source of an illness, Dr. Snow is widely considered the father of epidemiology, the study of the patterns, causes, and effects of health and disease.

The study of health and illness has since expanded and for even the most obscure clinical query, there are usually numerous researchers who have looked at it.  This poses a problem though.

If ten researchers study the same problem, but five get one result and the other five the opposite, who is correct?

Archie Cochrane, a medical researcher, had the solution.  He created a group that would later become the Cochrane Collaboration.  Their first project collected all the studies that had ever been done on giving drugs called corticosteroids to women in premature labour and brought all the data together to provide the best answer.

Doing this, they found this simple intervention cut in half the risk of infants dying from the complications of prematurity.

Because no one had systematically reviewed the research until that point, many infants needlessly died because clinicians were unaware of an effective intervention.

That is the power of clinical epidemiology.

That is what this column is about, but not in an esoteric way.

I want to look at the questions that matter to you, but with an eye to the evidence.

No myths.  No miracles.  Just the real deal.

Questions like:

What is the least effective but most commonly used method to lose weight?

Does anything Dr. Oz recommends actually work?

Are multivitamins necessary for healthy people?

Is the shingles vaccine effective?  Is it necessary?

All questions are fair game so long as they are not of a specific personal nature. I cannot treat you through this column, only educate you and do some good old-fashioned myth busting.

Along the way you’ll learn about tricks drug companies and researchers play, why even the most astute clinicians are still working with incomplete information, and why you can disregard almost everything about health you read on the internet and in the newspaper, or see on TV.

I’ve got plenty of material to work with, and will if need be, but I’d prefer the readers to lead the discussion.

So send your questions to nickonchuks@gmail.com and check back in the next issue for more.