Wednesday, July 30, 2008

All people have time bombs!

I received an email from a colleague that said..." here."

Ok, so to anyone surfing on the internet probably not a good thing to do right? My friend likely has a virus on his cpu, right? Well, being the avid risk taker I am...I click. Guess what I find.

A blog called the Belligerati...interesting name, but the blog has argument is all wrong.

"Many will see the headline Congress Passes Bill to Bar Bias Based on Genes and be pleased.
The legislation, known as the
Genetic Information Nondiscrimination Act, prohibits health insurance companies from using genetic information to deny benefits or raise premiums for individual policies. (It is already illegal to exclude individuals from a group plan because of their genetic profile.)

Employers who use genetic information to make decisions about hiring, firing or compensation could be fined as much as $300,000 for each violation.

Not me."

The blogger then goes on to detail why they think it is a bad thing. The major argument and one I have been seeing a lot of lately is based on pure fallacy and demonstrates how a very smart and educated person can be completely illiterate in genetics and genomics. I would say that about 10% of the population understands genetic risk when explained to them....that's about it.

From the blog:

There are many forms of luck in our society that we allow people to capitalize upon. For example, citizens keep the majority of the returns from wealthier parents, natural talents, being born into a rich and free society, their appearance, and temperament. Yet congress has passed a law that says that people may not capitalize upon their generic luck. This makes us less free, and ultimately less wealthy as well.

Genetics as luck....interesting. Perhaps they don't know that most heritable genetic changes are for the bad. Mistaken concept 1, in addition, Genotype + Environment = Phenome.

What sense of justice legitimizes forcing those who are poor but blessed with rich genetic endowment of healthy genes subsidize those that are middle class and endowed with a genetic propensity for several diseases? As I have said before on this blog, the way (the just way, if any) to address the suffering in our society is to give money to the poor. These back door methods, like this genetic non-discrimination rule, are often more unfair then the ills they prevent

This is super Bass-Ackwards. What sense of justice forces those with no control of their poor genetic make up to be excluded from health insurance....Man...this blogger is crazy.

His argument is that by genetic testing we should benefit from our "protective genetic make-up" and that GINA will prevent us from doing this.....

The second concept I want to clear up for everyone is this. "We can test for healthy genetic variation".....Let's get this straight. We know very little about the genes in our bodies that are protecting us from crappy environment. Eric Topol talks about this. For a cardiologist, this guy has done a great job of becoming a genetics Hacker! He says we should study the healthy, not the ill. I think he is right.

The third concept......we understand what genetic changes cause common disease. Let's get a clue. We know that several genetic changes have been weakly linked to (to be read as associated, not causative) common diseases. We also know of some very strong monogenic links to diseases like cancer and heart disease. But these are not the most common.

Francis Collins says "Everyone has at least 5 or 6 genetic time bombs in their genomes"
From the guy who headed the HGP....I'll take it at face value. We will only know this for sure by doing whole genome scans on everyone. By whole genome, I don't mean these chips that "claim to be whole genome" I mean, base by base, methylation by methylation, histone change by histone change, genome sequencing.

So if that is the case....why should insurers test for something that no one knows is a risk or protective allele. To them, it makes no sense to have meaningless data. But to have accurate tests for actuarial evaluation. That would be most worthwhile. My guess is that if they were to use this unvalidated and suspect data that everyone would be getting higher rates. So this argument from the Belligerati demonstrates the lack of genetic knowledge even in the most sophisticated and educated public.

There are other arguments against GINA. But I say, right now it is the best start we have at protecting our citizenry.

"GINA is the first major new civil rights bill of the new century," said Senator Edward Kennedy (D-MA), who cosponsored GINA in the Senate with Senator Olympia Snowe (R-ME). "Discrimination in health insurance and the fear of potential discrimination threaten both society's ability to use new genetic technologies to improve human health and the ability to conduct the very research we need to understand, treat, and prevent genetic disease," said Kennedy

I agree wholeheartedly. With so many people having at risk these SNP studies at least 1 % of the population has to carry these SNPs....That means 3 million people at a minimum are at risk of one thing or another. Genetic Discirimination is the new racism.....I hope not to see its ugly head rear for a very long time.

The Sherpa Says:
Confusion and misinformation can lead to making poor choices. That is why I advocate for education and guidance in the field of genomic medicine. How can we expect even the most sophisticated population to understand this on their own? It tooks me years of study to be where I am. And I learn something new every day! That's why we are going to launch a brand new wave of education and service shortly......

Tuesday, July 29, 2008

You gotta love it!!!

When I open medical news today, I read this headline
"Brain Differences Visible In Symptomless Carriers Of Alzheimer's Gene"

Sounds fantastic right? Well........
It turns out that the n on this study was 12...that's right. 12 patients with APOE e4 and 16 controls. To my friends at AlzMirror, this might be right up your ally. Buy an fMRI machine and blammo, Wharton School of Business winner all the way!

This finding needs serious rounds of replication. What were the confounding factors? Prior stroke? Cholesterol level? Amyloid burden..........etc.

They scanned these patients and in the ApoE e4 carriers they found reduced connections......
No mention of statistically significant findings mind you. Just a finding. Why it leads Medical News Today, I have no clue. It is, frankly, a finding and should never lead a site of that quality. Which is why, I have to say....they need some more sites which could actually properly rate articles and findings reported.

If you look at the article. 1 person rated it 5 stars. I doubt it was a physician. At least I hope not. IMHO this article is a 1-2 star article. I wonder why their isn't a better way to report this stuff and have it pushed down or up the list according to scientific merit and relevance. It shoudl be done at an hourly rate....and not be ranked until at least 5 people have voted. How's that for scientifically valid???

The Sherpa Says:
With articles like this and no counter certainly makes the public easy pickins for bogus over hyped, over marketed, "healthcare" companies....... Especially given the lack of health literacy out there. 40% give or take 10% in the worse.

Monday, July 28, 2008

Out of touch...

Sorry about that. I have been busy writing a book that will hit to store shelves in a couple of months. Here's an excerpt................... "If you were looking for a college level description of personalized medicine, buy another book." As I write the book, I include the raging debates......

Lot's of things continue to rage. Including the debate on genetic test regulations. Debate is a good thing. Disservice to patients is not. This article in the Washington Post covers it well. And the CDPH is not going to back down from that debate . I think that some DTC companies are providing even better online service than most healthcare providers terms of providing information. But are they providing better healthcare? No. They don't provide healthcare. So there is a huge gap here. What about the doctor who would be willing to guide a patient in choosing genetic testing? What about the doctor who would be willing to tell the patient "You don't need that need this test" That would be a nice service. I just await the Fed's response....

On another debate front, I had a clinician chide me for advocating genetic testing to avoid adverse drug reactions. He said...."The science is too young" I said to him "Well maybe your practice style is too old".....he then said..."Show me the data, and I will consider using it" I promptly asked him if he would like help in interpreting the tests....He scoffed. I wonder if he saw the recent study on statins, or heard the CliniCast on Warfarin and genetic testing?

That is the huge debate in medicine right now. Doctors who think they can interpret the tests, but aren't wiling to use them. Doctors who can't interpret the tests and are using them. Doctors who can't interpret and aren't using.......and guys like Helix Health of Connecticut.....The latter being as rare as a dinsoaur egg. But don't worry. We are priming up to pull a Jurassic Park move. Don't worry, we have thought about the ethics and legal issues first and foremost.

The ethical debate has been huge...including Thomas Goetz's push for Autonomy over Beneficence. You know.....I am often quoted as saying "Genetic testing left medicine, when you could give your DNA via sputum instead of blood". I just don't see how a change in body fluid, changes our outlook. I am not certain that spit is an different than blood. Ethically, they are the same when I collect them.

Speaking about ethics......I am certain we are going to see a lot of fly by night companies trying to "Deliver genetic care, without training". Personally, I think that a provider needs about a year of intense apprenticeship to get up and running. Anything less than that would be just pulling the wool over your eyes.

The Sherpa Says:

Yes, I have been out of touch with the blogosphere.....I have been working on some really big things. Don't worry, I haven't been out of touch with the revolution. I have been helping to foment it.....from the inside ;)

Tuesday, July 22, 2008

Index of Suspicion

There is an age old adage in medicine "You miss 100% of all disease X that you don't look for" It is stolen from an old golf adage that you miss 100% of all putts that you leave short. Big surprise, doctors stealing golf lines.

But I maintain, it is the same reason why we have been missing genetic causes of disease for the last 30 years. Yes, my friends in the Ivory Towers will tell you that they have a healthy index of suspicion for Every disease. I have worked in a community hospital and 2 Ivory Towers. I am here to tell you, that you miss 100% of a disease which you have never heard of or have never been taught about.

It's just that simple. Even more simple is that by thinking common things happen commonly only reinforces the lack of detection of genetic diseases which could actually be much more common than we know of.

I know that is a lot of jargon. But look at it this way. If you never test to detect a disease, you will never know how common it is. By not testing, you only reinforce your false belief of how "uncommon" a disease is. This is the case with things like the "Autism" epidemic. We are now looking for autism and are very good at detecting this multifactorial disease. Therefore prevalence goes up, and we look for it more often now......Sometimes, OVERDIAGNOSING it.

Why do I ramble about this today? Well, because a colleague of mine and I are having a debate. I think that Tony Snow's cancer is clearly heritable. In a very monogenic sense. The other physician thinks it is due to his other contributing multifactorial/genetic disease.

You see Tony Snow had Ulcerative Colitis(UC) at for 26 years prior to developing colorectal cancer(CRC). The risk of CRC in UC is pretty high. And often, the GI doctors invoke this "Inflammatory God" instead of keeping the index of suspicion of genetic causes, higher on the list. According to a nice review from MedScape

the cumulative probability of developing CRC is significantly higher in chronic ulcerative colitis than in the general population. Data from a comprehensive meta-analysis suggest that this probability is 2% after 10 years of disease, 8% after 20 years of disease, and 18% at 30 years after a diagnosis of chronic ulcerative colitis.[2] By comparison, the lifetime cumulative probability of developing CRC for the general population in the United States is approximately 5%.[2,3] Described in terms of relative risk, chronic ulcerative colitis increases the relative risk of CRC 5.7-fold compared with the general population.[3,4] The risk of developing CRC increases as a greater proportion of the colon is involved by inflammation.[5]

It is interesting to note that some populations of chronic ulcerative colitis patients do not have an increased risk of CRC compared with the background population. Data from these populations suggest that the risk of CRC in chronic ulcerative colitis can be modified. A Danish population-based cohort reported the cumulative probability of CRC was 0.4% after 10 years, 1.1% after 20 years, and 2.1% at 30 years after a chronic ulcerative colitis diagnosis.[6] These probabilities are comparable to those of a US population-based cohort, where the cumulative probability of CRC was 0% at 5 years, 0.4% at 15 years, and 2.0% at 25 years after a chronic ulcerative colitis diagnosis.[7]

2.0%, that is not inordinately high!

Why am I talking about this? Because, I put out to the world that NOT checking for a single gene risk and instead ascribing his CRC to UC would be a huge miss. In Fact, I still hold this opinion. Why? Tony Snow's mother DIED at 38 years of age guessed it......CRC! To be fair, family history of CRC does increase risk of CRC in UC.....but in my mind that is likely due to defective DNA repair genes anyways.....

So, in my mind. The likelihood of her having UC AND CRC is pretty damn unlikely. In addition, UC is genetic....but there are 30 some genes ascribed to IBD......and none of these single genes cause the disease all on their own. For this to be autosomal dominant transmission of UC with a predisposing risk to CRC is a pretty big stretch.

Now to firmly believe the opposite of this and NOT test for HNPCC through pathology testing of Tony's original tumor is a big miss. I don't agree with anyone who says it isn't. Why?

What is the likelihood that Snow's mother passed a single gene on to him that increased his risk for CRC? Well, if she had the gene....50%.
What is the likelihood she had the gene?
Well from another great MedScape review approximately 24% of CRCs at 35 years of age or younger were germline positive (i.e. had Lynch Syndrome, the genetic cause I am suspicious caused Tony's cancer). So 3 years is a stretch, but let's just say the same data applies to a 38 year old....who likely had the cancer initially at 35 maybe 36. So what is 50% of 24%? 12%, a much higher incidence than that 2.0% in the cohort presented earlier. But not higher than the meta-analysis which included poorly controlled individuals. Which I am certain Tony was not.

So I ask you once again..........Was a lack of suspicion appropriate? I submit to you, it was completely inappropriate. In fact, I repeat. Not testing Tony's tumor for HNPCC was a HUGE miss, If in fact they did not do MSI and IHC testing. If they did, good for them!

Why is this important? Tony has a family that could benefit from identifying their risks for HNPCC. Why? Cancer prevention. Plain and Simple...

The Sherpa Says:

Index of suspicion is a funny thing. If you don't maintain it, then you miss a lot of bad things. If you have too much, you over diagnose and over test. I ask you. Now that Mr Snow has passed, which would you rather have? I vote for a high Index of Suspicion when it comes to an underdiagnosed condition like Lynch Syndrome! And when death is on the line!

References From Medscape
1. Clevers H, Colon cancer--understanding how NSAIDs work. N Engl J Med. 2006;354:761-763.
2. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526-535.
3. Canavan C, Abrams KR, Mayberry J. Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease. Aliment Pharmacol Ther. 2006;23:1097-1104.
4. Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen T. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005;100:2724-2729.
5. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med. 1990;323:1228-1233.
6. Winther KV, Jess T, Langholz E, Munkholm P, Binder V. Long-term risk of cancer in ulcerative colitis: a population-based cohort study from Copenhagen County. Clin Gastroenterol Hepatol. 2004;2:1088-1095.
7. Jess T, Loftus EV Jr, Velayos FS, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Gastroenterology. 2006;130:1039-1046.

Monday, July 21, 2008

Brave New Epigenome

Daniel at Genetic-Future asks "Which baby do you want? A dilemma for the 21st century parent-to-be"

There is a lovely recap of an article from Nature News.....from Daniel's blog,
Nature News has an intriguing article on the next three decades of reproductive medicine: essentially a series of short musings from scientists working in the field about the issues we will be facing in 30 year's time.

I would say we are facing issues with this technology today. I just saw an IVF baby without a large intestine. I brought up an issue here that is not so well tracked or publicized. I mentioned in the comments that there is evidence of increased risks of birth defects and epigenetic changes that include overgrowth syndromes......But what I found out a few days ago sent chills up my spine. It turns out my institution's REI group is not tracking these "congential anomalies" as part of due process......not good. At least someone is...

What is the evidence for or against?

  1. Here is a nice review....preimplantation and risk to epigenetic modification.
  2. A nice n=1 review of the promise of PGD for aneuploidy.
  3. Increase in genetic mutations after ART with normal sperm
  4. ICSI not so good.
  5. A Great NEJM review that is a must read! This one is good too.
  6. Not just risky for the baby. The mother is at risk too.

The Sherpa Says:

These were the highlights when I pubmed searched IVF and congenital outcomes.....There are many more indicating the risks. I wonder if all patients are properly counselled about these things? Which baby will you choose? Great question....I don't have the answer. But it seems to me, neither do the REI specialists......

Saturday, July 19, 2008

Reason to Love George Church and Michael Crichton

Did anyone get to see George Church's love article in Wired. I am at a point here where I begin to truly appreciate what he is doing. This article gave me some insight. You fight and fight with people about this....I think he has some merit. I think that the algorithms to assess family history risk should be open source.....I think the computational side should absolutely be free. Do I think that it could be open source....yes. Do I think that VC want it open source?

No. But it would be grand if it were. As for the data-mining as open source.....well, perhaps George still is 20 years ahead of his time. People are too afraid for this part. That is why I think getting 100,000 people without offering them healthcare could be tricky. Getting 100k without HIPAA could be tricky too. But unlike the commercial efforts, I admire George for getting Harvard's IRB review. Now what he needs is an ICOB like the Coriell Personalized Medicine Project.

Here's what I envision......NEXT.....did anyone read that book?

In the Author’s Note, Crichton comments on some serious issues.
1. Stop patenting genes. This may never happen fully

2. Establish clear guidelines for the use of human tissues.
3. Pass laws to ensure that data about gene testing is made public. Meaning results of gene therapy trials.

4. Avoid bans on research.
5. Rescind the
Bayh-Dole Act (that allows universities to patent and make money off their research).

I am reminded of this as George's lab is creating stem cells from the fibroblasts in each participant's skin cells. This could be very attractive for each participant, but I am brought back to the opening scene of NEXT when in that scene a postdoc is running to commit corporate espionage by trading some stem cells that were developed in a University lab for a bundle of cash. Only to be done in by a Russian Prostitute and some Nitrogen.

Another story gets me,
The tale of a man who carries a gene that is apparently no longer his own property, having been patented by a biotech company in an extension of eminent domain that boggles the mind. But not when put in the light of the PGP and Dr Church. George would have this gene as open source.....a nice idea. But what about when the Harvard endowment rears its ugly head??? Who gets that stuff then?

“Next” draws upon a courtroom case in which U.C.L.A. was accused of covertly using tissue from a leukemia patient to develop and patent a lucrative cell line; the court ruled that the man had no property rights to his discarded tissue, and that the university, as a government institution, could claim this material under the doctrine of eminent domain.

I have fallen in appreciation with Dr Church again. After fighting with Jason at Personal Genome, I never thought I would. But after reading the Wired article I have all over again. Why? Because when he fell in love with code at 9, I fell in love with DNA at 8. That's all it took.

You go George! I love the opening pic, too bad you are on the back pages of Wired. I would have had you lead instead of that beautifully vapid(maybe not so vapid) Julia Allison. But I am certain she pulls off the high heels better than Dr Church would.

Tomorrow, I will cover
Tony Snow and colon cancer..... If his PMD didn't test him for HNPCC, it wouldn't be a surprise. But it would be a huge miss.......

The Sherpa Says:
We are entering the NEXT phase of genetics and genomics, SNP testing was only the beginning. There are many more things we will discover and many more things that will have even greater clinical applicability. George is helping ramp that up. Me Too......

Wednesday, July 16, 2008

How do we educate physicians?

I want to point you to a brilliantly written post by Carl Wieman

While there is still much to be learned, there is enormously more known now than existed when the teaching methods in use in most college classrooms today were introduced and standardized. Briefly summarizing a large field, research has established that people do not develop true understanding of a complex subject like science by listening passively to explanations.

True understanding only comes through the student actively constructing their own understanding through a process of mentally building on their prior thinking and knowledge through “effortful study”.(2) This construction of learning is dependent on the epistemologies and beliefs they bring to the subject and these are readily affected (positively or negatively) by instructional practices.(3,4) Furthermore, we know that expert competence is made up of several features. (1,2)

Why do I mention this now. Because I was asked by a very learned student.....How do we teach doctors about genomic medicine? How do we get it out into practice?

I told him......"Look around. Do you see this wonderful institution with new buildings coming up? Those buildings are dedicated to molecular medicine. You would think some of the dollars spent on building....would be spent on building knowledge and understanding of the practitioners of today AND tomorrow"

The sad isn't, and Dr Wieman has some wonderful reasons why....

Faculty members’ responsibilities are far different from what they were several decades ago. This is particularly true at the large research universities that stand at the top of the higher education pyramid and train nearly all the higher education faculty.

The modern research university now plays a major role in knowledge acquisition and application in science and engineering, through the efforts of the faculty. Running a research program has become a necessary part of nearly every science and engineering faculty member’s activities, and it is often the most well recognized and rewarded part.

This is so true....when an institution becomes known for how many Howard Hughes Investigators they have rather than how many X award Teachers there are. Are there any comporable awards in teaching? This is a very telling sign..... I mean each institution has its own....but are there any great national awards???? That pay for that person's teaching efforts each year?

He concludes that effective teaching is:

The most effective teaching of science is based upon having the student fully mentally engaged with suitably challenging intellectual tasks, determining their thinking, and providing specific targeted and timely feedback on all these relevant facets of their thinking to support the student's ongoing mental construction process.


The Sherpa Says:

The rate limiting step in genomic medicine is education. Yet why are our major universities failing to teach? Because that's not where the money is at......Sad how we reward knowledge acquisition but not applicability. That'll catch up with us. especially as we have new knowledge but no one to use it..........not exactly a good business model....or a way to run the healthcare system.

Tuesday, July 15, 2008

Minority Report meets Gattaca!

"I don't want to say it is a crime gene, but 1 percent of people have it and scored very high in violence and delinquency,"

This comes from the sociology professor Guang Guo lead researcher who discovered a novel variant which supposedly puts you at risk of delinquency and crime....

His team, which studied only boys, used data from the National Longitudinal Study of Adolescent Health, a U.S. nationally representative sample of about 20,000 adolescents in grades 7 to 12. The young men in the study are interviewed in person regularly, and some give blood samples.

This was a replication of a study published last year

It is important to note that this set of studies only apply to MALES!!! Others have weak associations in females.

So here's the million dollar it valid and can should we screen?

Whoa......let's evaluate the study first!!!

Guo's team constructed a "serious delinquency scale" based on some of the questions the youngsters answered.

"Nonviolent delinquency includes stealing amounts larger or smaller than $50, breaking and entering, and selling drugs,"

They then sampled some blood to check for prior demonstrated genes.....Those were the monoamine oxidase A (MAOA) gene, the dopamine transporter 1 (DAT1) gene and the dopamine D2 receptor (DRD2) gene.

The prior study showed that men with a 2R in MAOA report a level of serious delinquency and violent delinquency in adolescence and young adulthood that were about twice (CI: (0.21, 3.24), P=0.025; and CI: (0.37, 2.5), P=0.008 for serious and violent delinquency, respectively) as high as those for participants with the other variants.

I do await the publication for August to really get into the nuts and bolts of the study and I will get back to you with that. If you look at the other 3 studies, they are very well done. This has also been published in the European Journal of Human Genetics.

This new study tidbits have been released. It turns out that these predisposed individuals like everyone else with predisposition for anything....may require some environmental these young men the following are triggers..

The effect of repeating a grade depended on whether a boy had a certain mutation in MAOA called a 2 repeat, they found.

And a certain mutation in DRD2 seemed to set off a young man if he did not have regular meals with his family.

"But if people with the same gene have a parent who has regular meals with them, then the risk is gone," Guo said.

I will tell you some more when I know some more....

The Sherpa Says:

One thing is for sure....these genes sure seem replicated. But the risk of "Crime" is only 2 fold.....Is that really grounds for keeping someone in jail upon parole hearing?

Resistance is Futile

I was reading some peer review comments of an article I am submitting and it got me thinking.....How can we combat certain resistant to change mindsets? For example from the anonymized reviewer:

I strongly disagree that because there aren't currently sufficient numbers of genetics providers (even if you add up clinical geneticists and genetic counselors, as suggested above) that this means that the only solution is to move genetics into primary care. ...........

Ok, you can disagree.....but.....when you say this......

First of all, the demand for genetics services has not yet led to long waiting periods or other crises.

Ever tried to get into a cancer genetics or clinical genetics office in less than 1 month? More likely less than 3 months. That being said...even this reviewer acknowledged that there is not a massive amount of referrals.......

What number of trained genetics providers are needed and what are the barriers to educating, producing and hiring more and supporting their work? secrets that I will be publishing soon......

Can the authors imagine another group of specialists (for example, brain surgeons) deciding that there aren't enough knowledgeable brain surgeons, so primary care providers need to be trained (via a short course, perhaps) to do brain surgery?

The term is Neurosurgeon....and this argument is a fallacy..... They trained for 7 years and brain surgeons don't operate on Alzhemier's

I think statements about moving genetics into the primary care arena need to be much more carefully thought through and evaluated -- what are the outcomes likely to be associated with the suggested interventions??

Other than earlier pick ups in cancer predisposition, MI predisposition, adverse drug reactions, improved medication dosing, more cost effective utilization of care, less "loss of chance" malpractice....I could go on and on.....but I won't

The Sherpa Says:

This is the resistance we face ladies and gentlemen. Why do I have to learn something, just because there aren't enough specialists???? There is something called continuing medical education.......just because they didn't discover DNA when you were in medical school, doesn't mean you don't have to learn about it........Resistance is Futile....

Monday, July 14, 2008

When you know the Books are Cooked

I finally had a chance to sit down and review Genetics in Medicine for the month of June. Yes, I am a month behind.....leave me alone. I have been doing some other things for the last few weeks........So take it easy on me.....

Have you ever had the feeling that the results of a study need replication? Especially because the results do not match up with clinical reality. What am I talking about?....Wylie Burke's study on how many PCPs have ordered a genetic test. There is an age old adage that on self-report tests for will get 2 answers.....80-85% and 15-20%.....By that I mean, most physicians don't want to say they do something all the time, or none of the time.....By that I mean, most physicians lie on self reports.....even when anonymized....

This is why I saw malarky on this study, recently published....

Methods: Survey of a random sample of 2000 primary care physicians in the United States (n = 1120,

62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care.

Results: Nationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing.

Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial.

Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities.

Conclusions: Reduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities.

OK, Wylie, you are an excellent physician scientist, but you know this to be intrinsically garbage. If even 30% of PCPs referred just one patient for services, then the entirety of the genetics community would be rapidly overwhelmed.

I would bet that those tests sent off were Factor V Leiden tests for hypercoaguability work up(Now considered fairly worthless tests post clot)

There is no way 74% of PCPs even know a geneticist to refer to. This study is so flawed and I am embarassed to see it actually passing peer review. Who in there right mind would believe any of these data.

74% is awfully close to 80%....this is a fishy smelling study and I am blown away that it got published.

How did I know that they probably didn't sense the anomaly I did? Because they are all PhD's not a single community based doctor in the bunch......


The Sherpa Says:
If you believe this study, then I have a bridge to sell you.........Further proof, you can't always believe what you read....Not much has changed in 5 years since the NEJM study, so I doubt that this study is true.

Thursday, July 10, 2008

New Gene in Atrial Fibrillation

Did anyone see the New England Journal of Medicine? They published an article on a new gene involved in atrial fibrillation. Don't know what A-Fib is? You have 4 Chambers in your heart.....the top 2 are called atria.....Atrial fibrillation can put you at risk for heart failure, heart attack and stroke.

The last of these is the most ominous. This is one of the major reasons people take Warfarin. Which BTW, can have up to 45% of your metabolism tested for by genetic analysis of CYP 2C9 and VKORC1....And recent studies support its use.

You can get your testing through DNADirect......even if your physician says there is no reason to test for it(They are dead wrong).....Some physician with the company will order it.....The question is, "Whose responsibility is it to tell results to the doctor who put the patient on Warfarin?"

Personally, I think you should be tested if you are on Coumadin or starting Warfarin (same drug as coumadin).... The FDA may now consider it standard of care.....

So this raises an interesting question. I have been against DTC testing with these GWAS studies......especially because they are not even close to mainstream excellent medical care.....but what about when the doctor isn't doing the standard of care? Doesn't a patient deserve the standard? Yes.....I want to remind everyone that the standard of care is the usual standard of practice in one's community. But if you listen to Dr Gary Marchant Law Professor at ASU, that all may be changing.

According to Dr Marchant, since we now have the internet....the "standard of care" may become what's usual practice in the nation.....or maybe even internationally...

So I put it out there for all of you........should we sell DTC genetic testing for a condition which may put you at risk for adverse events? Even when the doctor won't order it?

I can see the malpractice case now......."And why didn't you order the test Doctor?.......(doctor) see..........the patient told me they had ordered it."

The Sherpa Says: Rare gene variants may or may not be helpful in understanding this soon to be epidemic condition. It is certainly a good family study. But, I think no one will be offering DTC testing of this gene variant.........It is just to rare. This Warfarin thing is going to get complicated now that a patient could technically order this online.......

Tuesday, July 8, 2008

You Know It's Bad

You know you are in for a grilling when the SACGHS says......"While we laud you for coming to participate in the conversation, part of that participation means that you may not like what you hear(More or less quoted from the webcast)"

Then in an "Interesting" Move.......

They ask "Would you be willing to sacrifice your bottom line to offer these services at say 100 USD?"

Wha???? This is such a crazy question.....This Assumes that the data they are presenting is valid, actionable and worthwhile....... All of which.....are debatable...AND that the public would want such services....

What am I talking about? I am talking about the opening of the 30 minute interrogation that was the end of the SACGHS meeting

They even asked the question "Do you have an IRB for all this 'research?'"

The response.................."We're workin on it"

Well, not really the end.....That was reserved for clean up hitter Kathy Hudson...(Whom, BTW I think is brilliant)

Her slide set covers some very key issues and the presentation did as well....

She even manages to quote Joseph Schumpeter, elegantly...

Schumpeter thought that the institution enabling the entrepreneur to purchase the resources needed to realize his or her vision was a well-developed capitalist financial system, including a whole range of institutions for granting credit.

This is very true, but what she quoted him on was this....

“process of industrial mutation that incessantly revolutionizes the economic structure from within, incessantly destroying the old one, incessantly creating a new one.

I.E. Let's destroy the Healthcare System via DTC Genetics.....Interesting....I wonder how the committee of healthcare players liked that slide? I wonder if anyone mentioned his other theory where advanced capitalism doesn't allow entrpreneurism to flourish because of regulations and the creation of a welfare state. Hmmmmm me thinks not...

When looking at the concerns, this slide explained them pretty well

Concerns About DTC Marketing
• Consumers can’t understand genetic information; it is complicated.
•Consumers vulnerable to exaggerated claims.
•Consumers may get tested without adequately considering consequences to themselves and family
•Consumers may forego standard treatments or make dietary or lifestyle changes without proven benefit
• Consumers may seek and receive unneeded and costly care

Companies may not adequately protect privacy of genetic information
•The tests that are offered may not be valid
• The laboratories that perform the tests may not be competent
• Test claims unsupported by evidence
• Inadequate protections for research participants
•No legal barrier to surreptitious testing of another

She Says the Options are

  • Let the Buyer beware
  • Demand transparency: information as
    the antidote
  • Require third party review of accuracy
    and safety
  • Take action against false claims
  • Create a category of OTC LDTs
  • Expand HIPAA
  • Expand common rule

I personally think there are many more...And I am workin on that!

The Sherpa Says:

When speaking anonymously with a panelist they said...."It was surprisingly tame" When speaking anonymously with SACGHS attendees they said "This spells the end of unregulated DTC" So it sounds to me like the 2 sides may be engaged in a conversation where no one is listening to each other.......Or the may not be communicating effectively......

Priority=Public Enemy?

I hope all of my readers get the GenomeWeb Daily News.

Today the headline read.....

This meeting is currently underway.....the webcast is live here!

Here are some snippets from the case you are an infovore and got bored by the text (HT Daniel)

A US Department of Health and Human Services committee plans to vote in December on the recommendations it will supply HHS Secretary Michael Leavitt concerning the state of genomics in the US, particularly concerning consumer genetic testing and pharmacogenomics.

Paul Wise, who chairs the Secretary’s Advisory Committee on Genetics, Health, and Society’s Priority Setting Task Force, told members of the committee in Washington, DC, today that the group will likely focus on standards to monitor direct-to-consumer genetic testing



The specific clusters the task force will look into in the coming months include

  • the need to develop more evidence for personalized medicine;

  • training and education of health professionals in genetics and genomics;

  • evidence-based guidelines for genetic technologies;

  • coverage and reimbursement for genetic services;

  • Medicare and Medicaid reimbursement for DNA tests

  • genetics and health disparities among minorities.

This all spells disaster for DTC tests that costs as much as a night at the Burj Al Arab, especially those with little evidence (where the paper count is n=1.5)

The three words that jump out at me.....evidence, evidence and educate.......maybe there's something to that...

The Sherpa Says:

If you think the US is bad....did you hear about the UK's governmental push to shut DTC genetic testing down??? It is going to be a long road here.....all because of a few bad apples....and a few people looking to practice medicine without a license....Most of these companies have great people working for them or with them. They could do very well in this regulated environment.........the companies just need a little redirection, that's all..

Monday, July 7, 2008

A little story

I want to wish everyone in the US a happy 4th of July. The fateful day took tremendous amounts of courage to stand up against status quo. Our Founding Fathers risked life and limb of not only themselves, but also their families. They would not stand for the tyranny and taxation that was levied upon them.

Too bad our medical community isn't as courageous.

I want to tell you a story. I was a resident at the time.

JT was a 16 year old boy who had just been diagnosed with ulcerative colitis. It is an inflammatory condition of the bowel. He had been having episodes of horrible diarrhea and when he received the diagnosis he was started on a medication called 6-MP. If you must know, I was training in Internal Medicine at the time. Prior to this I trained in pediatrics......You see, in pediatrics before we start this medication, we do a genetic test.

6-MP can cause horrible suppression of your immune system and bone marrow. It actually has been used as a chemotherapy in the past. We do this genetic test as essential standard of care in pediatrics. Unfortunately, that was not the case in Adult Medicine. You see, there are adult GI doctors still starting this medication and watching to see if the toxins build up and case a drop in the white blood cells....(Sound Familiar?)
Well, JT went home on 6-MP and was doing great. In fact the week before his birthday he had no symptoms at all. He even skipped his check up and lab draw. But something terrible was going on in JT's body. On his birthday, he went to the bathroom and collapsed. He was unable to get up and was so weak he couldn't call for help. Luckily he had his cell phone on him and while he was in the upstairs bathroom he called his home phone.

His father picked up. "Help dad! I can't get up! I am in the upstairs bathroom"

His father raced up stairs and brought him into the ED. That's where I come in. I saw that JT was just started on this medication a little under a month ago. I ordered some labs and started JT on antibiotics. Based on the fact that he looked white as a ghost, I knew.....he had bone marrow and immune suppression. My lab values came back confirming the diagnosis. JT had the worst side effect from this medication.

While in the ICU/hospital (For 2 weeks and over 30,000 USD in charges) he fought of a bacterial infection in his blood. He received multiple units of blood and injections to stimulate his bone marrow. The Adult GI doctor THEN sent off the genetic test. Guess what? He was a NON-metabolizer of this horrible medication. That's why he did so poorly.

I recently asked my friend (Head of GI at a very respectable hospital) why they ONLY now are recommending genetic testing in Adults. He said, there was "very little evidence behind dosing patients according to genotype". Huh????? I asked if now there existed an algorithm to adjust dosing in poor and intermediate metabolizers. He said "NO"

Yet now, genetic testing is standard of care for dosing 6-MP.

So I ask you.

With an algorithm in place for Warfarin, FDA recs on the label, an FDA approved test and established evidence behind the basis of genetic testing, why do the adult doctors demand "MORE EVIDENCE"? When they obviously can see the aftermath of hundreds of JTs.... Or maybe they can't see the aftermath?

I guess just a few more thousand deaths from Warfarin toxicity need to happen.............

The Sherpa Says:

Sometimes, you just have to err on the side of protecting the patient. With GINA in place, adult doctors everywhere have nowhere to hide when it comes to this. Just ask my colleague, Gary Marchant JD, PhD............. He stated it explicitly in our last CliniCast(TM)

Thursday, July 3, 2008

Pfizer cuts on Education.....What abour Us?

Does anyone read the WSJ Health Blog? I do....everyone should.

In a post yesterday they say

Doctors and pharmaceutical companies have been getting beat up lately for their intimate ties (see here, here and here). Now Pfizer is backing off a bit from one of its connections to medical practice: funding for physicians’ continuing medical education, or CME, courses.


“The reason we’re not going to directly support them has to do with mitigating the perception of a conflict of interest, if a direct payment is going from a company like Pfizer to them,” Cathryn Clary, VP of US external medical affairs, told Dow Jones Newswires.

Ahh, the ol' conflict of interests argument. Why do they get hit with that, but the Nephrologist teaching residents does not get hit with that? Here is why?

Hippocrates asks all of us to teach those who wish to learn.....Did he understand that creating doctors did not create competition? I think so. In fact........educating physicians does not create creates market share.

This is why I am not surprised by Pfizer's stance....interestingly enough...

The drug maker has decided to end payments for CME are provided by for-profit, third-party companies. It will continue funding courses offered by academic medical centers, teaching hospitals and medical societies.

What makes me laugh is that the 3rd parties are probably making less off of CMEs than the huge academic Behoemeth's like Harvard........

In fact the Genetic Basis of Adult Disease course is well attended and the course costs a whopping 650 USD....but the course may fall to the wayside! Why? They cannot meet budget.....My guess is that the institution gets a huge vig for any CME course....leaving the directors with little to work with in budget.....Just a hunch...

So.....there you have it....Pfizer openly acknowledging that providing CMEs to doctors is a conflict of interests.......I wonder if any of the genetic testing businesses have thought about that? Do you think Myriad will pull back its sponsorships? What about us at Helix? Nawh...we're physicians I guess we are exempt.....sort of.

I wonder what the other corporate testing companies will do to respond to that? Do they even plan on doing CMEs? (I took the 5 question Navigenics test for CMEs....) Hopefully, they will prepare a defense to the argument which Pfizer has heard over the last 20 years......or maybe they will heed Pfizer and not get into the education business at all...

The Sherpa Says:
The physicians at Helix Health of Connecticut will always do their utmost to teach the public and other physicians....regardless of the "Conflict of Interests" Why? Patient care is in all of our interests.

Wednesday, July 2, 2008

15 a week....not even close to 100 in 10 days.

I wanted to tell everyone about what the Wellcome Trust has been doing. Aside from their new commitment to 90,000 genomes, they now have reached the 1 terabase.

That is.... the staggering total of 1,000,000,000,000 letters of genetic code that will be read by researchers worldwide.

From Medical News Today
The amount of data is remarkable: every two minutes, the Institute produces as much sequence as was deposited in the first five years of the international DNA sequence databases, which started in 1982. It is a global milestone.

This is tremendously important as we begin to start databasing terabases......How much informatics and storage will we need. This issue has been covered excellently by
Daniel at Genetic-Future
Drew at Think Gene
Yann at His Blog
The debate goes on.......

The bottom store the data you need AND to analyze it takes some serious cashola!!!

Not to be exaggerating, but the 1000 genomes project is getting moving....

"The 1000 Genomes Project is exploring the genome at a resolution nobody has attempted before," says Dr Richard Durbin, who co-heads the Project. "Our goals are ambitious and all of us are still learning, but we can already see that, through the efforts of the Sanger Institute and our partners in the consortium, the results will have a major impact on our understanding of human genetics and disease."

The Sherpa Says:
All that is fine and dandy.....but what use is it without phenomes and family history data???? You need Trios, You need cohorts over years......this is nice, but it is only the first steps..