Neglected Diagnoses: Putting you at risk!

I have decided to let the rest of the Forbes article analysis rest for today. Instead I wish to relay to you a story which deeply troubled me.

Today I saw a patient that was referred to me for the diagnosis of Osler Weber Rendu. Also Known As Hereditary Hemorrhagic Telangiectasia (HHT). What blew me away was not that it was picked up. Although alot of physicians may miss this if they fail to look in a mouth or carefully investigate nose bleeding in a patient. Trust me, these 2 things are very, very commonplace in medicine.

But what flabbergasted me was that this patient had all over his chart "May have Osler Weber Rendu"

So you may be asking yourself...Why does this matter? The answer is forthcoming. First a little bit about HHT. There are 3 types of this disease

• Type 1 is due to a mutation in the gene endoglin, there are significant problems including masses of maldeveloped blood vessels in the body. The worrisome ones are located in the brain and lungs. If these bleed, then you can have some really bad problems including death


• Type 2 is due to a mutation in the gene ACVRL1 and often have involvement of the liver. Unfortunately these patients need liver transplantation.


• Type 3 is not associated with a gene mutation........Yet

The outcome in most of these diseases if left untreated is death. Either by heart failure, liver failure, or bleed in your brain.

My point and why I am so frustrated is that you can detect these AVMs and treat them BEFORE you get the horrible outcomes!!!! How? MRI of the head, CT scan of the chest, Abdominal ultrasound, and Echocardiogram.

When I spoke with the referring physician and asked why none of these studies had been done. "The answer was I didn't know to do that, neither did my colleague. I thought these things only happened in childhood. Shouldn't it have been done there?" My response was......"well you should do it now and adults have genes too." This man has a daughter and grandaughter, he has familial implications that could have been addressed prior to the birth of his grandaughter.

The Sherpa Says: No you do not have HHT if you have a nosebleed.....But you might if you have funny things on your tongue and chronic nosebleeds. Please don't assume your doctor knows how to do the right thing. Be proactive, take charge of your healthcare. And if you need to email the Sherpa.

Forbes and Genetics Part 4

Ok,
Sorry I took off Sunday. I just want to take the time to make a public service announcement. Please talk with you loved ones about your wishes if you were to have a terminal illness. Sometimes these wishes can not be conveyed and this will lead to horrible outcomes. So please, please have a living will.

Thanks.

Now back to the slugfest!
I have received even more emails about these postings. Luckily none from Lawyers yet ;)

Round 4 BRCA1 and BRCA2:
From the article-One in 500 women have mutations in one of these genes, which normally keep tumors from growing. That gives them a 50% to 80% lifetime risk of breast cancer and a higher risk of ovarian cancer, too. The test costs $385 for women of Jewish ancestry who know they are at risk for a particular mutation. A broader test looking for any defect costs $3,120.
Succinct, accurate, and applicable. However, they did not get into BART testing as I had posted about in my Blame Portugal segment. The also did not point out that BRCA testing can detect pancreatic and prostate cancer risk as well. This could have been much more informative and useful............Sherpa 3 Forbes 2

Round 5 OncotypeDX:
From the article-This test looks at 21 different genes that can be out of whack in a breast cancer tumor and predicts how likely cancer is to come back after surgery. That helps women decide whether or not to get chemotherapy, which can cause side effects such as nausea, hair loss and numbness. The test costs $3,500 and is covered by MediCare, UnitedHealthcare and Aetna.
I am not so sure "out of whack" is the best way to describe this testing. Perhaps, "whose expression leads to poor outcomes and recurrence" is a better way to describe it. Well, I am one to mince words myself so I can't get too picky. But the answer is...Absolutely an important test. This has been proven, validated and replicated.
No doubt this round goes.....Sherpa 3 Forbes 3!

Round 6 TCF7L2 testing.
From the article-This variant, in a region called TCF7L2, doubles the risk of adult diabetes if you have two bad copies of it--10% of people do. It is the strongest diabetes-promoting gene yet discovered. DeCode Genetics sells a test for $500 via online test provider DNA Direct.
Ok, before I go slicing into this test several caveats. 1 I absolutely abhor testing for the sake of testing. Especially when the result is not definitive. It leads to confusion, poor compliance and a false sense of security. I am disgusted by this type of testing. Especially when just one sibling with diabetes gives you greater information.

Now to the dissection of this claim. First, this polymorphism is a good and replicated polymorphism. But not everyone with diabetes has this change. The gene is about risk and there is no study available which show there are significant steps you can do to mitigate this specific gene risk. True you can diet and exercise just like you would to prevent diabetes anyways. In addition, the increased risk given by just this one polymorphism is not that significant. What is more likely to change your life is a panel such including genes identified by Dr Collins et. al. This study was published before the Forbes article and they easily could have mentioned all of these genes in one part. But they did not. Why? I think it has to do with the ties to deCODE. But that's just the conspiracy theorist in me.

I have an issue with this quote-"It is the strongest diabetes-promoting gene yet discovered."
Wow!! In what population? There are other genes in populations not northern European that have higher risk. This statement is almost false!!! Frankly I think we should take a point away from Forbes for this. But I won't.

Sherpa 4 .... Forbes 3

The Sherpa Says: I love how the media mixes true things into their agenda. It is a sneaky way to appear factual and credible. If they would have to submit these things to peer review before publishing, then we would have a different story. How come no one holds journalists to scientist standards? Especially when writing about Science!!

Forbes and Genetic Part 3...The Genes

So after that long and drawn out search I am most interested with the genes that these guys chose and why they chose them. I am surprised this article wouldn't have been written by a scientist or maybe a clinician. They would probably be in a better position to say how these gene polymorphisms/tests will perform.

1. Complement Factor H LOC387715; In people with bad copies of these genes, chances of macular degeneration progressing from an early, mild form to a severe one increase 10-fold to almost 50%, according to a study in the Journal of the American Medical Association. Ok so this is true. There is another gene HTRA1 that should have been included. Together these two gene polymorphisms increase your risk of AMD by 40 fold! Also there should have been some mention of the fact that there is some preventative measures you can take now with this disease including eye drops, antioxidants and diet (Fish). Also carotenoids (so eat your carrots!) Or you once you get AMD you could get injections into your eyeballs to prevent progression...Carrots are sounding a whole lot better! 1st round.......Forbes 1 Sherpa 0
2. The next up Apolipoprotein Epsilon 4 variant. The problem...Alzheimers Disease, we have gone over this problem before here. Jim Watson PhD knew that this predisposition was iffy at best. But as I state in my previous post perhaps with analyzing GAB2 we can come up with a clearer picture. But if Dr Watson doesn't want the results....Why should you. I gotta say this pick is pretty poor...for now. Especially because they don't even mention the possibility of modifier genes or Prevention (any ideas?) Round 2......Sherpa 1 Forbes 1
3. Number 3 isn't even a gene. It is a linkage locus. Chromosome 9p21 and the name deCODE shows up! OMG, this one has got me hopping mad. There are so many other linkages, why does this one show up? This increases your risk by 30% only if you are a Caucasian Perhaps a genetic panel should be mentioned. Well, I could name 4 polymoprhisms that show greater risk. And a family member with a heart attack at any age increases your risk 250% take that deCODE! Round 3 goes to the Sherpa, ....Sherpa 3 Forbes 1

The Sherpa Says: I think breaking these up into groups of 3 will be better for all of us. Tomorrow I will write about 4-6. Are you already getting the sense that these guys had no clue what they were talking about?

Forbes and Genetics Part Two

Given the recent emails I have received I will now present the other author to the 12 Gene Tests That Could Change Your Life Matthew Herper. It turns out I am not the only person trying to find out who Matt Herper is. But I am slightly daunted given the fact that WikiAnswers hasn't been able to answer this question.

Why investigate the authors? Because they are telling you that these tests could CHANGE YOUR LIFE! Frankly, I wonder who advised either of these guys. True, they are medical writers for several years. But there is always someone who advises a writer......

So once again I dial up spy-engine Google.....

According to the NewsBios 30 Under 30 Awards

Mr. Herper focuses on science and medicine both for the print and online editions of Forbes and is tasked with devoting about half of his time to each.

What kind of Bio is that? So he is under 30 years old. So that tells me something. He is not likely a PhD or MD although he could be either without post doc training..... Wait a second.....Under 30? I bet he has a LinkedIn profile. I know that I do.

Bingo Whoah. I got the feeling that he is hiding his credentials. Why? Even his profile is extremely spartan. Sketchy.....He moderated a biotech Industry panel and I thought his credits might be found there......no luck

Finally 11 pages deep into the google search I find this From the Counterpoint Archives at MIT

Matt Herper '99 (mjherper@mit.edu)
drinks occasionally but finds that reefer makes him ill.

Graduated in '99 could be 29 now....Sounds like we have our power player. Guess what MIT and Matt Herper find.....Friendster Impressive bio. Nothing here nor there indicating his opinion on Myriad or deCODE.

So now that I have identified the authors. We can take a look at the tests one by one.

First up Complement Factor H polymorphisms.......

Thank You!!!!

I just wanted to thank all of you who read this blog daily. I am so excited about personalized medicine and the promise it brings. Without your comments and opinions I would only be one voice in this sea. In addition I would like to take the time to thank you for landing me in the Health Care 100! Sponsored by Edrugsearch.com the ranking is a set of the top 100 health care blogs in the blogosphere. I am proud to be part of that 100 after just 3 Months of posting. I can't wait to say 3 years of posting. I can't wait to say 30 years of posting. I lastly want to thank those who accepted me into this community so warmly. Namely, Hsien Lei, Bertalan Mesko and Ricardo Vidal. We may not agree on everything, but we definitely agree on how great the future of medicine and genetics will be. To anyone else I failed to mention I thank you as well, just leave a comment and tell me how mad you are that I forgot to include you ;)

The Sherpa Says: Here's my promise; To guide you through the progressive realization of Personalized Medicine, To keep you from adverse drug reactions, To help you Prevent disease, To help you identify risk, and to protect you from charlatans looking to make a quick buck at the price of your health. I dedicate myself to this for the sake of all of us.

Forbes and Genetics

Way back in 2004 Forbes published an excellent article on inflammation and heart disease. That article introduced me to deCODE. In fact, I was so impressed with their model I began to read about their founder voraciously. More importantly I began to see the wonderful role the media has to play in this new revolution. They can influence the demand just as much as Myriad spending 1 million in Denver to market to consumers. Granted these publications don't have the Oprah Effect (Did I mention that Dr Oz is going to meet the Sherpa?), but they do have some teeth!

But I was also distressed when Forbes published an article that I had a tough time swallowing. In fact it brought me to tears. How can this publication blindly validate and promote these tests without any medical guidance, or suspect guidance at best. I am certain you have all read this article, but you can read it here. The wonderfully hyped name 12 Gene Tests That Could Change Your Life says it all. But before I get into the article, which is misleading and not factual enough to guide decision making, I will investigate the authors via my favorite little spy...uh I mean Search Engine Google ;)

Robert Langreth. He has written many articles some good, some bad. He has been writing about deCODE since 2003 prior to the Big Forbes cover story in 2004. He has been writing about personalized medicine since 1999 as Staff Reporter of THE WALL STREET JOURNAL. He also has written many scathing reports about drug companies, which is why I find it ironic that he endorses deCODE's diabetes test. Which does not tell you as much about your risk as if you had a first degree relative with diabetes. Mr. Langreth was a Staff Reporter at the Wall Street Journal from 1995 to 2000 and an Associate Editor at Popular Science from 1992 to 1994. It was at this time in my search when I figured it out

From a chat in 2002
mherper: What's Kari Stefannson like in person?
LANGRETH: Kari is a charming and very emotional person. He literally had to sell his radical database to an entire country. He did it by a grass-roots campaign, going and speaking to anyone who would listen. He eventually by weight of personal charm won the day over his opponents.
mherper: How can you write about DeCode Genetics when their stock is at $2?
LANGRETH: I wasn't recommending them necessarily as an investment, although I'd argue that it is not a terrible deal right now. I chose them because Kari is doing something that will very likely change the course of science and lead to fundamental discoveries. Whether it leads to a successful business is another question entirely. But since you ask, I figure that unlike many tiny biotechs, DeCode has something unique--the genetic access to an entire country. It doesn't mean they won't go out of business someday. But in the meantime, they are almost certain to have a big impact on science.

Does he have stock in DeCODE??????? It did track up on the day of publication.

We have to be careful to fully investigate our sources. Whom do you trust when giving you information about genetic testing? The company spokesman? The company that sells the tests? What about the middle man? We are entering nebulous waters where the lines of relation can still be hidden. Even from google. When you publish for a peer reviewed journal you have conflict of interest disclosures required. How come we don't have the same for a well read and respected magazine/website?

The Sherpa Says:
Mr Langreth has done some crack reporting on several topics, but to include the DeCODE TCF7L2 test as one that will change your life is a HUGE LIE!!! This test is a party trick at best, a distraction that could lead you to not getting your fasting blood sugar tested (The standard of care for early diagnosis). At best he just boosted deCODE stock. At worst he led you down the wrong trail. Be careful, some who play sherpas actually have stock in the pack the tell you to carry.

Personalized Medicine since 1986???

First I would like to apologize for the lack of postings on interesting topics lately. I am glad that others have picked up my slack. Notably Hsien and Bertalan's interesting posts this week. Or for an in depth post on the politics of health care and the reform movement check out VentureBeat

What I want to pay attention to today is the question I inevitably get asked when I speak to other physicians. "Is what you say feasible in a 7 minute consult world?" The answer is inevitably NO. I do not feel in my heart of hearts that we will ever be able to practice personalized medicine in a 7 minute consult world.

What's needed is a Revolution. We need a place where the patient has access to their records and their physicians 24/7. We need a place where the patient is given the skills to understand and manage their disease. My friend's 12 year old son can quite effectively manage his diabetes, how come a 45 year old venture capitalist cannot? Support is the key and learning is the motion required to open the lock. How do we make these things easier? How can we get doctors to teach their patients? What ever happened to true continuity of care? These are big questions that need answers. I don't have them all. But I am working with some great people who will find those answers.....

So the next question is "How can we have the knowledge to practice these things?" I often tell physicians to go back to college or read a book on genetics. If you don't have the time to do that, then you will fail your patients. This often meets an uproar of disbelief......I am pretty good at pissing people off. Just ask Lisa Lee at DNADirect ;)

In all honesty, we need some clinics who offer personalized medicine consultations. These specialists need to guide care in collaboration with PMDs. I am building this model in NYC! We will be seeing patients in July. Give me a call and we can arrange to start the relationship.

But there has been someone doing this since 1986!!!! Wha??? The HGP was only 3 years in and they were providing these services. Yes that is correct. Greats such as David Rimoin and Maren Scheuner helped form and develop this practice. It goes by the "trademarked" name GenRISK Adult Genetics Program. It has been in practice since 1986 offering several tests that you can see on their site. I have been critical of predisposition tests unless clinically indicated. This is an example of how a personalized medicine practice can be run.

The Sherpa Says: Genomic and Personalized Medicine need to be given in a continuity of care. Family history changes, medical history changes. A one time consultation cannot deliver that kind of service. Oh and what about pharmacogenomics?