I never thought I would be reading the Aesthetic Surgery Journal.....but when the word BRCA pops up, I have to take notice.
From Medical News Today
"Plastic surgeons must play a part in monitoring women who come in for cosmetic breast procedures. These patients should be assessed for potential breast cancer risk by a physical examination as well as a family history evaluation," said Foad Nahai, MD, President of ASAPS and Associate Editor of ASJ. "It is imperative that these patients understand their potential risk, if any, as well as the implications breast surgery may have on future screening, in order for them to make the best possible decision regarding their own care."
I never thought I could tell the guys from Nip Tuck to do a 3 generation pedigree.....Well, Now I can. There is a problem though...I don't think plastic surgeons are the most astute genetic counselors out there.....
So what does this article say?
"Before every elective breast surgery, special attention should be paid to any family history of breast or ovarian cancer."
The reason? Since you are working with young women, this is the ideal group to identify these risks.... They demonstrated the PAT model and also show the gail model.......Both are not the best choices and can underestimate risk. Still with the BRCAPRO model, physicians need to know that limited family structure can play a role...something most physicians miss.
From Medical News Today:
Some key considerations for patients at high risk for breast cancer include:
- BRCA1 and BRCA2 related breast cancers generally occur in younger women, making detection by mammography difficult because of the denser breasts.
- The current screening recommendations for patients who test positive for BRCA1 and BRCA2 mutations include monthly self breast exams starting at age 18, semiannual clinical breast exams starting at age 25, and annual mammography and breast MRI starting at age 30.
- All breast reconstruction methods are available to patients with genetic predisposition for developing breast cancer; however, every high-risk patient must be counseled carefully and thoroughly to enable her to arrive at a decision suitable for her.
- For patients with BRCA mutation, it is important to note that bilateral reconstructions can be very lengthy and a staged approach may be advisable, and must be coordinated with the oncologic and gynecologic surgeons during combined procedures.
"Close cooperation between oncologists and plastic surgeons will improve patients' psychosocial outcomes and decrease the psychological burden for patients who have been diagnosed with a genetic predisposition for breast cancer," added Dr. Soltanian.
The Sherpa Says:
How sad is it that the only time a woman may get her family history evaluated is when she is seeing a plastic surgeon for breast augmentation......BTW did you notice that Dr Soltanian did not mention Medical Geneticists....I wonder if they know medical genetics exists????
Friday, February 29, 2008
I never thought I would be reading the Aesthetic Surgery Journal.....but when the word BRCA pops up, I have to take notice.
Wednesday, February 27, 2008
Sunday, February 24, 2008
And in 2005 when Eddy Curry, then the center for the Chicago Bulls, refused a genetic test to learn if he was predisposed to a heart ailment, the team traded him to the New York Knicks.
Saturday, February 23, 2008
I was flipping through the Wired blogs today and came across something pretty interesting. A microbiologist named Carl Woese says that evolution is pretty complex and therefore, like quantum mechanics, should not be taught in high school.
So first I said who the heck is this guy? I was perplexed. Why? Because I think we should be teaching the simple concepts of DNA and Genetics IN grade school. A quick wiki-search definitely gives him some street cred, when it comes to evolution.
He says this in response to all the hulabaloo in Florida about teaching evolution. Why not just skip it until the student is an adult and has a choice? Well, I hate to say it but.....He is dead WRONG! Complex concepts will need to be taught at an earlier and earlier stage if we ever hope to progress as a a society. Just because we don't teach quantum mechanics in grade school doesn't mean we shouldn't.
How will the US ever develop the home grown scientist if we don't nurture our children early? I say this as I sit and watch less and less citizens go into science, less and less children go into medicine, less and less go into engineering. Yet I see a scientist in every 2 year old I have ever taken care of.
Blame it on Brittney! And now blame it on Carl Woese. Hey Oprah! How about a teach your child science day?
The Sherpa Says:
I know that this is not the least bit related to Genomic Medicine and Personalized Medicine directly. But in the end it has everything to do with this path. It's time to make Science sexy again!
Thursday, February 21, 2008
I couldn't figure out whether I was hallucinating from the fevers or if the email I received from a reader was correct. He said "Could you explain this to me, from 350k now to 1k? How could this be"
He was of course speaking about the PacBio (Like Pacific Sunwear/PacSun) technology and press release that Reuters put out there. Man why can't I get on Reuters at the drop of a hat?
From the release
" A California company predicts it will soon be able to sequence an entire human gene map in four minutes, for just $1,000."
"It will change health care forever if it works," Hugh Martin, the chief executive officer of the company, said in a telephone interview on Monday
Martin thinks Pacific Biosciences' new technology will be able to get a human genome done in about 4 minutes.
Yes, my wonderful readers. These are the key words in this news release. From that tone, it sure doesn't sound like a finished deal yet! There are several things to consider with this new technology including the cost to implement and its fidelity of genome analysis. But don't be surprised if someone builds a better mousetrap soon. But the short answer is....Genome for a Grand? Don't hold your breath.
That being said....I want to re-emphasize the benefit of directed testing. This is a good market and now DNADirect it appears has a direct competitor. DNA Traits dot com is a place where you can get free genetic counseling. At rock bottom prices of 75/hr at DNA Direct I am flummoxed on how they actually pay their counselors. Now you go and say that their service is so insignificant that it is FREE? Come on....where is the business plan here? Some way they have to be making a profit...Dr Bettinger covers this company very nicely on his blog.
Their list of advisors includes a Critical Care Medicine/Population Geneticist. Great for geneaology....."Doron Behar has multi-year background experience in the development of genetic testing for the public using a direct internet based customer approach." It appears he IS a mitochondrialist! Unfortunately on the site I couldn't find the names of the genetic counselors willing to work for free :(
The website even has the DNA Direct feel to it. Interestingly, now I may have figured out where my Houston readers are coming from. Houston, Redwood City, Mountain View, Cambridge, San Fran, NY, DC these are all my hotspots for daily readers. I wonder why.
Lastly I saw a quote from Dr. Bruce Korf. I will email Dr Korf today and as how he feels about his name on the DNA Traits site.
DNATraits agrees with the recommendations set forth by the American College of Medical Genetics in their Statement on Direct-To-Consumer Genetic Testing. In this statement, Bruce Korf, MD, PhD, says, "It is critical that individuals ask for a referral to a genetic expert who can help in determining what tests might be advisable and in interpreting results."
More importantly, if testing is even advisable at all. I have some difficulty with FREE counseling without stating what those counselors are actually working for. I hope it is not commission......
The Sherpa Says:
No I am not hallucinating. The genetic and genomic market just got a little more crowded. Once again.....I ask that we make informed decisions regarding our testing and get some professional advice. FREE advice is just that. Even a free initial eval should be followed up with care that is paid for. As for an MD only reviewing POSITIVE results...what about the Maybes? Is a Negative really a negative? I would want an MD to review all results. Why? Because it is just good care and should be the standard of care. We can't cut corners in genetics, no matter how stretched we are. This goes true for a sodium level or an extremely complex genetic test.
Wednesday, February 20, 2008
As I sit here shivering, febrile and with myalgias, I had a thought. "Hey wait a second....I got the flu shot this year". Yes, it is true. For the first time EVER in my adult life I had received the flu vaccine. It's funny, becuase if you think about it, Flu Vaccine IS personalized medicine/Genomic Healthcare.
You may be saying, HUH? But it is the truth. The flu vaccine is a combination of two genes...well the protein products of those genes. Yes, much like humans there are several different types of the "flu" Influenza virus. They are classified according to these genes Hemagluttinin and Neuraminidase.
Hemagglutinin also called H and then subtyped by number, is useful for the little influenza to stick to the cells it wishes to invade.
Neuraminidase also called N and then subtyped by number is used for the "little bastard" (sorry, it is just the cytokines in my body speaking) to escape from infected cells and spread to other cells.
So when a vaccine is made they actually put components of these subtypes together with their "Best Estimate" of which viruses are likely to infect during a given year. Hence "Personalized Vaccine Medicine"
Well this year guess what. Our best guess was.....WRONG and now I sit here with the flu. This is not the only thing wrong in personalized medicine land. We have long known that sometimes we make a mistake in subtyping a woman's breast cancer for the Her-2 protein. Now we are finding a better way....through chickens. So how's that Chicken Soup for the Genomic Soul. Her-2 is used to direct therapy of a Her-2 Monoclonal antibody. For more, see the Personalized Medicine article.
The Sherpa Says: The best laid guess is as good as anybody's This is why we need to always view these technologies very carefully. Imagine getting a flu shot thinking you will have better protection, only to get the flu for the first time in years. Now imagine taking herceptin only to find out it doesn't work for you. We have to be careful and double check what we are given and what our results are. Too many people take printed reports AND clinicians at face value. While usually a good thing (Only if we understand the language) it can have some bad outcomes. Including my own illness ;)
Saturday, February 16, 2008
So without much ado let's get started!
First the basic science. It is on the shoulders of these giants which Sherpas like me stand when we implement the clinical action. We are all different, every single one of us unique. What makes us this way? Well Yann Klimentidis shares with us some of his thoughts on the SNPs and genes that may make each population special. How can we trak what population you are from? Well, one good way is through mitochondria and now we have a more visual way to look at the mitochondrial genes. Made by a "mitochondrialist" (I would love to see what that conference looked like) the MitoWheel is poised to help those who need just a little more visual model.....May the Force Be With You.
At least if you have blue eyes, then things are looking up. Blaine over at Genetic Genealogist covers that family tree. Now I bet Tom Cruise doesn't feel as special anymore.
Other things make us special. The stuff with which we arrogantly called junk, including introns is proving to make us pretty special. Larry at Sandwalk elegantly covers some of the hot topics in Intronic Junk. This makes him the Tony Soprano of genetic waste management! Nice post.
It's not all about the Homo Sapiens. Even birds get their say at GrrlScientist where the argument for earlier flight is posed. Not really a gene post per se, but it is a Rock vs DNA clock battle. Speaking of evolution, what makes a fish go blind and how do they get that sight back? Greg Laden's blog will show you how. Better blind than dead, but if I have to go, I would like to skip the Black Death. Especially after reading Archeozoology's coverage of the Yersina Pestis Genome. Well maybe I will eat myself to death...or a higher level of evolution. Nature Blogs cover the Big Mac controversy. Nature versus Nurture debate will never end!
So how do we take this to the road? How can we translate these unique findings?
First we have to educate the physicians and get them up to speed. But can we do it? I will be presenting at the Association of Program Directors in Internal Medicine precisely on this topic. The blog PredictER gives some insight as well. Some may say we should just bypass physicians, let's here about our Genetic Future. After that good laugh we can head to Berci Mesko at Scienceroll and find a "23 and Me Hacker" who has created a pretty useful tool to help.
We all know that these technologies will only continue to improve. Unfortunately most MDs don't have the time to keep up. Here's a hint for them....Visit the Gene Genie, which will be at Sciencebase next.
For those who need a quick set of new tests!
deCode first with the PrCA gene, cute fellas, real cute. Hsien and Ramunas both cover this one.
Soon we won't need all of these tests. Especially if the 1000 genomes projects get things scanned quickly. I am certain all sorts of novel technology will be created. This will shake things up.
Until that day we have Family History. I was with a patient and one of our geneticists today. When a patient asked him how many patients he had seen he said "I have been doing this counseling before they even had the test." In heart attack land, family history is still the king predictor of MI risk. But I doubt that the company selling the Kif6 test want you to know that. Well maybe someday I will show up on the WSJ health blog too.....
Thanks to all those who submitted. I hope you enjoyed this. Thanks to Ricardo at MyBiotechLife for the excellent logo!
Thursday, February 14, 2008
I hope you remembered. I almost forgot, until 9 pm last night. Did you ever have the experience of fishing around the Hallmark aisle, hoping to get a card that is still "just right". Instead what you invariably end up with is a less than perfect card. My wife will never let me forget the year I gave her a card addressed to "My Dearest Friend" Not quite what I was shooting for but hey, it works.
But, somehow I don't think that the science of genetic testing will support the publishers model. I think The Sherpa should add Geneview to his hit list of genetic start ups heading straight for a court of law."
Tuesday, February 12, 2008
Unfortunately, she is not genetics literate. I then went to give her my counseling shtick and tell her that no one in her family has breast/ovarian cancer. "So why does that lower my risk?" she asked? This is why Ellen Matloff has her website. I am certain that this testing has identified many people not normally thought to be at risk because of limited family structure i.e. all men relatives (But they still could have prostate, pancreatic, or even breast cancer)
The real question is, what will happen when 23andMe advertise? What about Psynomics?
I am preparing a talk for the Fairfield County Medical Association. What is it about? Well, I would love to have talked about the benefits of genomics. But the pressing topic for community physicians is "Personal Genomics and Liability for the Community Physician"
I had a physician come to the office the other day, she had heard me speak at her hospital's medical staff meeting. She said "The other day when you and your counselor spoke to us, I have to admit, I had no clue what the hell you were talking about" "But now I think I know what you were warning us about." She then handed me a 40 page set of a patient's testing done at Canyon Ranch.
The genetic testing done included such hot buttons as CYP 450 testing billed as "Detoxification Panel" and the loaded APOE testing. It began to finally sink in. These physicians have no clue what is coming. I could spend my days running from hospital to hospital preaching like Cassandra or I could create something just for them.
Anyone interested in helping please send me an email.
I said....."Well, there is certainly alot here." Has anyone seen this Canyon Ranch panel? The interpretation was done by a very nice physician. Clearly not a geneticist, nor an internist. But he told this 30 year old female patient that she needed a Coronary CT Angiogram. This in my humble internal medicine opinion is a little bit of overkill. Despite this testing, no where on the report was a significant family history. Her family history? According to this PMD...it includes longevity. Both parents into the late 90s. My professional opinion, barring trauma or accident, she'll live long enough to pay for all sorts of bogus screening tests.
When looking for this testing on Google, I only found 3 links! Turns out it is Great Smokies/Genovations behind the testing. Canyon Ranch has these pages hidden on their site. I hate to tell everyone, no matter how many poor studies you put behind a test, you still have poor studies and a poor test. It hesitate to point out that not only is Canyon Ranch involved in this testing.....so are some casinos.
Back to my point....Which is....Physicians will only wake up when a patient walks in their door and puts them at liability/malpractice risk. This is especially troublesome when I am trying to point out how they are actually LESS at risk when they appropriately refer to genetics/genomics services and not to Casinos.
The Sherpa Says: Getting these resort testing panels is a lot like playing craps. Put your money on the pass line and roll the dice. You may get something worthwhile, you are more likely NOT to. That's why the house always wins! These tests only stand to confuse and lead you off the trail of truly personalized medicine.
Monday, February 11, 2008
First I would like to thank everyone who voted on this very non-scientific poll. I extended the voting over a month, thousands of visitors later, we have our results.
You may be saying "Hey That's Only 98%" I say, "exactly" That's why it's not scientific. For all who may be reading, including my daily friends from Mountain View (that's right, everday)
Who exactly will be doing the suing? Maybe an Attorney General? If you are Myriad then that is the case. I prevously posted about this dangerous predicament these genomic companies could be in and the reposted last week about it.
As for Myriad, expect more BRACAnalysis ads to be coming. The WSJ reports that the Myriad ad campaign in the NY metro/NE area has increased sales of their test. from medical news today:
According to the Journal, sales of BRCAnalysis, which identifies the BRCA1 and BRCA2 genetic mutations, have increased by about 55% from $34.2 million to $53.1 million in its second quarter that ended Dec. 31, 2007.
Does this mean more patients at risk are getting identified? Most Definitely. Does this mean that their opponents are saying that more people are getting tested inappropriately? Most definitely. How did this campaign succeed where the one in 2003 fizzled? Primary Care Providers including OB/Gyns. Ask your local rep how many more tests came through these avenues and I think you will be surprised.
Now back to the wait. Navigenics is slated to open early this year. With GenomeBoy receiving an invite to the ball, I am certain to see this launch very soon. Will they follow Myriad's suit? I imagine a 3 million dollar ad campaign would work very nicely in the tri-state area. But then we have to warn them of the DTC testing laws in these states. Lest they end up like Myriad.
I guess anyone can file a suit these days. So here's a word to the Genomics Companies....."Be prepared".
As for the other companies not so well capitalized....."Be Afraid"
The Sherpa Says:
If I had a law degree, like the millions of lawyers out there who can do this work for free. I would bone up on genetics legal precedent, corporate protections and genetic discrimination. If you think a certain ex-candidate for president made a bundle suing OB/Gyns, you haven't seen the beginning of the legal fortune to be made in genomics.
Wednesday, February 6, 2008
In reading my mother in law's NY post, watching the blogs, and Good Morning America I am always amazed by how big a deal the press makes of novel things like a mitochondrial transplant. Which IMHO is still a little suspect.
Posted by Steve Murphy MD at 4:46 PM
Tuesday, February 5, 2008
New York State has laws on medical privacy, genetic privacy, and human subject protection, making it among the more restrictive states for the conduct of research or genetic testing.
New York prohibits the conduct of “genetic tests” without the prior written informed consent of the individual. A genetic test is defined as:
“…. Any laboratory test of human DNA, chromosomes, genes, or gene products to diagnose the presence of a genetic variation linked to a predisposition to a genetic disease or disability in the individual or the individual’s offspring; such term shall also include DNA profile analysis. ‘Genetic test’ shall not be deemed to include any test of blood or other medically prescribed test in routine use that has been or may be hereafter found to be associated with a genetic variation, unless conducted purposely to identify such genetic variation.”
According to the statute, prior to a genetic test, individuals must be notified, individual authorization must be obtained, and specific elements must be incorporated into the informed consent form including: a general description of each specific disease or condition tested for, the level of certainty that a positive test result for that disease or condition serves as a predictor of such disease, the name of the person or categories of persons or organizations to whom the test results may be disclosed, and a statement that no tests other than those authorized shall be performed on the biological sample.
Bottom Line- A separate consent for each disease which is tested for!
For clinical genetic tests, the informed consent must state that the sample shall be destroyed at the end of the testing process, or not more than sixty days after the sample was taken, unless a longer period of retention is expressly authorized. New York law requires individual authorization for sample retention for up to ten years if no genetic testing is performed; however, informed consent must be obtained prior to the conduct of genetic tests. Retention of a DNA sample past a period of ten years requires explicit consent for a longer or indefinite period of retention.
Bottom Line-A separate consent for DNA Banking
So what does the written consent look like? I wonder what dream team of lawyers have debated these issues. This is not the first time laws to protect the patient were devised. Back in 1997 we had some similar arguments.
In addition to the thoughts of individual consents for zillions of "possible" tests. Who constructs consents for tests never conceived? I imagine you will have to review the DTC testing legislation in each state. A nice review is here at Hopkins.
In my states (CT, NY) we have many prohibitive laws....
Regs.Conn. State Agencies §19a-36- D29(a)
Regs., Conn. State Agencies §19a-36-D32(a)
Laboratories may accept specimens only upon request of licensed physician or other personsauthorized by law to make diagnoses. Laboratories may report findings only to the licensed provider that ordered the test. Laboratories may provide results to lay persons upon written request of the provider who ordered the test. An official at the ConnecticutCLIA Laboratory Program confirmed that DTC testing is not permitted.
New York?N.Y. Pub Health Law § 576-b N.Y. Pub. Health Law § 577 10 NYCRR § 19.1(j) 10 NYCRR § 58-1.7 10 NYCRR § 58-1.8 10 NYCRR § 63.3(e)
In general, tests may be ordered only by licensed physicians “or other personsauthorized by law to use the findings of laboratory examinations in their practice or theperformance of their official duties.” Consumers are not listed among thoseauthorized. Test results cannot be sent directly to patients except with written consent of thephysician or authorized person, except blood type and RH factor can be given in writing tothe patient without written consent. DTC testing is permitted for tests that have beenapproved by the Food and Drug Administration for direct, over-the-counter sale to consumers.
The Sherpa Says:
Hordes of lawyers, genetic counselors, and States' Attorney Generals are investigating around here. More importantly, this should serve as a wake up call to all DTC testing companies playing around in CT and NY. Consider yourselves warned! DTC testing in these states is Illegal! Luckily we have trained physicians and counselors skilled at guiding you through the testing process. In the offices in Greenwich or New York, Or through our home visit service. You get the best of both worlds, testing AND consultation!
So I was looking at the scrolling news on the right side (left side for the MDs) of my blog. Yes, I do review some of the stuff on my blog. I found this interesting company that I was perplexed by. It is called Iris BioTechnologies. They have a "magical" product called BioWindows. I say magical because obviously they have not disclosed who in the hell they came up with their technology. They are going to beta this month and launch in the late spring.
What is BioWindows? From the site:
BioWindows is a very sophisticated artificial intelligence program that analyzes the genomic information from our nano-biochips. Comparing this information with a central repository of genomic profiles, patient survey profiles and reference data provides appropriate treatment scenarios for a variety of pathological conditions, ailments and diseases. We, as human beings, function best in a wholesome environment and your genes are no different. What you eat, drink and breathe and possibly think and feel impacts how your genes do their jobs. We all have disease predispositions and accumulate non-inherited mutations and inheritable epigenetic tags during our lifetime but the environment and our lifestyles also play their part in pushing us over the edge to disease.
By uncovering underlying lifestyle and environmental patterns and interfacing them with genomic profiles from our nano-biochips we hope to be able to pinpoint specific environmental and lifestyle triggering causes that may be pushing you and others from health to disease. Personal data, and the genomic data from our nano-biochips, will become part of an ever-growing international database to assist scientists in their search for personalized causes and cures for the many diseases that affect us.
So I have a few significant questions.
1. How in the hell do they come up with their treatment scenarios? I would like to see some more data on this? Even crazier. Is this web program designed to diagnose and treat? Because it would be pretty impressive to get FDA approval for that.
2. What does Sophisticated mean?
3. This material is "password" protected which is key. But it sounds like your data may be released to a 3rd party...hmmm, I hope it is completely de-identified, as best it can.
4. I imagine this will set up for a whole host of diagnostics for them. Yup.
The Sherpa Says:
One thing's for sure. I like 23andMe's educational videos a hell of alot better than Iris' Genomics 101. Seriously, I think this would be a great database for someone like George Church to use. But I don't think we should be enticing patients to pay to participate in research, we should be paying patients for research. In a true capitalist nature, what if we offered stock options to each participant? Now THAT my Nature Genetics friends is what I call a "Personal Stake" It is much more noble than stock options for the investigators.
Monday, February 4, 2008
Ok, so today I want to bring up a set of studies which I just finished reviewing extensively. I have to admit, we have some nice trends for genetic and genomic medicine here.
First, KIF 6 is identified as a risk for heart attack. Not super impressive with and Odds Ratio of 1.5. But it is replicated as well.
Second, the "Polymorphism in KIF6 Gene and Benefit From Statins After Acute Coronary Syndromes Results From the PROVE IT-TIMI 22 Study"
This is a good sequencing study of the bigger PROVE IT-TIMI22 study. More importantly it is a great representative of the retrospective analysis we can do on these great pharma based studies. The major limitation is the statistical flaws introduced by the method. So what is the major crux of this study.
The study population for this genetic study was derived from the PROVE IT-TIMI 22 trial, which has been described previously (14). Briefly, the trial comprised 4,162 patients who had been hospitalized for an acute coronary syndrome within 10 days preceding enrollment and who were enrolled while in stable condition and after any planned revascularization.
How well is this patient population a representative?
Because only 10.3% of the patients were nonwhite, which did not provide sufficient power for a separate analysis of ethnic groups, we included only the white patients in this genetic analysis.
If you are not caucasian, these results may not apply to you. The big problem I have with these studies is precisely their lack of diversity. This limits their applicability. But this is still an ok study.
Here is what makes this a good revisit. This study demonstrates a certain population at risk AND a benefit of therapy provided to that group. This is the essence of what pharmacogenomics and personalized medicine will bring to the table. The theory is nice, we will see if it stands
Carriers and noncarriers of KIF6 719Arg received significantly different benefit from high-dose atorvastatin therapy compared with standard-dose pravastatin therapy. Specifically, in carriers of the 719Arg allele, high-dose atorvastatin therapy 80mg, compared with standard-dose pravastatin therapy, reduced the risk of death or major cardiovascular events by 41% (adjusted HR 0.59, 95% confidence interval [CI] 0.45 to 0.77; p <>
This is a pretty good result. Funny how all the cardiologists I know pooh pooh'd the Coumadin genetic testing because there was no clinical outcomes(Not true BTW). Here we have some solid data coming from a cardio study. I maintain that these huge pharma sponsored cardiac studies will be the low-hanging fruit here. They have reams and reams of patients and their data already available, the genotyping should be the easiest part.
So sorry my cardiologist buddies, you got some learin' to do. It's ok, I will help you.
So here's a question. If this benefit is genetically mediated, will the non-carriers of KIF6 719Arg variant have a similar benefit?
In contrast, high-dose atorvastatin, compared with standard-dose pravastatin, was of no significant benefit in noncarriers (adjusted HR 0.94, 95% CI 0.70 to 1.27; p = 0.70) (Table 2). This difference in benefit between carriers and noncarriers was significant (p = 0.018 for interaction between KIF6 719Arg carrier status and treatment)
NOPE. So there you have it, the death knell to one drug fits all! If it stands....
"You hear that Mr Anderson?" (Hat tip Matrix)
Carriers of the 719Arg allele are at increased risk of fatal or nonfatal coronary events when not treated with statins (,  and ), and they clearly benefit from statin therapy, whether it be standard-dose pravastatin compared with placebo (8) or high-dose atorvastatin therapy compared with standard-dose pravastatin. In contrast, noncarriers not only were at lower risk than carriers in the ARIC and WHS trials and in the placebo groups of the CARE and WOSCOPS trials, but noncarriers also received less benefit from statin treatment than did carriers in the CARE, WOSCOPS, and PROVE IT-TIMI 22 trials.
There are some limitations, I agree. Despite the limitations it is the blueprint that matters most. This is the start of the new model! We shall see more of these redux studies shortly.
The Sherpa Says:
One of the biggest sellers in the pharma world, now has a target group that receives maximal benefit. Hey Hank, send me the check in the mail please.....You gotta love Personalized Medicine. Now we need 10 minute genotyping for those patients with chest pain. Or maybe they could use their NAVIGENICS or 23andME screen which their PMD pooh pooh'd? But you would need a geneticist to interpret that!
After listening to a great lecture by Berci this afternoon I got so amp'd that I decided to submit my rebuttal to the Nature Genetics editorial. At the same time I was doing that I read an email from a good friend of mine Dr Colby.
He tells me about a little known company called Psynomics.
From the site:
"Our first two products:Psynome™ – tests for two mutations of the GRK3 gene that are associated with bipolar disorder.
Psynome2™ –tests for gene mutations in the Promoter L allele gene that predicts patient response to serotonin-based drugs, the most commonly prescribed drug therapies in psychiatry today. These tests are useful to your doctor in making a timely and accurate diagnosis of your condition and prescribing the right medication. The tests can be ordered individually or combined. "
So what are the studies backing up these tests????
The company sites one journal article (Barrett 2007 entitled " Further evidence for association of GRK3 to bipolar disorder suggests a second disease mutation") and it so happens the primary journal author is also the VP at Psynomics....hmmmmmmm
What's the gist of this paper? Basically you have a paper saying “this gene contains some mutations related to bipolar disease"
From the paper-
In summary, we have identified at least two distinct haplotypes in GRK3 which demonstrate evidence for association with disease, raising the possibility that there may be more than one BPD risk mutation at this locus.
Brandon's point and I concur "Do you think that with this mystery still unsolved it is a good idea to sell the testing?" Even better. If you test positive, how do you stop the bipolar disorder? The website even acknowledges this.
The Sherpa Says: Another spit kit, another sucker. SNPs aren't everything, we still have to evaluate copy number variation, epigenetics.......We need to look at what ApoeE4 can show us. (Hat tip to Steve) Let's pick off something we can sink our teeth into. Let's regroup at base camp.
Sunday, February 3, 2008
I only mention this because I got a little blasted for tying 23andME with Tuskegee. Well, not really blasting, just a blog post from a really great new blog called Genetic Future.
First, we said "Is this a viable business model?" The answer, a resounding yes
Second we said "Will patients be ok with us giving their data to Pharma companies?" The answer, maybe...but only if they received something back.
Thirdly we said "Is it ethical to sell your patients' data?" We had seen it done. So we went to some notable ethicists....
What occurred during that time? CRO scandals, researcher kickbacks, fradulent studies, all things poised to make physicians look less than hippocratic.
That's when we abandoned the idea of physicians selling this data without EXPLICIT permission of patients. We did not want to revolutionize medicine AND look like profiteers. If we were not to tell our patients EXPLICITLY, we would just be pulling a scam. I couldn't exactly find the words but then...
The term Slel then came across my radar. It was brought up again by Jason Bobe
Slel: To take DNA from someone against his will, to create avatars of him, or perhaps children.
Well Avatars may not being created and it may not be unwillingly, but a profit could be made. I say could, only because it is not being made yet. Data acquisition is going to be required first.
Why do I react so vehemently against this? Because I sit on the Yale New Haven Health/Greenwich Hospital IRB. The US is a little different than those boys across the pond!
What do ethicists feel? Here is a great take.
7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies:
(1) value—enhancements of health or knowledge must be derived from the research;
(2) scientific validity—the research must be methodologically rigorous;
(3) fair subject selection—scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects;
(4) favorable risk-benefit ratio—within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks;
(5) independent review—unaffiliated individuals must review the research and approve, amend, or terminate it;
(6) informed consent—individuals should be informed about the research and provide their voluntary consent;
(7) respect for enrolled subjects—subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored.
So I ask 23andME, deCODE, Knome...Who OWNS the saliva and DNA contained therein?
Friday, February 1, 2008
The Sherpa is back....and with a vengeance. First, thank you to all who wished myself and my family well. We are doing fine. The family had a member get struck with cancer. It never ceases to amaze me how this horrible disease can bring families to their knees. I look forward to the day which we can detect these malignancies prior to their metastases. Even better, before they ever start.
I just spent the afternoon with Genome-Boy Misha Angrist. With Bertalan Mesko coming on Monday I feel like the Blues Brothers. Misha and I had a fun filled lunch and interview. I can't be sure who was interviewing whom, but I am certain both of us walked away more informed. I honestly admire those 10 PGP'ers. Imagine not knowing that these corporate genomics companies would be making such a huge imprint on the face and change the genomic debate. Their decisions to enlist took true courage. That being said, I loved it when I heard Misha say, just because we can sequence doesn't me we should......or shouldn't do it. He said "We just need to lower our expectations of what 600k or a million SNPs can tell us."
I agree. Which brings me to my next point. For those who read the Nature Genetics Editorial entitled positively disruptive...let me issue a huge wake up call. I am currently drafting a submission outlining the huge leaps of faith this article takes. Before I leak that info, I just want to say how can we expect physicians who went to high school before the central dogma to apply genomics? Even worse, how can we blame them for being so dismissive, when they don't appreciate what personal genomics may SOMEDAY bring?
How can we blame physicians when they don't even speak the language of genomics. I don't think I need to get into how few physicians ever received any training by a geneticist. They can learn, for sure. But it will take them about 1-2 years of consistent study. Somehow I doubt they will shut their practice doors to go back to school. Here's what gets me about this editorial...
It is not beyond most physicians' skills to explain the quantitative risks conferred by— and the research underlying—the health predictors they currently use: BMI, cholesterol, blood pressure, age and sex.
Malarky- It has been well studied that most physicians cannot even explain terms such as number needed to treat. Their innumeracy has been demonstrated time and time again in the literature. Their study is ongoing and the answer is, quantitative risk is extremely difficult to explain. This assumes that most patients are prepared and health literate.....WAKE UP PEOPLE!!! How will an internet based report ever size up whether the patient is health literate? There exists such tools, but their administration requires face to face care. But even then this type of evaluation is difficult.
Over 40% of adults in the US are either barely health literate or are frankly health illiterate. So how can we expect them to understand genomic data even written in the 6th grade level?
The individual gains a personal stake in the ongoing research effort and a huge incentive to find out more. A personal stake in finding out something that was not previously known is the key to getting students into research and may well be a powerful tool to educate and interest members of the public in the details of their own health and functioning.
Really? I just saw 13 diabetics yesterday. Not a single one feels that "Personal Stake" and they are afflicted with disease. What will make genomic information in an asymptomatic patient so special? I would love to see some STRONG data on this one. Remember, patients have to be health literate to understand the implications of their disease or pre-disease.
The pressure of information also creates a need for genetic counselors, but if uptake and use of individual genomics spreads as fast or widely as it seems likely to do, the counseling curriculum will undergo a rapid shift of emphasis away from rare mendelian diseases to both rare and common genetic determinants of common diseases and will acquire a new set of courses to deal with evaluating environmental risks.
Hmm <3000,>300 million US citizens, >120 million who are health illiterate. The majority who went to high school before the 80's or even the 90's When was the last time academia moved at the rate of anything other than Glacial Speed?
In the meantime, individual genomics will have informed thousands participating in one of the most exciting areas of biomedical research, and it may recruit participants in prospective studies that they will have funded partially from their own pockets.
Likely unwittingly.......Hat Tip 23andME
That being said, they are co-investigators, not patients, and the experiment will be conducted on their own terms!
The Gene Sherpa Says:
Pollyana get a grip, take of the rose colored glasses and smell the thorns. For us to reap the benefits of genomic health, we need public education, physician education. What these corporate genomics companies need is some ethics classes, an IRB review course, and some restraint. I look forward to seeing how Navigenics moves thorugh this maze. I am certain it will be better than giving away free kits to steal your genome. Disruptive technologies require an ability for the public to utilize them rather quickly....I am not certain this is that case. Which brings me back to Genome Boy's point. "Just because we can sequence doesn't me we should......or shouldn't do it. We just need to lower our expectations of what 600k or a million SNPs can tell us."