Swine Flu Concerns

From Wikipedia

Several complete genome sequences for U.S. flu cases were rapidly made available through the Global Initiative on Sharing Avian Influenza Data (GISAID).[104][105] Preliminary genetic characterization found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in U.S. pigs since 1999, but the neuraminidase (NA) and matrix protein (M) genes resembled versions present in European swine flu isolates. The six genes from American swine flu are themselves mixtures of swine flu, bird flu, and human flu viruses.[106][107] While viruses with this genetic makeup had not previously been found to be circulating in humans or pigs, there is no formal national surveillance system to determine what viruses are circulating in pigs in the U.S.[108] The seasonal influenza strain H1N1 vaccine is thought to be unlikely to provide protection.[109]

However, this type of H1N1 Influenza can be treated with Oseltamavir and Relenza. By the this time next week Helix Health of Connecticut will have an adequate stockpile for its patients and employees. We are prepared. Are you?

The Sherpa Says: This genetic "Mongrel" is spreading rapidly and my guess is that the United States Government may be ready. But the towns and states may not be as ready. You can be ready by washing your hands, staying home when you are sick, covering your mouth when you cough and keeping people home who can't do those things. If you have fevers, go to your doctor or to the Emergency Room. But remember, those at highest risk have had contact with those from or returning from Mexico.

Why Family History Matters

I am often asked by my patients why I take such an extensive family history. They also often ask, why their other doctors have never done so before.

The short reason, you very rarely find anything you that aren't looking for. True there are incedentalomas of CT scans that end up saving someone's life. But those are the rare cases.......True, there are some doctors who are so busy that they order a zillion tests in a shotgun approach because they are too busy to think through a case, let alone take a 10 minute family history.

But I am not one of those doctors.

Just yesterday patient comes in with increased thirst and increased urination......this case was classical diabetes. But I also decided to take a family history.......

It turns out he has early onset cancers in the family. A stomach and an ovarian. 2 very rare cancers which most doctors would not have caught. Why? No one teaches you about Lynch Syndrome in Internal Medicine residency. More importantly, they wouldn't have had the time to work out the pedigree if they were double booked seeing 20 patients a day.

So in addition to the diabetes work up this patient is getting, he is also getting a cancer genetics evaluation by myself. Something I am very good at. Something I teach my residents about everyday. Why? Because I know they won't get this stuff anywhere else.

So when I see a blog post from a DTC company that says Family History isn't enough, I laugh. Compared to the testing that this company is offering, Family History IS everything and more than a 2500 USD test could offer.

"Navigenics assesses genetic risk for many common health conditions, including Alzheimer’s disease, breast cancer, type 2 diabetes, prostate cancer and heart attack."

As you can see from the links...genetic testing here just isn't that useful.....Which is why it is a shady practice to misrepresent it as USEFUL.

Family History as well as a good physical exam with our current risk algorithms does a far better job than a non-clinically validated SNP scan that costs 2500 USD does......

The clinical ramifications of this man's family history make SNP scan testing foolish, but Tumor sample and Germline testing the STANDARD OF CARE. No SNP scan would lead me to do either of those tests.........But the right family history? You bet your bippee.....

In a world where Comparative Effectiveness Research is taking place, we will soon see the SNP scan placed in a lower level of test and probably not be in the clinicians armamentarium.......unless of course the results (good, bad or useless) can get patients to do something that a good relationship with a doctor has not been able to do......i.e. quit smoking, lose weight, etc.

The Sherpa Says: I am sick and tired of journalists hired as "Health Writers" hyping a false product to improve sales.....This is a crappy thing to do to vulnerable people reading your swill....

Why the hullabaloo about Swine Flu?

I already wrote a little bit about it here. But if you would like I can recap for you.

Swine Flu normally doesn't spread to humans, but this type does. Even crazier is that this type can be spread between humans. To quote the CDC

"The viruses contain a unique combination of gene segments that have not been reported previously among swine or human influenza viruses in the U.S. or elsewhere. At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment of infection with swine influenza viruses. The H1N1 viruses are resistant to amantadine and rimantadine but not to oseltamivir or zanamivir. It is not anticipated that the seasonal influenza vaccine will provide protection against the swine flu H1N1 viruses. "

New viruses are formed when a minimum of two viruses merge. Pigs are known to be especially efficient genetic recombinators. The new swine virus has gene segments of the bird flu, one gene segment from a human flu and two gene segments from a pig virus.

But when I hear everyone talking about bioterrorism tests I tend to chuckle nervously. Why?
Well, for one even though this may be a "Never Before Seen" Virus, we have only been surveilling very aggressively over the last few decades....

The second reason I chuckle is because it makes all this Personalized Medicine for prevention and DTC Genomics look REAL silly. As in not nearly as important as stopping a pandemic......

The Sherpa Says: If you haven't been to Mexico or in contact with the people from San Diego, Kansas, NYC, TX, or the 1 case in Ohio. Stop, take a deep breath and relax. Wash your hands and call your doctor if you feel ill......

Buying a lab? Selling a lab? Someone's not being kosher....

First,

Happy DNA Day! I will be teaching the younglings about Bases and Epigenetics. Just like I did on Thursday at Danbury. What are you doing for DNA Day?

What I am doing other than the teaching is pointing out some fishiness in the Sequencing space. Mind you Affy is a public company......

Read carefully here.

"Navigenics said that the move to acquire in-house screening capabilities was driven in large part by a growing interest in the company's genome testing services, through increased online sales to consumers and physicians as well as expanding enrollment in clinical study programs with partners such as Scripps Translational Science Institute and MDVIP."

"Vance Vanier, chief medical officer of Navigenics, said: "Acquiring our own clinical laboratory gives Navigenics the flexibility and capacity to better respond to the growing demand for our genome testing services."

Now, that these guys are so convinced about how great the space is.......let's here the story from a publicly traded company's CEO, who ultimately could go to jail if he "lies"

Quintin Lai - Robert W. Baird & Co., Inc.
And then Kevin, in March we saw an announcement that you were handing over the CLEO Lab stuff to Navigenics. How does that change any revenues that you once had in 2008 that you won’t get in 2009?

Kevin King *CLEO IS A MISTRANSCRIPTION OF CLIA*
"The CLEO Lab revenues weren’t really that significant for us. The big learning that we had here and the big reason for starting the CLEO Lab a couple years back was really to enable our partners to get to a test, right, a lab developed test and then ultimately too a path for FDA clearance. Initially we thought that this could actually be a big recurring revenue stream for us. So, we had lots of partners, 15, 20, 30 partners that we would be working on projects. Often times the projects were fairly small and when the projects were over and they had their test validated the first thing they said to us was they wanted to open their own CLEO Lab.

So, it really wasn’t much of a recurring revenue stream for us, it was more of a job shop, which was fine, because we are enabling our partners to use our consumables and so forth. But, it really wasn’t going to turn out to be the big multi-million dollar business model that I think at one point in time we thought it might be."

The Sherpa Says: It seems to me that someone is not being honest to themselves and the public here and my guess is that it isn't AFFY. Happy DNA Day!

The argument maybe defused. Quacksalvers?

Ok,

So what happened in the DTC market was a fractionating of services with different "legal" arguments for what they were doing in attempts to avoid regulations which comes with all sorts of health care practice.

At that time I argued that these firms WERE DOING healthcare and should be regulated as such.

Astute legal times from Navigenics and 23andME said.....we aren't doing medicine. We are only using algorithms to process results of biospecimens .....Despite receiving cease and desists

They even said, we don't NEED CLIA because we aren't doing clinical testing.......

Yes, in hindsight these arguments did seem silly......they seemed silly to me at the time as well. But then these businesses fell in line, sort of..... Paired with CLIA labs and then we all moved on. But what they didn't do is submit their algorithms to regulation as well. We now see this problem getting larger. Especially as Muin Khoury and the CDC argue for complete transparency of what these "algorithms" are.

Why? Because the CDC, like me feels that they are providing some sort of healthcare service. One that will likely exist in the future as well. So much so that it needs to be regulated now, to prevent all sorts of shenanigans like those that existed even in 20th century healthcare.....

Cocaine for headaches and depression?

Traveling medical shows where women all sat in a train car and......

Mercury to sure mania? We saw that all of these things were used without regulation or guidance, exposing people to significant harm.....

Like the financial industry, the argument that regulations will prevent us from being the world leader in genomic technology is pure B.S. Just like it was with Finance

In fact, I do remember all of these money making brokers saying the exact same things I hear now from Genomicists mouths......

Scary, if you ask me.

So what about these "algorithms"?

Well, a few people confirmed that in California we have some new drafted legislation which could affect all players in this DTC and lab space.....

• This bill would require an entity that provides post-CLIA bioinformatics services, as defined, to contract with a licensed clinical laboratory to process biological specimen collection kits, except as specified.


• The bill would require an entity that provides post-CLIA bioinformatics services to employ a specified expert for approval of the algorithms used in the interpretation of the biological data of a customer.


• The bill would further impose on an entity that provides post-CLIA bioinformatics services specified privacy, recordkeeping, disclosure, and audit requirements, and would impose specified duties on the State Department of Public Health in that regard.


• The bill would also subject those entities to specified provisions of existing law prohibiting unearned rebates, refunds, and discounts, a violation of which constitutes a crime.


• Because the bill would expand the scope of a crime, the bill would impose a state-mandated local program. The California Constitution requires the state to reimburse local agencies and school districts for certain costs mandated by the state. Statutory provisions establish procedures for making that reimbursement.


• This bill would provide that no reimbursement is required by this act
  for a specified reason.

We will see if this bill passes. But if it does, it may mean the end of Auctioning Off Genome Scans......

Which puts this technology right in line with the rest of healthcare, where it is ILLEGAL/Ethical Violation to discount, rebate, guarantee or refund.

The Sherpa Says: In my mind, this argument seems to be: "You are healthcare or you are Novelty. You cannot chose both" If this law passes it would be in line with the government of California as well as New York......

Surprise, Surprise, Genetic risks in Diabetes and Melanoma!

The Annals of Internal Medicine has a great article this week on genetic risks so does the ACMG Genetics in Medicine Journal for May.


The take home point is something which people may find interesting and it is something I feel is very real. I have begun to think that these Genomic tests act a lot like a placebo. They often don't add anything clinically. Hell, they may not even do anything to guide therapy (Pgx and high penetrance genes aside)


But they often act psychologically, either for good, or for bad.


First in the Annals of Internal Medicine; People have been arguing that perhaps testing only ONE snp and representing its risk is for disease is silly and in fact taht the REAL way to represent these risks is with a multiSNP panel. In Fact, this is what has been perhaps the selling point of some DTC genomics companies.


Even with this possibilty, the CDC and NIH are not satisfied with what the DTC companies are representing as risk.......Psychologically, that could be devastating to the would be consumer. Lack of public trust is a BIG DEAL......even in this era of lack of trust in everyone.


So let's look at what a multiSNP panel would do. The deCode/DNADirect T2 test looks at TCF7L2 (rs12255372), CDKAL1(rs7756992), PPARG( rs1801282),, CDKN2A(rs564398)





The Annals did a scientific study looking at these SNPs as well as loci including HHEX (rs1111875), IGF2BP2 (rs4402960), SLC30A8 (rs13266634), WFS1 (rs10010131), CDKN2A/B (rs564398, rs10811661) and KCNJ11 (rs5219).





What did they find?

The GRS significantly improved case–control discrimination beyond that afforded by conventional risk factors, but the magnitude of this improvement was marginal: Addition of the GRS increased the AUC by only 1%.






This is why I love science. The Journalists and Public read the word SIGNIFICANTLY different than I. In this case, statistical significance (which this word connotes) is essentially a useless guidepost. Becaue the enhanced effect was ONLY 1% better rates of prediction.....But my guess is that a crafty PR propaganda firm would USE the word Significantly in a far different way to manipulate the public.






Hence, placebo effect by hyped study results. The result? Buying more tests? Ask DeCode or DNADirect about that one.







But in this case if the results caused a patient to lose weight and exercise, that would be great. I am STILL waiting for that study.






It seems though as if the genetic risks gods have answered my request, at least with melanoma.

What if we could identify risk and the clinical or medical things we could do to prevent offered no benefit?






Hence the case with testing for Melanoma risk genes. Myriad said that Melaris testing would cause a patient to get more skin exams which would ultimately "reduce incidences and detect melanoma earlier." The data for that are not there to make any judgement on its ability to reduce disease.

But what about the psychological effects? Well, in an article to be published in May's edition of Geneitcs in Medicine it turns out that people with a family history of the skin cancer melanoma show reductions in anxiety and depression after getting tested for a high-risk gene mutation.

Over one hundred patients with a FAMILY HISTORY of melanoma were offered testing for CDKN2a, yes one of the diabetes genes.....







Myriad has this test and it is called Melaris. It turns out ONLY 25 got tested.....so this is not exactly what I call a very powerful study...nonetheless....patients who found they carried the high-risk gene had a significant reduction in scores for anxiety at two weeks after testing. Depression scores were also decreased, and remained so at one-year follow-up.






The Australians are particularly sensitive about Melanoma and it turns out it this case like to "feel" proactive.







Hence, Placebo effect, as we aren't sure if clinical exams prevent disease. But also perhaps some therapeusis if the begin to start wearing sunscreen. Something you hoped they would have done based merely on their family history...If the risk was ever conveyed to that member







The Sherpa Says: Placebo effect works, we know this in medicine. The real question is whether it is worth 99,000 USD.......or even 399?

The Genome App Store.....

I was reading an article in the economist the other day, a good article mind you. It turns out that Drew Y was correct. It appears that the hype for DTC Genome scans is waning......

That being said, in the article George Church says something which sticks with me:

"Dr Church even argues that genome sequencing “will in effect be available free” because companies will give away sequencing to sell other services, such as genetic interpretation—much as mobile operators “give away” handsets to get customers to sign up for lucrative service plans. And when this happens, he reckons, “it will be just like the internet: once all this information is floating around, a lot of creative people with PCs will nose around and develop applications.”

Daniel over at Genetic Future put this out there. But it seems that the only discussion is about when the APP store will come to be.....Not if and how....

When I imagine genome applications for the next 5 years, the majority revolve around researchers......Why? That's where the market is. If you want to look at what Google thinks is a cool app, just look at the 23andMe site. They are doing precisely that. Developing apps.

I think GenomeApp is a good name here. Genome Tools on the other hand is a horrible name here. Why? Well, most of these things aren't really tools. They don't help you get work done by expending less energy.....

A programmer friend of mine tells me a story about the guy who created a facebook App which tells you your IQ. You answer some questions and voila! IQ score. It turns out that this guy just picked random questions, didn't scientifically validate his design and put out an APP, which tells EVERYONE, that they're a genius.

It turned out millions of people took the APP......Millions

Is that what we can expect from the genome APP store?

“it will be just like the internet: once all this information is floating around, a lot of creative people with PCs will nose around and develop applications.”

Yeah, just like the IQ App.....

What is the DTC SNP app that is being sold right now? Risk prediction about heart disease, stroke, diabetes etc....

But, it turns out that these "APPs" add absolutely nothing to the clinical predictive models for these diseases......

That being said, there are some non-medical uses that people find excellent. These predominantly lie in the realm of ancestry tracing. A very cool and perhaps useful tool. But this APP took years to create, not just a bunch of programmers hacking around and making "APPs"

I think George is a little naive here, or he seriously thinks it is ok to create Crap APPs and put them out there for consumption.

In this case, I wonder if these new Genome disease prediction APPs will be just as good as the IQ app....

The Sherpa Says: Everyone is free to make crap, everyone is free to buy it. But it is also the responsibility of the public health officials, press, medical and scientific communities to scream from the rooftops when the Crap could be harmful. Rather than play the game "All Ships Rise with the Tide"