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Old 12-13-2012, 01:29 PM   #16
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Sounds like the Insurance companys are making hay while the sun shines. If the major portion of the bill is not even effective, it seems like they'll get us riled up enough to help them keep the costs inflated. Sure helps them, just a thought.......
You do realize that the companies you are speaking of are regulated by each state in which they operate by a state government agency and that each premium increase that is implemented must first be approved by that government agency of that state that has a sole purpose of protecting it's citizens? Right? These evil insurance companies cannot increase prices willy nilly because the CEO wants a new swimming pool? Before you ever see your bill, a government official has approved it.

Premiums that you pay are based on past and expected claims experience, as well as fixed costs. Past claims have not changed. Fixed costs have not changed. What is pushing up prices even faster now is the additional coverage that is being forced by Obama Care. We're seeing prices right now that we would not have seen for probably 6+ years without Obama Care.

In my personal opinion, we'll have a single payer system within a decade. I believe the private health industry has screwed itself by not fighting Obama Care.
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Old 12-13-2012, 01:37 PM   #17
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You do realize that the companies you are speaking of are regulated by each state in which they operate by a state government agency and that each premium increase that is implemented must first be approved by that government agency of that state that has a sole purpose of protecting it's citizens? Right? These evil insurance companies cannot increase prices willy nilly because the CEO wants a new swimming pool? Before you ever see your bill, a government official has approved it.

Premiums that you pay are based on past and expected claims experience, as well as fixed costs. Past claims have not changed. Fixed costs have not changed. What is pushing up prices even faster now is the additional coverage that is being forced by Obama Care. We're seeing prices right now that we would not have seen for probably 6+ years without Obama Care.

In my personal opinion, we'll have a single payer system within a decade. I believe the private health industry has screwed itself by not fighting Obama Care.
Well the private insurance industry has not done well so far protecting us with Wealthcare instead of Healthcare, however maybe a new way of doing things maybe better. As to your reference to regulation, it sure worked well with the banking industry and wall street. Just an observation.......
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Old 12-13-2012, 02:25 PM   #18
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Well the private insurance industry has not done well so far protecting us with Wealthcare instead of Healthcare, however maybe a new way of doing things maybe better. As to your reference to regulation, it sure worked well with the banking industry and wall street. Just an observation.......
Regulation with the banking industry and wallstreet was just fine until the government loosened the requirements. The LACK of regulation is what caused the problems. The insurance industry was not tied to those changes. It's as tight now as ever. It's also regulated on a state by state basis at more of a local level than the federal government, so all 50 state controlled Department of Insurance are in cahoots to allow the evil insurance companies to rape and pillage... Your personal negativity toward the financial industry and big business does not make them all evil.

What exactly is "Wealthcare"?

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Old 12-13-2012, 03:06 PM   #19
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however maybe a new way of doing things maybe better.
If by a new way, you mean 3-6 month waits after your doctor orders a CT scan or 9 months wait for a mammogram, then we are probably headed for a new way. I recently posted an article where a world health watchdog organization showed the U.S. was number one in the ability to get recommended tests and care in a short period of time. Our system is often belittled because of poorer healthcare outcomes than many socialized healthcare countries. But we are a much larger country with a much larger diversity both racially and economically, and we have one of the most sedentary lifestyles in the world - especially among the lower socioeconomic groups. But when it comes to getting care quickly when you need it, no one comes close to the U.S. - whether you have health insurance or not. You will probably get your "new way". Come back in a few years an let me know how you like it.
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Old 12-13-2012, 03:17 PM   #20
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Regulation with the banking industry and wallstreet was just fine until the government loosened the requirements. The LACK of regulation is what caused the problems. The insurance industry was not tied to those changes. It's as tight now as ever. It's also regulated on a state by state basis at more of a local level than the federal governement. Your personal negativity toward the financial industry and big business does not make them all evil.

What exactly is "Wealthcare"?
I've found that life makes it difficult for one to serve two masters. Either we'll have a system that is geared towards health or one thats geared towards profit. The system that we had clearly wasn't working and there was nothing being done until Obamacare or the Affordable Heathcare Act or whatever its called these days. So now I guess we'll all see what comes next. So no need to stress, good, bad or ugly we're moving towards something new and we are all in it together. Personally, I've never paid a thousand dollars plus a month for heath insurance, however my healthcare premiums over the last 25 + years has risen almost every year. I participate in a private company ran system that is administered by a third party, ergo my company pays huge sums of money for tens of thousands of employees and their families. 25 years ago our family premiums were around $55 to $65 a month for heath, vision, and dental. Now they are about $500 a month. Fortunately for MY family I can afford to pay more, but there are many others who cannot. Anyway I apologize for interupting your thread, I used to frequent this forum a while back when Patrick had it, and I was looking for news about that C7 Vette!! Anyway I'll keep on lovin' Chevy cars and bass guitars...........Peace.
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Old 12-13-2012, 03:24 PM   #21
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I've found that life makes it difficult for one to serve two masters. Either we'll have a system that is geared towards health or one thats geared towards profit. The system that we had clearly wasn't working and there was nothing being done until Obamacare or the Affordable Heathcare Act or whatever its called these days. So now I guess we'll all see what comes next. So no need to stress, good, bad or ugly we're moving towards something new and we are all in it together. Personally, I've never paid a thousand dollars plus a month for heath insurance, however my healthcare premiums over the last 25 + years has risen almost every year. I participate in a private company ran system that is administered by a third party, ergo my company pays huge sums of money for tens of thousands of employees and their families. 25 years ago our family premiums were around $55 to $65 a month for heath, vision, and dental. Now they are about $500 a month. Fortunately for MY family I can afford to pay more, but there are many others who cannot. Anyway I apologize for interupting your thread, I used to frequent this forum a while back when Patrick had it, and I was looking for news about that C7 Vette!! Anyway I'll keep on lovin' Chevy cars and bass guitars...........Peace.
Of course costs increased in the past 25 years. Have you considered the costs of new technology and medical care? What do you think health care pays for?

What did a Corvette cost 25 years ago compared to today? Try about a 140% increase. Health care hasn't trended to bad compared.

You should be thankful your employer is paying the majority of your premium. Instead you complain like it's an entitlement.
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Old 12-13-2012, 03:56 PM   #22
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Was I dreaming or did the President say that his health plan would lower costs?
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Old 12-13-2012, 04:06 PM   #23
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And I've been licensed and sold the products we are discussing for the past 17 years, licensed with multiple health insurance companies selling both individual and group plans in two states.

I think I'll stick with my expertise.

The transformation is taking place right in front of your nose.
http://www.youtube.com/watch?v=f3BS4C9el98

By the way, rate increases in the past 24 months, since the time the Affordable Health Care Act was passed, have been more than double those of previous years. Why is that? You can't provide MORE coverage for LESS money. You can't remove exclusions and charge less. You can't keep your kids on the plan until they retire and charge less. Only a liberal would fall for the political lies.
Hmmm...if what you are writing is true, I'd say after 17 years it's about time for you to find another vocation.
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Old 12-13-2012, 04:10 PM   #24
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Hmmm...if what you are writing is true, I'd say after 17 years it's about time for you to find another vocation.
I'm diversified in many other lines besides health, or I'd agree with you. Majority of my income is from commercial liability and personal home and auto. No way in the world, I'd expect to survive selling only health coverage.

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Old 12-13-2012, 04:11 PM   #25
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I'm diversified in many other lines besides health, or I'd agree with you. Majority of my income is from commercial liability and personal home and auto. No way in the world, I'd expect to survive selling only health coverage.


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Old 12-13-2012, 04:12 PM   #26
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Was I dreaming or did the President say that his health plan would lower costs?
That's because it will be "free" when it becomes single payer.

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Old 12-13-2012, 04:35 PM   #27
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That's because it will be "free" when it becomes single payer.



Well, I have a bit of a different take...and I too am in a way employed in the healthcare industry...though at its base. If you look at organizations like Kaiser Permanente, UPMC Healthcare System, The Mayo Clinic, The Cleveland Clinic, and Harvard Partners Healthcare System I believe you will see the future of "commercial" healthcare. These are systems with very large member bases, tied to state of the art hospitals where the physicians are effectively on a salary and the procedures have a fixed cost. They have managed to keep their yearly increases to their subscribers well below the national averages while not sacrificing in any way the care they provide. More and more health insurance companies are building their own hospitals with the intent to mimick these organizations...it is, to be short, the only way they can/will survive in what is becoming a competitive marketplace. And the competition will be driven by Obamacare (government backed healthcare) and the industry itself. In due time you will see the cost for healthcare plateau and with any luck, begin to decline. Not unlike car insurance (which saw the rise in rates out of control back in the late 60's and into the 70's) as more competition came forward the cost for auto insurance stabilized and now people can shop around if they don't like the price they are paying. You will see the same thing happening in healthcare insurance...no doubt.
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Old 12-13-2012, 04:41 PM   #28
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Of course costs increased in the past 25 years. Have you considered the costs of new technology and medical care? What do you think health care pays for?

What did a Corvette cost 25 years ago compared to today? Try about a 140% increase. Health care hasn't trended to bad compared.

You should be thankful your employer is paying the majority of your premium. Instead you complain like it's an entitlement.
Interesting analogy the corvette has evolved in spite of EPA regulations and costs are extremely competitive regardless of the increase in technology through good business practices. The same good business practices could be applied to health care. My corporation could be better served spending more of its profits towards growing the business hiring more people to contribute to creating a more competitive business and lowering unemployment. . Not an entitlement but cooperation. More money in the coffers better health care for all. Pharmaceutical companies advertise drugs that promote a better sex life or something that will grow hair. What a waste. I never hear them speak on developing technology that prolongs life instead of erections. That stuff sells though.
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Old 12-13-2012, 05:01 PM   #29
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Was I dreaming or did the President say that his health plan would lower costs?
You weren't dreaming but the President was.
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Old 12-13-2012, 05:30 PM   #30
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I never hear them speak on developing technology that prolongs life instead of erections.

Not at all true. Human DNA Sequencing is a game changing technology that will impact you in your lifetime.



Home News Clinical Sequencing News


Q&A: Sharon Plon on Baylor College of Medicine's First Year of Clinical Exome Sequencing

December 05, 2012




By Julia Karow


This is part one of a two-part interview. Click here to read part two.

Name: Sharon Plon
Age: 57
Position: Professor, Department of Pediatrics and Department of Molecular and Human Genetics; member, Human Genome Sequencing Center, Baylor College of Medicine
Chief of Cancer Genetics Clinic, Texas Children's Hospital

Experience and Education:
Fellow in medical genetics, Fred Hutchinson Cancer Research Center, University of Washington, 1990-1993
Postdoctoral fellow, National Cancer Institute, 1988-1990
Residency training, internal medicine, University of Washington, 1987-1988
MD and PhD from Harvard University, 1987
SB degrees in chemistry and chemical engineering, Massachusetts Institute of Technology, 1980 and 1981

As a member of Baylor College of Medicine's Whole Genome Laboratory management committee, Sharon Plon has been a leader in establishing Baylor's clinical exome sequencing diagnostic test, which was launched last November.

She is also one of two principal investigators for Baylor's grant under the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Project program (CSN 2/1/2012), which will explore exome sequencing for childhood cancer patients.

Since Baylor's WGL started offering its clinical exome test a year ago (CSN 11/16/2011), it has received more than 600 samples and issued about 400 clinical reports.

At the Personal Genomes and Medical Genomics meeting at Cold Spring Harbor Laboratory last month, Plon gave a report of the lab's experience after its first year of testing. Clinical Sequencing News caught up with her during the conference and the following is part one of an edited version of the interview, which provides an overview of the test. Part two, which will appear next week, will address how the lab handles interpretation and reporting for the test.

--------------------------------------------------------------------------------

How has demand for the test developed over the last year?

There has been a big upsweep in the last couple of months, so we have gotten several hundred samples just in the last two months or so. The awareness is clearly going up; I think that people are starting to hear about successes, certainly many of the physicians who have sent us samples have sent us more than one, and I think that as physicians are having diagnoses made, they are of course much more motivated to have other samples come in.

The other thing is, a lot of these patients are only seen periodically often physicians will see them once a year and as patients are coming back into clinic, they are now being told that this is a new test that's now available, and they get ordered at that time.

What types of doctors have sent you samples, and who are their patients?

Over 50 percent are from clinical geneticists ordering the test. The next largest group is pediatricians some of these may have sub-specialty training and then neurologists. Over 85 percent of the initial 300 samples were from pediatric patients, and about 15 percent were adult.

Samples came from all over the country. Clearly, Baylor-affiliated hospitals have submitted samples, but not the majority of the samples. Baylor is a large academic testing lab; there are many different hospitals that use Baylor as their genetic testing lab, and many of the same physicians are now sending samples for exome sequencing.

The most common diseases patients present with are neurologic phenotypes. By that I mean children who have severe learning disability, autism, epilepsy, or unexplained seizures.

I think the difference between our experience and others is that since we launched it as a clinical test, any physician who feels that it's helpful to their patient can submit a sample. So, for example, the first of my patients I submitted was a child with severe leukemia who had unexplained toxicity to one of the chemotherapeutic agents, and we had a question whether that could be genetic in origin. It's really up to the individual physicians, although clearly, parents of children with intellectual disability really want an answer, and a large proportion of those children have been otherwise undiagnosed.

Have you obtained reimbursement from health insurance for the test?

We handle it as we do any other test. When the sample comes in, we go through an insurance verification. There are a small number that get held up at that point, but this test is really in line with the cost of other genetic tests the institutional price is $7,000 it's non-invasive, and many insurance companies have covered it.

In a nutshell, how is the exome test conducted?

We focus on blood samples, although we will take DNA from fibroblasts or other tissues if that's appropriate. We use a capture platform that is commercially available [from Roche NimbleGen] but that Baylor helped to optimize, so we have had a lot of experience with it in our research sequencing. We use Illumina as our sequencing platform; we started with a GAII for a very short period of time, then we switched to a HiSeq, then to a couple of HiSeqs, and now we are looking to use even newer equipment, the HiSeq 2500, for some of the indications where you really need a fast turnaround time. The sequencing is done to a quite deep coverage. We aim for 95 percent of the target at 20x or greater coverage, and our experience over the last 200 clinical exomes is that we normally hit around 97 percent.

In addition, we recently added the mitochondrial genome to our test.

We currently confirm positive results by Sanger sequencing. I think that over time, we will all become more comfortable with which mutations are correct 99.9 percent of the time, and which aren't. And also, we do Sanger testing to confirm the parental inheritance, so we are going to do it anyway. For the majority of the mutations, we will probably continue to do it for the major findings in the report.

We also use a SNP array that was really introduced as a QC measure. It's a way to confirm that the mutations that are read from the sequence match the genotype calls from the array. If we do see a large copy number change, we will report it out. But I think that patients should have a high-quality diagnostic array before having exome sequencing. We do not require it, but as a clinician, I highly recommend it you get the result in a couple of weeks, it's less expensive, and also, it can be very helpful. For example, if the patient has a deletion of part of a gene, and then the exome finds a new mutation in that same gene, you could make a diagnosis of a recessive condition with those two pieces of data together.

How do you think Baylor's clinical exome test differs from others?

One of the things that varies among them is whether they do the exome on a trio or just the patient.

We have put a lot of work into using the academic resources at the medical school in the reporting. For example, I just got an e-mail yesterday from the lab, there was an unusual variant in a cancer gene, and they wanted my opinion about that variant, whether I think it should be reported. I think we are doing a lot of intellectual curation. We are really trying to use the resources of the school to provide the best information to the doctor, as opposed to some of the tests that provide longer variant lists upfront, for some of the physicians who want to do more of the interpretation on their end.

Our reporting is very much focused around what the patient's problem was. So what we report out actually varies with the patient, whereas there are some systems where the report is essentially the same, independent of what the patient's problem is.

You said the test has a 25 percent diagnostic yield. How does this compare to existing genetic tests?

Actually, very favorably. If you look at the early data using arrays as a diagnostic test, it was about 10 percent, and people were very impressed by that. Now we have better arrays, maybe it's about 15 percent, in a child with, for example, intellectual disability. But Christine Eng, the lab director, actually looked at all of the tests we offer, and the majority are in the 5 percent to 20 percent range, most holding around 10 percent positive results. So we have been quite impressed.

And I think it's important to realize that this is version 1. For example, we have now added the mitochondrial genome to our test. We and others are certainly aware that the exome doesn't cover every single clinically relevant gene, so we are looking at using other chemistries to try to sequence those difficult-to-sequence exons and to generate a more polished exome. There is going to be constant improvement.

So the question about the remaining 75 percent of patients, is it simply if we did an even better job with the exome, we would find a mutation? A number of those patients may have methylation abnormalities, or they may have abnormalities in non-coding regions. And until we all just do more testing, we won't have an answer.

Can Baylor's test be ordered for a healthy individual?

That's actually something we discuss quite frequently. I think that it surely could be ordered by a physician for a healthy patient. In our focused report, they would predominantly get incidental findings, autosomal recessive carrier status and some pharmacogenetic loci. There are other tests designed for healthy adults where the focus is more on pharmacogenomics and things like that.

I think we have had one or two healthy patients, and we have certainly talked about expanding that. And looking at, if we are going to focus on more of a screening-type test for healthy adults, what should we do to make a better test for that scenario?

What have been the greatest challenges in the first year of running this test?

It's been an amazing year. At Baylor, there was a very large group of highly experienced people who came together and said, 'Let's get it done!'

I think the biggest challenge has probably been turnaround time, and trying to make sure that we adequately annotate and report out while dealing with impatient physicians who of course want a result for their patient. Because there are many MDs around the table, we all understand that feeling, but doing it right, especially when you are new, takes time.

Our turnaround time is about three months, and we have worked hard to get that down. Part of it is just having done more; we now have a much better database of frequent positives in the pipelines and things like that, we have gotten more feedback from the molecular diagnosticians of what annotation they need in the informatic pipeline to make their job easier in the end. That's been, probably, the biggest back and forth, between the people doing the reporting and the people creating the pipeline to try to get as much information as possible into the pipeline so that their job is easier at the end.
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