Sunday, March 27, 2016

An Analysis About What?

In a recent article in JAMA Oncology there is a study about the alleged usefulness of PSA tests. Simply stated they did the following:

1. Examined 18 variations on a theme, namely PSA levels and duration between tests.

2. Costs associated with procedures resulting from the tests.

3. Determined the cost of each life year saved compared to not testing.

The result if the QALY measure, that  generally useless, essentially banned by the ACA from use in any medical care. But alas, here it comes.

Their conclusion is simple:

For PSA screening to be cost-effective, it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease.

We know that PSA is problematic. But we also know:

1. That PSA testing makes sense if and only if we examine it over time, specifically over a 5 year window of annual data at the very least. It goes up and down and it changes as the prostate grows. So like fasting blood sugar it all too often just tells us what happened last night.

2. Family history is also a significant factor. If you have no relatives with PCa then you have a good chance that you will not have it. Bayes to the rescue. But the corollary is not really true. Namely if you have a first degree relative you may have an increased risk. To be determined.

4. PCais not simple. It is a complex genetic disease and it is highly heterogenetic in its spread. 

5. PCa is all too often  not that serious but when it is it really is. Yet we do not know that boundary.

6. Calculating QALYs without taking the above into account is really really bad in my opinion.

Thus the more of these results that get published the more we confuse the patient. We just do not really know. Remember, if all else fails, listen to the patient. Let them be part of the informed decision process and please keep the QALYs in the UK whee they belong!

Forces on the Nano Scale

The book by Butt and Kappl is a must have for anyone working in the field of surface interactions, especially the developments of nano technologies. The classic work was done to understand colloidal solutions and their dynamics, often lasting many decades, and also the issue related to van der Waals forces. The development of the quantum understanding expressed in London forces as well as the various varieties developed over the past few decades are both highlighted and detailed in this work.

The first major Chapter is on van der Waals forces and its derivatives. The authors have a wonderful style combining simple explanations along with detailed but readily understandable derivations. The clarity of the work is truly exceptional. One can almost see the Gecko feet adhering to the walls as they climb!

The Third Chapter details measurement techniques. Again the authors present the principles employed in a clear and readily understandable manner and then progress to explain the actual implementation.

They then move through electrostatic forces, capillary forces, hydrodynamic forces, and inter facial forces. All are explained simply and then in detail. They continue with such topics as friction and polymers surface energies.

Although this is presented as a text book it is truly an exceptional reference work because of both its breath and depth.

My only issue is that perhaps they could have discussed some of the specific applications to nano materials. Specific materials such as nano Selenium where one tries to best understand the surface stickiness on the one hand and the bacteriostatic behavior on the other.

Overall this book is a necessity for anyone working in the area of intermolecular forces and their impact on adhesion and interaction.

Understanding Cancer Signalling

The book by Robert, the Textbook of cancer signaling, is one of the best works on cell signaling available as an introduction. As the author indicates in the preface the intent is for oncologists to obtain a better perspective of the issues associated with the wealth of new therapeutics as well as some of the key issues behind their introduction. For the most part the work is a high level, but not simplistic, organization and presentation of the key signaling paths. The general approach is to detail one class of paths after another and describe in excellent detail the elements of those pathways and how they function. Then there is a brief exposition of how aberrations in the pathways lead to oncogenic effects and then a discussion on pharmacological possibilities. This is done chapter by chapter.

The author’s collection and organization is superb and it presents the reader with an organization that they can come back to time and time again. He covers kinases, including MAP and other elements, cytokines, TGF, G protein, Wnt, Notch, and Hedgehog. He also discusses integrins and a collection of adhesion molecules. There is a discussion of B and T cell issues including Toll Like receptors and lymphocytic receptors. He ends with excellent discussions on cell cycle control as well as apoptosis.

The Appendices are superb summaries of DNA control, gene expression and protein activity. Overall this is a book that should be on the desk of almost every oncologist and it is an excellent summary for those involved in pathway analysis and their implications.

The most important elements of the book are the author’s organization and integration. It is simple, straightforward and touches on all the current elements under consideration.

This is not a book for the specialist but it is worth reading by those deeply involved in that work to see haw one person who truly understands the depth and breadth sees it structured.

On the side of a critique, and this is hard given the superb effort displayed, issue such as epigenetic factors should have gotten some bit of discussion. Specifically the issue of methylation and miRNA silencing need to be integrated into the overall signaling fabric. However that would clearly have extended and expanded the work

Also the reader should not look at this as a reference book, it was not intended as such.

Finally my only one negative is the lack of an Index. That most likely is a publisher problem and not the author’s problem. The lack of an index is not that serious since the author has organized the book so well it is almost not necessary.

I would strongly recommend this book for anyone seeking to learn pathway issues in cancer and those who are deeply involved already. The logical wholeness of the work is worth understanding by all.

Friday, March 25, 2016

The Three Horsemen

In a set of recent JAMA Viewpoints three of the key players in the delivery of the ACA are giving their updates on the progress of the bill.

First is the assessment from the one who seeks to just pass on when he turns 75 I believe[1]. His assessment is mixed but full of praise. What is most telling is his last set of comments. He states:

Even though the ACA is not a perfect bill, it has improved the US health care system. If venture investing is a trustworthy indicator and if additional reforms enabled by the ACA, such as more payment change and drug cost controls, are implemented, Americans can be optimistic about the future of the US health care system.

This single paragraph is in my opinion the most telling. First he admits the ACA is not perfect. Far from it. As we have already noted it has added some 15 million new participants costing the taxpayers about $15,000 per year per participant. This is more than Medicare participants who being older should have been costlier albeit having paid some 50 years’ worth into the system. The conclusion of efficacy is not justified. Second the grab to venture investing as a proof of success is truly mind blowing! There is no basis for this assertion. Why not indicate the rise of ISIS as well? Coincidence is not correlation is not a proof!

The second horseman is the fellow who brought us Meaningful Use and the EHR[2]. As we have seen since its inception the CMS mandated HER has in my opinion led to higher costs, less patient interaction, and less inter physician communications. The design in my opinion is fatally flawed by setting up islands of non-interconnected data elements with the patient nowhere to be found. As he states as a key step in his proposal[3]:

Third, Shift the Business Strategy From Revenue to Quality: Maximizing revenue continues too much to dominate the business models of health care organizations. That reflects short-term thinking. A better, more sustainable route to financial success is improving quality. This requires mastering the theory and methods of improvement as a core competence for health care leaders. It also requires that the CMS and other payers continue to unlink incomes from input metrics, such as “relative value units” for specialists’ incomes, which are not associated with quality and drive volume constantly upward.

Now as we have noted frequently the term Quality is in the “eye of the beholder”. Quality means what and to whom? The CMS has also promulgated mandatory “quality” measures. If one looks at them there is nothing more than a useless list of check marks adding costs and detracting from the delivery of services!

Now the third horseman. He was the strategists again on health care information. As he stated just after the ACA[4]:

The widespread use of electronic health records (EHRs) in the United States is inevitable. EHRs will improve caregivers' decisions and patients' outcomes. Once patients experience the benefits of this technology, they will demand nothing less from their providers. Hundreds of thousands of physicians have already seen these benefits in their clinical practice.

And how did that work out for us. More cost and less care. We have physicians becoming typists or if they can’t type hiring a third party to sit in the examining room typing away and interfering with patient-physician contact. The result, better patient care and lower costs, it does not seem so.

In his most recent paper he states[5]:

Given some Americans’ skepticism of foreign experience, home-grown examples may be more compelling. The Commonwealth Fund State Scorecard suggests that

(1) if US health spending per person averaged the same nationally as among the 5 lowest-cost states (Utah, Arizona, Georgia, Idaho, and Nevada), an estimated $535 billion (approximately 20%) less would have been spent on personal health services in 2014;

(2) if rates of health insurance coverage averaged the same nationally as among the 5 areas with the highest rates (Massachusetts; Vermont; Hawaii; Washington, DC; and Iowa), an estimated 20 million more Americans would have been insured in 2014; and

(3) if the national levels of mortality amenable to health care averaged the same as among the 5 states with the lowest rates (Minnesota, Vermont, New Hampshire, Utah, and Colorado), an estimated 77 000 fewer deaths would have occurred in 2014.

Let’s look at the above and examine it for facts. First the states of Utah, Nevada, and Arizona have high Mormon populations. Mormons live health life styles. So perhaps it would cost less. Georgia just has less access.

Second, Massachusetts has world class hospitals that do leading edge care. Idaho does not. Vermont is a socialist state in many ways and people pay for that. Hawaii always has high costs, buy a gallon of milk!

Third, look at the demographics of the states with lowest mortality. I reside part time in New Hampshire. It soon will see a rise as obesity takes its toll but for the most part it is rural and of modest income.

Frankly in my opinion this type of sweeping ad hoc propiter hoc argument is baseless. One must ask why. But that does not seem to be in the vocabulary.

It is worth reading the comments of these three who played so much of a role in what has happened. This is the left wing of medicine, yet they managed in my opinion to set the agenda for the next generation, and the cost may be overwhelming.

Then of course one asks who is the Pale Horse?

Thursday, March 24, 2016

Doing What You Were Not to Do

In a recent Healio piece they describe a study evaluating QALY on PCa. This was frankly expressly prohibited by the ACA for any service provided thereunder. But the cat is out of the bag. The study states:

Under selective therapy, men with lower Gleason scores (< 7) and clinical stage cancer ( T2a) would only receive treatment after clinical progression. All other cases underwent contemporary treatment practices. Key study endpoints included life-years (LY), quality-adjusted life-years (QALY), direct medical expenditures, and cost per LY and QALY gained. Researchers evaluated cost-effectiveness as willingness-to-pay thresholds ranging from $50,000 to $150,000 per QALY. When compared with no screening, all screening strategies increased LYs (range, 0.03-0.06) and costs (range, $263-$1,371). Costs ranged from $7,335 to $21,649 per LY gained.

 Not really clear what was concluded. Was the cost low compared to the benefit? They conclude:

“Our work adds to the growing consensus that highly conservative use of the PSA test and biopsy referral is necessary if PSA screening is to be cost-effective,” Roth and colleagues wrote. “Among the strategies considered, less frequent screening and more restrictive criteria for biopsy resulted in greater chances of PSA screening being cost-effective — particularly when combined with selective treatment strategies that do not immediately treat low-risk, screen-detected cases.”

 This of course is studying on the basis of past practises and having not a clue what causes or differentiates the disease.

The Cost of the ACA

The CBO has a report describing the anticipated costs of the ACA, exclusive of Medicare for those who have paid in and are over 65.
We depict this above. It will soon exceed $200B annually and that is for an increase of some 14-15 million people. That amounts to an insurance premium of some $15,000 per person enrolled! Now the Medicare participant over 65 has paid in some 50+ years worth at 3% of their gross income plus some $2,400 per year plus a Medigap plan and a Part D plan costing an additional $4,500, plus a deductible, at a total in excess of well above $7,500. That is in addition to what they paid for 50 years!

So who are these people. Read the report and moan!

Tuesday, March 22, 2016

Why People Buy Apple Computers

For the past few weeks, yes weeks, I have been struggling with a dying W7 computer. Each death is different. In this case it was a result of what we think is registryoma, a malignant condition in the Microsoft Registry. We all know that Microsoft has designed this devilish system to control its world but one small base pair mismatch and if you think melanoma is bad try this on for size. There is no immune therapy available and there is not way to block the pathways.

The first symptoms are insidious. Google desktop stops. It just disappears. It was akin to a small mole, just a small change, just a little sensitive. So you do a work around. Then Quick Books fails. The mole starts to bleed. Maybe I scratched it, denial. Another work around. I will do my books on another machine. No problem. Put another bandage on it, how bad can it be.

Then the web systems fail to connect. No problem I can use Filezilla, another work around. It is another mole popping up where there was none before. I do not see lungs becoming engorged with metastatic patches.

Then I try Skype. Dead. It will not even load. It has spread to the brain. The patient does not know it yet. But Office is not loading properly, it freezes up all the time. Firefox has to be loaded 2 or 3 times before it starts. The patient has a seizure.

At this point  I would say the patient is a goner! Well I got another machine. Started all over again. New patient, left the old one in the basement. Not totally dead but it is hospice care for the dying!

Microsoft has with its Registry invented a malignancy that makes cancer seen benign. It starts slowly and then spreads and infirm the "patient" and the user. There is no cure, just put the old guy in a hospice and let him die. Kind of like the ACA approach. Thanks Microsoft, you make cancer research looks trivial!

Monday, March 7, 2016

Spy vs Spy

Ad Blockers have become a common thing. I use Badger on Firefox. One can see masses of white space where the ads were before being blocked. I now see that Wired senses the ad blockers and then blocks the page. Cute game, but I just switch to somethi9ng else.

The worst of these techniques is the pop up video, silently I work, check out a headline on Feedly and then WHAM! Blasting video. Now stopped by Badger.

Do these people really think that if I accept the ads I will in any way be persuaded. Rather to the contrary.

How do I find things? Well look at Lookeen, I had an indexing problem. Most likely some Microsoft update on W7. Killed Google Desktop. So I searched Google for an alternative and got a better result. Did I ever see them in an ad? No. Would I have responded to an ad? No.

Marketing folks really do not understand the consumer dynamic. Pity!

Wednesday, March 2, 2016

Great Product!

I have never endorsed any products before but when my Google Desktop crashed and would not reboot I panicked since my life depends on indexing my some 300,000 files! So after a few tries I stumbled on Lookeen, a German company, and for about $50 you get a fantastic indexing system. It is one of those simple things that you find a better part each time you use it. It is what Google Desktop could have become.

Moreover their customer support is fantastic! Real people answering real questions to make the experience better. So for any of you who want a great indexing system for a PC I would strongly suggest you try them out! No disclosures to make here, just that when one relies on a good indexing system and the only one you had is no more it is a God send to get this one! Hope they do well.

Tuesday, March 1, 2016

How Stupid is the USPTF?

First they did away with mammograms. Women went ballistic. Then they did away with PSA tests. Men were silent. Now they are doing away with vision testing for the elderly. At least the JAMA folks complained.

The USPTF states as of today:

The U.S. Preventive Services Task Force released today a final recommendation statement on screening for impaired visual acuity in older adults. The Task Force concludes that the evidence is insufficient to make a recommendation for or against screening in older adults without reported vision problems within a primary care setting.

In contrast JAMA states:

In 2009, the US Preventive Services Task Force (USPSTF) concluded that there was insufficient evidence to warrant recommending visual acuity screening of older adults. A recent update, published in JAMA,1 reaches the same conclusion. How (one might ask) can that be, especially as the USPSTF also concluded that impaired vision is common among elderly adults and that the major causes of impaired vision that the recommendation targets—refractive error, cataract, and age-related macular degeneration—are prevalent among elderly individuals and responsive (often dramatically) to clinical intervention? 

It appears that these medical wizards always come up with recommendations that impair health and reduce costs. Remember we said seven years ago that this would happen!

Have any of these brains heard of ARMD, dry or wet, it leads to blindness! Any second year medical student should recognize drusen on a retinal exam.  Did these folks ever do one in their life?