MEANINGFUL=MEANINGLESS

It occurred to me, as it might have to scores of others in the legion of medical care that there is something very disturbing going on. Now before we get ourselves in bunches, let me say, this only affects the physicians in very meaningful ways. (There, I’ve lost the majority of the readers). For those still hanging on, lets look at what is exactly going on.

Remember the Electronic Medical Records (heretofore mentioned as EMR or EHR interchangeably)? I’m sure you do. But here is the rub, When the powers that be, all comfortably seated in deep cushioned chairs on marbled floors designed the concept, they failed to understand the basic patient-physician interaction. After all their paradigm was based on the ICD and IPT coding mechanics buried within a sea of paper data within the vaults of the Centers for Medicare and Medicaid Services (heretofore called CMS). The digits when subjected to the rigors of algorithms would displace all worries. So using their best or only information, they (the powers to be) deduced that if all information could be inputted by the physicians directly into the digital format, why, then the CMS could make meaningful decisions, such as appropriate payments for services rendered. Rampant in that thought process like dust scattering from an ailing fantasy was the concept of cost-containment. After all the cost of healthcare was going up and usurping 18% of the Gross Domestic Product. “That could not be!” they cried. So the EMR “Meaningful Use” was invented. Some coddled the green fantasy as well, “Less paper invoice use would save the trees!” Nothing better than that, sliced bread, apple pie and gaia-hood all packaged in one.

The carrot placed upon the dying breed of physicians who really cared for their patients was, “If you implement an EMR in your medical practice, CMS would give you “X” amount of dollars. Doctors felt, “Hey why not. I get to digitize my medical records and have them available 24/7 to me for decision making.” A win-win concept they thought. “Everything on my little smartphone or tablet.” Not so fast, you graphene-loving-silicone-dependent gadget lovers, not so fast.

Along came an enterprising agency with the best ceramic wafers, bestowed as “the EMR provider” by the CMS, whose CEO had paid a significant amount of money in election campaigns, and won nearly half if not more of the software/hardware installations across the global field of healthcare in the United States. But the software was proprietary and therefore not easily, if at all interactive, with other software vendors vying for the same multi-billion-dollar pie (not in the sky). The doctor’s records could not interface with the hospital medical records nor with other physician’s and lo and behold silos developed within the software empires where dollars were raining down by the bushels. from millions into billions overnight, just like the tech-boom of 1999.

Physicians, oh yes lets not forget those “middlemen” as some called them, were stuck with thousands of out of pocket dollars in purchasing, implementing, training employees and themselves, losing hundreds if not thousands of hours that should have rightly been spent in caring for their patients. The reward after expensing a large supposedly reimbursable “X” amount from CMS they were shocked to realize that of they paid $30,000.00 for a system and $10,000 for implementation, the reimbursement was around $16,000.00 - $18,000.00. But, hey the Return on Investment would be the speedy reimbursement from CMS that would take a bite out of the Medical Revenue Cycle, and that, the physicians thought was worth the loss they were incurring. The only caveat was if you were tied to medicare for reimbursement for services rendered and you did not dive into the EMR business you would face a cut in payments also.

Not so fast Watson, CMS decided to implement the ICD-10 coding system and told physicians to take a loan for keeping themselves afloat during the governmental transition and delayed payments. Oh okay, but everything would be alright afterwards. No worries!

The stick followed the carrot in lock-step. And as we all know accepting money from a governmental agency is filled with a stack of papers that have to be signed, boxes to be checked, “Ts” crossed and “Is” dotted. The next hammer was a Medicare (CMS) Audit of all the physicians who had claimed the EMR bonuses. If the use was not “Meaningful” in the auditor’s opinion then doctor would have to return the bonus back to CMS. Oh and by the way, the auditors were outside agencies empowered to go and find out those that had not complied and these auditors for their efforts were to receive 20-30% of the returned bonus bounty. This might sound sarcastic, but the incentive for the auditors makes them slightly porous to the wild idea of “dinging” the doctors (agency theory) to improve their own bottom line (hey that’s human nature -  don’t blame me, I’s just pointing it out to you).

Meanwhile studies started tumbling down the express corridor that “EMR Meaningful Use” had not improved medical care for the patient at all. In fact patients began complaining (as if anyone was listening to them in the bureaucratic stronghold of CMS) that the doctor spent more time looking at the computer screen then at them. The doctors ambushed with costs, audits, denials of service, patient dissatisfaction, became disillusioned and depressed (over 54% if not more). They were told that their expertise was subpar to the algorithm based on some wide eyed, bushy-tailed 18-year old software engineer and may not based on decades of experiential reference. Oh no, the codes told the story and treatment had to be based on the codes or the rain of sparking embers from CMS would engulf the physicians into a spectacular conflagration. Care would be based on Costs from now on and more and more Societies and expert physician bodies mirrored the meme of this rapidly unfolding paradigm. 

The story goes on…

The fingers keep pointing at the patient - physician interaction and at the physicians. In one breath Healthcare costs ($3 TRILLION) are tied to care delivered by the physician to his or her patient. No where is mentioned the 800lb businessman/woman gorilla that loves to ransack the honey-ladened spread under the tent.     

Don’t get me wrong, there are a few bad (apples) physicians and other providers in the healthcare field that give a bad name to us all. But they are few and can be weeded out easily without destroying the best medical care in the world.

The answer… cometh soon.

TARGETING LUNG CANCER

Lung cancer is the second most common cancer in both women and men, eclipsed only by breast cancer in women and prostate cancer in men. ACS estimates 221,200 cases in 2015 with 158,040 related cancer deaths. It accounts for 13% of all cancer occurrences and 27% of all deaths related to cancer. Early diagnosis and treatment meets with cures although only 15% of the NSCLC are diagnosed early.

NSCLC treatment has mostly revolved around, surgery, radiation therapy and chemotherapy for the longest time. The marginal successes have had little impact on overall survival. Today the era of Molecular medicine hopes to change that paradigm.

Non Small Cell Lung Cancers are grouped into Adenocarcinoma (50%), Squamous Cell (30%) and Others (20%). Each subset carries its own characteristics of genetic mutations, although overlap is commonly seen amongst the groups.

Common known Mutations in Adenocarcinoma: 

1. Epidermal Growth Factor Receptor (EGFR) is the most common one and is present in 50% of the Asian patients and 10% in the non-Asians.
2. KRAS mutations in 25% of cases are less common among smokers and absent in Asians.
3. ALK and EML4 fusion is present in 2-7% of the NSCLC (mostly adenocarcinoma) non-smoker patients.

Targeted Inhibitors designed to target these molecular structures include:

1.              Erlotinib and Geftinb are most effective in cases with exon 19 deletion, exon 21 L858R, and exon 18 G719X. The Pan-Asia study showed a 9.6 months survival in gefitinib-treated patients, versus a 41% ORR with a median duration of response of 5.5 months for the carboplatin/paclitaxel chemotherapy group. (Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24. 362 (25):2380-8). However resistance is noted after one year of therapy with these Kinase Inhibitors. A specific mutation noted at the exon 20 T790M is found in the resistant cell lines. these mutations have been targeted effectively with another Inhibitor Afatinib with modest success. In the LUX-Lung Trial, results showed the Afatinib group’s progression-free survival (PFS) was 11.1 months compared with 6.9 months for those treated with pemetrexed/cisplatin chemotherapy regimen. (Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Jul 1)
2.          However Cetuximab a monoclonal antibody to EGFR noted to have activity in NSCLC (adenocarcinoma) without the EGFR mutation, later a post hoc analysis revealed that the EGFR mutation status conferred a better response rate.
3.          For patients with ALK mutations Crizotinib and Ceritinib have modest efficacy. Trilas showed response rates of approximately 50% to 60% with crizotinib. Response duration was 42-48 weeks. (Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28. 363(18):1693-703). (Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27. 370(13):1189-97).

In (Squamous Cell Cancer or SCC) NSCLC The demonstrated impact of molecular targeting is less clear since the targets have as yet to be clearly defined. in about 5% of SCC cases the EGFR, KRAS and ALK mutations are noted presumably from the mixture of cell types (adenocarcinoma + Squamous Cell) these patients after a Cisplatin based chemotherapy regimen show a 18% response rate to the small molecule targeted inhibitors such as Erlotinib, Afatinib. SCC is a well known entity that occurs secondary to dysplastic changes in smokers and other environmental toxins. These dysplastic cells have variable damage to the genetic structure early on. Further oxidative stresses to these dysplastic cell lines increases the genetic mutation burden and leads to cancer.

The following targets have shown success in SCC:

1.        Monoclonal Antibody PD-1 (Nivolumab) and (Pembrolizumab or MK-3475 an Anti PD-1) an immune checkpoint blockade in unselected SCC cases lead to a 16-23% response rate and disease control rates of up to 50%, especially with the PD-L1 over-expressers. Smokers seem to benefit from the anti PD-1 and PD-L1 checkpoint blockades. Anti PD-L1 agents currently in Phase i/II trials with encouraging early results include MPDL3280A (atezolizumab) showing a 25% improvement over Docetaxol in a head to head comparison.
2.        Anti CTLA-4 (Iplimumab) that restores downstream immune activation against the cancer has had limited success in SCC with Phase I/II trials in progress against advanced NSCLC SCC patients.

We have come a long way in securing newer targets to attack against Lung Cancer. The success will ultimately depend on the durability of the response in improving overall survival hopefully with improvement in the Quality of life as well. Combinations of molecular targeted therapy with Immune checkpoint blockade as well as Restoring Immune surveillance in limited disease lung cancer can be personalized to the patient in the future.

There are many other paths that have yet to be travelled...

Only the curious have, if they live, a tale worth telling at all - Alistair Reid

PHILOSOPHY OF PATIENT CARE

"There are more things in heaven and earth, (Horatio), than are dreamt of in your philosophy"

-Shakespeare



Cold or warm, tired or well rested, despised or honored, hated or loved, happy or sad, we all face life in its many varied forms. The trauma of existence is placated only by the moments of free thought, of fulfilled desire, of understanding. So what is in these many moments where life exists that makes us want more.

Turns out, if you have time to pay attention to little matters of time where true grit as true happiness lives, you might come away with that it is in seeing the joy in another’s face.

Nowhere is life more evident, more clear, more raw as in caring for another human in need. Physicians qualify in this realm more than in any other discipline.

Physicians live in a unique world of elation and despair. The wildly gyrating confines of this existence gives motive and cover to the mind of a physician. That one patient who finds cure from an interminable illness promises the healing for the many in despair. Each person is a life, each person a story, each person a face of society, brings with him or her a quality unique to humanity. No two individuals are alike. Therefore no two can be treated alike.

The former President Jimmy Carter just made news with a report from his recent cancer follow up MRI that showed complete radiological remission of the brain metastasis from the malignant melanoma.  His treatment included radiation therapy and Keytruda, an anti PD-1 immune therapy. There are several interesting and promising signs from this reveal. First, healing an individual and especially a former president at the age of 91 is worth noting. So age should not be a limit to proper treatment at any age. Notwithstanding experts like Zeke Emmanuel, MD who implied that after 75 years of age, people should not be treated and that they should be retired to the pastures. The obvious flaw stands out in stark relief now, doesn't it? Second, aging individuals have a lot of wisdom to offer and the young ones should take note of any pearls they drop in their communications. it is obvious that President Carter has a lot to say about his life and the world he has inhabited. Whatever that wisdom is. Wisdom is a philosophy on to itself. And you ask what is Philosophy? nothing more than the “love of wisdom” as Pythagoras called it, or the knowing the underlying fundamental nature of reality. One can tease at the fibers of this philosophy fabric and even in its threadbare form it reeks of some ancient understanding steeped deep into the veins of knowledge-keepers where blood flows.



Philosophy must be wise and therefore rational? Right? “ça dépend!” It depends on many things, but most of all on the questioning of all that is there. An individual’s philosophy would differ, based epistemologically on his or her beliefs, ideas, attitudes of the community and nurturing.

Our philosophy is nothing more than an improvement in our understanding of nature and ourselves. So should we then change the current thought paradigm that places age and cost ahead of fixing illness?

Consider this question; Should we advocate death as the primary focus in healthcare? Some will proffer the cost as a major hurdle for treating the elderly. They will claim that healthcare costs are currently 17% of the GDP in the United States. But they fail to recognize that costs are not due to the care administered, but as New York Times recently pointed out; a direct result of the business people involved in administrating the business of medicine.  So if that vital middling managers can be eliminated, the cost of care would come down drastically and become at once really affordable. More people would get treated and their insurance carriers would not be averse to paying for the care while still making oodles of money for their CEOs (Median total compensation in 2014 for the 117 CEOs for whom Modern Healthcare collected compensation data was $5.4 million, with a median increase of 9.6% over the prior year) and their shareholders.

Consider another question; Should we use a standardized lesson plan of “Choosing Wisely” as advocated by the American Board of Internal Medicine and co-opted by other entities like American College of Physicians as the correct model of patient care?  Experts say these programs are based on “Evidence based Medicine.” What is “Evidence?” I ask. Evidence changes as new information is received. So what is standard today becomes an “old thought: tomorrow. And further if the evidence is conjured by a set of tortured statistics, that furthers the illness within the science of medicine, how exactly does that further the agenda of good patient care? It is akin to building a perfect emptiness contained within straight lines in a chaotic world. Most of us would love to live within those bounds of comfort, happily suckling on sweet nectar without a care, but is that reality? Defining evidence is at best difficult! Yet if we claim “Evidence” as evidence enough to change belief of the majority, then all is pardoned and acceptable. And therein emerges the concept of “Evidentialism,” writ large "Evidentialism is a theory of justification according to which the justification of a conclusion depends solely on the evidence for it." The new subconscious is derived from consciousness at individual level and new belief becomes the new zeitgeist for that individual. And justification upon justification becomes the unwieldy latticework difficult to untangle for most except for those independent thinkers.

As the Big Data scientists gather their tools and computers, a cry from one of its own Hannes Leitgeib said, “ Overall and ultimately, mathematical methods are necessary for philosophical progress.” Ah yes, this progress, where we find the sinews of medicine wasting away today under the hard, weighty chains of pseudo-scientific tortured statistics. The general and special belief system slowly mutates to the turn of their statistical screw.

So, what is your philosophy as a physician in caring for your patient?

Maybe it is time for some Critical Thinking?
Maybe it is time for some thoughtful analysis?
Maybe it is time!

KARL AND HIS CHI SQUARE

Poetic Solution to the Two Variable Problem...

(O = OBSERVATION, E = EXPECTATION)




O Karl of the Pearsons
What have you done?
Created a mythic creature
Of sum.
The misfolded law
Of manifold
Exposes the ignorance

Of the many who hold
The reins of power
Who count the gold.

From observations squared
We extract expectations
Squared above and below
To arrive at conclusions;
Significant or not
Based on a number
between the freedom
In degrees and artificial bounds;
Where confidence grows
Capturing more ground.

Alas Chi is riddled with
Axioms, which rankle the soul
Expectations, what are they?
Where do they grow?
When did we arrive?
And what do they show?
Do we know?
Is it the premise of Bayes?

Or the wanton expectation
Of expectation
From where we derive that
Significance when looking at
observations?

So Karl
How do we measure the real
Truth, that hides beneath?
Do we add another decimal to soothe
Conscience’s sheath?
Or do we live on
in ignorance
Tied to the strings of your
laudatory treatise?

Ah but Karl is not here
The drama we face
Must go on
Incalculable in calculus
yet calculable
From eugenics to philosophy
Rewards so Faustian.
So square the difference and
Divide by the axiom
And live the dream
Of a dream,
in statistical fiction!

The many proofs we seek
Are weak
Diluted in jest
Under the wild eyed guess
Of a once nobleman
Who sought to nurture
The world
With Marxist Justice
And a function of
Probability when nothing else
Lurked to soothe the
Possibilities in a distant future.

The distributed frequencies
Of exclusive events
Sparkle in defense
Blossom and glow
To fill the particularity
That connives within
The Theory,
Resident in it

Stately distribution.
Proof it is, the falconer claims
As the falcon spirals in its gyre
Yet lift precedes the game.

Now probability has risen
To proof
And Null, where is null?
But the ever sinking hull
Of the ship
Beneath a sea of categories
Numbered to negate
The existential
Commonness of reality
Bound between intervals
That remain arbitrary.

How man in his infinite jest
Has clamored to
Bring the best of the best
And numb their minds
Of reality.
From an irrational number
A fraction of a fraction
which goads
And boasts that
Brass is gold.

Oh wicked, wicked
hymns of sharks
preying on the branches
of age old trees
that tilt to the breeze
in defiance
but remain rooted in place.
No sound, no fight
Just woosh,
They are free!

Maybe like the trees
Understand the force
Bend to its will
Yet forge a path
To raise your mind
Above the rest
Feel the breeze
And know the difference

What is

And
What is real.


THE DILEMMA OF THE TWO VARIABLES:

                 Yes                No              Total

Yes             x                    y                 x+y

No              z                    d                  z+d

Total          x+z                 y+d               n


FORMULAS BELOW:

                  Yes                No                Total

Yes       (x+y)(x+z)/n   (x+y)(z+d)/n      x+y



No        (z+d)(x+z)/n   (z+d)(y+d)/n      z+d

Total          x+z               y+d                     n

SHAKESPEARE AND THE DOCTOR

A SICKNESS IN THE WITLESS KINGDOM

“In my heart there was a fighting that would not let me sleep…Our indiscretion sometime serves us well, when our deep plots do pall; and that should learn us there’s divinity that shapes our ends…”

Such are the pains that grow and grow and keep us from living a comforting life. The tumult that shudders and causes pain relives in our dreams. We march to the cry of the pained and the harmed to sooth and comfort as our comfort is discomforted, yet we march on in search of love for humanity. The wakeful moments when sleep surrounds and the flesh is laid bare, the white sinews glisten as the red blood congeals under the surgeon’s scalpel. Time is spent to heal.

“Tis dangerous when the baser nature comes between the pass and fell incensed points of mighty opposites.”

The argument ensues between the physician adamant and rigid in his demand to serve his fellowman comes face to face with the mandates of the powerful and finds himself at odds to do right or acquiesce to the tyranny. And yet when all the power is drained from the powerful the end is the same between the two: “A man may fish with the worm that hath eat of a king, and eat of the fish that hath fed of that worm.” What lies at the end is the monument, a testament to the grave-maker; “the houses he makes last till doomsday.” The power like time is fleeting. The madness is also passing. The arrow of time flies and having flown it brings a strange opacity to the past and color to the future. Some are bewildered by the strangeness of that hue, easily moved and rendered unmoving to all other voices save their own. Reason is imprisoned by their desires. All is material. All is passion.

“Give me that man that is not passion’s slave and I will wear him in my heart’s core, ay, in my heart of heart…”

Through reason and deductive efforts the doctor must understand the nuance of a wince, a groan, a loss of desire, of melting flesh, of fragile bones and via that knowledge plead with the consolation of his virtuous thoughts to end what nature or nurture has begun. In doing so, end the “thousand natural shocks that flesh is heir to…” and render health or find the blanket of comfort and soothe to console the imperiled life. A doctor is indeed the very firmament of reason. His virtue is in to mend, to heal, to seek and to reason.

“The spirit that I have seen, may be a devil and the devil hath power t’assume a pleasing shape…”

When with suddenness and without warning there follow uncalled for unexpected riches in the name of ‘good for the many,’ the spark of question must also follow. Is the individual not the portion of the whole community or society and does not making him or her, the sole purpose of all endeavors? Healing him may yet heal the whole! Yet in these heady times the good of the many betrays the good of the one. He or she is lead to the gallows forsaken under the premise of ex-multis. The powerful then “abuses me to damn me.” Ruthless desires overtake to circumvent the need of the one under the egalitarian umbrella. After all such actions are the consequence of thought that churns and bleeds the fiscal brain with the comfort of; “What is a man if his chief good and market of this time be but to feed and sleep.” And think, “That capability and godlike reason to fust in us unus’d,” is but bestial oblivion.

“What a piece of work is a man, how noble in reason, how infinite in faculties, in form and moving how express and admirable, in action how like an angel, in apprehension how like a god! the beauty of the world, the paragon of animals—and yet, to me, what is this quintessence of dust?”

The physician devotes his life in the learning, finding new ways to limit agony, new methods to purge disquiet and new techniques to ward off discomfort. He marches to the beat of the infirmed and the vulnerable. Power and riches do not entice him or her; the need drives him. To quell, to soothe and “to take arms against a sea of troubles and by opposing end them,” is the quintessence of his being. The wretchedness of the body’s decay, do not fend him or her off. She whispers softly and labors with, “grunts and sweats under the weary life” each day and night to bring solace to her fellow being. The doctor in her cries as she looks upon her patient, “What is he whose grief bears such an emphasis, whose phrase of sorrow conjures the wand’ring stars and make them stand like wonder-wounded hearers?” This then is also her salvation. The quiet and hum of life, healed! For  most physicians feel as Hamlet feels; "O God, I could be bounded in a nutshell and count myself a king of infinite space, were it not that I have bad dreams." And those dreams are the voices of sorrow, of pain, of anguish and anxiety.

“We defy augury.  There’s a special providence in the fall of a sparrow. If it be now, ’tis not to come. If it be not to come, it will be now. If it be not now, yet it will come—the readiness is all. ”

We act as if our actions have little or no negative consequences. The unintended ones lurk underneath and yet we defy the omens, the dull grey beads of disaster that come in slow but hypnotizing fashion clouding the brain. “I shall win at the odds,” is the only thought and doggedly marches to that drumbeat. Neitzsche observed, “ Not reflection, no – true knowledge, an insight into the horrible truth, outweighs any motive for action…” We do arrive at incremental truths about the state of the state in medicine and yet with a flourish of this and that we do away with the warning signs and blink them into obscurity. Their minds are made up. It is what they must do and there the illogic fails for the powerful. For in the end, “And thus the native hue of resolution  is sicklied o'er with the pale cast of thought, and enterprises of great pith and moment with this regard their currents turn awry and lose the name of action.”

Polonius advice to his son, Laertes: “This above all: to thine own self be true, And it must follow, as the night the day, Thou canst not then be false to any man,” is remarkable in its hypocrisy. Whereas he is the meddling intellectual that proffers from the inferences he draws to influence the mighty king, he simultaneously offers that Hamlet, without proper reasoning, is mad, “Though this be madness, there is method in’t.”

There are many who embody the flesh of Polonius. They contrive and conjure to manipulate circumstance. These clever and studied orphans of untruth live in the dichotomy of their stardom and villainy; one desired the other earned! They spin from the wombs of their mentality a web so intricate that it confounds the minds of many. The complexity so intricately weaved that only simplicity alone can undo. Yet the wandering, believing minds that cannot chart the course to reason find ways and means to consolidate their thinking and in so doing any words to the contrary that attempt to alienate such unholy wisdom are demonized. The vile mechanism meanwhile feeds the; “Eyes without feeling, feeling without sight, ears without hands or eyes, smelling sans all…” There are also many a Rosencrantz and Guildenstern in society willing to take on the task of distraction, of execution of opinions and reviling sense with nonsense to gain favor and trust of the kings. These are fools that “cleave the general ear with horrid speech, make mad the guilty and appal the free, confound the ignorant and amaze indeed the very faculties of eyes and ears.” These are charlatans, whose folly is only known to those that reason and think and who understand and wait with patience and true knowledge. For villainy “though it have no tongue, will speak with most miraculous organ.” Eventually!

“Make you ravel all this matter out

That I essentially am not in madness,

But mad in craft…

O shame, where is thy blush?

Rebellious hell…”

" HELLO "

The current zeitgeist in medicine encompasses a wide range of “DO NOTs.” The kind that limits a physician’s input in the care of the patient. Without the shade of a thought that medical evaluation is being reduced to a set of guidelines; the “DO’s.” It all stems from the mantra that was proffered some time ago, “Hospital Stupidity Costs 85,000 Lives and $35 Billion Per Year.” After the much ballyhooed report there were fixes attached to the follies that created the problem of these “premature deaths” Everyone in the bureaucratic industry ran amuck with the paper in hand and started pointing fingers and laying blame across the threshold of sanity. The bureaucratic jungle is a flourishing canopy of protective veil that hides its own flaws to the detriment of all. The medical world was stunned, actually stunned by the reporting and not having any numerical values of their own, starting nodding their heads in unison when the media poured out their venom by using simple arithmetic to get higher ratings with the likes of “Medical errors kill enough people to fill four jumbo jets a week.” 

The foothold had been granted and the bureaucratic “dogs of war” had been unleashed. The entire medical care industry was soon tied up in knots with regulatory fiat. Many well-wishing physicians started to move in lock-step with the mandates and guidelines and other entrepreneurial spirited ones devised their own schemes to rip a page off the book of the incipient collective thought and created the terminology of the “public good.” One such entity; The American Board of Internal Medicine ABIM organization added to their once a lifetime certification examination the process of a 10-year recertification process and as the bureaucratic voices within grew their penchant for luxurious items and high salaries grew as well and they added the Maintenance of Certification process; a biannual process that reaped more than $130 million in 7 years.

While these spectacular shenanigans were going on the bureaucrats, policy wonks and legislators wanted to quantify every communication between patient and physician in a “meaningful” way through coding for billing. The CMS or Centers for Medicare and Medicaid Services gave the dog and pony show to the American Medical Association to come up with more lipstick on the pig with the ICD coding system. The ICD-9 codes numbered in the 17,000 for all medical diseases and each coded was fitted with an “appropriate payment.” Seeing a potential for a follow up revenue to the tune of $200+ million the AMA upped the ante by creating the 70,000+ coded-ways to describe medical illnesses with the ICD-10 coding system. This was a bonanza for the AMA, whose survival no longer seemed to depend on membership of physicians but on its alliance with the industry, governmental affairs cash cow and the data mining wonks. This coding system, they surmised would help the medical insurance industry to actually see how and when and where the illnesses occurred, maybe in the hopes that further legislations would help create more checklists and legislations for the common folk with the “DO NOTs” and give the insurance legitimacy in payment denials to the physicians and other care givers. A win-win for all they said.

Meanwhile the patient and physicians started to see barriers erected in the empty space that existed between them. Once the physician would sit and listen to the patient, eyes locked, hands touching to determine the malady, a soothing voice to comfort against the pathos of the cellular machinery now suddenly the space had thick walls of checklists, guidance, warnings, etc. erected between them.
Communication, once a simple process of speaking and listening, soon became a legal verbose jungle that had to be done for the perfect patient understanding of the expressed information. The voice that once said, “Hello Mrs. Smith” now was broken down into the nuance of implied meanings in the word “Hello!” Was there any implied empathy expressed in that word or was their implied coercion or threat? What was the meaning of the word "is" soon took reins. Empathy leaders sprung up all over the medical education landscape to fill that chasm. Linguistic experts were hired to determine the shades of the meaning within the meaning of the word itself. Meanwhile as the sentence was being analyzed by the billion-line codes of the software algorithm, the payment for services rendered by the physician was being held in abeyance till resolution was reached. Ah! no empathy...no claim...denied! Each step of the communication with its many turns and twists had to be carefully scrutinized. Any deviation from the norm coded into the algorithm was rejected and the physician reprimanded for his behavior. At that point payment was not even on the physician’s mind because a much higher fine could be imposed for such a misdeed. This is where we find ourselves today. Ignorance is no bliss.

The universality of error-making, the inevitability of it and the humanness of it are now a forgotten knowledge. What remains is the “DO NOTs” and the “DO’s.” We have ceased to learn from errors. We only need the errors to find fault and point fingers of blame, because it soothes the bureaucratic mind to do so. The bureaucrats and other wonks seem to think that the current knowledge is the last drop from the fountain of wisdom and there are no more springs or pools of knowledge left to behold. That, what is, is IT! What they don’t understand that today’s knowledge will be supplanted by tomorrow’s discoveries and become laughable if not outright disdained. As they print out their mandates and grind to a halt the very machinery of human excellence, a hefty price will have to be paid, someday soon. Economics teaches us the same thing. Forever tinkering with fiscal policy will have its day of reckoning. Sometime the illogic of the rampant bureaucracy blunts even the Occam’s razor with its layers of Matryoshka Russian nesting dolls approach.

The rabbit hole has gotten deeper and deeper as more blinding rain water flows through it. The deluge from the bureaucratic mindset has flooded the lands and only an Arc will save us now.

ME and YOU

If you did not read, would these words have meaning?
I write this in hopes that you might read.
You read and comment in hopes to further thought.
Our very being, presupposes an eye, an ear, a mind, comprehension!
So then dear reader are we linked for our existence?
If we are, then does not our existence imply mutuality?

Heisenberg's duality exists.

Count you out
Is counting me out.
Particle or wave,
we are linked,
through sight.
My presence is through your eyes
My absence in yours.
Our desperate lives, lived in hope
Of connection.

Eve had Adam
To sooth his aching cage.
Shakespeare's idiot, his spectators and stage

My words persuade you to comment;
We are connected.
In your words, I find existential happiness.
In your absence a deeper sorrow.
The art of belonging is the art of love.
The art of neglect, a demented loneliness.

Without you, I am not me
And without me, are you?
Ambiguity lives
And then it is no more
Schrödinger's cat lives!

The CURIOS CASE of UNCERTAINTY

There is an inimical power distribution curve that covers a lot of area and devours all thought’s food. It is the charade of certainty. The power exudes directly from the certainty of the word “certainty.” Projecting something with the net of realism and a confined future within certain artificial bounds is tantamount to being a prophet. And there are a lot of prophets to behold. In fact prophesizing has now reached epic proportions in the 21^st Century.

Let us look at some of them with a critical eye.

 1. Life Expectancy: In the United States, an adult male expects a life expectancy of 80 years. Barring all the other natural shocks that the flesh is heir to, that might not be too certain. Things happen. There is no certainty here, except that projected and demanded by the experts and lawyers. “ He should have lived…”

      2. Regulations are for the Public Good:  Nancy Thorner wrote about the Dodd-Frank Bill; “Its purpose was to create a sound Economic Foundation to grow jobs, protect consumers, rein in Wall Street and big bonuses, end bailouts, and "too big to fail," as well as prevent another financial crisis.” Paul Atkins stated, “…the 2,319 page bill is basically rubbish. Dodd-Frank created thirteen new offices and agencies, the government only got rid of one agency.” And according to Oversight and Investigation Subcommittee Committee Chairman Rep. McHenry, "Rather than institute market discipline and a clear rules-based regime, four years later Dodd-Frank's failed policies have only worsened the risks within the financial system and recklessly handed financial regulators a blank check for taxpayer-funded bailouts." 

    

      3. Quantitative Easing will prevent a financial Crisis: Thus far the wealth of the nation has increased with fiat money and aggregated in the 1% population. The median income and wealth effect has diminished steadily since 2009. The United States Debt has ballooned to almost $19 Trillion (around 108% of GDP) and counting. Someone will have to pay in some form or another. Food hyper- inflation that matters to an average individual is eating away at his or her meager earnings while adding energy and electronics into the calculations makes the inflation picture appear tame for the time being to the politicians and the economists. All good for the forecasting experts. Hey if you cannot afford food, you can always take a selfie. “We have continued economic recovery…”

      4. ACA is a boon for Healthcare in the United States: 9 million souls are covered by the ACA while 33 million still have no insurance, this from five-thirty eight. Meanwhile those that had personal or private coverage have had to relinquish their insurance and are forced into a substandard coverage with high deductibles and higher co-Pays. Insurance denials are rampant and “Less is More” is the mantra of the experts. The tail has wagged the dog into a state of panic. The experts keep drumming the virtues of a failed system while the ordinary citizens walk around dazed and confused. The countercoup injury to reason appears devastating at present. “The Affordable Care Act!”

       

      5. ACA affords Quality Medical Care: Physicians are burdened by the morass of paperwork where they spend more time trying the “Meaningful Use” of a computerized binary logic of medicine in an uncertain human pathology, while the patient gets less and less time of meaningful encounters. How does one measure “Quality” is the question asked often. The answer still evades even the most sophisticates. Using metrics of cost and time and resource usage is one way this is being calculated currently. “Call it the stupidity of the American voter or whatever…”

      6. Patients are getting quality Care: Patients who are newly forced into the Medicaid system are unable to find doctors who participate in the overly regulated Medicaid environment and thus are left seeking help many miles away from home, leading to delay and detrimental care. If that is quality, there is a bridge in Brooklyn ready for sale. “If you like your doctor, you can keep your doctor…”

      7.  Electronic Medical Records: A physician’s time is spent trying to get reimbursed for rendered care so as to continue feeding the managerial beast of burdensome regulations within their private and hospital practice. The demands by the regulatory body for compliance and the need for the hospitals to make a profit to pay for the 3000+% increased managerial staff pits the doctor against the patient in providing the best care. All that time spent in clerical computerized tasks is, time away from the patient; time is wasted in the bureaucratic jungle. "Initially you drop about 30 percent [of productivity following an EHR implementation], sometimes more.” John Rodgers MD.

8. A Purell in every corner to arrest spread of germs: When did washing hands become a rarity in everyday life before eating? The simplest and best form of defense against acquiring infections from others is still Agnes Simmelwies’ well documented and proven “Washing hands to prevent transmission of infections,”  in “Die Aetiologie, der Begriff und die Prophylaxis des Kindbettfiebers” (“The Etiology, the Concept, and the Prophylaxis of Childbed Fever”) Purell unlike hand-washing might have unintended consequences; might help mutate the exposed bacteria at a faster rate to gain access to the human body. The dream for another antibiotic is kept alive. Just a thought, take it for what it’s worth. Purell in every Walmart and Grocery store.

9. Vaccination will lead to eradication of viruses: Although vaccination is an important landmark in population health against disease, it crackles the imagination that a virus will acquiesce and lay down its arms for survival against this sea of defense. Viruses mutate and they will, to find a foothold again. Eradication is impossibility, because paramount in the viral code is its own survival. Polio virus keeps making a comeback as does the tuberculosis bacterium, the devastating mycobacterium. The human immunity learns to live over time with microbial adversaries. The elusive dream of certainty remains elusive. "There is no cure for polio, it can only be prevented." - World Health Organization. Unfortunately pockets of Poliomyelitis still exist but with a more virulent mutated form of the virus. (here)

10. The Food Pyramid:  That pyramid was responsible for the current obesity rate in the world to a large extent! It was a well-meaning platform by some health experts. What it touted was the fairly excessive use of carbohydrates. The hunter gatherer had not so easily transitioned from the meats to the carbs so quickly and storage of excess not-utilized carbs turned into fats for later use. The human girth exploded as a consequence. Since there was little chance of a famine given the burgeoning racks of food varieties in the supermarket, more and more fat storage occurred that is now threatening chronic illnesses, heart disease and cancer in 36% of the population? The Big Gulp addiction continues. Again an ill-advised certainty gathered on the shoulders of giants in the academia has now become the bane of existence. And a new industry is born; wearables! The uncertainty of human certainty creates a new uncertainty!

11. Volkswagen: The bosses were almost certain that the cool software that fooled the emission standards software was undetectable, were proven wrong once again. Back to the Enron days a similar set of rules were used and we know what happened there. The confirmation bias exists only in the mind and uncertainty has a habit of redressing it. "I personally am deeply sorry that we have broken the trust of our customers and the public,"- Martin Winterkorn, Volkswagen's CEO."

We live in a world defined by the Fallacy of Anecdotal Evidence used as a surrogate for certainty. An anecdote is cited and the drumbeat follows. The poor are richer by world standards in the United States but they are told they are poorer. Healthcare in the United States has spawned the most innovation and continues to do so yet we are told that we have the worst care in the developed world by using some arbitrary metrics that satisfy the academia and the politicians for their personal fortunes. Even Heisenberg's Uncertainty Principle about Nature's fuzziness seems to have escaped the minds of the elite to their own peril.

There appears only one certainty in this world today and that is the certainty of invoking fear. The media is complicit. The politicians love it. The experts spawn it and the populace drinks their Kool-Aid. Disaster looms at the sound of daylight. Fear rides at the tick of the second and citizen helplessness is the all-encompassing fait accompli. Entitlements abound, hope is touted, change is demanded and through all this the human dignity suffers a little with each passing moment. The only certainty in life is death. Life is a terminal disease.

Maybe we might consider that certainty in an uncertain world is the utopian creed. Chaos is the norm, admit it! Certainty is a human mind construct to feed it’s sense of security. After all it is in the uncertainty that innovation is made and progress stimulated. In certainty, life becomes a mournful indignity, a known, known; an exposed drudgery.

“We sail within a vast sphere, ever drifting in uncertainty, driven from end to end.” – Blaise Pascal

CRISPR, GENE EDITING & CANCER

There are more things in heaven and earth, Horatio,Than are dreamt of in your philosophy. - Hamlet

Funny you should ask about CRISPR. It is the most talked about latest technology to hit the media. In fact the two ladies; Jennifer Doudna and Emmanuelle Charpentier were nominated for a potential Nobel Prize in Chemistry. So that brings us to the question, what’s the buzz about?

It is a big as in B I G buzzy development! Let us look at where this CRISPR came from first and then address how it might help us down the stretch.

Bacteria and viruses happen to have survived on this planet much longer than humans. Those two microbes have developed a relationship with each other. Since no one wants to be vanquished by another, the bacteria have developed a strategy to prevent the viruses from using its cellular interior from being used as a factory for producing more viruses and then discarding it to the “file cabinet.” You see, viruses that infect bacteria are called bacteriophages and in so doing, they insert their DNA into the bacteria to circumvent the bacterial machinery so they can produce more of their own progeny. Kind of like your in-laws visiting your home, staying in it for a long time and eventually by proxy taking over the ownership.  

Bacteria for obvious reasons don’t like that. It is akin to the Hepatitis virus infecting the human liver cell and using it for its own propagation to the detriment of the host cell, causing inflammation of the liver as a whole and sometime death of the infected individual; Infect a cell, multiply within (CCCs) and then infect more cells and the parade goes on until the immune system kicks in and the fight leads to the hepatic inflammation.

Okay, so the bacteriophage (virus) has attached itself to the bacterium surface and injected its DNA within it. The Bacterium also happens to have its own piece of coded DNA in place and within it is this nifty fragment called the CRISPR (clustered regularly interspaced short palindromic repeats). These repeats are so called “Spacers” (25-30 nucleotides) and sandwiched within these repeated palindromic segments of nucleic acids are cleaved portions of the infecting virus’s selected DNA fragment. There are many such repeats and bottled in between two CRISPRs is a unique fragment of the viral DNA. Multiple fragments from the same virus or one or two from many different viruses reside here.

One can look at it as a “Guest House” All guests visiting the Great House must live in there. Each guest has a bodyguard on duty, where, if they are noted to have mischief in their DNA will be handled swiftly by the bodyguards and delivered to the police (in this case Cas9 protein) without harming the owners of the great house beyond.

As I was saying, the CRISPR holds these fragments in check and when a similar virus happens to stroll along that has previously caused mischief by injecting its DNA to cause harm, the CRISPR goes into full throttle, slashing and killing the deadly DNA.

The CRISPR segment creates a messenger RNA that merges with the single strand of the DNA of the double-stranded virus (guide RNA or gRNA) and then is rapidly segmented further by being cleaved containing multiple smaller strands each containing a viral DNA fragment and the CRISPR spacer called the crRNA. These fragments attach to the transactivated RNA or tracrRNA and that helps bind to the Cas9 protein and then the orgy begins.

The Cas9 protein cleaves (cuts) away all the crRNA that are attached to the viral DNA in exactly the spots where they are attached thus fragmenting the viral DNA and rendering it useless from further replication! Imagine the simple ingenuity of the Bacterium. But here is the kicker, the viruses don’t sit back and take this kind of bullying within the CRISPR Guest House either. They perform Single Nucleotide Polymorphisms (SNP) or colloquially, single point mutations and thus try to hoodwink the bacterium from recognizing the DNA strand. That single SNP is enough to throw the whole game asunder. And it does. But the slow-poke bacterium compared to the Ferrari driven viruses adapt albeit slowly and incorporate the new segment within and thus the battle for survival and supremacy proceeds anew. When the bacterium divides the latest CRISPR information also goes with it to the daughter cells to help protect them. And the species survives!

And you might ask, how does this help us?

And rightly you ask the most daunting of questions. The answer is simpler than you think. If we can use the nuclease enzyme to cut out a bad portion or multiple bad portions of the human DNA and insert the healthy version into the stem cell, Voila, we have a healthy being! But before you go drinking and smoking hoping for the CRISPR to save your DNA mutations, consider this, we are a long way away from using this technology in humans. The unintended consequences in tinkering with a single gene insertion for a single gene = single disease paradigm might be low but inserting mRNAs that enhance or suppress gene functions and placing them as lords over the genome might have serious pitfalls. You might cure the cancer and kill the patient with some other evil. Happens!  As you are aware that “the hip bone is connected to the leg bone…”and so on, a change here might make a big change there. If you are into the butterfly effect the analogy fits well here. Reminds me also of the Lorentz strange attractor, but we will leave that for another day.

We certainly can keep this wonderful technology in the laboratory and mess around till we have more data to configure the monster of Lamarckian twists that lurk within this technology. Many hundreds if not thousands of experiments are needed to evaluate the hypothesis in a controlled environment and after validation, with trepidation move ever so slowly in the human sphere. But those in love with the “Disruption” fall madly in love and leave caution to the wind. And the wind can be destructive. There are pernicious consequences in the split between what is and what could be. So careful out there, girls and boys!

In cancer for instance, one might snip away a mutated oncogene or have a RNAi sitting adjacent to and enhancing a tumor suppressor gene to shut down the cancer process. The possibilities are endless. Similarly Infectious Diseases could be rendered moot by vaccinating individuals at risk with a CRISPR Cas9 system to destroy the invading bacteria.

Speaking of vaccinations, this is nature’s way of vaccinating against an invader. Plug in the coordinates and destroy the target. Mission Possible!

The mechanism and the understanding are not as daunting as one might think, but using them without safeguards is akin to future genetic disasters. Just sayin!

We have infectious diseases, cancers, chronic illnesses, hereditary genetic misfortunes to consider in alleviating the burdens on humans but we have time and some hard work ahead.

https://youtu.be/2pp17E4E-O8