The dx from Hell anniversary

On March 29th, 2017 my younger daughter Danielle got the devastating news, via an abdominal CT scan rad report confirmed by a liver biopsy px, that she'd been found to have Stage IV metastatic pancreatic cancer. 

In the wake of two successive chemo regimens that eventually failed to halt or reverse the progression of the disease (as expected via the clinical literature), she is now under home hospice care and not expected to survive much longer. We're keeping her comfortable and riding herd on pain management. Things are day by day, often hour by hour here.

See my prior post "A tale of two sisters." I will update things there as time permits.

Words fail to capture the unrelenting stress and sadness. I have been on continuous "tilt" for a year.

Above, I found this while rummaging through and cleaning out my late Mother's stuff some years back.

Below, my revised iPhone wallpaper.

The other day I fired up my iPhone in video mode, and Danielle and I frankly talked through some difficult end-of-life issues where we still had some loose ends hanging. That was difficult, but very good. I won't be posting that.

Final note for now: words also fail to express my gratitude for the grace and strength of my wife through all of this. We came together 44 years ago this month. She embraced the role of stepmom without hesitation. Cheryl has consistently gone above and beyond the call of duty where the kids are concerned. And she is all over it right now.

Below, Danielle and Mom during our November "bucket list" retreat to Manzanillo.

ERRATUM UPDATE

In my mailbox yesterday, latest issue of Science Magazine.

Lots of progress (and persistent problems). Too late for us personally, but others will eventually surely benefit.

If they can afford it. From the "Sticker Shock" article:

Summary
Physician Peter Bach at Memorial Sloan Kettering Cancer Center is appalled at the sky-high price of cancer treatments in the United States, and he is watching new immune therapies drive them higher still. Checkpoint inhibitors for various solid tumors cost about $150,000 a year, and a personalized treatment called chimeric antigen receptor–T cell therapy tops out at $475,000. Dozens more immunotherapies are in clinical trials, as companies race to reap the monetary rewards. For the past decade, Bach has immersed himself in health policy and economics to decipher and publicize what's driving these high prices. Science spoke with Bach last month...

I've lost track of what Kaiser has spent on Danielle. Safe to say it's well into six figures.

Another article of concern in the issue:

Too much of a good thing?
Summary
As the growing wave of excitement over immunotherapies has swept through the cancer field, a concern has arisen in its wake. Are there now too many clinical trials for these novel treatments, which enlist the immune system to battle tumors? One recent tally found more than 1100 studies combining a popular new class called checkpoint inhibitor drugs, which unleash suppressed immune cells, with other treatments. Some academic researchers, pharma executives, and other experts have decried this explosion of trials as a counterproductive glut motivated more by the race for money than good science and warned that many of these efforts may not finish because of a lack of participants. Other researchers, however, think the competition is healthy—and that the best studies and combos will prevail.

I'd like to hear from the folks at Science Based Medicine on this area of concern. Searching their site with just the phrase "clinical trials" turns up a spate of posts.

JUST IN AT STATNEWS

The government wants to free your health data. Will that unleash innovation?

In health care, breakthrough cures are no longer just hidden in the innumerable mysteries of biology and chemistry. Increasingly, they are locked away in a place even harder to access: electronic patient records.

These files could help establish which patients, with which backgrounds and disease characteristics, respond best to certain therapies — secrets that are often carefully guarded in service of patient privacy, and private profit.

But the federal Centers for Medicare and Medicaid Services is seeking to open the data floodgates. The agency wants to put patients in charge of their information instead of the hospitals and insurers that collect it and keep it locked within their own systems. And it wants to do so explicitly to help app and device makers gain access to high-quality data…

We shall see. The impediments remain legion and formidable.

OVERBOOKED

Across the past four years or so, I have averaged reading about two books a week (plus all of my periodicals, and daily online source reading). There's just so much to continue to learn.

Lately, though, given Danielle's increasingly serious decline, my stash of only partially read books has piled up. A few days ago I ran across a book review post at Science Based Medicine commenting on this book:

I got it and am about halfway through it. Highly recommended. Great primer on the fundamentals of both "medical ethics" and the scientific method as relevant to medical R&D and clinical applications (and the BS of "alternative treatments").

YET ANOTHER ONE ON DECK

April 1st -- My son had to leave to go back home to Baltimore today. I had NPR on the car radio during the trip to OAK airport and back, and heard a "Hidden Brain" segment involving this author:

"Consider that we have known the functions of the three other basic drives in life—to eat, to drink, and to reproduce—for many tens if not hundreds of years now. Yet the fourth main biological drive, common across the entire animal kingdom—the drive to sleep—has continued to elude science for millennia.

Addressing the question of why we sleep from an evolutionary perspective only compounds the mystery. No matter what vantage point you take, sleep would appear to be the most foolish of biological phenomena. When you are asleep, you cannot gather food. You cannot socialize. You cannot find a mate and reproduce. You cannot nurture or protect your offspring. Worse still, sleep leaves you vulnerable to predation. Sleep is surely one of the most puzzling of all human behaviors..."

Stay tuned. Just got it. Very interesting. Will tackle this stuff in a forthcoming post.
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More to come...

"Relational Leadership™?"

"Relational Leadership™" -- key component of an effective antidote for clinician burnout?

Read an interesting piece at STATnews that put me on this topic:

I experienced trauma working in Iraq. I see it now among America’s doctors
By ELIZABETH MÉTRAUX

...Clinician burnout is frequently chalked up to the eight-minute visits with patients, the six hours spent each day entering data into electronic health records, and the demands of a profession where life-and-death decisions must routinely be made. But this short list of factors doesn’t get to the real wounds of practicing medicine…

It’s not just the eight-minute visit: It’s that an eight-minute visit means physicians can’t provide whole-person care to patients whose diagnoses aren’t easily logged into a computer. It’s not just the six hours of daily data entry: It’s that it takes clinicians’ eyes off their patients, missing the very connection with humanity that drove them into this work. And it’s not just the problematic quality metrics that physicians are subjected to: It’s that those metrics have crowded out deeper connections with patients to help them manage triggers and navigate treatment…

…if we continue to disregard the epidemic of trauma among our physicians, lives — of patients and providers — will be unnecessarily lost.

During a panel at last year’s Aspen Ideas Festival, Morris-Singer offered a simple challenge: “The next time you wrap up a visit with a health care provider, ask him or her, ‘How are you doing?'”

I echo that. Let’s start a conversation with our health care providers and listen, really listen, to their needs. As William Osler, father of modern medicine, famously remarked, “Listen to your patients. They are telling you their diagnosis.” Clinicians, too, are telling us their diagnosis. It’s time we responded.

FROM A COMMENT

Most innovations have disempowered physicians to use their clinical thinking. Instead, we have morphed into data entry “experts.”

Take EHR's. Aside from distracting physicians from patient encounters, the software dictates what minutes remain of the “clinical interview.” There is minimal time for conversation that might reveal the context of the patient’s concerns. Physicians are forced to ask exhaustive lists of check boxes, some of which are usually irrelevant to that one patient. They have little to no discretion about guiding the interview to what’s relevant or even recording what he learns. There is literally no place for that on some software. If such a text box exists, the volume of unrelated data obscures what might be helpful to the next covering physician.

In fact, most every step of diagnosing, treating, and discharging a patient involves the physician surrendering his expertise to a computer record that presents “yes and no’s” data without nuance or direction. Any shift in treatment from implicit or explicit protocols is fraught with more paperwork and little freedom to follow physician judgement.

In the end, the computer “wins” and administrators are satisfied. The medical record has “evolved” into a billing form. The doctor and patient are left out of that loop. - Peggy Finston MD

"It’s not just the six hours of daily data entry: It’s that it takes clinicians’ eyes off their patients, missing the very connection with humanity that drove them into this work."

More on the "six hours" trope in a bit (dubiety spoiler alert), but the author and the commenter raise undeniably fair points.

UPDATE: AN ADDITIONAL, CONTENTIOUS COUNTER-COMMENT

This fellow is unsympathetic, to put it mildly

I have several comments regarding this article and the implications made by it. First, I get a quasi-nauseous feeling when people start talking about poor, overworked doctors – overworked mostly by having to code the transactions they make – who are suffering from depression and anxiety, which has now morphed into PTSD. And now the article about these “wounded” docs is being written by someone who has PTSD from slipping on a slick tile floor during a brief firefight. Try watching your best friend’s face get eviscerated from an IED blast.

But that isn’t my main problem with this article. The main thing is that, according to the author, we have PTSD-depressed docs running around treating people with real illnesses and then going home feeling sorry for themselves because they had to spend time on paperwork. Do you have any clue as to how many people in this country die – as in DEAD – from Preventable Medical Error! Over 400,000 every year. And when you count Serious Harm into those statistics the numbers jump into the millions. And now you tell me that some poor guy whose finger hurts from writing codes on a billing statement thinks he had PTSD?? No wonder we have so many people dying over here. We have thousands of Physicians feeling mistreated because they are asked to perform a bureaucratic function. I’ll tell them the same thing I’ve said to other physicians to there face. If you are so put off (‘nee Traumatized) by your job, go be a Hedge Fund Manager. At least we would all know what kind of person we are dealign [sic] with then. - LARRY W PIERCE

Yikes. Make of that what you will. Bit of randomness in that rant.
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Broadly, you might want to see my prior post "Are structured data the enemy of health care quality?" See also my snarky"Clinic Monkey" spoof site.

In addition, some of my prior riffs on "Leadership" seem to be relevant, e.g., starting with "What exactly is 'Leadership,' anyway?"

Given my dire family circumstance these days, I could scarcely be more attuned to the physicians' - patients' dynamic, warts and all.

I reached out to the author, Elizabeth Métraux, Director of Communications and Development at

Note that I've posted a permanent link to them in the right-hand links columns. Lots of interesting material there. I'm just starting to search out any independent socio-psych literature supporting this "model." Everything relating to clinical organizational culture is of intrinsic interest to me.

They have an "Institute" -- "RLI" (pdf)

I've uncovered one 2006 paper thus far (pdf).

From the paper's conclusion:

Conclusion
Relationships—rather than authority, superiority, or dominance—appear to be key to new forms of leadership (Drath, 2001). Yet, while relationships are at the heart of many of the new approaches emerging in the leadership literature, e.g., distributed (Gronn, 2002), distributive (Brown & Gioia, 2002), shared (Pearce & Conger, 2003), post-heroic (Fletcher, 2004), and complexity (Marion & Uhl-Bien, 2001), we know surprisingly little about how relationships form and develop in the workplace. Moreover, investigation into the relational dynamics of leadership as a process of organizing has been severely overlooked in leadership research (Hosking, 1988; Hosking and Fineman, 1990)...…

We need to move beyond a focus on the manager–subordinate dyad or a measure  of relationship quality to address the question of, what are the relational dynamics  by which leadership is developed throughout the workplace?

Such an approach opens up the possibility for relational leadership as moving toward a more “postindustrial” model of leadership (Rost, 1991)—one that is not hierarchical, can address various forms of relationships (not just dyadic and not just “leader–follower” relationships), focuses on relational dynamics (rather than a more static state of relational quality with antecedents and outcomes), and allows us to consider leadership as a process of structuring (Giddens, 1984; Murrell, 1997). Investigating relational leadership will require richer methodologies than over-reliance on cross-sectional survey data using limited measures (Bradbury and Lichtenstein, 2000; Bryman, 2004). It would allow us to consider processes  that are not just about the quality of the relationship or even the type of relationship, but rather about the social dynamics by which leadership relationships form and evolve in the workplace. In this way, it moves leadership beyond a focus on simply getting alignment (and productivity) or a manager’s view of what is pro ductive, to a consideration of how leadership arises through the interactions and negotiation of social order among organizational members.

This monograph is 12 years old. Have we made significant progress in this area across the past dozen years? 

Curiously, I find no mention of the word "empathy" in the body of the foregoing UNL paper (though the term appears in the end-note citations referencing one prior wok).

UPDATE

From across the Pond:

6.6 RELATIONAL LEADERSHIP
Leader-Member Exchange (LMX) Theory (Graen & Uhl-Bien, 1995), also known as the vertical dyad linkage theory, proposes that the quality of the relationship between the leader and the subordinate influences performance-related outcomes (for both the leader and the subordinate). The leadership theories discussed previously have a group-level focus; that is, the leader treats all subordinates in the same way. For example, transformational leadership is usually considered to be a group-level construct. However, LMX theory focuses on the relationship between the leader and each individual subordinate. This model is most appropriate for understanding how a leader manages a team of individuals. As a leader interacts with his or her team, the leader will classify individuals as members of either the in-group or out-group. These classifications, once established, tend to remain fairly stable over time. Although it is not entirely clear what governs the leader's allocation of subordinates to the in-group or the out-group, goal congruence seems to have an influence, in that individuals with similar goals to the leader are selected to the in-group (Uhl-Bien, Graen & Scandura, 2000).

Research in the area of LMX has established the positive benefits for both the leader and the subordinate of being in a high LMX relationship. High quality LMX leads to enhanced employee satisfaction, performance and OCBs (Ilies, Nahrgang & Morgeson, 2007; Phillips & Bedeian, 1994; Settoon, Bennett & Liden, 1996). Furthermore, high quality LMX has a positive impact on leader behaviours. For example, Mayer, Davis and Schoorman (1995) found that leaders in high quality LMX were more trusted by their subordinates, who were in turn, more trusted by their leader. This resulted in leaders delegating tasks to these subordinates and being more willing to empower them. Although there has been considerable research looking at the impact of high quality LMX, there has been less attention given to low quality LMX. In these relationships, the subordinate performs in-role behaviour (i.e., activities required by the job), but does not put extra effort into their work or engage in OCBs (Bauer & Green, 1996). Furthermore, Townsend, Phillips and Elkins (2000) demonstrated that low LMX is associated with negative consequences, such as retaliation behaviour (see Unit 3 in relation to psychological contracts). Recent research has focused on identifying situations in which leaders and subordinates are motivated to invest more work effort within low LMX relationships (Kacmar, Zivnuska & White, 2007).

The strength of LMX theory is its emphasis on the role of both the leader and the subordinate and its recognition of leadership as a dynamic interactive process. However, although there is broad support for LMX theory, there is currently little understanding of the wider context within which dyadic relationships take place. As LMX theory focuses upon each individual dyad, the theory does not take into account the influence of the group or organisational context.

OK. "Relational Leadership™"? A new, useful (albeit electic, incrementally improved) model? Or "old wine in new bottles?" As I've remarked before, I'm more interested in being lean rather than 'Doing Lean," being agile rather than 'Doing Agile," and, now, being relational in lieu of ""Doing Relational."

But, I have much more to learn here.

"PRIMARY CARE"

Primary care practices (e.g., IM, FM, Peds) still rank close to the bottom of the physician compensation bar chart (2017 data).

"Doing more with less..." The "productivity treadmill" bane.

During my two stints in federal Health IT initiatives (DOQ-IT and Meaningful Use) my turf was comprised principally of ambulatory primary care (including OB/Gyn). I remain pretty sensitive to the workflow problems (pdf) they continue to face.

See some of my prior blog riffs on "workflow."

This was interesting:

“The next time you wrap up a visit with a health care provider, ask him or her, ‘How are you doing?'”

 I do that routinely. When I asked it of my cardiologist not too long ago, he almost couldn't stop talking, once he got over his surprise.

Point taken, Elizabeth.

Just getting started here. Gonna post this and go do some caregiver stuff.
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UPDATE: ON "TROPES"

Specifically with respect to the "docs spending 6 hours a day entering EHR data" lament.

Like @POTUS, I tweeted

I too have "the best words."

apropos, see, e.g., my old post "Clinical workflow: 'YAWL,' y'all?"

SOME OF MY RECENT YEARS' READING RELATED TO "LEADERSHIP"

The latter book (Tomasello) provides great science on the evolutionary utility of "prosocial/cooperative" behavior (which goes to its relevance regarding this topic). The tagline of the Marx book is "the price we pay for expecting perfection." Which pairs nicely with Kathryn Schulz's book. Maccoby's work in the Leadership area is both broad and deep. Jeffrey Pfeffer's book is a take-no-prisoners piece of iconoclastic skepticism, highly recommended. Dr. Toussaint is one of my heroes in the lean health care leadership space. My fav quote from him: "Manage processes, lead people."

I've cited, excerpted, and linked all of these on this blog.
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More to come...

The "costs of unchecked innovation?"

Is "innovation" an unalloyed societal good, and thus a no-brakes-necessary technological and economic priority? A staple "conservative" political stance opposing "government regulation" it that "stifles innovation." The libertarian-leaning entrepreneurs and venture capitalists of Silicon Valley and beyond regard the fevered pursuit of "innovation" as a cardinal virtue.

Inferred in the common definition "introduction of new things or methods" is that innovation always implies "improvement."**

** Attempts at innovation that don't bear fruit obviously don't count. Efforts that do make the cut, though, should be subjected to an honest accounting of "net utility," comprising candor with respect to the extent and consequences of "side effects" / "adverse outcomes."

It shouldn't be difficult to come up with counterexamples upon the briefest reflection. For one thing, there are frequently casualties among those "disrupted" by "disruptive innovation." Relatedly, consider the new "Tracking Point XS1" Artificial Intelligence-enabled assault style semiautomatic rifle.

An "innovative" way to more effectively "disrupt" a person's life? Permanently, in the worst case. As a military weapon, its net utility is rather obvious. It is not, however, simply a "deer rifle" or personal protection appliance, marketing spin of its manufacturer notwithstanding.

No, "innovations" (and those who develop them) don't rightfully get a moral blank check. apropos, see my November post "Artificial Intelligence and Ethics." See also my post on "Slaughterbots."

OK, comes a new wrinkle, reported at WIRED:

Meltdown, Spectre, and the Costs of Unchecked Innovation

…Even if Intel wouldn't quite agree that Moore's law is over, its real-world performance benefits may be substantially erased after Meltdown and Spectre are tamed. The long-standing computing trope that should be even more concerning in this context, however, is "it's all just ones and zeroes." We're not just talking about bits once those bits drive our robots, drones, and 3-D printers. New technologies now often manifest in the real world, since for now that is still where most of the money is, but even Bitcoin melts the polar icecaps.

On the mind-boggling cosmic scale, these exploits will affect our ability to create and edit organisms, but on a more tangible level, they also decreased the operational speeds of both processors and online timing measurements, thereby reversing advances we thought we'd made both in hardware and with the general sophistication of the web as a platform. In both fields, we had quite literally been racing toward something terrible.

We’ve built technology too quickly for our own good, quantifiable now in dollars and microseconds, using a wide range of tools and metrics even though SharedArrayBuffer is no longer around to take the measurements. Anything that seeks to reshape the infrastructure built by our past selves should deserve our most aggressive scrutiny, regulation, and suspicion. If backtracking overeager technology is already proving so catastrophic for the cheap chips in our laptops and phones, then we certainly have no hope of reversing its changes to our homes, cities, and oceans. Some things can't be patched or safely versioned. We just have to get it right the first time.

Yikes. Read all of it. Broad implications.

See also my January 2017 post "Disruption ahead on all fronts, for good and ill."

Another good read relevant to the topic:

"...The financial markets were changing in ways even professionals did not fully understand. Their new ability to move at computer, rather than human, speed had given rise to a new class of Wall Street traders, engaged in new kinds of trading. People and firms no one had ever heard of were getting very rich very quickly without having to explain who they were or how they were making their money..."

Lewis, Michael. Flash Boys: A Wall Street Revolt (p. 17). W. W. Norton & Company. Kindle Edition.

INNOVATION UPDATE

Google Naked Capitalism Uber. Bring a Snickers; you're going to be a while.

FROM SCIENTIFIC AMERICAN

Intelligent to a Fault: When AI Screws Up, You Might Still Be to Blame
Interactions between people and artificially intelligent machines pose tricky questions about liability and accountability, according to a legal expert

By Larry Greenmeier 

Artificial intelligence is already making significant inroads in taking over mundane, time-consuming tasks many humans would rather not do. The responsibilities and consequences of handing over work to AI vary greatly, though; some autonomous systems recommend music or movies; others recommend sentences in court. Even more advanced AI systems will increasingly control vehicles on crowded city streets, raising questions about safety—and about liability, when the inevitable accidents occur.

But philosophical arguments over AI’s existential threats to humanity are often far removed from the reality of actually building and using the technology in question. Deep learning, machine vision, natural language processing—despite all that has been written and discussed about these and other aspects of artificial intelligence, AI is still at a relatively early stage in its development. Pundits argue about the dangers of autonomous, self-aware robots run amok, even as computer scientists puzzle over how to write machine-vision algorithms that can tell the difference between an image of a turtle and that of a rifle.

Still, it is obviously important to think through how society will manage AI before it becomes a really pervasive force in modern life…

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More to come...

Theranos in the news again

I've taken multiple shots at Theranos and Elizabeth Holmes before. e.g., see here for a thread of some of my prior posts on the topic.

The USA Today story.

SAN FRANCISCO — How did disgraced biotech start-up Theranos become a $9 billion darling? The old-fashioned way: Through star power, dazzling promises, deep pockets and devout believers.

But the Palo Alto company, whose founder Elizabeth Holmes was stripped of her leadership role Wednesday by the Securities and Exchange Commission, wound up with a story line worthy of Icarus.

Theranos rose quickly from being a college dropout's idea to revolutionize the blood analysis industry to a hot tech bet that accrued $700 million in funding and many famous names for its board.

Anchoring it all was Holmes, now 34, whose smarts, fierce determination and Steve Jobs-inspired look (a black turtle neck was her staple) were critical to recruiting believers for a secretive company that ultimately could not deliver the technology required to do complex blood work based not on vials but mere drops of blood…

Perhaps the civil sanctions are punishment enough. But, she and her CEO apparently committed multiple counts of criminal fraud ongoing. I would favor prosecution, for a full, on-the-record airing of the particulars. to wit, from Forbes:

Lawyers: Elizabeth Holmes Could Still Serve Time In Prison
By Ellie Kincaid and Michela Tindera

Elizabeth Holmes agreed to settle with the SEC on fraud charges that she deceived investors to raise $700 million for her blood-testing company Theranos. She and the company didn't admit or deny the allegations, but lawyers say she could still face jail time if prosecutors decide to pursue her.

“She could very well serve time,” said Elliot Lutzker, the chair of New York City commercial law and government relations firm Davidoff Hutcher & Citron’s corporate group, who has decades of experience handling noncriminal matters with the SEC. “She is subject to criminal charges because she outright lied.” Theranos declined to comment for this story…

From THCB:

On Theranos: It’s Time to Throw the Book at Healthcare Tech Frauds
Mar 14, 2018

Huge news hit today as Theranos, its Chairman and CEO Elizabeth Holmes and its former President and COO Ramesh “Sunny” Balwani were charged with “elaborate, years-long fraud” by the Securities and Exchange Commission. The litany of supposed violations of the Securities Act of 1933 and the Securities Exchange Act of 1934 are almost as dizzying as the detailed factual allegations of repeated, willful fraud perpetuated by Holmes and Balwani on investors who likely should have known better.

Reviewing the SEC complaint against Holmes, it’s stunning to see the extent to which Holmes and Balwani were able to pull the wool over investors’ eyes…

"White collar criminals rarely face criminal investigations and charges for defrauding corporate investors. Sympathy is hard to come by for VCs who fail to do the due diligence to see through an amateurish con pulled by a neophyte founder and a President and COO shrouded in mystery..."

Yeah. But...

Search "Theranos" on Google news. Plenty of coverage.

UPDATES

The folks over at Naked Capitalism are not amused.

Jay Clayton’s SEC Lets Theranos Founder Elizabeth Holmes Get Away With Brazen Fraud
Posted on March 16, 2018 by Yves Smith

Due to the state of my internet connection (barely functioning), I’ll have to be terse and limit myself to a few high level comments about the pathetic punishment meted out to Theranos founder Elizabeth Holmes. This case proves that the Trump SEC is setting new lows by giving get out of jail nearly free cards to fraudsters.

Holmes settled with the SEC, paying a puny $500,000 when she raised and torched $700 million of investor funds. She also surrendered 18.9 million shares and give up control of the company by converting her Class B shares, which give her voting control, to Class A shares. She is also barred from serving as the director or officer of a public company for 10 years. That bizarrely means she remains as CEO of Theranos. She did not admit or deny guilt.

The Department of Justice is dutifully reported by the press to be looking at a case against her. If you believe that, I have a bridge to sell you. The SEC refers cases to the Department of Justice when it thinks they merit criminal charges and the two agencies work together. It is possible that the Department of Justice could pursue FDA-related charges against Holmes, but the securities law claims were a slam dunk, and the Department of Justice is highly unlikely to pursue a case on its own, particular since it is plenty busy with things like suing California over passing legislation that defies its crackdown on sanctuary cities.

We’ve embedded the filing at the end of the post for your entertainment.

As bad as the overall picture is, some of the items in the SEC filing are eyepopping. Holmes told investors she expected to have over $100 million in revenues in 2014 when she had only $100,000. She told investors that her largely vaporware blood tests didn’t need FDA approval when they did (and why did no reporter bother to check that claim out?). She presented prospective investors with a binder of endorsements with pharma company logos. But only one was real. The rest were made up by Theranos and the put the logos on the page. Holmes also claimed that Theranos was making its own equipment. That should have elicited a lot more study from investors and the press, since that would require engineering expertise that was notably absent on the Theranos team, plus seeing the facilities where the equipment was being made should have been part of the usual investor dog and pony show and apparently wasn’t.

It was disturbing to see so much of the press reports lead with the SEC’s line that the SEC had charged Holmes with “massive fraud” yet for the most part treat the punishment with “just the facts, ma’am” deference, as opposed to seeking expert comment on its suitability. In the Twitterverse, many pointed out that pharma bro Martin Skrelli was just sentenced to seven years in prison, and that even though he had engaged in brazen fraud, he had arguably not lost investors any money in the end. But he was so smug and full of himself that that alone guaranteed he’d get a harsh sentence…

Then there's this:

James Mattis is linked to a massive corporate fraud and nobody wants to talk about it
Better let a scandal slide than risk a nuclear war.

Secretary of Defense James Mattis is implicated in one of the largest business scandals of the past decades, described by the Securities and Exchange Commission as an “elaborate, years-long fraud” through which Theranos, led by CEO Elizabeth Holmes and president Ramesh “Sunny” Balwani, “exaggerated or made false statements about the company’s technology, business, and financial performance.”

Basically, their biotech startup was founded on the promise of faster, cheaper, painless blood tests. But their technology was fake.

Mattis not only served on Theranos’s board during some of the years it was perpetrating the fraud after he retired from US military service, but he earlier served as a key advocate of putting the company’s technology (technology that was, to be clear, fake) to use inside the military while he was still serving as a general. Holmes is settling the case, paying a $500,000 fee and accepting various other penalties, while Balwani is fighting it out in court.

Nobody on the board is being directly charged with doing anything. But accepting six-figure checks to serve as a frontman for a con operation is the kind of thing that would normally count as a liability in American politics.

But nobody wants to talk about it. Not just Trump and his co-partisans in Congress; the Democratic Party opposition is also inclined to give Mattis a pass. Everyone in Washington is more or less convinced that his presence in the Pentagon is the only thing standing between us and possible nuclear Armageddon…

The hits just keep on comin'.

MORE...

STATnews has an interesting article up.

Getting past the bad blood of Theranos through collaboration
By LAUREN LEIMAN and SEEMA SINGH BHAN

This week’s news that the Securities and Exchange Commission charged Theranos and its CEO with fraud put the troubles of the company back into the spotlight. For those of us in the field of liquid biopsy, Theranos has cast a long and persistent shadow on what’s clearly one of the most promising areas in cancer care — using blood tests to improve detection, diagnosis, and treatment and, more broadly, advancing the reality of precision medicine in cancer.

The long-unfolding Theranos story has chilled investment and primed clinicians to be wary of emerging blood tests, all to the detriment of patients whose cancer care may benefit from less invasive blood-based biopsies that can detect and pull critical information from genes, proteins, and cancer cells that have shed into the bloodstream.

What’s the silver lining for those of us in the field? The Theranos saga set the stage for an unprecedented level of collaboration and data-sharing across companies working to develop liquid biopsy technologies…

 "Liquid biopsy." I'll get to that in a moment. The article sums up:

Though the Theranos story served as a backdrop for the collaboration in liquid biopsy, there is a lesson here for all those innovating in the life sciences sector. Any new technology or approach can, and should, be met with healthy skepticism by all stakeholders, including investors, clinicians, professional societies, patients, and insurers. Without a critical eye on the science, we will find ourselves in a scientific Wild West instead of exploring a promising new frontier...

Doing transparent science. Real science. Check out the author's website.

apropos of which, from a recent edition of my (paywalled) AAAS Science Magazine:

Cancer detection: Seeking signals in blood

Most cancers are detected when they cause symptoms that lead to medical evaluation. Unfortunately, in too many cases this results in diagnosis of cancers that are locally invasive or already metastatic and hence no longer curable with surgical resection or radiation treatment. Medical therapies, which might be curative in the setting of minimal tumor burden, typically provide more limited benefit in more advanced cancers, given the emergence of drug resistance (1). On page 926 of this issue, Cohen et al. (2) describe a strategy for early cancer detection, CancerSEEK, aimed at screening for multiple different cancers within the general population. This study challenges current assumptions in the field of blood-based biomarkers and sets the stage for the next generation of cancer screening initiatives.

Given the potential curative advantage of earlier diagnosis and treatment, why have so many cancer screening approaches failed? In the past, efforts at screening healthy populations for cancer have relied on tests that were insufficiently specific. For example, most men with rising serum prostate-specific antigen (PSA) do not have prostate cancer but instead have benign prostatic enlargement. However, where accurate tests exist, there have been dramatic improvements in cancer outcomes (3). For example, advanced cervical cancer has virtually disappeared in countries where Pap screening is the standard of care; although less reliable, mammography and screening colonoscopy are recommended for early detection of breast and colon cancers in individuals above ages 40 to 45 and 50, respectively, and screening heavy smokers by use of low-dose chest computed tomography (CT) scans reduces deaths from lung cancer (4). However, these tests are imperfect, and cost-effectiveness for broad deployment remains a challenge, particularly because a multitude of false-positive test results may lead to extensive diagnostic evaluations and unnecessary medical interventions. Unfortunately, for the majority of cancers no effective early screening tests are available…

Detection and localization of surgically resectable cancers with a multi-analyte blood test
SEEK and you may find cancer earlier
Many cancers can be cured by surgery and/or systemic therapies when detected before they have metastasized. This clinical reality, coupled with the growing appreciation that cancer's rapid genetic evolution limits its response to drugs, have fueled interest in methodologies for earlier detection of the disease. Cohen et al. developed a noninvasive blood test, called CancerSEEK that can detect eight common human cancer types (see the Perspective by Kalinich and Haber). The test assesses eight circulating protein biomarkers and tumor-specific mutations in circulating DNA. In a study of 1000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity of 69 to 98% (depending on cancer type) and 99% specificity.

Abstract
Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

Given the plights of my daughters (both of whom were dx'd presenting symptoms at Stage IV), my interest here should be obvious. Won't help us, but perhaps numerous others will benefit.

FINALLY, FROM WIRED

THERANOS DIDN'T NUKE THE DIAGNOSTICS BUSINESS
 
...A couple of years ago, Theranos, a company claiming to be able to almost magically do all sorts of medical tests on a single drop of human blood, fell apart. A brilliant Wall Street Journal investigation showed that its technology didn’t work; this week the Securities and Exchange Commission brought fraud charges against its founder. Diagnostics start-ups extracted a few lessons: Have actual, peer-reviewed data and, like, don’t lie to investors. But the Theranos debacle didn’t stop their work. That game has been on since at least 2000, and doctors, patients, and insurers are still clamoring for those tests. Nominally they might reduce health care costs, but more than that they promise new, faster diagnoses and better care…

A good read.

MARCH 19TH UPDATE

More from STATnews:

Investigators say his fingerprints are all over financial crimes at Theranos. Why is he a virtual ghost?
By REBECCA ROBBINS @rebeccadrobbins, DAMIAN GARDE @damiangarde, and ADAM FEUERSTEIN @adamfeuerstein MARCH 19, 2018

Fallen wunderkind Elizabeth Holmes is the face of the Theranos scandal. But the next act of Silicon Valley’s biggest blow-up rests on a mysterious tech entrepreneur with almost no digital footprint.

Ramesh “Sunny” Balwani is a virtual ghost — despite serving nearly seven years in the No. 2 position at the blood-testing startup that turned out to be too good to be true. While the black-turtleneck-clad Holmes graced magazine covers and spoke before adoring crowds, Balwani, her former boyfriend, stayed in the shadows. He has almost no internet presence, and the only verifiable photo that STAT could find of him was a grainy image from his 1988 college yearbook.

Now, he’s at the center of a legal showdown that could tear open a new chapter in a scandal that has rocked the business world and captivated the public imagination. And it could set up a daytime-TV legal defense: My ex-girlfriend duped me…

The SEC’s court documents paint Balwani as a hyperactive manager who operated with cunning and methodical intensity. And they find Balwani’s fingerprints all over Theranos’s alleged financial crime scene. The allegations: He lied to investors and partners about the blood test’s capabilities. He falsely claimed it was being used on military helicopters. He promised $1 billion in annual sales despite booking just $100,000. He orchestrated a campaign of secrecy within the ranks of the company, instructing employees to use code names for the third-party machines used in lieu of the company’s proprietary technology to process blood tests…

Long, detailed article. Kudos to the authors. Well worth your time.

"Financial crimes?" Prosecute, I say.
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More to come...

An Epidemic of Wellness?

"What's the definition of a 'well person'?"

"A patient who hasn't been adequately worked up."

 

- Old physician joke

LOL. Goes to the "medicalization of life" itself. IIRC, it was the curmudgeonly Dr. Thomas Szasz who once riffed irascibly on a "humanectomy" px.

Wish I was at the Mardi Gras of Health IT this year, #HIMSS18. to wit,

Among the goodies in my latest Harper's is an essay by Barbara Ehrenreich.

apropos of our exuberantly-touted mobile digitech-enabled "culture of wellness" of late.

Running to the Grave

By Barbara Ehrenreich, from Natural Causes, which will be published next month by Twelve. Ehrenreich is the author of more than a dozen books, including Nickel and Dimed (Henry Holt). She holds a PhD in cellular immunology.

The pressure to remain fit, slim, and in control of one’s body does not subside with the end of youth — it grows only more insistent as one grows older. Friends, family members, and doctors start nagging the aging person to join a gym, “eat healthy,” or at the very least go for a daily walk. You may have imagined a reclining chair or a hammock awaiting you after decades of stress and physical exertion. But no, your future more likely holds a treadmill and a lat pull, if you can afford access to these devices. You may have retired from paid work, but you have a new job: going to the gym. One of the bossier self-help books for seniors commands:

Exercise six days a week for the rest of your life. Sorry, but that’s it. No negotiations. No give. No excuses. Six days, serious exercise, until you die.

People over the age of fifty-five are now the fastest-growing demographic for gym membership. Mark, a fifty-eight-year-old white-collar worker who goes to my gym, does a six o’clock workout before going to the office, then another after leaving. His goal? “To keep going.” The price of survival is endless toil.

For an exemplar of healthy aging, we are often referred to Jeanne Louise Calment, a Frenchwoman who died in 1997 at the age of 122 — the longest confirmed life span on record. Calment never worked in her life, but it could be said that she worked out. She and her wealthy husband enjoyed tennis, swimming, fencing, hunting, and mountaineering. She took up fencing at the age of 85, and rode a bicycle until her 100th birthday.

Anyone looking for dietary tips will be disappointed; Calment liked beef, fried foods, chocolate, and pound cake. Unthinkable by today’s standards, she smoked cigarettes and sometimes cigars, though anti-smoking advocates should be relieved to know that she suffered from a persistent cough in her final years.

This is “successful aging,” which, except for the huge investment of time it requires, is supposedly indistinguishable from not aging at all. It has many alternative names: “active aging,” “healthy aging,” “productive aging,” “vital aging,” “anti-aging,” and “aging well.” In 2012, the World Health Organization dedicated World Health Day to healthy aging, and the European Union designated that year its Year for Active Aging.

Popular science and self-help books on the topic are proliferating. Among the titles currently available on Amazon are: Successful and Healthy Aging: 101 Best Ways to Feel Younger and Live Longer; Live Long, Die Short: A Guide to Authentic Health and Successful Aging; Do Not Go Gentle: Successful Aging for Baby Boomers and All Generations; Aging Backwards: Reverse the Aging Process and Look 10 Years Younger in 30 Minutes a Day; and, of course, Healthy Aging for Dummies. A major theme is that aging is abnormal and unacceptable. Henry Lodge, a physician and coauthor of Younger Next Year, writes, “The more I looked at the science, the more it became clear that such ailments and deterioration” — heart attacks, strokes, the common cancers, diabetes, most falls, fractures — “are not a normal part of growing old. They are an outrage.”

Who is responsible for this outrage? Well, each of us is individually responsible. All the books in the successful-aging literature insist that a long and healthy life is within the reach of anyone who will submit to the required discipline. It’s up to you and you alone, never mind what scars — from overexertion, genetic defects, or poverty — may be left from your prior existence. Nor is there much concern for the material factors that influence the health of an older person, such as personal wealth or access to transportation and social support.

There is a bright side to aging: declines in ambition, competitiveness, and lust. When Betty Friedan was in her seventies, she wrote a book called The Fountain of Age. As her subjects grew older, she observed, they became “more and more authentically themselves.” They didn’t care anymore what other people thought of them. I can add from my own experience that aging also comes with a refreshing refusal to strive — I feel no need to take on every obligation or opportunity that comes my way.

But even the most ebullient of the elderly eventually come to realize that aging is above all an accumulation of disabilities, often beginning well before Medicare eligibility or the first Social Security check. Vision loss typically begins in one’s forties. Menopause strikes in a woman’s early fifties, along with the hollowing-out of bones. Knee and lower-back pain arise in the forties and fifties, compromising the mobility required for successful aging. The US Census Bureau reports that nearly 40 percent of people aged sixty-five and older suffer from at least one disability, with two thirds of them saying they have difficulty walking or climbing. Yet we soldier on. “You don’t become inactive because you age,” we’ve been told over and over. “You age because you’ve become inactive.”

The goal of successful aging is often described as the “compression of morbidity” into one’s last few years — in other words, a healthy, active life followed by a swift descent into death. But the truly sinister possibility is that for many of us, all the little measures we take to remain fit — all the deprivations and exertions — will lead only to the extension of years spent with crippling and humiliating disabilities. There are no guarantees...

This book ought be a beaut. From the Amazon blurb:

Bestselling author of Nickel and Dimed, Barbara Ehrenreich explores how we are killing ourselves to live longer, not better.

A razor-sharp polemic which offers an entirely new understanding of our bodies, ourselves, and our place in the universe, NATURAL CAUSES describes how we over-prepare and worry way too much about what is inevitable. One by one, Ehrenreich topples the shibboleths that guide our attempts to live a long, healthy life -- from the importance of preventive medical screenings to the concepts of wellness and mindfulness, from dietary fads to fitness culture.

But NATURAL CAUSES goes deeper -- into the fundamental unreliability of our bodies and even our "mind-bodies," to use the fashionable term. Starting with the mysterious and seldom-acknowledged tendency of our own immune cells to promote deadly cancers, Ehrenreich looks into the cellular basis of aging, and shows how little control we actually have over it. We tend to believe we have agency over our bodies, our minds, and even over the manner of our deaths. But the latest science shows that the microscopic subunits of our bodies make their own "decisions," and not always in our favor.

We may buy expensive anti-aging products or cosmetic surgery, get preventive screenings and eat more kale, or throw ourselves into meditation and spirituality. But all these things offer only the illusion of control. How to live well, even joyously, while accepting our mortality -- that is the vitally important philosophical challenge of this book.

Drawing on varied sources, from personal experience and sociological trends to pop culture and current scientific literature, NATURAL CAUSES examines the ways in which we obsess over death, our bodies, and our health. Both funny and caustic, Ehrenreich then tackles the seemingly unsolvable problem of how we might better prepare ourselves for the end -- while still reveling in the lives that remain to us.

Can't wait to read it.
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Relatedly, I saw this over at The Atlantic:

Why So Many of Us Die of Heart Disease
Evolution doomed us to have vital organs fail. For years, experts failed us, too.
The Assyrians treated the “hard-pulse disease” with leeches. The Roman scholar Cornelius Celsus recommended bleeding, and the ancient Greeks cupped the spine to draw out animal spirits.

Centuries later, heart disease remains America’s number one killer, even though medical advances have made it so that many more people can survive heart attacks. Some parts of the country are especially hard-hit: In areas of Appalachia, more people are dying of heart disease now than were in 1980.

Haider Warraich, a fellow in cardiovascular medicine at the Duke University Medical Center (and an occasional Atlantic contributor), is at work on a book about how heart disease came to be such a big threat to humanity…

Certainly of interest to me these days. And, that article led me to this book:

From his NPR Fresh Air interview last year:

Doctor Considers The Pitfalls Of Extending Life And Prolonging Death

Humans have had to face death and mortality since since the beginning of time, but our experience of the dying process has changed dramatically in recent history.

Haider Warraich, a fellow in cardiology at Duke University Medical Center, tells Fresh Air's Terry Gross that death used to be sudden, unexpected and relatively swift — the result of a violent cause, or perhaps an infection. But, he says, modern medicines and medical technologies have lead to a "dramatic extension" of life — and a more prolonged dying processes.

"We've now ... introduced a phase of our life, which can be considered as 'dying,' in which patients have terminal diseases in which they are in and out of the hospital, they are dependent in nursing homes," Warraich says. "That is something that is a very, very recent development in our history as a species.”…

I've just started on this book.
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I'll close for now with a bit more Barbara Ehrenreich:

In 2000, an Italian immunologist named Claudio Franceschi proposed the neologism “inflammaging” to describe the entire organism-wide process of aging. Far from being a simple process of decay originating in individual cells, aging involves the active mobilization of macrophages to deal with proliferating sites of cellular damage. Today, Franceschi’s theory is widely accepted. The hallmark disorders of aging — atherosclerosis, arthritis, Alzheimer’s disease, diabetes, osteoporosis — are all inflammatory diseases, characterized by localized buildup of macrophages. In atherosclerosis, for example, macrophages settle in the arteries that lead to the heart and gorge themselves on lipids until the arteries are blocked. In type 2 diabetes, macrophages accumulate in the pancreas, where they destroy the cells that produce insulin. Osteoporosis involves the activation of bone-dwelling macrophages, called osteocytes, that kill normal bone cells. The inflammation associated with Alzheimer’s was first thought to represent macrophages’ attempts to control the beta-amyloid plaques that clog up the Alzheimer’s brain. But the most recent research suggests that the macrophages actually drive the progression of the disease.

These are not degenerative diseases, not accumulations of errors and cobwebs. They are active and seemingly purposeful attacks by the immune system on the body itself. Why should this happen? Perhaps a better question is: Why shouldn’t it happen? The survival of an older person incapable of reproduction is of no evolutionary consequence. In a Darwinian sense, it might even be better to remove the elderly before they can use up resources that would otherwise go to the young. In that case, you could say that there is something almost altruistic about the diseases of aging. Just as programmed cell death, called apoptosis, cleanly eliminates damaged cells from the body, so do the diseases of aging clear out the clutter of biologically useless older people — only not quite so cleanly. This perspective may be particularly attractive at a time like the present, when the dominant discourse on aging focuses on the deleterious economic effects of aging populations. If we didn’t have inflammatory diseases to get the job done, we might be tempted to turn to euthanasia...

Yikes.

On this broad topic of aging and chronic maladies, I am reminded of Dan Lieberman's fine book.

I cited and reviewed it here.

UPDATE: MORE READING

Was recently apprised of this book.

Looks very interesting. I am reminded of Einer Elhauge.

BTW, another new read I'm just starting.

Heard this one touted on CNN on Sunday.

ERRATUM

apropos of my recent #NeverAgain posts.

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More to come...