Clever Firm Predicts Patients Most at Risk, Then Tries to Intervene Before They Get Sicker
The diabetic patient hit the danger zone.
Ideally, blood sugar, measured by an A1C test, rests at 5.9 or less. A 7 is elevated, according to the Diabetes Council. Over 10, and you're into the extreme danger zone, at risk of every diabetic crisis from kidney failure to blindness.
In three months of working with a case manager, Jen's blood sugar had dropped to 7.2, a much safer range.
This patient's A1C was 10. Let's call her Jen for the sake of this story. (Although the facts of her case are real, the patient's actual name wasn't released due to privacy laws.).
Jen happens to live in Pennsylvania's Lehigh Valley, home of the nonprofit Lehigh Valley Health Network, which has eight hospital campuses and various clinics and other services. This network has invested more than $1 billion in IT infrastructure and founded Populytics, a spin-off firm that tracks and analyzes patient data, and makes care suggestions based on that data.
When Jen left the doctor's office, the Populytics data machine started churning, analyzing her data compared to a wealth of information about future likely hospital visits if she did not comply with recommendations, as well as the potential positive impacts of outreach and early intervention.
About a month after Jen received the dangerous blood test results, a community outreach specialist with psychological training called her. She was on a list generated by Populytics of follow-up patients to contact.
"It's a very gentle conversation," says Cathryn Kelly, who manages a care coordination team at Populytics. "The case manager provides them understanding and support and coaching." The goal, in this case, was small behavioral changes that would actually stick, like dietary ones.
In three months of working with a case manager, Jen's blood sugar had dropped to 7.2, a much safer range. The odds of her cycling back to the hospital ER or veering into kidney failure, or worse, had dropped significantly.
While the health network is extremely localized to one area of one state, using data to inform precise medical decision-making appears to be the wave of the future, says Ann Mongovern, the associate director of Health Care Ethics at the Markkula Center for Applied Ethics at Santa Clara University in California.
"Many hospitals and hospital systems don't yet try to do this at all, which is striking given where we're at in terms of our general technical ability in this society," Mongovern says.
How It Happened
While many hospitals make money by filling beds, the Lehigh Valley Health Network, as a nonprofit, accepts many patients on Medicaid and other government insurances that don't cover some of the costs of a hospitalization. The area's population is both poorer and older than national averages, according to the U.S. Census data, meaning more people with higher medical needs that may not have the support to care for themselves. They end up in the ER, or worse, again and again.
In the early 2000s, LVHN CEO Dr. Brian Nester started wondering if his health network could develop a way to predict who is most likely to land themselves a pricey ICU stay -- and offer support before those people end up needing serious care.
Embracing data use in such specific ways also brings up issues of data security and patient safety.
"There was an early understanding, even if you go back to the (federal) balanced budget act of 1997, that we were just kicking the can down the road to having a functional financial model to deliver healthcare to everyone with a reasonable price," Nester says. "We've got a lot of people living longer without more of an investment in the healthcare trust."
Popultyics, founded in 2013, was the result of years of planning and agonizing over those population numbers and cost concerns.
"We looked at our own health plan," Nester says. Out of all the employees and dependants on the LVHN's own insurance network, "roughly 1.5 percent of our 25,000 people — under 400 people — drove $30 million of our $130 million on insurance costs -- about 25 percent."
"You don't have to boil the ocean to take cost out of the system," he says. "You just have to focus on that 1.5%."
Take Jen, the diabetic patient. High blood sugar can lead to kidney failure, which can mean weekly expensive dialysis for 20 years. Investing in the data and staff to reach patients, he says, is "pennies compared to $100 bills."
For most doctors, "there's no awareness for providers to know who they should be seeing vs. who they are seeing. There's no incentive, because the incentive is to see as many patients as you can," he says.
To change that, first the LVHN invested in the popular medical management system, Epic. Then, they negotiated with the top 18 insurance companies that cover patients in the region to allow access to their patient care data, which means they have reams of patient history to feed the analytics machine in order to make predictions about outcomes. Nester admits not every hospital could do that -- with 52 percent of the market share, LVHN had a very strong negotiating position.
Third party services take that data and churn out analytics that feeds models and care management plans. All identifying information is stripped from the data.
"We can do predictive modeling in patients," says Populytics President and CEO Gregory Kile. "We can identify care gaps. Those care gaps are noted as alerts when the patient presents at the office."
Kile uses himself as a hypothetical patient.
"I pull up Gregory Kile, and boom, I see a flag or an alert. I see he hasn't been in for his last blood test. There is a care gap there we need to complete."
"There's just so much more you can do with that information," he says, envisioning a future where follow-up for, say, knee replacement surgery and outcomes could be tracked, and either validated or changed.
Ethical Issues at the Forefront
Of course, embracing data use in such specific ways also brings up issues of security and patient safety. For example, says medical ethicist Mongovern, there are many touchpoints where breaches could occur. The public has a growing awareness of how data used to personalize their experiences, such as social media analytics, can also be monetized and sold in ways that benefit a company, but not the user. That's not to say data supporting medical decisions is a bad thing, she says, just one with potential for public distrust if not handled thoughtfully.
"You're going to need to do this to stay competitive," she says. "But there's obviously big challenges, not the least of which is patient trust."
So far, a majority of the patients targeted – 62 percent -- appear to embrace the effort.
Among the ways the LVHN uses the data is monthly reports they call registries, which include patients who have just come in contact with the health network, either through the hospital or a doctor that works with them. The community outreach team members at Populytics take the names from the list, pull their records, and start calling. So far, a majority of the patients targeted – 62 percent -- appear to embrace the effort.
Says Nester: "Most of these are vulnerable people who are thrilled to have someone care about them. So they engage, and when a person engages in their care, they take their insulin shots. It's not rocket science. The rocket science is in identifying who the people are — the delivery of care is easy."
“Young Blood” Transfusions Are Not Ready For Primetime – Yet
The world of dementia research erupted into cheers when news of the first real victory in a clinical trial against Alzheimer's Disease in over a decade was revealed last October.
By connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier.
Alzheimer's treatments have been famously difficult to develop; 99 percent of the 200-plus such clinical trials since 2000 have utterly failed. Even the few slight successes have failed to produce what is called 'disease modifying' agents that really help people with the disease. This makes the success, by the midsize Spanish pharma company Grifols, worthy of special attention.
However, the specifics of the Grifols treatment, a process called plasmapheresis, are atypical for another reason - they did not give patients a small molecule or an elaborate gene therapy, but rather simply the most common component of normal human blood plasma, a protein called albumin. A large portion of the patients' normal plasma was removed, and then a sterile solution of albumin was infused back into them to keep their overall blood volume relatively constant.
So why does replacing Alzheimer's patients' plasma with albumin seem to help their brains? One theory is that the action is direct. Alzheimer's patients have low levels of serum albumin, which is needed to clear out the plaques of amyloid that slowly build up in the brain. Supplementing those patients with extra albumin boosts their ability to clear the plaques and improves brain health. However, there is also evidence suggesting that the problem may be something present in the plasma of the sick person and pulling their plasma out and replacing it with a filler, like an albumin solution, may be what creates the purported benefit.
This scientific question is the tip of an iceberg that goes far beyond Alzheimer's Disease and albumin, to a debate that has been waged on the pages of scientific journals about the secrets of using young, healthy blood to extend youth and health.
This debate started long before the Grifols data was released, in 2014 when a group of researchers at Stanford found that by connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier. There was something either present in young blood that allowed tissues to regenerate, or something present in old blood that prevented regeneration. Whatever the biological reason, the effects in the experiment were extraordinary, providing a startling boost in health in the older mouse.
After the initial findings, multiple research groups got to work trying to identify the "active factor" of regeneration (or the inhibitor of that regeneration). They soon uncovered a variety of compounds such as insulin-like growth factor 1 (IGF1), CCL11, and GDF11, but none seemed to provide all the answers researchers were hoping for, with a number of high-profile retractions based on unsound experimental practices, or inconclusive data.
Years of research later, the simplest conclusion is that the story of plasma regeneration is not simple - there isn't a switch in our blood we can flip to turn back our biological clocks. That said, these hypotheses are far from dead, and many researchers continue to explore the possibility of using the rejuvenating ability of youthful plasma to treat a variety of diseases of aging.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence.
The data remain intriguing because of the astounding results from the conjoined circulatory system experiments. The current surge in interest in studying the biology of aging is likely to produce a new crop of interesting results in the next few years. Both CCL11 and GDF11 are being researched as potential drug targets by two startups, Alkahest and Elevian, respectively.
Without clarity on a single active factor driving rejuvenation, it's tempting to try a simpler approach: taking actual blood plasma provided by young people and infusing it into elderly subjects. This is what at least one startup company, Ambrosia, is now offering in five commercial clinics across the U.S. -- for $8,000 a liter.
By using whole plasma, the idea is to sidestep our ignorance, reaping the benefits of young plasma transfusion without knowing exactly what the active factors are that make the treatment work in mice. This space has attracted both established players in the plasmapheresis field – Alkahest and Grifols have teamed up to test fractions of whole plasma in Alzheimer's and Parkinson's – but also direct-to-consumer operations like Ambrosia that just want to offer patients access to treatments without regulatory oversight.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence. We simply haven't performed trials to test whether dosing a mostly healthy person with plasma can slow down aging, at least not yet. There is some evidence that plasma replacement works in mice, yes, but those experiments are all done in very different systems than what a human receiving young plasma might experience. To date, I have not seen any plasma transfusion clinic doing young blood plasmapheresis propose a clinical trial that is anything more than a shallow advertisement for their procedures.
The efforts I have seen to perform prophylactic plasmapheresis will fail to impact societal health. Without clearly defined endpoints and proper clinical trials, we won't know whether the procedure really lowers the risk of disease or helps with conditions of aging. So even if their hypothesis is correct, the lack of strong evidence to fall back on means that the procedure will never spread beyond the fringe groups willing to take the risk. If their hypothesis is wrong, then people are paying a huge amount of money for false hope, just as they do, sadly, at the phony stem cell clinics that started popping up all through the 2000s when stem cell hype was at its peak.
Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.
The real progress in the field will be made slowly, using carefully defined products either directly isolated from blood or targeting a bloodborne factor, just as the serious pharma and biotech players are doing already.
The field will progress in stages, first creating and carefully testing treatments for well-defined diseases, and only then will it progress to large-scale clinical trials in relatively healthy people to look for the prevention of disease. Most of us will choose to wait for this second stage of trials before undergoing any new treatments. Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.
Who’s Responsible for Curbing the Teen Vaping Epidemic?
E-cigarettes are big business. In 2017, American consumers bought more than $250 million in vapes and juice-filled pods, and spent $1 billion in 2018. By 2023, the global market could be worth $44 billion a year.
"My nine-year-old actually knows what Juuling is. In many cases the [school] bathroom is now referred to as 'the Juuling room.'"
Investors are trying to capitalize on the phenomenal growth. In July 2018, Juul Labs, the company that owns 70 percent of the U.S. e-cigarette market share, raised $1.25 billion at a $16 billion valuation, then sold a 35 percent stake to Phillip Morris USA owner Altria Group in December. The second transaction valued the company at $38 billion. While the traditional tobacco market remains much larger, it's projected to grow at less than two percent a year, making the attractiveness of the rapidly expanding e-cigarette market obvious.
While Juul and other e-cigarette manufacturers argue that their products help adults quit smoking – and there's some research to back this narrative up – much of the growth has been driven by children and teenagers. One CDC study showed a 48 percent rise in e-cigarette use by middle schoolers and a 78 percent increase by high schoolers between 2017 and 2018, a jump from 1.5 million kids to 3.6 million. In response to the study, F.D.A. Commissioner Scott Gottlieb said, "We see clear signs that youth use of electronic cigarettes has reached an epidemic proportion."
Another study found that teenagers between 15 and 17 were 16 times more likely to use Juul than people aged 25-34. In December, Surgeon General Jerome Adams said, "My nine-year-old actually knows what Juuling is. In many cases the [school] bathroom is now referred to as 'the Juuling room.'"
And the product is seriously addictive. A single Juul pod contains as much nicotine as a pack of 20 regular cigarettes. Considering that 90 percent of smokers are addicted by 18 years old, it's clear that steps need to be taken to combat the growing epidemic.
But who should take the lead? Juul and other e-cigarette companies? The F.D.A. and other government regulators? Schools? Parents?
The Surgeon General's website has a list of earnest possible texts that parents can send to their teens to dissuade them from Juuling, like: "Hope none of your friends use e-cigarettes around you. Even breathing the cloud they exhale can expose you to nicotine and chemicals that can be dangerous to your health." While parents can attempt to police their teens, many experts believe that the primary push should come at a federal level.
The regulation battle has already begun. In September, the F.D.A. announced that Juul had 60 days to show a plan that would prevent youth from getting their hands on the product. The result was for the company to announce that it wouldn't sell flavored pods in retail stores except for tobacco, menthol, and mint; Juul also shuttered its Instagram and Facebook accounts. These regulations mirrored an F.D.A. mandate two days later that required flavored e-cigarettes to be sold in closed-off areas. "This policy will make sure the fruity flavors are no longer accessible to kids in retail sites, plan and simple," Commissioner Gottlieb said when announcing the moves. "That's where they're getting access to the e-cigs and we intend to end those sales."
"There isn't a great history of the tobacco industry acting responsibly and being able to in any way police itself."
While so far, Gottlieb – who drew concerns about conflict of interest due to his past position as a board member at e-cigarette company, Kure – has pleased anti-smoking advocates with his efforts, some observers also argue that it needs to go further. "Overall, we didn't know what to expect when a new commissioner came in, but it's been quite refreshing how much attention has been paid to the tobacco industry by the F.D.A.," Robin Koval, CEO and president of Truth Initiative, said a day after the F.D.A. announced the proposed regulations. "It's important to have a start. I certainly want to give credit for that. But we were really hoping and feel that what was announced...doesn't go far enough."
The issue is the industry's inability or unwillingness to police itself in the past. Juul, however, claims that it's now proactively working to prevent young people from taking up its product. "Juul Labs and F.D.A. share a common goal – preventing youth from initiating on nicotine," a company representative said in an email. "To paraphrase Commissioner Gottlieb, we want to be the off-ramp for adult smokers to switch from cigarettes, not an on-ramp for America's youth to initiate on nicotine. We won't be successful in our mission to serve adult smokers if we don't narrow the on-ramp... Our intent was never to have youth use Juul products. But intent is not enough, the numbers are what matter, and the numbers tell us underage use of e-cigarette products is a problem. We must solve it."
Juul argues that its products help adults quit – even offering a calculator on the website showing how much people will save – and that it didn't target youth. But studies show otherwise. Furthermore, the youth smoking prevention curriculum the company released was poorly received. "It's what Philip Morris did years ago," said Bonnie Halpern-Felsher, a professor of pediatrics at Stanford who helped author a study on the program's faults. "They aren't talking about their named product. They are talking about vapes or e-cigarettes. Youth don't consider Juuls to be vapes or e-cigarettes. [Teens] don't talk about flavors. They don't talk about marketing. They did it to look good. But if you look at what [Juul] put together, it's a pretty awful curriculum that was put together pretty quickly."
The American Lung Association gave the FDA an "F" for failing to take mint and menthol e-cigs off the market, since those flavors remain popular with teens.
Add this all up, and in the end, it's hard to see the industry being able to police itself, critics say. Neither the past examples of other tobacco companies nor the present self-imposed regulations indicate that this will succeed.
"There isn't a great history of the tobacco industry acting responsibly and being able to in any way police itself," Koval said. "That job is best left to the F.D.A., and to the states and localities in what they can regulate and legislate to protect young people."
Halpern-Felsher agreed. "I think we need independent bodies. I really don't think that a voluntary ban or a regulation on the part of the industry is a good idea, nor do I think it will work," she said. "It's pretty much the same story, of repeating itself."
Just last week, the American Association of Pediatrics issued a new policy statement calling for the F.D.A. to immediately ban the sale of e-cigarettes to anyone under age 21 and to prohibit the online sale of vaping products and solutions, among other measures. And in its annual report, the American Lung Association gave the F.D.A. an "F" for failing to take mint and menthol e-cigs off the market, since those flavors remain popular with teens.
Few, if any people involved, want more regulation from the federal government. In an ideal world, this wouldn't be necessary. But many experts agree that it is. Anything else is just blowing smoke.