Clever Firm Predicts Patients Most at Risk, Then Tries to Intervene Before They Get Sicker

Health firm Populytics tracks and analyzes patient data, and makes care suggestions based on that data.
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."
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman