Aging in Bursts and Other News

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.‌

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University, and we’re trying to get closer to the truth about health and healthcare. We typically have a guest, but once a month we’re trying to do a deeper dive into what’s going on. There’s a lot of news. It’s always hard to even parse it out. So I have a few items, you have a few items, and I’m eager to hear your thoughts on any number of the topics. So why don’t you take it off first?‌

Harlan Krumholz: Well, thank you, Howie.‌

Howard Forman: Yeah.‌

Harlan Krumholz: That’s so nice of you.‌

Howard Forman: That’s true. It’s true.‌

Harlan Krumholz: It’s so good to see you.‌

Howard Forman: It’s good.‌

Harlan Krumholz: We’re in that studio together.‌

Howard Forman: It is. I mean, again, for our listeners, we’ve known each other for 29 years, 30 years, and this is really most—‌

Harlan Krumholz: I look forward to seeing you every time—‌

Howard Forman: Me too.‌

Harlan Krumholz: ...we get together. Yeah.‌

Howard Forman: When we do this. It’s fun.‌

Harlan Krumholz: Yeah, no, this is great.‌

Howard Forman: Yep.‌

Harlan Krumholz: Look, I thought I would tack a little bit towards the business side in the beginning today because I’m just fascinated by this thing with Walgreens. Everybody knows Walgreens, they’re on every corner, right? It’s like—‌

Howard Forman: Yeah.‌

Harlan Krumholz: ... what’s going on. I wanted to dig into this a little bit with you because, well, you’re a business school teacher.‌

Howard Forman: Yeah.‌

Harlan Krumholz: Right? So you can help me understand this. So they go private, Walgreens—‌

Howard Forman: They kind of go private. Yeah.‌

Harlan Krumholz: Well, Walgreens Boots Alliance is being acquired by a private equity firm, Sycamore Partners, for about $23.7 billion, but actually it’s not $23.7 billion in the sense that this is about debt and other liabilities.‌

Howard Forman: Right.‌

Harlan Krumholz: So shareholders get about, I don’t know, 12 bucks per share up front, potentially another $3 per share if there’s monetization of these assets from VillageMD, Summit Health and CityMD.‌

Howard Forman: Right, which they’re in the process of selling. Yeah.‌

Harlan Krumholz: That’s right. So this supposed to close by the end of Quarter 4.‌

Howard Forman: Right.‌

Harlan Krumholz: ...this year, subject to all regulatory and shareholder approval. But I thought this was so interesting because you take this company, it’s well known. It’s actually a British Company, isn’t it? Because Boots bought them.‌

Howard Forman: So Boots bought them, right. Walgreens was a U.S. company, but Boots, which is an old, old, old company, bought them, I don’t remember how many years ago, but they’re part of that.‌

Harlan Krumholz: So their peak valuation was a hundred billion dollars.‌

Howard Forman: That’s the fascinating part.‌

Harlan Krumholz: Right. So about, it was just about a decade ago, and the current deal valuation is really about $10 billion.‌

Howard Forman: Correct.‌

Harlan Krumholz: Because that’s what the equity value is.‌

Howard Forman: That’s right.‌

Harlan Krumholz: And it is just this significant deterioration in value. We think about CVS, we’ve often talked about, well, but they’re tied up in Aetna and they’ve got all these other things. They’ve got PBMs and so forth. Walgreens is much more of a straight play. But then they got involved with these, with healthcare delivery. And this is where I thought still, I know, we have talked about this before, but this was like, people get this bright, shiny object of being able to do primary care and being able to do it well, and I think it didn’t work out that well for them.‌

Howard Forman: Oh, my God. I mean, just let me just say this. This is such a complete destruction of shareholder value over a relatively short amount of time, and there’s no real accountability. If you go back to the people who are integral to making that decision, they’re not giving back the millions of dollars of compensation they got. It’s sort of “heads I win, tails you lose” shareholders. They’ve obviously had some losses in the shares they own, but my God, the comparable type of destruction of shareholder value is when Time Warner was acquired by AOL.‌

Harlan Krumholz: Well, that’s the famous one, right?‌

Howard Forman: Yeah, I mean—‌

Harlan Krumholz: That’s incredible.‌

Howard Forman: But it’s just such an abject failure of leadership.‌

Harlan Krumholz: But and the part I wanted to just take a few minutes to sort of unpack with you, so Walgreens was initially invested in VillageMD with the hopes of transforming from a traditional pharmacy retailer into a more integrated healthcare services provider. They were getting into the healthcare delivery business, and now their VillageMD now includes Village Medical, but also these other two that were delivering primary care mostly around New York City, in the Northeast, Summit Health and CityMD.‌

And so they sort of wrapped it all together. But as part of this deal, it’s important to know that VillageMD owes Walgreens approximately $3.4 billion in debt as of early 2025. And this has a 19% annual payment in kind interest rate, meaning it compounds significantly if not serviced properly. And when people say, “Well, how does this work?” well, Walgreens owns these entities, but for these entities to continue, they sort of were essentially borrowing money from the mother ship and now have on the books this—‌

Howard Forman: Right. Liability.‌

Harlan Krumholz: ... 3.4 billion-dollar, 19% payment in kind.‌

Howard Forman: Yeah. I didn’t know that part. That’s crazy. That’s crazy.‌

Harlan Krumholz: And so due to these pressures, Walgreens seeking to monetize these assets through its divestiture, but they couldn’t make, really, this VillageMD thing work. And so VillageMD was supposed to be this highfalutin primary care that was going to be like MinuteClinic within the pharmacies, and it just didn’t go.‌

Howard Forman: I mean, again, to me, they follow the lead of CVS and Walmart and several others that have in-store clinics and they executed poorly or they made the wrong choice of acquisition. But whatever it is, all I look at it and I just am reminded of the fact that real shareholder value was destroyed in the process. And I think we’re going to see more such things over time. I think a lot of companies, the Amazons and the Googles, when they destroy shareholder value, it’s sort of a rounding error inside these trillion-dollar-valuation companies. But we’re see more companies having done this. Look, Aetna purchased Oak Street. I certainly hope that was a good acquisition, they’re going to make money off of it, or at least that they made a smart choice and that Oak Street is going to transform healthcare in a positive way. But that’s another one to watch.‌

Harlan Krumholz: Yeah. So just to kind of wrap this, to me it was so interesting because, so in 2015, they’re worth a hundred billion dollars before they become a healthcare delivery company. They are a retail pharmacy.‌

Howard Forman: They do a good job. Right.‌

Harlan Krumholz: It’s a very good business.‌

Howard Forman: Yeah.‌

Harlan Krumholz: And then what they do is they put a billion into this VillageMD in beginning, in initial investment—2020. 2021, they put another $5.2 billion, bringing their stake to 63%. They start bringing in these others, and before you know it, it sort of sinks the ship, because—‌

Howard Forman: I mean, the leadership sunk the ship. I mean, it can’t be just VillageMD, but they took the eye off the ball. They made this their focus and they ultimately created a nub. Now, it is possible that in these private hands, they’re going to recoup a tremendous amount of this value. And again, it will actually be, in my opinion, somewhat dishonorable if there really is $50 billion in value there, and they’re going to now be able to untap into it when they go private, because then the shareholders lose twice. But we’ll have to see how that turns out. But there’s no question, this is a case study for business schools to look at about destruction of shareholder value.‌

Harlan Krumholz: And I do want to say that it is interesting because VillageMD brings in about $6 billion in revenue now. It’s projected to decline about 22% for 2026. So it’s not like it wasn’t generating...‌

Howard Forman: Revenue.‌

Harlan Krumholz: Revenue. But they couldn’t figure out how to do it. So I think in the end, this was this retail mindset versus healthcare reality. Gosh, we know how to sell drugs in the drug store, or we know how to do retail, so we should be able to do healthcare. They couldn’t. The challenge of integrating and merging the high cost structures and integration challenges, all that stuff ends up bedeviling them. ‌

Howard Forman: It’s sad. I mean, it’s just very frustrating to watch. I think in the current climate of higher interest rates and a stock market that’s unstable for a number of reasons, we’re going to see more such failures.‌

Harlan Krumholz: So my question is going to be, is Amazon going to make One Medical work? I mean, that’s the one that’s sort of still standing.‌

Howard Forman: Right. If One Medical and the coordination, like I said, of Aetna along with...‌

Harlan Krumholz: The Oak Street.‌

Howard Forman: Oak Street, and then the...‌

Harlan Krumholz: Oak Street, they also purchased Iora, right? That was the...‌

Howard Forman: Yeah. Did Oak Street? I lose track of who. We also had, Rubicon was acquired by Oak Street, I think. Right? Was Rubicon acquired?‌

Harlan Krumholz: Anyway, they’re all trying to figure this out.‌

Howard Forman: We’ll see.‌

Harlan Krumholz: It hasn’t been a big win. Meanwhile, just on a coda here for primary care: My friends at Mass General tell me that they told the employees of Mass General, “You should go to One Medical because we have no capacity for primary care here and you need to go elsewhere.” So the big medical centers are also struggling with primary care.‌

Howard Forman: And One Medical is really a group that targets richer-than-average people with commercial insurance.‌

Harlan Krumholz: Yeah. They’re not focusing on poor.‌

Howard Forman: Yeah.‌

Harlan Krumholz: Okay, hey, let’s go to something on your mind.‌

Howard Forman: Yeah. I have a number of things. Maybe I’ll just start off with from the top of my list here. The Trump administration this week issued a new regulatory statement about the ACA for this coming year. So we’re talking about really November, December, January. And people sometimes ask, “How...” I think you may have even asked, “How can the Trump administration impact Obamacare without legislation?” And there are a lot of ways; this is just one quick example I’ll mention. They can reduce the enrollment period, which they’re going to do by one month, make it one month shorter so people can enroll.‌

Harlan Krumholz: And I was having trouble tracking the rationale for that. I mean, maybe the rationale is to hurt Obamacare, but they did articulate something that was a reason that they thought made it more efficient. Did you see that?‌

Howard Forman: I mean, they want to reduce the amount to spending on it, and they want to reduce the effort for navigators. I mean, it costs. Everything that you do to keep things open, it has a cost. So there are, you could make a legitimate case of cost. They can say that people have the opportunity. They also want to reduce the adverse selection that might occur by allowing people to sign up very late. So those are some reasons that they can offer, but without a doubt, it will reduce enrollment. We’re just going to see that. They don’t see that as a metric of their success. I do. They’re also removing eligibility for DACA, which is the Deferred Action for Childhood Arrivals. These are people who arrived here in this country undocumented as immigrants, but they arrived sometimes as neonates or infants or even five-year-olds. They have no choice in the matter. They’ve now been here for a long time. They are currently qualified as DACA, as Deferred Action for Childhood Arrivals. And under Biden, DACA recipients qualified for Obamacare exchanges if they qualified, and they’re taking that away.‌

They’re also reducing coverage for transgender children and adults under the ACA exchanges. On the margin, each one of these things will impact enrollment and coverage that’s out there. So I’m just raising it for people to understand what’s going on. This is within their remit, unlike a lot of other things that I think are very much subject to court rulings against them. And I think a lot of things will be overruled by the courts. This is one of those things where on the margins, they’re allowed to change regulations. They have to have public comment, and likely these things will hold.‌

Harlan Krumholz: That’s amazing. Yeah. But, and I feel like we’re just getting started, right?‌

Howard Forman: So much that’s going on right now, and we promised to give an update on the nominees during this episode, and I think it would be premature to do too much of that because we’ve had some hearings, but we haven’t had confirmation votes. But again, as I’ll mention when we get up to talking a little bit about measles, again, it’s a reminder that our health institutions are not necessarily delivering on science right now. There’s a lot of ideology. I’m going to talk more about that in the next segment.‌

Harlan Krumholz: So the buzz on going through the committees for the nomination, just to say one thing about it, was that they sort of flew through. Was there anything you heard or picked up on in those really pretty short sessions that they had with Bhattacharya and Makary?‌

Howard Forman: I think that Jason Abaluck, who’s our faculty member at the School of Management, a health economist who’s been widely quoted in the press about Bhattacharya, I think said it best that in many ways a lot of people look and say, as much as you can criticize about Bhattacharya, and as much as there are some real inconsistencies between the things that he’s espoused and the things that he previously believed and the things he’s saying now, at the same time, anybody who would replace him would probably be worse. He’s a very smart man. He’s trained very well. He has done really good work in the past, and so there’s this almost a concession at this point that these are not the people to fight in a big way because you could get much worse.‌

Harlan Krumholz: He’s an outcomes researcher, so.‌

Howard Forman: Yeah. No, he’s a smart guy. It’s really unfortunate that we’re in the situation we’re in right now.‌

Harlan Krumholz: Yeah. All right, let me pivot to, since we’re talking politics, so just let me, I’ll stick with this for a second.‌

Howard Forman: Yeah.‌

Harlan Krumholz: So as you know, Republicans are proposing significant cuts in Medicaid as part of a broader budget negotiation framing, and they’re talking about a focus on waste, fraud, and abuse. This is now becoming the keywords that people are using. Central to this argument is a controversial report by a conservative think tank, Paragon Health Institute, and another one, Epic, which claims that the true scale of improper Medicaid payment is far greater than previously reported. The arguments are that the aim to reduce Medicare spending by more than $880 billion in offset is going to be able to focus a lot on this waste, fraud, and abuse issue.‌

And the conservative think tanks argue that the real figure is not the $500 billion that has been discussed in some official government reports, but is as high as $1.1 trillion because the government audits excluded significant eligibility and verification errors. Here’s what I wanted to ask you, Howie. First of all, of course there are concerns that this is coming from people who’ve got an agenda, but even if you take the $543 billion in waste, fraud, and abuse, how did we get to that in Medicaid? Because it does seem like there is some agreement that maybe that’s the low-end spec, whether it’s $1.1 trillion or not. I saw on TV that people were sort of arguing saying, “Well, it’s not $1.1 [trillion], it’s only $543 billion.” I’m going like, “What?”‌

Howard Forman: So I think the first thing for people to understand, I’m not an expert in this, but fraud is fraud. Fraud is illegal. Most of the fraud that we see with Medicaid is with provider-side fraud. It’s people creating mills where they bill for things that they didn’t do or creating encounters that they didn’t have, so on and so forth. A lot of what is included in this report is in the category of waste and abuse. And in those categories, there are lots of areas where there is true waste going on, where in a given state, they may make a payment for a patient who actually is not enrolled anymore. There are cases where they’re spending, I mean, one example that I saw of a good example of sort of waste is, it’s a southern state. I don’t want to pick on it right now because I’ll probably get it wrong, that they actually are spending way too much money trying to root out work requirements in that state. So there’s lots of different areas. I happen to think there’s probably a lot of wasteful spending in Medicare and Medicaid and private insurance and all, and we should root as much of it out as we possibly can.‌

Harlan Krumholz: But these numbers are so large and a lot of what’s being said, I mean the Democrats are saying, “Look, these are administrative errors rather than intentional fraud.” Like you’re saying, it’s not that people are sitting there trying to do these. And a lot of what’s being called out are eligibility errors, saying that there are a lot of people on the rolls who are being given these benefits who don’t quite meet it, and it could be insufficient documentation, failure to conduct timely eligibility reassessments, misclassification.‌

Howard Forman: Yeah. A lot of them do qualify, but they’re not in the system as having qualified. So a lot of it is somebody let something terminate. If they go back and check, they’ll find out the person does qualify, but they didn’t during that encounter. And so it gets kicked back and has to be reclassified at some point. Remember, we’re talking about those numbers over a ten-year window. We’re not talking about those numbers—‌

Harlan Krumholz: It’s still a lot of money.‌

Howard Forman: It is a lot of money. And we should pursue it.‌

Harlan Krumholz: Let me just say, one thing that strikes me is that people who are critical of this are basically saying the exact i wasn’t dotted and the t wasn’t crossed.‌

Howard Forman: No. Right.‌

Harlan Krumholz: But that largely, these are people who need healthcare.‌

Howard Forman: Right.‌

Harlan Krumholz: It’s not like there are wealthy people who are being considered to be Medicaid. It’s just that we’ve got a system that we leave so many people out and some of these people, yeah, they get sort of rushed onto the rolls. And but, I bet if you really studied who’s getting the benefits, these are largely people who can’t afford healthcare.‌

Howard Forman: I think that’s still true. And I think that even, let’s take that at face value. We should consistently do as much as we can to root out every example of waste, fraud, and abuse. It is ironic, of course, that one of the first things that was done by this administration was to fire the inspector general and the Office of the Inspector General for HHS. That is literally the entity that every year does thorough investigations to find fraud, root it out, refer cases where they need to be referred, to do audits where they need to be audited, to tell Congress what they might do legislatively to fix the problems.‌

That was fired right from the beginning. And I’ve looked at those reports in the past. They are brutal. I mean, the things that are wrong in our system are widespread. We should be doing more about that. I just find it, this is becoming unnaturally convenient to be able to put this on the backs of somehow people are living off the system very large when in fact most of what we’re talking about on the margin are mistakes of either data entry, coding, and classification.‌

Harlan Krumholz: It does seem to me that the real solution here is not just saying we’re going to make these large-scale cuts but to modernize the system so that we can execute on the programs with greater confidence that we are in line with the legislative mandates. And I mean, I would just love to see a strong emphasis on saying we can improve the way we’re doing the system rather than... The cuts are likely to maintain the percentages of fraud, waste, and abuse. It’s not necessarily elevating performance.‌

Howard Forman: I think that one of the things in one of these two reports was really targeting the fact that most states in this country have figured out how to game the formula for payments.‌

Harlan Krumholz: And there’s incentives for them to do that.‌

Howard Forman: Huge incentives. And as far as I know, as of a couple of years ago, it was like all but one state. I mean, everybody has figured out how to game the system. Congress can fix that. Congress can fix it. If that’s what they want to fix, they should fix that.‌

Harlan Krumholz: Although one of the reasons to game the system is that Medicaid is underfunded. And so all the states are losing money on Medicaid. So what they’re trying to do is to figure out, they’re not doing it to make immense profits. They are state governments. What they’re trying to do is to figure out how to keep float the ship. And—‌

Howard Forman: Exactly.‌

Harlan Krumholz: ... I think I’ve told you before, a third of the states in the U.S. spend more than half of their budgets on healthcare, of which Medicaid is a big part.‌

Howard Forman: But there’s two things that states have big budget items: Medicaid and education. And you want to maintain them both. They have both importance.‌

Harlan Krumholz: Yep.‌

Howard Forman: Another topic, again, this is related to politics, but I’m really going to try to spin it a little different way. The New York Times reported about hundreds of words that the agencies under the federal government are being told—‌

Harlan Krumholz: I saw that.‌

Howard Forman: ...to avoid or filter. And the words include things like “bias,” “health equity,” “biological male,” “DEI,” and like I said, about a couple hundred more things.‌

Harlan Krumholz: We’re going to make sure we don’t use any of those words in our grants.‌

Howard Forman: No, exactly. Got to get rid of a lot of words. And this is what I’m getting at here. So we’re now seeing more reporting of how private firms, and in this case I’ll talk about Google, are responding to this emphasis. And Google has replaced the word “health equity” with “health optimization.”‌

Harlan Krumholz: You saw that you don’t have a health equity officer anymore? They have a...‌

Howard Forman: Health optimization officer. And their website’s, everything, same thing. And by the way, those two terms do not mean the same thing. Certainly health optimization is at the root of health equity, but if we really want to talk about health equity, it’s not just health optimization, it’s more than that. Instead of using the phrase “drivers of structural and social determinants of health,” which is a term of art that is used in health services and in the public health literature, they now say “non-medical drivers of health.” And so we’re refining our language because we’re afraid of the overlords, of the people.‌

Harlan Krumholz: How brilliant was George Orwell?‌

Howard Forman: I know. This is exactly.‌

Harlan Krumholz: How brilliant was he?‌

Howard Forman: Right? I mean, we really are living through this... Nineteen Eighty-Four, but it’s a little late. Google... and Google’s—‌

Harlan Krumholz: He was just off by a few years.‌

Howard Forman: A few years, right? Google’s not alone. I know of people in a large array of organizations—and we both know them—who are afraid of using certain terms in their grants because they know that it’s going to trigger.‌

Harlan Krumholz: Everyone.‌

Howard Forman: Right.‌

Harlan Krumholz: Everyone.‌

Howard Forman: Right. And I’m sympathetic to these individuals, and I’m not being judgmental at all. I think if I were submitting a grant, I would look at ways to be cautious about the way I use words. And as long as I’m not compromising what my goals are, I would feel comfortable with changing the words if it achieves the same goals. But it is really, really unfortunate this is what we’re living through right now.‌

Harlan Krumholz: It’s having a major effect. It’s a major—‌

Howard Forman: Absolutely.‌

Harlan Krumholz: I think it’s a major effect how people think, how people talk, how our... what’s going on with—‌

Howard Forman: Our leaders.‌

Harlan Krumholz: How our leaders are conducting themselves. And like you said, it’s going across all industries, but...‌

Howard Forman: And the public sector. Our governors and mayors are afraid to say things to offend.‌

Harlan Krumholz: All right. I’m going to go to something a little more whimsical.‌

Howard Forman: Yep, go ahead.‌

Harlan Krumholz: I thought I just to add a little lightness to this.‌

Howard Forman: We need it.‌

Harlan Krumholz: So have you seen these headlines about asking the question whether we age in spurts? Have you noticed this thing?‌

Howard Forman: From you only, honestly. I had not seen it until you told me about it.‌

Harlan Krumholz: No, no. But people are talking about it. There’s a New York Times article about it recently that was... and these headlines are leveraging off of a Stanford-led study that’s suggesting that we don’t age steadily. It’s not like one year after the other. And the thing that surprised me was that the message came out that we age in two distinct bursts, one at age 44 and one at age 60. And then, like I said, a lot of popular press jumped in on this.‌

And by the way, it sort of makes sense that some years things happen or you may age faster. But let me just put this in perspective. This Stanford study tracked 108 people, only 108 people. And these people were aged 25 to 75, and they did, Mike Snyder and his group, Mike had affiliation with Yale at one point. Mike, they used extensive sort of multiomics data. They basically looked at every single thing they could measure biologically about these people, the microbiome, proteomics, transcriptomics, the genome, and so forth, everything they could do.‌

And they said that they observed nonlinear molecular changes suggesting ages may occur in waves rather than steadily. And they found these two crests. But here’s the weird thing. The study didn’t say, “Here were thousands of people that we measured things in every year over the course of their lifetime.” They have people along a wide range of ages, only 108. The median follow-up time: 1.7 years. So they took a couple measures over a couple of years.‌

Howard Forman: So it’s much more cross-sectional than temporal. Yeah.‌

Harlan Krumholz: There’s a mini-longitudinal piece to this, but this is really speculative. And by the way, I think it’s interesting to say now there’s a hypothesis and we need to be able to study it. But gosh, it is such overreach to say you’ve got a hundred people of wide range of ages. You get a couple measurements over a course of a couple years on typically. And then you’re going to be able to say that there are two distinct spurts at age 44 and at age 60? I mean, this is what we would call overfitting the data. You’ve got data and you’re kind of finding that.‌

Howard Forman: I’m happy to hear you be critical of it because it really, I mean, it did shock me a little bit when you sent over the article to look at it. I thought you were going to take a different view on it. And I don’t know enough to be skeptical of it. These people are real scholars; I’m not in this topic. But I am enormously skeptical. I think people individually probably do age in spurts, but they age at their own pace.‌

Harlan Krumholz: Yeah. So it can be true, true, but they’re unrelated. It can be true that there are waves. That’s an interesting idea. My concern also was that people start getting in their heads, something special happens to everyone at age 44 and everyone at 60, and this study just didn’t have the gas to be able to do that at all.‌

Howard Forman: I’ll say from the point of view of a radiologist who looks at abdominal CT scans all the time and brain CT scans all the time, it is shocking to me how much people differ in terms of their aging. There are people that you look at a CT scan and you’re reading it and you’re thinking they’re 39 and they turn out to be 65, and then the reverse happens as well. And the other day I was looking at a head CT on somebody and I was thinking to myself, “Oh, that’s unfortunate. He’s got a problem in his cranium, and but otherwise looked really well-preserved.” So I was looking, how old is he? He was 103.‌

Harlan Krumholz: Oh, my goodness.‌

Howard Forman: A hundred and three. And if you would have asked me how old that person was without knowing anything else, I would have said pretty old, probably in their 70s or 80s.‌

Harlan Krumholz: And this is where we really do want to understand the super-agers. And I will tell you where I think that the non-linearity takes off where people no longer, “it’s one year equals the next year.” It is at the upper age spectrum. I mean, the difference between 80 and 90 is a much different than 40 and 50. But still, there are people who seem immune to it. My mother-in-law, she is amazing. And she had a major fall, broke her ankle, a compound fracture. She had it repaired. And she’s doing wonderfully now, wonderfully now. But there’s many other people who, like, one trigger, they just don’t have the resilience, and it sets them in a different direction. And thank goodness, I know your mother’s recovering and...‌

Howard Forman: She’s doing great. She’s, I think, doing very, very well. But I agree, you look out there at the spectrum of people, a lot of people, sudden decline and that’s it.‌

Harlan Krumholz: So we have a lot more to learn about that.‌

Howard Forman: Yeah. So I got a topic that is good news. It may not be whimsical, but it’s good news at least. The CDC reported a new paper, with including our own Linda Niccolai from the Yale School of Public Health, professor.‌

Harlan Krumholz: The CDC is putting out papers now?‌

Howard Forman: The MMWR, the...‌

Harlan Krumholz: Is now publishing.‌

Howard Forman: Is back to publishing again. And I was almost surprised that this came out. It was almost like purposely timed this way. It was on the effectiveness of the HPV vaccine.‌

Harlan Krumholz: Oh.‌

Howard Forman: And it’s just an observational report. It’s not the greatest science in the world. I’ll tell you what it is, and you’ll understand why I’m saying that. But the vaccine, for our listeners, was introduced by Merck in 2006. And as most of our listeners know, HPV, human papillomavirus, has been implicated in multiple different types of cancers. And the most common ones are cervical cancers. And when you’re talking about cervical cancer, the time from infection to late-stage cervical cancer death is actually a long, long time.‌

So the vaccine was never tested to prove that it prevents death. It was tested to prove that it prevents HPV infection, with the idea that that would prevent death and morbidity with that. And so what did they do? They looked, since we’re now 19 years after the introduction of the vaccine and the recommendation by the CDC that all adolescents get vaccinated, they looked at what are the rates of HPV cancers, or in this case, pre-cancerous lesions.‌

So they looked at pre-cancerous lesions and they found that among the youngest cohort, I think 19 to 24, they reduced the likelihood of having these pre-cancerous lesions by 80%. Now, it’s not that they looked at people who were vaccinated, they looked at the entire population and saw a reduction of 80% in these cancerous lesions over time. So they’re not matching it to the individual, they’re just looking at the—‌

Harlan Krumholz: Over time, yeah.‌

Howard Forman: Over time. And they found a 37% reduction in a slightly older age group, which also makes sense because that group had a less likely chance of having been fully vaccinated prior to the initiation of sexual activity. So those people had a greater likelihood of getting HPV even before they got their first shot.‌

Harlan Krumholz: So how did they take into account that younger people are having less sex today than similar cohorts in the past? And by the way, fewer teenage pregnancies, maybe people attribute it to screen time or the way in which people are socializing now, how are they able to take that into account?‌

Howard Forman: They really can’t. I mean, they’re just making an observation here, and I think we’re going to get a lot more data on that. I don’t think that we’re seeing 80% less sexual activity.‌

Harlan Krumholz: No, that’s true. That’s true.‌

Howard Forman: And so I think that we’re seeing a real effect here. I think it’s going to grow. I also think it’s important to know that less than 80% of people are vaccinated, which suggests that there’s even, I mean, just suggests—this is a stretch, they don’t say it—that is a herd effect, which is to say that fewer people that are getting infected mean fewer people are spreading it to people even if they’re not vaccinated.‌

We’re going to continue to watch this. I bring this up and the reason why I say it is political is there is an argument made by RFK Jr. and his law firm that the HPV vaccine has untoward effects as all vaccines do, but some that have not been disclosed. And so there are lawsuits that are continuing even now against Merck for the HPV vaccine. But this is yet more evidence that the vaccine does actually work and has protective effects for both the uninfected and the unvaccinated.‌

Harlan Krumholz: And the reason I was asking you how they took that into account, I could imagine you could normalize it based on—you know, sort of understand it better—by looking at the rates of other sexually transmitted diseases. And so if those have been going down, you could just sort of adjust by—‌

Howard Forman: It’s a valid point.‌

Harlan Krumholz: ... the ones that wouldn’t be infected by a vaccine. But that sounds very interesting. I’m really glad they did it. It’s always the question, which is there’s an expectation that that’s going to happen, but it’s good to confirm it in practice. All right, I got one more for you.‌

Howard Forman: Yep.‌

Harlan Krumholz: Here at the end, because I know your favorite virus is norovirus.‌

Howard Forman: Yes.‌

Harlan Krumholz: And I know it’s not your favorite.‌

Howard Forman: No, I know.‌

Harlan Krumholz: We’ve talked about noro—‌

Howard Forman: We’ve talked about it several times.‌

Harlan Krumholz: ...noro before, for how it can put people off. So this, just to remind people, highly contagious virus causing acute gastroenteritis and particularly severe in older adults. But it really knocks folks out. I mean, this is one of the worst things that you have. And it spreads. This is the kind of thing on cruise ships that basically...‌

Howard Forman: It’s not as infectious as measles, but it’s damn close.‌

Harlan Krumholz: Not as infectious as measles, but it’s close. So there’s a new oral norovirus vaccine tablet that’s shown some promising early results in older adults. And of course there’s a very early trial. It’s a phase one. It goes phase one, phase two, phase three is when we largely tested in large numbers of populations to see if it’s safe and effective. So this is basically just trying to look at it. But norovirus affects maybe 20 million people a year with this sort of illness and causes 70,000 hospitalizations, 800 deaths. Vaccine would be really helpful.‌

This oral tablet uses a non-replicating recombinant adenoviral vector to deliver norovirus antigen. So what it essentially does is, it’s able to, in a pill form, expose you to sort of a non-disabling type of something looks like the norovirus and help you to develop immunity to it. Easy administration, no needles. This is just, some people take a pill. Of course, it is a gastrointestinal thing. In this study, just to tell you quickly, 65 healthy adults received the vaccine or placebo at three different dose levels, and it was safe and well tolerated.‌

They had almost no side effects. And that it induced a robust dose-dependent antibody response detectable in the blood to norovirus. And this is what to me was the most important thing, mucosal immunity. So people talk about this because we’ve talked about this with COVID. If you could get the nose at the level of the interface between the air and your body, that’s the mucosa of your nose, to resist the virus, you could keep it from entering your body. In this case, the norovirus, they’re seeing mucosal immunity. That is the villi, the...‌

Howard Forman: Yeah.‌

Harlan Krumholz: What’s going on in the gut, right at that—‌

Howard Forman: How we absorb food.‌

Harlan Krumholz: ... surface level.‌

Howard Forman: Yeah.‌

Harlan Krumholz: Exactly. You see IgA [immunoglobulin A] detected in saliva and in the mucosal lining, nasal lining suggested that it could protect the entry points for the virus. Anyway, I just thought it was pretty interesting.‌

Howard Forman: But you did say, which shocked me a little bit, that we’re actually getting immunity at the blood level as well. So the antigens are making it through that barrier and getting some blood immunity as well, which is interesting to me. It is important for our listeners to understand, though, that the reason why you can give this as a pill is because you want the mucosal immunity more than anything else. A lot of other pills would get digested up in the stomach and somehow they’re able to at least get past that as well.‌

Harlan Krumholz: And I think the way it would be used is if there was an outbreak, if there was, if risk elevated, people could take this.‌

Howard Forman: Listen, if it works well, as we talked about before, norovirus is lethal in the youngest and the oldest. I mean, that’s where it’s risky. If it works, I think we would more broadly use it.‌

Harlan Krumholz: Maybe people going on cruises.‌

Howard Forman: Yeah, right? I would. So I’ll give you one last quick thing just because I think it’s still worthwhile to talk about measles. I give a quick update on that.‌

Harlan Krumholz: Yeah, people are going to want to know.‌

Howard Forman: Yeah. So we’re up to 14 states right now that have at least one measles case. The biggest outbreak remains this West Texas outbreak, which is 230 cases and 23 hospitalizations and one death in Texas, and then in adjoining two counties now in New Mexico, 33 cases and one death in an adult. That’s where the biggest outbreak is. It’s hard to know whether any of the other cases relate to the Texas outbreak, although there’s a lot of suspicion that the two newest cases in Oklahoma are related to that outbreak. But most important that I just want to convey again and again, I won’t stop saying it for our listeners, is to understand sporadic cases that come from an international traveler, while bad, we’d love to avoid them, are not catastrophic. Because if a sporadic case moves into a community that has very high vaccination rates, there will not be an outbreak.‌

You might get one more case, even two more cases, you won’t have an outbreak per se. The thing that we’re most worried about, all of us, you, me, our listeners should be worried about is if any of these cases lands in another community like Gaines County that is grossly under-vaccinated, we will get a massive outbreak. So when you hear that someone was seen at Johns Hopkins Medical Center or in I think BWI Airport, or maybe it was Dulles or LAX airport and that that person was known to be infected while they were passing through a very busy area, that’s where we should start to worry about having another nidus starting up in another area. And then it can go on from there to there to there, and you could have thousands of cases.‌

Harlan Krumholz: And do we have any evidence of people who have been vaccinated, even those in that sort of period, 1957 or something to 1963 or something, we were talking about that before. Any evidence that any of those people are among these who are infected?‌

Howard Forman: We know that there are, I believe it’s five cases in the West Texas outbreak. None in New Mexico so far, but five in the Texas side of the outbreak that claim to have received one or more vaccinations and got it. None of the death—‌

Harlan Krumholz: A long time ago?‌

Howard Forman: We don’t know the dates of that. I mean, it’s very limited the information we get, unfortunately. I think the good news, I hope, because I really do think this will happen, is the CDC will publish much more detailed reports. We’ll see it, hopefully in The New England Journal of Medicine and elsewhere, that will start to drill down about exactly what these cases look like. But as of now, we don’t know more than that.‌

Harlan Krumholz: Well, that’s great. Thanks for the update. You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.‌

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, email us at health.veritas@yale.edu or follow us on any social media, particularly LinkedIn or Bluesky.‌

Harlan Krumholz: And we love your feedback. Feel free to send it to us, rate us. It helps people find us. We read all the stuff that comes in.‌

Howard Forman: We really do. And I have thoughts about something that we’ll follow up in future weeks. If you have questions about the MBA for Executives program at the Yale School of Management, reach out via email or for more information, go to our website at som.yale.edu/EMBA.‌

Harlan Krumholz: Health & Veritas is sponsored by the Yale School of Management and the Yale School of Public Health. And we are fortunate to be working with our stellar students, Sophia Stumpf, who’s here with us today, as well as Inès Gilles and Tobias Liu, and with our fabulous producer Miranda Shafer, who somehow still puts up with us every other week.‌

Howard Forman: We are really fortunate. We’ve got a great machine and we’re saddened to know that Sophia and Inès will graduate this year, but we’re happy that they will graduate nonetheless.‌

Harlan Krumholz: Yeah, they’re stars. All right, talk to you soon, Howie.‌

Howard Forman: Thanks very much, Harlan. Talk to you soon.‌