An HIV Breakthrough and Other News

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

Howard Forman: 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. Usually once a month right now, we’re aiming to have one segment, one episode without a guest. Today, we’re in the studio together.

Harlan Krumholz: It’s great to see you, Howie.

Howard Forman: It is, and it’s fun. It really has a very different feeling when we’re together.

Harlan Krumholz: Yeah, summer session. Students aren’t around. It’s hot outside.

Howard Forman: It’s hot outside. We’re both in polo shirts, as opposed to any type of dress uniform.

Harlan Krumholz: Suit and tie.

Howard Forman: Suit and tie, of course.

Harlan Krumholz: We’ve got tuxes.

Howard Forman: Yes, the tuxes. It gives us an opportunity to really cover a lot more hot topics.

Harlan Krumholz: Oh, my God. Every week we want to cover so many things, and we just don’t have time.

Howard Forman: We can’t do it. So today, what do you got for us?

Harlan Krumholz: Well, let me give you a couple of quick things. First of all, you know last week I was at Aspen Health.

Howard Forman: I know you were. I know, with all of our friends.

Harlan Krumholz: I’m so indulgent, so indulgent. It’s a beautiful scenery. There’s a lot of smart people there, a lot of people from government. You know what bugged me was, almost everyone I ran into said, “Howie really influenced me. He really made such a difference in my life.” I hear that one more time, I’m just going to—

Howard Forman: There were a lot of friends there. And to be fair, a lot of those people were texting me and saying, “I ran into so-and-so, and they said hi.” It was very nice. Even though I wasn’t there, I felt like people were including me.

Harlan Krumholz: I thought it was a great session. It was a good place to learn about what’s going on in government. Ruth Katz, our friend we had on a couple of weeks ago, runs it. And it was a really great event. So anyway, I wanted to at least highlight that. This week is our first issue of JACC. It was known as the Journal of American College of Cardiology. Actually, we’re going to change the name just to JACC, because people seem to just like to say “JACC.”

Howard Forman: There’s not going to be a K in it. It’s still going to be J-A-C-C.

Harlan Krumholz: It’s J-A-C-C, J-A-C-C.

Howard Forman: Yep. Congratulations. You haven’t even officially started.

Harlan Krumholz: Well, so July 1st I’m supposed to start. But the first issue is out. Anyway, I just wanted to say to anyone on the podcast, you can take a look at the first issue. It’s full of great science. It’s got a great review of medical history, cardiovascular history with lessons for clinicians and researchers. It’s got a great piece by Rohan Khera on artificial intelligence. The FDA commissioner—

Howard Forman: I saw you tweeting that, yeah.

Harlan Krumholz: ... came in and wrote a great piece about the relationship FDA to cardiovascular care. Eugene Braunwald, sort of the grandfather of—

Howard Forman: Cardiology, up in Boston.

Harlan Krumholz: ... cardiology also wrote a welcoming piece. And I have a piece that talks about the new era of JACC. And one of the reasons I took on this position as being editor in chief of a major journal was maybe it’s an opportunity to really reshape what medical publishing is going forward and move it away from this very hierarchical model to one in which it’s more about partnership, working together. We each have roles. We only have limited space within a journal. But I think we can be working more synergistically with the community in the common purpose of advancing global cardiovascular health and using the platform, not just the idea of pushing out issues but using the platform in this way.

Howard Forman: Look, and you’ve, just for our listeners, been involved in publishing not just from publishing your own papers for a long time. MedRxiv, which is one of the open access—

Harlan Krumholz: Co-founded with Joe Ross.

Howard Forman: Joe Ross. And that’s been over 10 years now, right?

Harlan Krumholz: Maybe. I think we might have started around 2019. It’s actually been about five years.

Howard Forman: It’s been a while. Okay.

Harlan Krumholz: And that’s been a wonderful experience. I was an editor before. We’ve talked a lot about data sharing and ethics within publishing. So yeah, this was—

Howard Forman: Journal Watch. You’ve been active.

Harlan Krumholz: I was editor of Journal Watch with New England Journal for a long time. But this was an opportunity to take a major journal, it’s a family of 10 journals, and really try to see whether or not we could change it. Some of the things I wrote, I sent out a bunch of tweets and videos. “Transitions are opportunities... full of possibilities, marking a juncture that combines an end and a beginning.” And the hope is that this is a moment to both honor the past and really shape the future. I wrote also that I thought that I envisioned “JACC, with... its strengths as a transformative platform for building community, elevating strong science, influencing clinical practice, supporting career development and improving patient outcomes.” I mean, this is the thing. It’s not just simply standing up on the mountain and letting authors make the trek up to see you, but actually seeing if we can work together holding hands to actually improve outcomes, make things better. So I’m real excited about it.

Howard Forman: Does it feel more or less overwhelming right now that you’ve got one issue out?

Harlan Krumholz: Oh my God, this has been overwhelming to the extent that really trying to think hard about, how do you reshape medical publishing and bring together community people to do that? So I wouldn’t say so much overwhelming as energizing, but yeah, there’s been a lot to do.

Howard Forman: A lot of work.

Harlan Krumholz: A lot to do.

Howard Forman: Yeah, I could tell that.

Harlan Krumholz: Yeah. So hey, what’s your first thing this week?

Howard Forman: So I don’t know, certain topics get me really excited, even if they’re not in my primary field at all. Lenacapavir is an injectable HIV drug that is investigational and undergoing testing for both treatment and prevention of HIV infection. And there are a few things about this trial that just came out that stand out. And by the way, Gilead’s the manufacturer of this. So there are three, actually I think there’s four trials that are underway, testing how effective this is in preventing HIV in at-risk individuals and then also in those who already have it.

The first trial, that completed enrollment and now they did their immediate analysis and stopped the trial because the findings were so shocking, but this was done in cisgender women in sub-Saharan Africa. And by the way, adolescent girls and young women are 63% of all new HIV infections. And that high incidence is continuing despite the impressive improvements the last decade. And the only way you’re going to eradicate HIV is if you can get to this population in particular, which in America is not the population you think about.

Harlan Krumholz: Rates are still high in Africa?

Howard Forman: Very high. And across the world, over a half million people die of HIV. Every year we have a couple of million new—

Harlan Krumholz: You sort of think of it as under control, but—

Howard Forman: Yeah, it’s not. And a substantial part of infections in Africa and in the emerging world are untreated even that exists. So there’s a lot of work that needs to be done.

Harlan Krumholz: Yeah, that’s an issue, treatment.

Howard Forman: Lenacapavir is a twice-yearly injectable drug and it was compared to—

Harlan Krumholz: Subcu injection?

Howard Forman: I believe that’s the case. That’s what it said, subcutaneous. And it was compared to the usual standard of Truvada, which is PrEP. PrEP is pre-exposure prophylaxis, which is widely available in the United States. And it has enormous protection for gay men in preventing HIV spread. Right? So you take Truvada, I believe, every day.

Harlan Krumholz: Why do you say “gay men”? Why wouldn’t it be anyone at risk?

Howard Forman: Because nobody’s done all the studies. And that was part of the reason why this was so important. And without going into too much details, there are biological reasons, rectal mucosa, anal mucosa versus vaginal mucosa, right?

Harlan Krumholz: How they’re getting it. Right, yeah.

Howard Forman: Yeah. And so it is fascinating to actually read about it. But the thing with Truvada is you literally have to be taking it every day, just like the oral contraceptive pill only works if you take it every day. And in certain populations, compliance is going to be lower than that, and sometimes much, much lower. If you are a young woman who might not be sexually active but could become sexually active in the near future, it’s not enough to say, “Yeah, I’ll start taking it when I have to start taking it,” because it could be too late. So the trials ended early because the interim findings were really remarkable. Among 2,000 patients, zero cases of HIV compared to the Truvada group. Not a placebo group; Truvada group. Sixteen cases out of a thousand patients. So zero in 2,000. Sixteen in 1,000. So they stopped it early because it’s extremely effective, and you don’t have to worry about the compliance other than getting them to come back every six months.

This is incredibly encouraging because, like I said, half a million people die every year. And even though it’s declining right now, and infections and deaths are declining, it’s still the second or third leading cause of death. And we’ve talked about tuberculosis and COVID.

Harlan Krumholz: Interesting. So while we’re waiting for a vaccine, vaccine hasn’t come, this intervention might provide the same kind of protection.

Howard Forman: That’s exactly what I’m thinking. I feel like we have spent 40 years, we have talked about a vaccine for AIDS and whether we could have a cure and a vaccine or whatever. And I’ll be honest, as a young gay man in the 1980s, I always thought 10 years is too long, almost. But you still waited and you thought, “Okay, 10 years. We’ll get it in 10 years.” It took about 20 years or close to 20 years to get to a point where you have something approaching a cure. But that doesn’t stop the spread. And there are a lot of people that don’t—

Harlan Krumholz: How does it work?

Howard Forman: Which, this drug?

Harlan Krumholz: Yeah.

Howard Forman: It’s I think a capsid inhibitor. I am overstating that. I’ve read it, but I don’t even remember.

Harlan Krumholz: Yeah, it’s okay.

Howard Forman: But it’s a different mechanism. It’s a mechanism that has been used in other ways, and I believe it will be used as treatment as well as prevention. But twice yearly.

Harlan Krumholz: Interesting.

Howard Forman: So you’ve got about 150 million women in Africa that are at risk. The cost of treatment is going to be really high for them. This is a poorer population. But this may be our first chance to really eradicate HIV globally. You can imagine now getting the reproduction rate for HIV down so low that you basically eradicate the entire disease from the world.

Harlan Krumholz: That’s incredible. That’s incredible. Thanks for sharing that. I hadn’t seen that.

Howard Forman: Yeah. I was blown away by that.

Harlan Krumholz: That’s terrific. So one thing I wanted to talk about, let me pivot now to another topic, this is a little bit different. It has to really do with social determinants. And I really want to tout this thing that’s going on at Rush, Rush Medical Center, major medical center in Chicago. You got Northwestern and you got Rush, essentially. But Rush is really the safety net major healthcare system. Of course it virtually runs Cook County, and it’s sort of managing large swathes of areas of Chicago that have people who are most vulnerable.

Howard Forman: Sort of like the Boston University, Boston Medical Center of Chicago.

Harlan Krumholz: They’re covering highly deprived deprivation areas and areas in greatest need. And I think they have the most visionary CEO in the country, Omar Lateef. Omar’s still young, was a chief medical officer within the Rush system. I mean his roots are actually taking care of patients. Wasn’t trained as—

Howard Forman: I think he is a cardiologist, right? Or—

Harlan Krumholz: No, no, no. He’s intensive care.

Howard Forman: And okay, because he’s a fan of yours. He’s reached out to me.

Harlan Krumholz: No, he’s great. Yeah.

Howard Forman: He’s a fan.

Harlan Krumholz: So I’m a big fan of his. So listen to what Omar’s done with his team at Rush. So they started thinking about, “Okay. How are we going to improve population health?” They really are committed to saying, “What are we going to do? We shouldn’t just be here treating patients. But we got to figure out some ways of actually preventing disease and improving things.” And they look around in the communities that are crack houses and poor, like I said, economic deprivation areas and so forth.

And they started thinking, “We have a lot of vendors at the hospital and we’re outsourcing to multinational corporations to provide services like laundry. So what if we worked with the community to help the community build the capacity to be able to provide some of these services to our healthcare system so we’re not just taking community benefit and giving charity to community. We’re actually building industry within our communities that are run by our community members, training people how to do it and putting them in a position to get jobs, create jobs, and to improve the quality of life for people around them economically as a central lever to improve health.” And it’s been extraordinary. Just today they’re opening a linen factory. I mean millions and millions of dollars are being spent by Rush and all the hospitals for these kinds of services. And what they discovered was there were people in the community who were willing to partner with them, actually own the enterprises, compete for the work. They’ve got to be able to—

Howard Forman: That’s the way to do it.

Harlan Krumholz: ... make it at a certain level. But they were actually holding their hands and helping them to get there. And what he told me was that this thing is just going gangbusters. They built this thing. Now other hospital and healthcare systems for uncompetitive reasons are looking to say, like, “Wow, it’s very cost-efficient. It’s a local business. We can also get our services from them.” And they tore down crack houses. They help, provide capital to be able to start these companies. And again, they’re owned by the community.

Howard Forman: Yeah. So this is good because you’re giving, it’s low-wage jobs in many cases. But it’s low-wage jobs that lead to higher-wage jobs. And it also shows people that enterprise can be a pathway to freedom.

Harlan Krumholz: It may not be lower-wage in the sense they could be given health insurance, they can be given—

Howard Forman: Yeah, exactly.

Harlan Krumholz: ... reasonable wages. Anyway, I was just so inspired by—

Howard Forman: That’s a great story.

Harlan Krumholz: ... that work and that visionary approach. They don’t have to do that. And I hope it’ll set an example for many other places around the country.

Howard Forman: Yeah. So I wanted to talk, you reminded me, I should mention the other issue around Vivek Murthy’s... I’ll do that a little later. But I wanted to just talk really briefly about his announcement yesterday about gun violence as a public health crisis because—and we talked about him just last week about social media. Gun violence is one of these third rails that too many people are afraid to touch. And he almost did not get appointed the second time because of his earlier speaking about gun violence before his first appointment to Surgeon General. So it’s a very difficult topic for a surgeon general to want to tackle. But gun violence is a public health crisis. And that’s what he came out with yesterday with the Surgeon General’s advisory on making the case that gun violence is a public health crisis. He highlighted a lot of statistics including the fact that as of 2020 firearm deaths are the leading cause of death in children and adolescents.

I mean, just think about that, because the other leading causes of death are cancer, cardiovascular disease. We would do anything to reduce cancer in kids, and we would do anything to reduce deaths from cardiovascular problems, congenital heart disease in kids. But when it comes to gun violence, we really don’t do a lot. Part of it is our instinct for the Second Amendment. Part of it is probably a fear of government in general. But for a lot of reasons we have not come together to do anything of substance to fight gun violence. And so his advisory highlights the issue. It draws attention to the fact that we need more research, that we need to do more work about preventive measures, measures around social determinants of violence, as he describes it, measures around translational efforts. How do we take things that we’ve learned and put them into practice and to change culture in communities to make protective measures so that children do not have access to guns?

Remember, a lot of these violent deaths are suicides in young adults and adolescents. So I thought one of the quotes that he said in his video that was attached to this was, “Our failure to address this public health crisis is a moral crisis. And we must now act with the clarity, courage, and urgency that this moment demands.” And we are this week two years out from Chris Murphy’s Bipartisan Safer Communities Act, which passed Congress and signed into law by President Biden. And it does seem to have had some effect on preventing people from getting access. It’s on the margin, it’s not big legislation, but it seems to have caused some change, and we are seeing some reduction in gun violence since that past two years ago.

Harlan Krumholz: Yeah, it’s still way too much.

Howard Forman: Way too much.

Harlan Krumholz: We talked about the social media. Let me just hit down that for a second. He got a lot of blowback about that question.

Howard Forman: About social determinants of violence?

Harlan Krumholz: No, no. Back on the social media advisory—

Howard Forman: Oh, yeah.

Harlan Krumholz: ... because the question was, “Is the science firm enough? Is for some people that beneficial?” So I thought that was very interesting. Then it was also interesting to, he follows right up with this... by the way, he was in Aspen also, with this thing about gun violence. I’ll tell you my reaction to this was, and we both have great admiration for him, I wondered if he should have waited until after the election. I’m not sure at the margin a surgeon general announcement like this is going to fundamentally shift what’s going on in the nation. I’m glad that he’s digging into it. But it also becomes a political issue.

Howard Forman: Yes. I’m terrible with the politics because I could make the opposite argument and say that a lot of people think Democrats need to stop being afraid of this issue.

Harlan Krumholz: But they’re going to vote for Biden anyway. Those people are voting for Biden—

Howard Forman: That’s probably true.

Harlan Krumholz: Anyway, I don’t know. At the margin, there’s some people who love their guns and are uncertain about Trump. This is just—

Howard Forman: Yeah, I hear you.

Harlan Krumholz: I’m just saying the politics you’re getting in the summer, it’s just months to it, he just announced social media, give six months now, come out with a big thing.

Howard Forman: So just in fairness to him and knowing how his office works, these are independently timed. These are developed and independently timed, and he probably has the latitude to say, “Don’t announce them on the same day,” but not timing beyond that.

Harlan Krumholz: Anyway, I’m just saying, look, I think you could give kudos to the Biden administration for not burying it.

Howard Forman: That’s right. That’s right. They could have buried it.

Harlan Krumholz: They’re giving him independence and letting him do it. But I think there is some political risk in this moment where we’re just months to November and this week it’s going to be very interesting on Thursday. This is going to drop on Thursday. Thursday night next week, maybe we can talk about what the debate was like. But anyway, that was sort of my thought.

Howard Forman: I hear you.

Harlan Krumholz: Hey, okay, let me pivot to something else I thought was kind of amusing, amusing in a kind of funny way actually. So JAMA Internal Medicine, one of the leading internal medicine journals publishes a paper this week, “Patient Navigation for Lung Cancer Screening at a Health Care for the Homeless Program: A Randomized Clinical Trial.” And Vinay Prasad takes off on this article.

Howard Forman: We are not fans of him for a lot of things, but we also respect the fact that he’s very bright.

Harlan Krumholz: First of all, he’s very independent-minded. And many of the things he says are true and unequivocally true.

Howard Forman: Right. But he’s a contrarian. This is what he makes his career on, is finding things to... which is good.

Harlan Krumholz: I don’t agree with him on everything.

Howard Forman: Right, exactly.

Harlan Krumholz: I’m sure he doesn’t agree with me on everything, and sometimes he’s—

Howard Forman: He’s right.

Harlan Krumholz: But this was very interesting. So he’s bringing up this paper. I always am loath to criticize someone’s paper. I know they spend a lot of time doing it. But he says, he talks about how this paper takes people who were ever homeless and randomizes them to an initiative to encourage CT screening for lung cancer or usual care. The result was, and I’m reading from his blog, “if you get a push,” the more likely you were to get a scan. But then he sort of goes on—

Howard Forman: By “push,” just to be clear, what they’re assigning them to is having a navigator sort of say, “You should go for a scan.” And these are people that come into the office. These are people that are not just a homeless person on the street but someone who’s already plugged into the system as a homeless patient in this clinic.

Harlan Krumholz: So I just thought this was funny because you see all sorts of different articles, and he’s taking this article, and he’s sort of showing table one, like characterizing. And there’s a very needy, socially needy group, homeless group. And he says, “Imagine this population and ask yourself: What’s the most important thing they need? An apartment, a job, basic blood pressure control, work on existing ailments, perhaps... a shower, a haircut, clean clothes, a hot meal.” And “1 in 4 has a drug or alcohol” problem, “85% are current smokers.” Maybe “they need some addiction medicine.” He goes, now these researchers are digging in and saying let’s get a screening CT scan, by the way, as part of an annual evaluation. Anyway, it just was a question, if you’re a researcher and you’re going to spend time doing things, he’s saying even if lung cancer screening works, it’s contingent on rates of follow-up and a whole range of other things that are probably largely inaccessible to this group. So I just thought it was kind of an interesting thing.

Howard Forman: You told me about this. I hadn’t seen it. It is in my field, radiology, the screening. And what I thought was the most important point he was making to me is just reminding us that we actually have no evidence that this actually saves lives. That is the saddest part, is that we’re investing this much effort into something where the weight of the evidence is still equivocal.

Harlan Krumholz: Well, I thought the reminder also was, what are we studying and how important is it to people?

Howard Forman: No, I get that. Yeah.

Harlan Krumholz: When we started in the Robert Wood Johnson program with this community-based research, one of the first things we learned was, you know, talk to folks that you’re trying to help and figure out what’s important to them. And oftentimes you go into communities and you say, “We want to do X, Y, or Z.” And they’re saying, “We’re concerned about trash and rats.” They’re basic things that you can’t get me to thinking about screening for cancer or my colonoscopy when—

Howard Forman: I’m with you. I’m just saying—

Harlan Krumholz: “I’m trying to put food on the table every week.”

Howard Forman: I’m just saying even for those that might say, but they deserve to live longer too. And wouldn’t this be a good intervention? There really is no strong evidence that this even works, which is what makes it the most painful to me. We do an awful lot in medicine for which the evidence of benefit to the patient may in fact be de minimis or zero. And this is one of them.

Harlan Krumholz: Well, in this case, this was about getting them one scan. But look, you got to build up from the beginning. The fact that they could get them in for medical attention is a good thing. I do want to salute a group that’s studying a very vulnerable population.

Howard Forman: Fair.

Harlan Krumholz: But anyway, it amused me.

Howard Forman: It does, particularly when you frame it that way.

Harlan Krumholz: Of course he’s a gifted writer. It was amusing, anyway. If people want to take a look at—

Howard Forman: I hear you.

Harlan Krumholz: ... the paper or what he wrote, it might be worth a look.

Howard Forman: So let me do quickly just about Murthy v. Missouri.

Harlan Krumholz: Murthy v. Missouri.

Howard Forman: Right. Which is the legal case. And by the way, a lot of people, when they say, “Every time I saw ‘Murthy,’ I didn’t realize it’s actually our friend, Surgeon General Murthy.” But one of the most important Supreme Court cases of this term was Murthy v. Missouri, which was attorney generals and a few other plaintiffs basically complaining to the government that the executive branch, the Biden administration, and that’s where Murthy comes in because he’s just one name among the long list of names, but he’s first.

Harlan Krumholz: But he’s the first.

Howard Forman: Right, so it becomes Murthy, is basically suppressing the speech of people on Twitter and Facebook and other social media through the heavy hand of government by telling them you have to censor this and you have to censor that. And the ruling came back today with a 6–3 majority opinion in favor of Murthy, not on the necessary merits of the case, but on standing.

And by “standing” we mean that they felt that all the people that were suing the attorney generals and others, that none of them were actually harmed by this. They were making a claim, but they had not harmed. So we haven’t really clarified the First Amendment issues per se, but it has been rejected by the courts. Now remember, this is overturning the Fifth Circuit Court of Appeals. So it’s a very big thing. The government has been limited from what they can do because of the court cases that led up to this. Six-three ruling. Amy Coney Barrett writing for the majority with Justice Roberts and the three liberal justices in the majority against, and I’m missing—Kavanaugh as well—against Gorsuch, Alito, and Thomas dissenting. So it was just interesting. I thought I’d bring it up because we’re talking about—

Harlan Krumholz: But is it going to come up again because this is just about standing?

Howard Forman: The issue will come up. But this particular case presumably won’t because if they couldn’t find someone with standing for this case, they’re not going to find it going back to 2020 to begin with. It’d be hard to dig somebody up for that. But the issue will come up again about, how much can the government sort of prod—

Harlan Krumholz: This wasn’t just about health information, though.

Howard Forman: No. It’s all about censoring. But it really was about COVID.

Harlan Krumholz: It was about the pandemic. Yeah, about the pandemic.

Howard Forman: Yeah. So it’s just interesting for our listeners to know, because this is healthcare. This is about freedom of speech. I listened to the arguments, the oral arguments on this case.

Harlan Krumholz: You did?

Howard Forman: And to me, yeah, it’s fascinating to do that.

Harlan Krumholz: You really are a policymaker.

Howard Forman: Oh no, I love this stuff. Yeah. I love the Supreme Court things. And it really was very compelling to me that there’s a big difference between saying to Facebook, “If you don’t do this, we’re going to figure out how to tax you more.”

Harlan Krumholz: I’m just curious, what side of this were you on?

Howard Forman: Oh, I was totally on Murthy’s side.

Harlan Krumholz: And people know that you’re not a Trump fan.

Howard Forman: Not a Trump fan.

Harlan Krumholz: So when Trump comes into office, if he does, and he now exercises this power, won’t you be concerned?

Howard Forman: Same test. The same test is should be put in place. Is there a legitimate threat? Is there actual harm being done to free speech? Are we taking away speech, or is it within the right of government to use its power to…. If somebody were to come to the federal government, then say, “By the way, this information is getting out there, it’s harming people. We can connect the dots to this. We would like you to take down this type of information.” I don’t think that’s unreasonable. And by the way, both sides make these mistakes. And we have civil litigation that has proceeded against Fox and against other companies over election denial.

Harlan Krumholz: Well, okay, look, election denial, I think that there are facts. Some of the things that they were talking about though in the pandemic, again, if you take our—

Howard Forman: Turned out wrong!

Harlan Krumholz: ... reference to Vinay Prasad, he might say that there are things the government thought were true that maybe in retrospect may not have been true, at least are controversial. And they were damping down the kind of public dialogue by making the kind of pressure to not say certain things.

Howard Forman: But at the same time, Twitter resisted, Facebook resisted. There’s a lot of examples where they resisted. It was not the heavy, heavy hand of government. It was government saying, “We learned about this. We think you should look at that.” And then letting them make—

Harlan Krumholz: You and I both feel like ivermectin or hydroxychloroquine, there was a right and wrong answer to those. Even today some people will disagree with us.

Howard Forman: Absolutely. And even today on those things, there is a difference between taking down the tweets and putting community notes on Twitter that say that you should at least know this more information.

Harlan Krumholz: Yep. Hey, I know we’re getting to the end. Just one other thing people might’ve seen in the news that kind of tweaked them was this thing about this sweetener xylitol and whether or not it was harmful. There was an article in the European Society of Cardiology journal European Heart Journal that looked at xylitol. Again, you see it in gum and different places.

Howard Forman: I’ve had it many times in different products.

Harlan Krumholz: I’m sure that even not even noticing sometimes, I think in toothpaste, other things. And the title of the article was “Xylitol Is Prothrombotic and Associated with Cardiovascular Risk.” Now, some of the listeners may remember, I talk about it sometimes, that I published this piece in The Wall Street Journal in 2017 that they put this title on “Why One Cardiologist Has Drunk His Last Diet Soda.” And I had drunk my last diet soda, haven’t had one since 2017. And at that time, I’d really looked at the preponderance of evidence about these sweeteners and was convinced that there was a fair chance that they were actually causing harm and perturbing our metabolic system, causing cardiometabolic abnormalities.

And there’s no evidence that anyone’s ever lost weight on these diet sodas. I spent decades pounding these diet sodas—

Howard Forman: Me too.

Harlan Krumholz: ... trying to control weight and do different things. But there’s not one bit of evidence that anyone who’s taken that strategy has actually been able to better control their diet. It made sense. Zero calories, it should be good, going all back to Tab, which was awful-tasting, but we used to drink it.

Howard Forman: Totally.

Harlan Krumholz: My mother drank it all the time to try to control weight. So this study I thought was very interesting. It had two pieces to it. One was an epidemiologic piece, one was a mechanistic piece. And what they did was in the mechanistic piece, they showed that that you could use a xylitol if you looked at indices of platelet reactivity. So the platelets are the components of the blood which help clot. And they can become sticky. And there’s certain assays you can run to sort of look at the stickiness of platelets. And it seemed as if this substance could increase the likelihood that blood clots would form.

And then they also looked in a large-scale cardiovascular epidemiologic study and approach. And it was suggestive—again, again, hard to be causal inference or hard to say for sure—but there was some suggestion that people who had higher levels in their blood of xylitol... So this was good. It wasn’t just self-report like “I drink diet drinks,” but actually people had higher levels where it increased cardiovascular risk. Look, this hasn’t been settled science. This is a good journal. It’s a reasonable contribution. I think in the absence of evidence of clear safety and of real benefit, people ought to be thinking more about water and tea and a range of other things.

Howard Forman: And again, you brought this up. We talked about this maybe a year ago, erythritol as well.

Harlan Krumholz: Yeah. Exactly.

Howard Forman: A lot of the sugar alcohols might be in this category.

Harlan Krumholz: Saccharin, sucralose, all these things have had questions raised about them, and yet entire populations have been exposed. And for what? Where is it really helping us? That’s the question. Look, we’re all about decreasing sugar, especially high-fructose drinks and so forth like that. But the question is, does substitution with these diet drinks, is it a net benefit or not rather than getting off this stuff altogether and trying to find other, healthier drinks? So anyway, I continue to be an advocate for people to think about alternative approaches, which move them away from both diet drinks and from high fructose.

Howard Forman: I gave it up for different reasons 14 years ago. But for me—

Harlan Krumholz: And your life has been wonderful since.

Howard Forman: Yeah, fantastic. But for me, the problem is I have all these protein bars. They all have sugar alcohols.

Harlan Krumholz: Yeah, that’s right.

Howard Forman: All of them.

Harlan Krumholz: Right?

Howard Forman: So these are the—

Harlan Krumholz: Sugar alcohols are another issue.

Howard Forman: But these types of things, xylitol, erythritol, no matter which one I look at, they have one of these types.

Harlan Krumholz: Oh yeah, I was thinking about the mannitol…. There was ones that actually blew up people’s guts.

Howard Forman: Different. No, I’m talking about this.

Harlan Krumholz: You’re absolutely right. These are the same things.

Howard Forman: And these are in the protein bars. We associate protein bars as being sort of healthy and healthful. I know that they’re not. I actually worry about them. And there are certain protein bars that I know are healthier.

Harlan Krumholz: So this is like what we talk about all the time. If you’ve got a drug, you’ve got to go through all these sort of hoops—

Howard Forman: I wish we’d do more.

Harlan Krumholz: ... safety and effectiveness. On the food side, let alone all the supplements—we are going to spend more time on the supplements in the future.

Howie, we’ve got to end. This is great conversation. Why don’t you end on a flu update. What’s going on?

Howard Forman: Yeah. We get a lot more information really quickly. So brief update. We still have no human-to-human transmissions. Tens of millions of birds in the U.S. have had the flu, the H5N1 bird flu.

Harlan Krumholz: Say that again.

Howard Forman: Tens of millions. I think it’s 90 million birds, 126 herds of dairy cattle in eight states. And then there are sporadic cases in other mammals, including mice and foxes. Three humans in the United States have been infected, but not from human-to-human transmission, two in Michigan, one in Texas. And there are anecdotes of other people with symptoms, but they weren’t tested. And the new news from yesterday, which is really good news, is that Michigan is taking a much more aggressive effort at surveillance. Their farmers are helping this, the state government is helping this, and they’re going to start doing both surveillance, sero-prevalence, testing blood, as well as testing people with or without symptoms and the animals, which is really good. So we got a lot of feedback from the last update.

I wanted to respond really quickly to a whole bunch of questions. One, someone asked about the case in Mexico where a man died. And I just want to mention that is unrelated to this outbreak. That is H5N2. Have no more information on it. I can’t explain why that exists. But it’s not related to this outbreak, so it should not change our thinking here. Somebody else asked me, “A friend had conjunctivitis, should they be worried?” because they knew that two of the three—

Harlan Krumholz: We talked about that.

Howard Forman: ... have conjunctivitis. So unless you have exposure to dairy cattle at this time, and I mean it, it is next to impossible to imagine that this is related to the current outbreak. We believe that the two cases of conjunctivitis were from direct contact with infected cows and probably from their infected milk. Another listener asked about whether cheeses are a concern. Remember we said raw milk’s bad? What about cheeses? If the cheeses made with unpasteurized milk, there is potentially heightened risk. So again, recommending avoiding it right now if they’re domestic cheeses from potentially infected herds. Another listener asked about vaccinations. And here’s another interesting thing that just we found out today, we do not have an H5N1 vaccination program in the U.S. But just this week, Finland became the first country in the world to begin vaccinating high-risk humans against the disease. So we’re going to learn more about that over the next few weeks and months.

And the last question that I got for today, a listener asked me about pasteurized milk, which we’ve talked about. I can’t say that there’s zero risk, but it’s got to be really close to zero risk because more than 99.99% of all viral particles are eradicated through pasteurization. And our digestive tract and our other immune mechanisms do a pretty good job to begin with. So presumably that’s enough. But I think we have to have humility about this, just like we did with COVID. We got to watch it, we got to see what’s going on. But at the moment, no cases from pasteurized milk. And one question not being asked is, “What about meat from infected cows?” And we don’t have an answer about that at all. So if I leave you with any good news on this, it’s that I believe we’re starting to see a major mobilization of scientists, public health workers, states, and farmers to start to wrap our hands around what’s going on.

Harlan Krumholz: That’s good. I think the public largely is still—

Howard Forman: In the dark.

Harlan Krumholz: ... in denial.

Howard Forman: Yeah. And in the dark. I don’t think we have, nobody coming out with regular pronouncements from the federal government. I think I’ve seen—

Harlan Krumholz: So what’s your guess here? Is this going to blow big or you think we’ll get over it without really—

Howard Forman: I think it’s going to percolate for a while. And whether it’s three months, three years, or a decade, I think at some point it becomes a problem. And I think the best thing we can do is learn as much as we can right now and be prepared so that if there is human-to-human spread, we know how to contain it quickly.

Harlan Krumholz: All right, great. Thanks for the update. I’ll continue to watch this. You’ve been listening to Health & Veritas with Harlan Krumholtz 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 of the many social media outlets.

Harlan Krumholz: Yeah, we want to hear your feedback. Anyone’s got any questions, you can see Howie’s answering questions here today. By putting up comments, it helps people find us. We really appreciate that.

Howard Forman: And if you have questions about the MBA for Executives program at the Yale School of Management, reach out via email for more information at som.yale.edu/emba.

Harlan Krumholz: Health & Veritas is produced with the Yale School of Management, where we are today in the Yale School of Public Health. Thanks to our researchers, Ines Gilles and Sophia Stumpf. And our producer, Miranda Shafer, just married. Congratulations, Miranda!

Howard Forman: Congratulations, Miranda.

Harlan Krumholz: Yeah, that’s terrific.

Howard Forman: Thanks very much, Harlan.

Harlan Krumholz: Talk to you soon, Howie.

Howard Forman: Talk to you soon, Harlan.