Howie and Harlan are joined by Zhenqiu Lin, senior director of analytics at Yale’s Center for Outcomes Research and Evaluation, to discuss how quality measures can make care more consistent and effective and improve outcomes for patients. Howie provides an update on research on repetitive head trauma among young football players; Harlan reports on new findings about the benefits of semaglutide for people with heart disease.
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. We’re trying to get closer to the truth about health and healthcare.
Harlan Krumholz: I’m really excited today to welcome Dr. Zhenqiu Lin. But first, let’s check in on current and hot topics in health and healthcare. Howie, I’m going to introduce Zhenqiu, so let’s flip the script here and let you go first on the podcast. I know you want to give an update on repetitive head trauma in the setting of football. Of course, football season’s now just getting started—what a great time to talk about this. Tell us what’s on your mind.
Howard Forman: Yeah, so back in October last year, episode 53, we first talked about concussions in young athletes, and then we were fortunate in April on episode 75 to have Dr. Michael Alosco of the Concussion Center and CTE Center at Boston University. My take-home messages from those podcasts and our discussions were, one, repetitive head injuries don’t have to cause concussions to cause real harm. Two, repetitive head injuries may cause meaningful and permanent brain injury leading to permanent behavioral and cognitive changes often associated with the pathologic diagnosis of what we call chronic traumatic encephalopathy or CTE. So fast-forward to this past week when a report comes out of JAMA Neurology led by Dr. Alosco, again, reviewing brains from 152 deceased young contact sports participants.
Harlan Krumholz: What’s “young”? What was “young”?
Howard Forman: I think 32 and under. I think 32 is the uppermost age. And by the way: what did they die from? They died from suicide or unintentional drug overdose, that was the most dominant causes. This was not a randomized trial. It’s called a convenience sample and, Harlan, you can explain to our listeners more about what that means. But basically, it meant that it’s patients whose brains were donated after death for evaluation. There was no randomization. But it does increase the concern that repetitive head injuries increased by either duration or severity of impacts, and that seemed to increase the likelihood of permanent brain injury. We need more research on this, but we have enough to know that elite athletes playing American football in particular are at high risk for this permanent harm, but it’s not limited to just them. It starts earlier, perhaps in late high school and certainly in college. And so as you said, Harlan, we’re entering high school, college, and the pro football season, I think it’s worth thinking about and talking about what can we do to prevent this epidemic of traumatic harm.
Harlan Krumholz: One of the things that really struck me about this field is that this isn’t just about people who...when we were playing football, back in the day, people would talk about someone’s bell being rung. It’s not about someone who gets hit so hard that they pass out or that their bell is rung. It actually, even just this repetitive head injuries that maybe seem incidental and people don’t even notice that much at the time—
Howard Forman: Yeah.
Harlan Krumholz: ...can cumulatively end up causing all this harm. So let me just ask you, you’re saying about prevention, are you saying you think we should start to ban high school and college football?
Howard Forman: Yeah, I’m not. I hope people get the message over time that in some ways I’m a pretty libertarian person. I think people have freedoms. But I do think we’ve not done a good job of communicating to the individuals who play, and in many cases their parents, of what the risks are. As we learn more about the risks, I think we have an obligation to do better with consent. And Harlan, you’ve written about consent in the medical setting, but I think we need to actually have informed consent here.
Harlan Krumholz: Yeah, people need facts about what they’re doing. By the way, you’re talking about football, but let’s talk about the “real” football with soccer, meaning worldwide, people refer to soccer as football, and these headers also. You think about soccer, you know, aren’t you using your feet and—
Howard Forman: Yeah.
Harlan Krumholz: ...you’re not. But actually the headers have some of the same issue. There’s headgear that you can wear, but nobody wants to wear it, and it hasn’t been mandated. This is a bigger deal than just talking about football.
Howard Forman: I did go down a rabbit hole in preparing for this talk, and I’ll say that the American Academy of Pediatrics has been on both sides of the issue. One can make a strong case that at the very least, we should stop teaching young people tackle football and leave it to a little bit later in their careers. You don’t have to necessarily ban it, but you can limit the amount of headbutting and head hitting during practices, for instance. Everything you would do to reduce repetitive head trauma seemingly would have a positive impact, and we should be looking at that.
Harlan Krumholz: Yeah. I remember when Dr. Alosco was here, didn’t he say that he wouldn’t allow his own kids to play football, right?
Howard Forman: That’s what he said. And I will tell you, the more I’ve read this, the more I am fortunate I have two nearly adult young women, my children, who don’t play football. So I don’t have to think about it personally, but if I had a son, I would not be letting him engage in football. I think it’s too dangerous.
Harlan Krumholz: Yeah, I actually don’t know. For me, football is a guilty pleasure. I really enjoy watching. I grew up in Ohio, I watched the Ohio State Buckeyes, I watched pro sports, and yet I do feel guilty about it because I think it’s like the American gladiators. These people are all putting themselves at risk. We’re talking about head injury, but there’s lots more. Many of them are disabled, they have marked disabilities in the long run. Yeah, I feel concerned about... By the way, do you know, does the American Academy of Pediatrics have a position on this?
Howard Forman: Yeah, they take both sides in a way. They have a position statement that says we should do more to mitigate, and parents should give informed consent, or something along those lines. I don’t know if they use the words I used. But then there’s a separate paper a year later from a group of very respected pediatricians who basically say the American Academy of Pediatrics is talking out of both sides of its mouth. If you believe the science, you can’t be saying, “Okay. It’s okay to do it, but just make sure parents know how dangerous it is.”
Harlan Krumholz: Yeah. Yeah. More to come on this, but let’s just say for many places in the country, football’s religion. It’s akin to religion, and it’s so embedded in the culture and as you know, economically—
Howard Forman: Yeah.
Harlan Krumholz: The NFL is a powerhouse. It’s the—
Howard Forman: And high school and college football are big business.
Harlan Krumholz: Exactly.
Howard Forman: So I’m not saying ban it, but boy, I do think that there should be more of a national conversation about it.
Harlan Krumholz: Yeah, I totally agree. Totally agree. That’s great, Howie. So hey, let’s get to our guest, Zhenqiu Lin. Howie, I’m really excited today to introduce our guest, Dr. Zhenqiu Lin, who works with me at CORE. Let me just get you the basics. He’s the senior director in healthcare analytics at the Yale New Haven Hospital Center for Outcomes Research and Evaluation and a senior research scientist at the Yale School of Medicine. He has over two decades of experience analyzing healthcare data to support quality measurement and improvement. He’s led numerous analytic projects funded by many of our national federal agencies. He has in-depth expertise in healthcare data, including claims, registries. You name it, he’s one of the top experts in it.
Just to give you a sense, he received his undergraduate master’s degrees from Beida, from Peking University in China. You should know it’s one of the top universities in China. Getting into it’s almost impossible—only the very best get there. He was one of those. Then he came to the US and got his PhD degree from Stony Brook and joined us at CORE in 1997 and has been with us for 26 years. And let me just tell you the real deal: he’s one of the people I respect most in the world. He has such deep integrity and remarkable wisdom.
He’s one of the world’s leading authorities in measuring healthcare quality and has contributed so much to the current state of US healthcare quality measurement systems. He’s kind, he’s a wonderful mentor and leader, everyone who works with him has utmost respect for him. He cares deeply about improving the world, and he’s a wonderful family man. He sets a great example for all of us. He’s been my partner at CORE for all these years. And let me just tell you, I couldn’t have even participated in groups that accomplished a fraction of what we’ve had without him. So Zhenqiu, let me first just say to you, thank you. Thank you for being part of my life. Thank you for being part of my teams. We’re so lucky. I’m so lucky to work with you. I’m so grateful that you joined us today.
Howard Forman: I talk about quality measures all the time. I’ve listened to Harlan talk about quality measures all the time, and we talk about it on the show frequently, but I don’t think, I at least, understand the depth and complexity of quality measures and why they’re so important but also why they’re so difficult to create and then measure. Can you give us a little sense? What are quality measures, and why do we care about them?
Zhenqiu Lin: Let me put it this way: two graphs capture my thinking on this issue. I’ve been using these two graphs to explain to new team members about what is quality measure, why they are important. One graph I use is from 1998 JAMA study, I think Harlan will know that study. I think the title is “Measurement Use and Effectiveness of Beta Blocker for Treatment of AMI Patient.”
Harlan Krumholz: So, for heart attacks. For heart attacks.
Zhenqiu Lin: Heart—
Harlan Krumholz: We have a lay audience. Yeah. Yeah. Go on.
Zhenqiu Lin: One other key finding is that older patients who were prescribed beta blockers at discharge had a better survival rate. That’s good news. You can treat patients with this medication. But another finding was striking. That’s what the graph captured. The graph is US map. For each state, we have the number of prescription rate for beta blocker for ideal heart attack patient. And if you look at the map, it was colored based on the rate for each state. And then you see all kind of colors indicating why variation across US states. I remember the highest five states, the prescription rate is in the 70s, and then the lowest five states in the prescription rate in the 30s.
Harlan Krumholz: Wow.
Zhenqiu Lin: So at the time I say, “Wow, look at this graph.” I would think anyone looking at the graph would say, “We need to do something about it.” This is effective treatment and simple, and yet we are not there. So two things jump out at me. Even the highest state, 70%, I don’t think that’s the top mark we want to hit. And then you see the variation of 30%. Think about if we can elevate everyone to 70%. It just indicated so much opportunity in there. We need to know where we are understanding the gap of performance identified opportunity. I’ve been using the graph to explain to the team members why we are doing quality measures. I think everyone look at the map and say, “Yeah, that’s not acceptable,” and then we need to do something about it.
And then another graph I use to explain to team member about quality measure is from a different study in 2019. It’s a JAMA Network Open paper. It’s about 20 years trend in outcome of heart attack patients. So next study showed that from 2009 to 2014, the number of heart attack hospitalizations decreased: 30-day mortality decrease, 30-day readmission decrease, one year mortality decrease. And to me when I look at the graph, that’s what we should shoot for. That’s pointing to the what is desirable, and more important, achievable outcome.
The one graph that jumped out at me is that we show the mortality rate for about four thousand hospitals in 2009 and we see another...so there’s a curve, kind of a bell curve for 2009, and then another curve for 2014. If you look at the graph, the 2009, the bell curves around 20% and in 2014, bell curve centered around 12%. Now you shift the whole curve from 20% to 12%. That’s a huge improvement. Not just that, if you look at the curve, you also see the curve for 2014 is much narrower, indicating that the variation among hospitals decreased. And to me, what we want is high quality of care for everyone everywhere. It doesn’t matter which hospital you go to, you should get good care. I thought that’s captured my thinking.
Harlan Krumholz: Yeah, I think those are really great examples. In that first example, we have an effective medication. We looked at people who had no contraindication, were ideal candidates for this medication, and there were so many people who weren’t being prescribed it in the 1990s. And then like you said, you fast-forward ahead in a period where we were focusing on improving that quality... and by the way, that quality improved a lot. By the time you got to 2010, it was more than 90% of people were on these drugs because of a lot of work that a lot of people around the country did that these measures helped stimulate and catalyze. And then in a period of 20 years where there wasn’t a new treatment that came out, but just improvements in quality, there were dramatic reductions in death rates, dramatic reductions in hospitalization rates, that I believe were really attributable to the fact that we were just delivering care more effectively, not that we had new miracle treatments.
It was introducing this idea that how we practice medicine can be such an important influence on how people do, beyond touting some new medication or breakthrough, we have to have breakthroughs in the way that we work so that we don’t let anyone fall through the cracks, and Zhenqiu played such an important role in our ability to do this.
I want to just pivot to one thing, Zhenqiu. I think we can be so proud of a lot of those accomplishments. There was one measure we did that became quite controversial. For you and me, we thought it made so much sense. It was readmission. CMS came to us and said they wanted to start measuring costs of care. We said, “If you measure cost in isolation, it’s not going to be very helpful.”
But how about readmission? Lots of people go home from the hospital, and we discovered even one in five people with heart failure end up back in the hospital within 30 days. That’s both a terrible outcome for the patient, because that means that they didn’t have successful recovery, and it’s expensive. We convinced CMS to allow us to start developing that as a measure, but a lot of people around the country and a lot of hospitals said, “It’s not our fault. These are the patient’s fault. We send them home fine, and they come up and end up being readmitted.” There were a lot of issues. How do you think about that readmission measure now, looking back, and what are your thoughts about the kind of reception that it received, and why it’s been so hard for us to improve readmission as much as we have death rates, survival, improved survival?
Zhenqiu Lin: Yeah, I think we did get a lot of pushback on readmission measures. I actually had a good story to share, right after the first I think three readmission measures were publicly reported, I went to Narragansett, Rhode Island, stayed in the bed and breakfast. In the morning when I had breakfast, there’s an older lady there. She asked me what I did. I said, “I’m doing all this quality measure development,” and it’s so interesting—she was an older patient. So: “Oh, I heard about readmission. So I was so surprised to learn that about a quarter of patients will be back in hospital within 30 days.” She said, “I found that’s a really high number,” and now I say, “Yes, I agree. I thought the number is just too high.”
So to me, there’s a forced dichotomy. People want to put us in the opposing camp to hospitals. I think we are in the same camp. We all try to serve patients well. Now even when we work with CMS, we’re not just making CMS happy, we want to have them do a better job serving all kinds of patients. I think no one will deny 25% 30-day readmission rate is unacceptable. We need to do something about it. And it’s true, hospitals, they cannot be responsible for every readmission. But I think we’ll agree that there’s a lot they can do to reduce readmission. Think about medication reconciliation, discharge disposition, instruction, how we prepare a patient, how we help to transition patients. I have seen some hospitals, they became aware of some rehab facility, some nursing home, they were not doing a good job. So they make a point not to send any patients to those places. So there are a lot of places that another area in the hospital can do.
I also remember one time in a conference, someone mentioned, “Oh, you couldn’t hold hospitals responsible for readmission.” And I asked him, I said, “Okay, so who should be responsible for that? Where do patients go to get better outcomes?” I think we have seen reductions in readmission. It is hard because healthcare is messy. It is not easy. To me, when I talk to an analyst, I say, “My patient quality and safety, it’s kind of like airplane quality and safety. You need to get everything right to get safety. It only took one part to go wrong to fail the whole thing.” So I think when we develop measures, we need to focus on patient outcomes, different providers, different hospitals, they can work their way to get there, but we need to focus on outcomes that can encourage, promote different kinds of intervention to get to the better outcomes.
Howard Forman: The paper you talked about, “Mortality After Heart Attack,” is actually a paper I show in class every year because I think it’s so important and it’s so graphical, and hopefully we’ll link it on our websites so our listeners can look at it, but it really is compelling. It gives me a lot of hope about what can be done. Is there another area of healthcare right now that gives you a lot of hope that you think we’re going to make a big impact through the quality movement?
Zhenqiu Lin: I think digital health. People complain about number of measures. My response is to say, “Okay, we need more measures.” So people will be really surprised, I say, “More measures but more useful measures. More timely measures, less burdensome,” with EHR [electronic health record] data, with computational facility and capability, I think we can do that. I think it’s this new type of measures that leverage better healthcare data, more timely data, and then sooner feedback to provider. A measure should be part of the learning healthcare system; it’s not isolated reporting. We should be able to gather information out of the system, provide feedback to providers right away, and they can act on it. So I think in the future, there’s so much potential if we can utilize digital health and there’s so many opportunities.
Howard Forman: We’re getting toward the end of this, and I want to make sure you have an opportunity to tell us what you’re most optimistic about right now. Is there one thing that gives you the most hope? You said about digital as far as progress in your field but within healthcare in general, is there something that gives you the most hope?
Zhenqiu Lin: Medicine is becoming increasingly a team sport. That’s what we need, because it is a messy system, knowing the system, right? You need people to work together. I see more and more integration like surgeon, nurse, clinician, they work together. I think that’s the way forward. And also big data like machine learning and natural language processing, any processing, gives us a lot of potential. We just need to tap into that. So I think the potential is huge that we can do so much better.
Harlan Krumholz: Zhenqiu, I just want to thank you for taking the time. I want to thank you for all the years of contribution, not only to our group but to the nation and beyond, and what a privilege has been to work with you. And thank you so much for joining us on Health & Veritas.
Howard Forman: The best is yet to come, so thank you very much.
Zhenqiu Lin: Thank you for giving me this opportunity.
Howard Forman: He is really an incredible man, Harlan, and you’ve been a key mentor and source of inspiration to him. He has inspired so many around him, so it was just great to hear from him. And we’re back from break. But semaglutide and the other novel anti-obesity drugs wait for no one. I know there’s been a lot of breaking news over the summer. What should little old me and our listeners know about this?
Harlan Krumholz: Well, you know I love talking about this, but there is so much that’s happened over the course of this—
Howard Forman: Yeah.
Harlan Krumholz: …and in addition, lots of talk about the pandemic and vaccine, so we’ll hold this for other podcasts. But this week I thought it would be good to talk a little bit about these new anti-obesity drugs. And while we were off, there were two big news flashes about them that I think are worthy of our attention.
Howard Forman: Yeah, so tell us about each of them. I know one’s heart failure, and I know that one was just a bigger study.
Harlan Krumholz: So first, one of the questions has been, we know that these drugs are very effective in helping people to lose weight. Remember, these drugs also have been used for a long time. These are the GLP-1 receptor agonists. They’re sort of hormonal drugs and they’ve been used for a long time for people living with diabetes to help them control their blood sugar. The FDA, you may remember, said, “We’re concerned about diabetes drugs. There’s some information that some of these drugs like sulfonylureas”—people may have heard of those kind of drugs—“may be actually increasing cardiovascular risk.” So the FDA said, “When you’ve got a new drug for diabetes, you’ve got to test it to see whether it actually causes harm. Even though it helps people control their blood sugar, maybe paradoxically it could be causing harm.”
So they said to the companies, “You got to do a safety trial.” And it turned out, when they did a safety trial with these drugs, unexpectedly I think, and out of proportion to the value that they provided on controlling blood sugar, they actually reduced risk. They lowered the risk of heart disease. So everyone was very excited about that. It already has that track record for people with diabetes, but lots of people have been saying, “We know this loses weight, but is it safe and does it have that same property of lowering risk in people who are being treated for obesity?” And there’s a large trial that Novo Nordisk, who makes Wegovy and Ozempic, which is made up of semaglutide, that’s the name of the generic of it….They did a big study of about seventeen thousand people where they compared semaglutide 2.4 milligrams with placebo, to see how it would prevent major heart events over a period of about up to five years.
They looked at people who were aged 45 and older who were overweight or had obesity, and these were people who had established heart disease. So this is what we call “secondary prevention but no prior history of diabetes.” So they wanted to make sure that this wasn’t among people with diabetes, because the SEC, you know, from regulatory, when there’s... what do they call this, “material information” or something becomes available, the companies have to immediately say it, so they made a big press release. They said, “Guess what? Positive study!” This study seemed to have the effect of reducing risk by about 20%. Now this is about what we saw for people with diabetes, but amazing news. We don’t have more information. It’s not published yet. It was just a press release, but highly anticipated, probably come out in November. But again, good news about this. And anyway, that was the first thing that came out.
Howard Forman: But the second one is the one by our former student and your former student? Mikhail Kosiborod?
Harlan Krumholz: Yeah, Mikhail Kosiborod. Remember, he was here with us and he joined us in the Clinical Scholars program and now he’s in Kansas City, Missouri. But he led this study that was published in The New England Journal of Medicine, presented at the European College of Society of Cardiology in Amsterdam. And here was the deal. There’s a kind of heart failure, that of all the people with heart failure, about half the people have a kind of heart failure where their squeezing function of the heart is normal but the relaxation of the heart is abnormal, and they can have all sorts of symptoms of heart failure. They get impaired, they’re hospitalized a lot, their life expectancies decrease. We have yet to find effective medications, FDA-approved medications, that actually help these people do better. So we’re really at sea with these people.
We have a lot of medications for people whose heart doesn’t squeeze well, that kind of heart failure we have treatments for. But this kind of heart failure, where the heart’s squeezing fine, we’ve really been at sea. And there was a question of, well, a lot of these patients actually have obesity also, and maybe the obesity and the heart failure are actually contributing to each other. That is, the obesity is contributing to the heart failure, and maybe the treatment of the obesity could actually help them with their heart failure. So they took a bunch of people, in this case a little over five hundred people, and they determined whether or not the treatment of these individuals with semaglutide—again, same medication, would improve their heart failure symptoms. And lo and behold, amazing.
Howard Forman: It was amazing. But Harlan, can you just tell us a little bit, I’m fascinated. You’re the first person to have talked to me about inflammatory markers and how inflammation is part of the mechanism of a heart disease. There were other measures unrelated to heart failure that also improved. So many things have improved with semaglutide that it’s beginning to sound more and more like this miraculous drug for a lot of aspects of cardiovascular care.
Harlan Krumholz: So we’ll just hit on that for a second. We know the C-reactive protein is an indicator of the body’s inflammation, and the mean change in the CRP level, it was a decrease of 43% with semaglutide versus about 7% with placebo. By the way, the weight dropped about 13% on the people on semaglutide, and only about 3% in the other group.
Howard Forman: That’s huge.
Harlan Krumholz: There was weight loss, there was decrease in inflammation, there was improvement in heart failure symptoms. Look, I think about these meds, you’ve heard me say this before, I don’t think about them as, “Hey, I can look better,” or even just as weight loss drugs, I think these drugs do treat obesity but are promoting health. They’re reducing risk. And I think as we learn more, obesity is associated with about two hundred different diseases, and there’s going to be lots of potential for marked benefit when obesity is concomitant with other conditions or when it may be ultimately a risk factor for future conditions.
Then that doesn’t even count that if actually we start treating obesity in our society, we might decrease the number of hip replacements that need to be done, the knee replacements, there’s a whole bunch of stuff here. So anyway, you know me, I’m always guardedly optimistic. I think we need to continue to monitor, see what happens when millions of people are treated. But I think this can be one of the remarkable interventions of our time to address something. Obesity, which I don’t think is a lack of will or willpower, it’s a metabolic condition many people have, in the context of our current society, and I think it can be treated, and the potential here is for marked benefit.
Howard Forman: And we’re going to have Ania Jastreboff as well as a bariatric surgeon on over the next few months as well, so this is not going to die out. It’s an important topic to talk about. The Inflation Reduction Act Medicare negotiation on these drugs is going to keep bringing this up again, because I think either next year or the following year, Medicare will add those drugs to the list of drugs that they’ll negotiate down the price and make it hopefully more accessible and affordable.
Harlan Krumholz: Yeah, we definitely have to be focusing on access and making sure that this doesn’t increase disparities. There’s a lot here to dig into. And by bariatric surgery, I wonder if it’s going to persist, because we’ll see. Lots of people would rather take the medications than have surgery with them.
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 keep the conversation going, you can find us on Twitter, X, or LinkedIn if you’d like.
Harlan Krumholz: Yeah, we’re still talking about Twitter and X and Musk. But anyway, for right now I’m at @H-M-K-Y-A-L-E, @hmkyale.
Howard Forman: And I’m @TheHowie, that’s @T-H-E-H-O-W-I-E. You can also email us at firstname.lastname@example.org. And let me just say to our listeners, please feel free to email us ideas, topics that you want us to answer, questions that you have, and we’ll do our best to answer them. Aside from Twitter and our podcast, I’m fortunate to be the faculty director of the healthcare track, founder of the MBA for Executives program at Yale School of Management. Feel free to reach out via email for more information on our innovative programs, you can check out our website at som.yale.edu/emba.
Harlan Krumholz: Health & Veritas is produced with the Yale School of Management, the Yale School of Public Health. Thanks to our researchers, Ines Gilles and Sophia Stumpf, and to our producer, Miranda Shafer, amazing as always.
Howard Forman: Thank God for them. They make a huge difference, and really we’re so glad to have them back as they start their junior year, for Sophia and Ines and Miranda always.
Harlan Krumholz: For sure. Talk to you soon, Howie.
Howard Forman: Thanks, Harlan. Talk to you soon.