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That's the way it's always been from time immemorial. And that is adopted into science. It's supposed to be so precise and evidence-based. It's really amazing. It's amazing. And it's so deeply embedded, not just in the technology like the EGFR, where it's automatic and doctors just accept it, you know, this automatic categorical adjustment for Black people. But it's also embedded, I think, just in a general way of thinking about humanity and what makes people human and what is common about us and different about us. It comes out in so many ways that have nothing to do with scientific evidence whatsoever. It's folklore that is seen as acceptable in the highest echelons of medicine and science. So I'll give you another example that comes to mind. There's an anthropologist, Duana Fulwiley. I mentioned her work in Fatal Invention, who for her dissertation worked in labs, genomic science labs, of people who are looking for genetic explanations for racial differences in health. One scientist in particular was looking for the African gene that caused Black children to have higher rates, well, actually, Puerto Rican children in particular, but Black and Puerto Rican children to have higher rates of severe asthma. And his theory was that because Puerto Rican children have a lot of African, you know, Black in them, that explains why they and Black children have it. So there must be some African gene. Now, never mind all the research that shows that the conditions in poor African American and Puerto Rican neighborhoods exacerbate asthma and that those children have less access to high quality healthcare. But he's looking for the African gene anyway. But one thing that Dr. Folwiley found in her research in the labs was that when the DNA samples came into the lab, they already came in marked by race. They were grouped by race and they came into the lab. So already you're starting from a racial framework, which is another big problem in a lot of this research. There's an assumption of racial difference, and then people look for the racial differences, and lo and behold, they find them. And even if it's the tiniest amount of difference, they'll make a categorical statement that Black people as a race are different in this measure from other people. But anyway, one thing she found was that they called African or Black DNA and white or Caucasian or European DNA opposites, opposite DNA. Now, there is absolutely nothing scientific about calling Black people and white people opposites or Africans and Europeans opposites. I mean, even if you want to look at it from a genetic level, first of all, all human beings descended from Africans. So all human beings have DNA that's a subset of African DNA. So you shouldn't be separating it in the first place. But if you do, why would you say Europe is the opposite? Europe is right across the Mediterranean from Africa. So wouldn't that be the closest? Because we know that genetic variation works, inclines gradually across the globe. So the closest should be the closest in geography. And they're right there. You can see Africa from the tip of Spain. And I won't go into all the genetics of it, but there is some vast genetic variation on the African continent, the most of anywhere in the world. And there are people in Africa who are genetically closer to people in Europe than some other groups in Africa. So it's just nonsensical. It's ignorant. It's not based on any kind of evidence. It comes from these folklorish and racist ideas about Black people's really, you know, that we're subhuman. That's where it comes from. We can be distinguished from all other human beings because we're not really human. And I know that doctors who use these categories and these diagnostic tools that separate out Black people would say, oh, no, but we're doing this for Black people's health. Of course, we can point out as well all the ways it harms Black people, but they'll still say, I'm not racist. I'm doing it for their health. But if you think about it and you study it, I mean, I actually don't think you need to think about it more than about five seconds, but if you're open-minded, but if you need convincing and you think about these ideas and where they came from. You would have to conclude they're racist ideas. They're racist ideas. It's not saying that anyone, and this has to do with the meaning of racism as well. This is not saying that individual doctors have racist motivations to harm Black people. But racism is not just prejudiced ideas. That's not even mostly what it is. It involves that, but it's not mostly. Racism is a political system of subordinating certain groups and giving power and privilege to others, especially one in the United States, white people, and especially if they're wealthy and men, especially. But white people as a group in our racial hierarchy have that position of advantage. And that's what racism is. And that's what we have to fight against. And it's not about weeding out the doctors who have prejudiced ideas because most of them don't or they won't't acknowledge it. You, you know, you can't even necessarily see it in a tester in training because they know what to say. And even, even the, these tests of bias, if they, if people really believe in their heart of hearts, this is how the world is organized, right? You're not going to see it. If we have been trained to believe, and I think this is true, the earth is round, and we say the earth is round, it's not going to come out as we're prejudiced against the earth. It's just that that's what we believe is the truth. And so what we have to do is include medicine in a political movement to bring down the structures of racism and white supremacy and the way in which medicine incorporates those and promotes those. That's what we have to do. And it has to be in conjunction with broader social movements, like the Movement for Black Lives, that are dedicated to radically transforming our world into one where human beings are equally valued. And we are all human beings, right? Yes. Yes. Yes. Professor Roberts, one of the things that struck me as you were talking was about the way that folklore about ourselves, about our history is all mixed into these conversations. And one of the many parts of my copy of Fatal Invention are highlighted, but one of them was when you talked about the slavery hypertension hypothesis. And particularly because I realized before I even arrived in medical school, that was something that I had internalized. I don't even know where I heard it. I don't even know where I heard it, but I'm pretty sure I had internalized it. I probably even told someone else that theory. And I think it's a particularly interesting one that probably a lot of folks who are listening to our podcast have in their head at some point, would you would you talk to us about that? come to medical school with these folklore narratives in their heads that they believe are true. And like you said, you may not even know where you got it from. And I just want to interject very briefly the study of medical students and residents at University of Virginia that found that a substantial number believed folklorish, absurd stereotypes about Black people's bodies, like Black people have thicker skin than white people. Black people have less sensitive nerve endings than white people. Now, where did they get that from? They came to medical school with that. But the problem is, then you come to medical school. And as you said earlier, every class reinforces Black bodily difference. And so you're reinforcing these stereotypes about Black people's bodies and other aspects of racial difference. And so yes, you come to medical school, if you believe the slavery hypothesis, it makes sense because everything you're learning in medical school supports this idea that Black people have hypertension because of some innate, you know, genetic or other kind of innate biological factor. Sometimes in the studies, they'll say genetic or other biological factor. They're very, very, very vague about what this might be. But it's some essence of Blackness that somehow developed. And with the slavery hypothesis, the theory is that the reason why Black people in America have higher rates of hypertension is because the gene pool of Black people was affected by the Middle Passage, where it benefited enslaved people, you know, spending months in the horrific conditions of the slave hold and ships, if they could retain salt, am I saying it right? They had a better chance of surviving. And so people who, the Black people who survived had this genetic predisposition toward retaining salt, and which also promotes hypertension. So in other words, because of the conditions of the Middle Passage, Blacks who survived were predisposed to a condition that also unfortunately predisposed them to hypertension. Now, let me say something there.
And so there's this idea that only Black people have these diseases that are good in some circumstances, but deadly in others. And I've seen this hypothesis of explanations for even infant mortality in the Black communities, you know, that there's something positive about it, but unfortunately, it also has these negative effects. And I think the slave hypothesis is a similar idea that it benefited Black people on slave ships, but it's harmful in the end when it comes to hypertension. Now, there are lots of problems with that hypothesis. One being that it is a supposedly genetic explanation for health inequities that are caused by social, unequal social conditions stemming from structural racism. So like all of these biological mythical theories, they divert attention away from the impact of structural racism. And they divert attention toward coming up with some kind of race-specific therapy instead of ending structural racism. That's one. Historians, geneticists, epidemiologists, I won't go into the details, but leading experts in all these fields have said, no, this did not happen. And the other, to me, one of the most persuasive arguments against this being an explanation for high rates of hypertension is that other places where these slave ships landed with African people who endured the same conditions do not have these high rates of hypertension, like Jamaica and other parts of the West Indies. If this were a condition caused by the Middle Passage, then why don't the descendants of enslaved people in other parts of the world have this problem? And, you know, there are all these theories to come up with why Black Americans in particular are biologically predisposed to bad health, because in some cases, they have worse health than in countries in Africa, in the Caribbean, you know, and other where the Black diaspora all over the world. And so there's a scramble to say, well, why is it that Black Americans are so unhealthy? Why is it? There must be some evolutionary explanation instead of just facing what is the obvious explanation, which is that racism is worse in the United States. That's so obvious. That's the other thing about this. Shouldn't we go down the path of the most plausible, well-supported hypothesis? Why come up with a zany hypothesis that makes no sense? And sometimes you can't even prove. I mean, one hypothesis that I quote all the time was in an article, a study that was reported in the American Journal of Obstetrics and Gynecology that was asking why it was that Black women in America have higher rates of preterm births. Now, there are so many reasons why. The stress from racism, lack of access to high quality prenatal care, the care given to pregnant Black women in labor, the neighborhoods that are unhealthy for growing up, because of lack of access to high quality nutrition, housing, the violence of police officers and the stress that produces, you know, we could go on for another hour just talking about all the factors. Well, these researchers ignored all of that. And their hypothesis was that Black race, independent of other factors, causes extreme preterm births in Black women. Why would you even want to try to prove that hypothesis? You can't prove that hypothesis unless you control in the study for all these other factors, 10 of which I just named, but we could come up with hundreds others. And what does it mean to separate Black race from all other factors? What does that even mean? What is Black race in this study? What is the concept you're relying on in the study? Never mind, how do you select the research subjects to include in the study? It can't be based on a social definition because you've excluded everything social supposedly from your study. And yet, of course, they based it on a social categorization. What is this factor you're looking for? How do you even describe what it is? Now, they ended up describing it in terms of genes, which they didn't study. They just speculated there must be some gene difference that causes it without proving that it had anything to do with genes or looking at genes. Not that that would have helped, but just the extent to which these ideas, backward, ignorant, absurd ideas can continue to circulate in contemporary medicine and biomedical research and pharmaceutical development and treatment of patients. It's very alarming. And, you know, we have to get, getting rid of those ideas is part of a broader anti-racist struggle within medicine and within our society. about it is how's race coming into our medical technologies and the algorithms that we use on the ward. So just yesterday, a new publication came out showing that Black patients are nearly three times more likely to have lower oxygen levels go undetected compared to White patients. These are data that have been published in 2005. And so, you know, I'm hearing from colleagues say, well, should we change the guidelines around what a low oxygen level is for a Black person versus a white person? And wouldn't that be race-based medicine? And how does that kind of match with what we've just been talking about? I know how you think through some of those more nuanced discussions. Yeah, yeah. Well, again, I go back to the meaning of race and the fact that it's an invented social category. It is not a biological category. So there are lots of ways in which these algorithms cut. When there's an automatic adjustment for Black patients, that is clearly based on a false concept of race. And there have been lots of studies that show how it can harm Black patients, including one recently that Dr. Neha was a co-author on that showed that in the EGFR, it has an actual impact of disqualifying Black patients for specialized care and placement on a kidney transplant waiting list. So I mentioned those myths that the medical students at University of Virginia held, and those were associated with undertreating Black patients for pain. And, you know, we could go on and on about how these automatic categorical adjustments harm Black patients and claimants and lawsuits. I mean, I won't go into the NFL, where there are Black players who have been denied settlement payments because the test for dementia, for cognitive capacity, is different that they use. Adjust for Black people, assuming that Black people's brains function differently. So that would take another hour to talk about. So there are those that harm. Then there are also supposedly race neutral algorithms that exclude Black patients or will disadvantage Black patients. For example, the algorithm that's used to determine who gets scarce resources, it might be applied to ventilators in this pandemic. And so there, because these allocation algorithms are based on the idea that the people who should get them are the healthiest people, the ones who are most likely to survive longer if they get the resource, that systematically disadvantages Black patients because of structural racism. Black patients, on average, are going to score worse on these tests to determine their likelihood of survival and their length of survival. So I think we can, you know, I can't go into details about all of these, but I would say that the corrections that are based on a false biological concept of race that adjust for Black race because of an assumed biological difference by itself, that those should be abolished. Now, what about algorithms that are going to disadvantage Black people because of Black people's experience of structural racism? I think that that's an ethical question that we could decide that there should be some kind of bump up or some kind of reparations or affirmative action. We could come up with the terminology, but the idea is that there should be some kind of benefit or compensation given because of the impact of structural racism. So on the one hand, we have algorithms that are denying to a group that has been historically disadvantaged by racism access to care. That is wrong. That's wrong. The others may be denying as well resources to Black patients because of their experience of structural racism. And there hasn't been a lot of thinking about this, surprisingly. I mean, these algorithms are used without a lot of critical thinking about what is the ethical and just thing to do. And so I think we do need to think about treating race as a political, you know, invented category, and the people in that category have been harmed by racism. how should we take that into account in ensuring that that disadvantage doesn't perpetuate more disadvantage? You know, so this is about thinking through these, what are the questions? What are the meanings that we're using? I think if we're clear on that, on the values, on the understandings, we can engage in a conversation, a dialogue, a discussion about what's the right and just and anti-racist thing to do. That's very different from saying, oh, well, we've used race in the EGFR for 20 years, but we just continue it because we know that Black people, whatever the reason is, is it maybe it's their greater muscle mass. Maybe it's, you know, whatever it is, their bodies work differently. No, forget that. I mean, that's, we cannot continue down that path.
And we don't have all the answers now because guess what? We haven't even started, barely started engaging it. We don't know what the right measures are. You know why? Because medicine's relied on race for so long. It doesn't know what's right. You know, this question, I was, when I was, I was inducted into the National Academy of Medicine in a year when we could all get together and I participated in a workshop on what is the right amount of pain medication to give. And the discussion was focusing on the opioid epidemic. And I raised my hand. I wasn't on the panel. I raised my hand and I said, we cannot have this discussion without talking about racism in the prescription of pain medication, including opioids. We don't know what the right amount is because doctors were prescribing it by race. They were giving white patients more because they believed in myths, which were part of the marketing of opioids, that white people would not become addicted to them because of some innate immunity to addiction, which is, again, absurd. Absurd. This is counter to reality, right? But anyway, that was part of it. And you can read Helena Hansen's work on this. And on the opposite end, according to the idea that Black and white people are opposites, sometimes we are treated as opposites. We're not genetically opposite, but we may be treated. And in the case of opioids, Black people were treated in the opposite way. There are studies that show, including a study of Black children in the emergency room suffering from appendicitis and severe pain that showed that Black children were far less likely to be prescribed opioid medication for their pain than White children. And we know that Black people were less likely to be prescribed opioids for pain. Okay, so now we're stuck with the prescriptions being made according to race, and with a general idea, which is, you know, it's controversial, but this is why, this is the reason that this discussion was going on at the National Academy of Medicine was that there's an over-prescription of opioids for pain. What do we do about it? Well, the truth is there, if there was an overprescription, it was an overprescription to white patients because of racist myths. There was an underprescription to Black patients. So what's the right amount? What's the right amount? We don't know. We don't know the right amount, but don't get, don't have a whole discussion about it as if, well, let's look at the evidence and what's the, you know, what, let's come up with an algorithm and let's look at logically what the right, you could, first you have to confront the fact that the reason you don't know is because you were racist, you're practicing racist prescriptions. And so we, so here's an example to me where race-based medicine has ruined this area of medicine. It's caused a controversy. It's caused a problem that we do not know what is the proper amount because of racism. It was, you know, they may deny it. They may just say, well, we have to calibrate it properly. We overestimated the amount. No, it's because you prescribed according to race. And so you don't, you have an amount for white people and you have an amount for black people. And now, and that was wrong. And now you don't know what is the right amount. But again, to figure out the right amount, you should not use race. You should look at what are the factors that should determine the amount to prescribe. They can't be based on race. As I was saying earlier, that's like putting a square peg into a round hole. Race is not the answer to how you prescribe opioids. There's something, there must be indicators that would tell a physician what is the right amount. Right? Like maybe how much pain the patient is in. But that has been determined by race throughout U.S. history. So even that has been determined by race. So, you know, throughout U.S. history. So even that has been ruined by race. But once we, I think, start to think about how can we do this without relying on biological concepts of race, that to me frees doctors and biomedical researchers to do a better job of figuring out how much medication to prescribe to patients, you know, figuring out the meaning of the EGFR and, you know, what, which numbers should suggest sending a patient to specialty care, which ones should suggest that they get a kidney transplant? Now, on top of that, once we get rid of that, all that biological, ridiculous ideas about race out of the business of medicine, then we also have to think about what does it mean to be an anti-racist doctor? I mean, I shouldn't say make it in a sequence because they're all part of the same struggle. But it's, I guess what I want to say is it's getting rid of, and it's also at the same time has to be transforming and creating an anti-racist medicine at the same time. But I think continuing race-based medicine is an impediment to doing that. And so it has to be part of an anti-racist struggle. Professor Roberts, thank you so much for that. You know, we've talked about so many things. I don't even know where to begin. But you've walked us through your definition of race. We've walked through the history. We've walked through some of the politics, the harm of focusing on race-based medicine. And you also talked to us about coming back to this central question of what is race whenever we, you know, are confused about where to begin, going back to making sure we understand that critical definition. And so that's so helpful, just as all your books are so helpful in clearing up some of these complex issues. I think that's something that I'll take with me beyond this episode. But one of the final ways that we like to end our episodes is by asking each of our speakers to tell our listeners who are going to go back into the clinical world tomorrow. What's one thing that they can take with them and start using right away? Oh, now you want me to be a doctor. You can't just hold on that award and not. I have to make use of my membership or prove the worthiness of my membership in the National Academy of Medicine. I'm trying to think of what the one thing would be. Well, I think one thing would be as you're practicing, you are getting rid of all you've been taught about taking race into account as if it were a biological category, that you also think about in what ways has structural racism affected my patient and what can I do about it? And I think there are lots of different ways you might want to do something about it. It might mean asking the patient questions that you wouldn't have asked otherwise. It might change your view about why a patient is acting a particular way or not? What's affecting your patient? And as I'm saying this, I'm thinking, am I imagining a Black patient only? Or, a patient of color, what about a white patient? I think structural racism affects everybody. And so you, I think it's relevant, regardless of what race your patient identifies with. But it also might mean doing things outside of the clinic as well. You know, it might mean joining a particular organization or supporting an organization that's working toward an anti-racist society. It might be working on abolishing the EGFR in your hospital. It might be giving support to medical students who are working to change the medical curriculum, you know, various ways. But I think asking that question, being aware of, you know, really practically aware of how racism affects health so that it's not just an abstract concept. I think that I've heard a lot of times when I've given talks to various audiences, including medical students and doctors, and this applies outside of medicine as well, applies in law, it applies in social work, it applies in lots of areas. Sometimes people, you know, it applies to academia, applies to law professors and sociologists. You know, we think of these questions as in the abstract and we abstractly understand, you know, that structural racism affects health. And then, and we leave it at that level. And I think how can we actually apply it? And, and as I was saying before, all of these questions, they're not ready answers to because these are new questions. I mean, I, I, you know, W.E.B. Du Bois asked some of these questions in 1899, the Philadelphia Negro, but they've been, they have been asked, but to be, you know, to be really seriously contended with and broadly contended with, I think we're seeing for the first time now.
I think we, but we, once we are serious about answering these questions and doing something about it, we can start collectively to come up with ways that, you know, doctors can be structurally competent. You know, what does that actually mean? Not just as a cool idea, right? The concept, but what does it mean on the ground engaging with patients? Yes. Thank you so much for sharing that. And I was going to just end with one, one closing reflection. And I was watching one of the talks that you gave Professor Roberts, and you closed one of the lectures with a quote from the science fiction author and the mother of Afrofuturism, Octavia Butler, that there's nothing new under the sun, but there are new suns. And that was very profound for me for a couple of reasons. Number one, because I think Octavia Butler and that you chose her and that quote is really meaningful. And for our listeners who aren't aware of that history, you know, she was a science fiction author, African-American author who was, I think, in ways ahead of her time. But in her genre, speculative fiction, she talks about how she was so enchanted with this genre because it was a space where she had no rules, no closed walls, where she can imagine anything and then she could write herself into worlds that don't exist. And I think that that's really powerful as we think about what it really means to reimagine. And I think even as we have these discussions, another thing that I've just taken from your work is, as you mentioned, some of these questions are old. They're not new. You know, these issues of racism are persistent. But the fact that we've broken down that race is invented, that it's been built, it makes me feel hopeful that the repercussions of all of that can also be deconstructed. And so that means it's not inevitable. And I hope that's what people take away from some of this as well as we strive towards justice and we find our new sons. It's persistent, but we can imagine a radically different world. And you're right that acknowledging that race was invented by people, it's not in our nature. It wasn't created by God or evolution. That means we can dismantle it. And we can think about what it means to be human and our relationship to other human beings in a radically different way. That is so inspiring and liberating, isn't it? Yeah. So I agree. I appreciate those words.
Hello and welcome back to this Annals of Internal Medicine audio summary for our April 7, 2009 issue. I'm Michael Berkowitz, Deputy Editor at Annals. We have another green and white issue for you this week, and we'll waste no time and launch right in to a summary of our featured articles. This week we're featuring a cluster of articles about smoking cessation. Most of the podcast focuses on that topic, but listeners who want to skip to the next small segment can go to about the 23-minute marker. Thank you. The authors observed an initially high level of engagement with the telephone counseling and a high level of uptake of pharmacotherapy among participants, but both decreased over time. They found no difference in patients' self-reported seven-day abstinence at the end of the trial. That was the study's primary outcome. But they observed abstinence in a subgroup of participants, but they conclude that the trial provides some evidence for a dose-response relationship between disease management and smoking abstinence. And perhaps more importantly, they conclude that a smoking cessation program that treats smoking as a chronic disease and supports patients in their quit efforts over time reaches many smokers who may not otherwise be identified as candidates for quitting and engage even those who are not even thinking about quitting Thank you. podcast, I spoke with Dr. Michael Steinberg, who talked me through the rationale of thinking about tobacco dependence as a chronic disease. And in this issue, he and his colleagues from the University of Medicine and Dentistry of New Jersey described what they found when they randomized 127 smokers with heart or lung disease or coronary risk factors to use of a nicotine patch alone or use of a nicotine patch and bupropion combined with a nicotine hailer as needed for nicotine cravings. Patients in both trial arms were given pharmacotherapy for as long as patients needed to quit. The investigators observed higher abstinence rates and longer times to relapse among patients given the combination therapy. Higher proportions of patients given combination therapy also reported anxiety and insomnia as adverse effects of the drugs, although equally small proportions of patients in the two trial arms discontinued the medicines because of adverse effects. Those findings lead the authors to conclude that flexible duration combination pharmacotherapy can be first-line treatment for patients who smoke, especially those with heart and lung disease or risk factors for coronary heart disease who are especially at risk for the complications of smoking. Finally, an editorialist frames the two trials as providing a glimpse of the future of tobacco treatment in the U.S. health care system. much of the work of counseling and follow-up, and we should be using as many therapies as are available and necessary to boost the effectiveness of available treatments. Because smoking cessation is so difficult, both for patients and for providers, I called the editorialist to see if I couldn't get other useful perspectives on the treatment of smokers and on tobacco control more generally. Dr. Nancy Rigotti is a professor of medicine at Harvard Medical School and is director of the Tobacco Research and Treatment Center at Massachusetts General Hospital, and she was gracious enough to talk to me about this issue's articles and about recent efforts at research and policy levels to control tobacco consumption. Dr. Rigotti, thanks so much for talking to me. Sure, happy to be here. In both studies we're publishing this week, quit rates seem to hover between about 20 and 35 percent. Those aren't higher than quit rates seen in past trials using single or dual therapies and without the creative implementations tested in this issue's articles. So what do you think it might take to get those numbers higher? Is that even possible? Well, I think you're looking at the results of a single quit effort or a quit effort over a shorter period of time. But, you know, tobacco dependence is a chronic disease, and it's one that has lots of relapses. Many of the patients that come to our offices and are seen in our practices who have not been able to quit on their own or haven't been able to quit with the brief interventions that we might deliver in our practices do need more. So I think we are struggling to get beyond that, but we need to keep trying. And my experience has been if I look at my practice, probably the quit rates of any one patient aren't any higher than anybody else's. But over time, the proportion of smokers in my practice has gradually dropped so that there are very few left. There are a few who probably are never going to stop smoking until they stop breathing. But most of the rest of them have at one point or another had something happen where they could put together the motivation to quit and the skills that they might have learned one place or another and the treatments and been able to do it. So I would argue that you could use a different measure that would look more positive than what proportion of a group of people who start a program on one day are not smoking a year later, two years later. How much of the problem requires insurance reform? Now nicotine replacement therapy isn't covered. Let's say insurance carriers covered it 100%, or even offered financial incentives for people to quit smoking. Would that be more effective than what we're doing presently? Yes. I think the evidence is clear that when pharmacotherapy for smoking is covered, more people use it and more people quit. And plenty of cost-effectiveness analysis showing that covering smoking cessation medications about it is the most cost-effective thing you can do. But the reason that they're not covered is primarily that most nicotine replacement products in the U.S. are over-the-counter. And historically, the insurance companies don't want to cover over-the-counter products because if they do that, it's sort of a slippery slope. Then they should be covering all the things that have gone from prescription only to over-the-counter. So unfortunately, the move to make nicotine replacement over-the-counter, which was intended to expand its availability and also to help the manufacturers make more money, has oddly made it harder to get in some ways because it's not covered by many plans. Now, there are some plans that do cover all forms of nicotine replacement. Some Medicaid plans, such as the one in Massachusetts, now will cover any kind of FDA-approved smoking cessation pharmacotherapy as long as there's a doctor's prescription. So I've seen in the last few years a lot of movement in the right direction, but there still is this sticking point about not covering over-the-counter medicines, and I think it's really a precedent issue. I think it's necessary but not sufficient. Even in systems where nicotine replacement might be free or medications are free, not all smokers use them, partly because they may not know about them. It's sometimes in the insurer's interest not to tell people about the benefit. Sometimes it's because they're not aware that there is something that can be done to help people quit smoking. I mean, a lot of smokers still think that smoking is like a bad habit or it's some sort of moral flaw, and they don't really see it as something that is an addiction or something that needs treatment, that something can be done about. So part of it is convincing people that there are treatments out there and that they can be helpful, that if they don't work the first time, maybe a combination of things or a different approach or a different time for using them will be successful, but to keep trying. And the special opportunity that physicians have is that we can try to connect people to treatment so that we can motivate them to try to quit because we know the evidence is quite clear that when doctors talk to patients about quitting, they do make more quit attempts, but they don't necessarily succeed more unless they are connected to good treatment. And at least the study in this week's journal that talks about the combination therapy is an example of how using a more sophisticated way of using our medications is one of the things that people like me who work in more specialized smoking cessation settings know all about and do all the time, but I don't think it's widely known that you can combine medicines in the ways that we are now doing. We used to only have a couple of things. Now we have a variety of agents that we're learning to use in the most optimal way. We're all intrigued by the idea of financial incentives. It's not entirely new. In fact, there have been some studies of pregnant smokers that have shown very clearly that a great way to get pregnant smokers to quit at least long enough so that their baby can be born without being exposed to tobacco smoke in utero is to pay especially poor pregnant women who smoke to quit. You basically pay them for clean urine. And that's been a very effective treatment, more effective than most other things we've been able to find. So it's well known. The problem with incentives is that when you take away the reinforcement, then the question is whether the behavior change is maintained. So that's the challenge, and I think that incentives are going to have to be paid for a while. The other downside is it's hard to imagine, given the health care cost concerns, that insurers are going to want to start putting out money to pay people to quit, even if you can make a cost-effectiveness argument for it.
That seems to me a way of giving people an incentive for using medications. In the public health sector, what a number of the state telephone quit lines, which offer free telephone counseling to smokers but actually get not a lot of use unless they're widely advertised on the media, which costs a lot of money for the states. They've found that a great way to drive business is to offer free nicotine replacement through the quit line. And there is a body of evidence showing that it gets more people to quit smoking. So it's a great way of expanding the reach of our treatment, which is what one of our challenges is, is to get more people to be exposed to the treatment that works. Even if the treatment isn't perfect, if more people are using it, our population quit rates will go up and our overall smoking prevalence rates will go down. And I think that we should take some of these population management ideas and bring them into the context of health care settings and supplement what doctors can do. I mean, one of the things that I liked about the paper by Ellerbach and others was that it was a great way of trying to apply population management strategies within the context of a health care setting. And not only was it a good idea to expand reach of treatment, but it had the nice benefit of unloading the doctors from having as much to do in the practice. Not that they shouldn't do anything, but that it was a way of reaching their smokers maybe at a time when they weren't coming in for care. And some of the work of getting someone to change behavior to lower risk could be done separate from the actual visit. I think that's the future for the health care delivery system. We see it in general for all of disease management, case management for chronic diseases. I think there's no reason that we shouldn't be dealing with tobacco in the same way. The House voted last week in favor of allowing the FDA to regulate tobacco. That bill now faces an uphill battle in the Senate. What would FDA regulation of tobacco look like, and what would it get us in terms of tobacco control? I think it's very important. Right now, the government has no regulatory authority over what's in tobacco products, over new tobacco products that are being developed and introduced, and it's critical that we have the ability to find out what's in them and to regulate them. To some extent, it would make a more even playing field because right now, any new nicotine replacement product has to go through FDA regulation, but any nicotine delivery product in the form of a cigarette or anything that has tobacco in it in any form doesn't have to be regulated. And that really is biased against the pharmaceutical companies that are trying to produce clean nicotine and trying to help people quit. One proposal would be to regulate the amount of nicotine that's allowed to be in cigarettes and basically wean people from smoking by reducing gradually the amount of nicotine in cigarettes. There's a whole body of research looking at whether that's a good idea or a bad idea. And there's been lay media reports about the tobacco industry being on board with FDA regulation of their industry. Well, right now, the leading bill that's been proposed has Philip Morris on board. The other tobacco companies oppose it. Philip Morris changed their strategy in part because since they have the dominant product in the market, which is Marlboro, the way it's set up, it would be hard for new brands to compete with them. So in a way, it's very much in their interest to support the bill. And I think that they look down the future and see that that's coming. Within the tobacco control community, there's a vigorous debate going on right now about how good the bill is that is currently out there being discussed and whether it's too generous. Sometimes people have said, well, anything that a tobacco company would support, we couldn't possibly support because there must be something in it that is bad that we haven't figured out yet. It's really an issue of incrementalism as a policy strategy versus waiting for the perfect bill. It's a tough call, but I think it would be a great advance if we could do this. The bill is really moving ahead because of the makeup of Congress and the fact that Barack Obama was one of the sponsors last year. A smoker himself, right? He may still be a smokerA recently called for U.S. Senate ratification of the Framework Convention on Tobacco Control. What is that, and what would we see if the U.S. became a treaty member? The Framework Convention on Tobacco Control is the first public health treaty that the WHO or World Health Organization has ever had. So it's like having a treaty, only it's not a political treaty. It's a public health treaty. And the countries at WHO came together and made agreement about what all countries should do from a policy perspective around tobacco control. And it included very good evidence-based things, raising taxes, restricting and banning advertising and promotion and marketing of tobacco, ensuring that workplaces, public places, restaurants and bars are smoke-free, increasing the visibility of warning labels to warn smokers about the hazards of tobacco use, that it was important for all countries to provide treatment. It was formally adopted in 2003, and then it had to go through a process of ratification. And currently, I think over 190 countries have ratified it, and most of the countries in the world. A notable exception is the United States. The treaty was signed by our previous President Bush, but it was never sent to Congress for ratification. And so we're hopeful that the new administration will take a look and put it forward to Congress. Now, some of the policies that are in there that we'll be signing up for are beyond where the U.S. is. In fact, we're not in the lead in terms of tobacco went up last week. What effect do you think that'll have? This is the first time that the federal excise tax on tobacco has been raised for, I think, 15 or 20 years. So it was well overdue. It's a great thing that happened. It was done to help fund the S-CHIP program, which pays for health care for poor kids. It is a regressive tax. It would be nice if there had been some provision that some of those dollars that smokers are going to be paying would go towards treatment for them so that they're not just being hit with extra money, which we know already discourages them from smoking, will cut down their consumption and encourage them to quit, but would be, I think, a more ethical approach if we were able to provide them some assistance as well. Unfortunately, that part of the bill didn't make it through. You were involved in a trial of a nicotine vaccine. What happened with that? I was involved in a phase two study looking at early efficacy of a nicotine vaccine, and it was very promising. It looked like if the vaccine worked and people got high levels of antibody, that it helped them to quit. In the people who didn't make high levels of antibody, it didn't help. So the key was figuring out who was going to make high levels of antibody. The antibody soaks up the nicotine that's absorbed from the tobacco smoke, and the complex of nicotine and antibody is too large to cross the blood-brain barrier. So essentially, the antibody keeps nicotine out of the brain. There are a number of vaccines that have been developed and are in clinical testing at various stages. The one that I worked with is going into its phase three testing soon. I'm hopeful that it will be a tool, but we have a ways to go to figure out. And a lot of it has to do with the science of how you can make it immunogenic enough and how long those antibodies are going to last. But you could imagine a day, someday, far away, not anytime soon, where you could imagine vaccinating high-risk children if the vaccine, say, lasted for five or ten years. Maybe you vaccinate ten-year-olds, assuming that it's very safe, and they don't smoke until they're 21, by which time they've hopefully matured enough to decide that they don't want to do that. Your editorial mentions that varenicline could also be used in combination therapy. That wasn't included in the trial we're publishing in the issue. The past year has seen continued reports of a possible association between varenicline and major depression and suicide. What's your understanding of those case reports and data? It's been difficult to know for sure. The company that makes varenicline has looked at its placebo-controlled trials to see whether there were any signs of these things in the data that they have. And from what I understand, they're not seeing much evidence of harm, and that was presented as an abstract at a meeting a few months ago. But the trouble with the existing trials is that they all specifically excluded people with a strong history of depression. And so we really don't know whether there would be an increased risk in people with a history of depression.
And then we can't really tell from case reports because we don't have a denominator. And the number of varenicline prescriptions, I'm told, is 9 million by now. So it's hard to make an estimate, but it seems like it probably isn't that common. Our clinical experience is that most people do pretty well with it. We've seen occasional people who've had mood problems and they need to come off of it. But I think it's important to realize that we don't have a lot of medicines for treating tobacco, and tobacco is the leading preventable cause of death in the United States. So I think it's important that we not lose the perspective that we're treating a disease that's also deadly, and we need to use the medicines that we have carefully. I think that the concern that's come out, which is very realistic, has to me reinforced the importance of following patients. If we did what we're supposed to do, which is see patients or at least contact them by telephone to find out how they're doing two weeks after they start the medication to make sure that they're okay, then we probably wouldn't have this to worry about. And it's just that what tends to happen in practice is that people get put on these things and don't get followed up. We wouldn't start somebody on antihypertensive and not see them back and make sure they're okay. But for some reason, we seem to think it's okay to do that with smokers. Dr. Rigotti, thanks so much for talking to me. Sure, glad to. That was Dr. Nancy Rigotti of Harvard Medical School discussing her editorial entitled The Future of Tobacco Treatment in the Healthcare System, and this issue's clinical trials evaluating disease management programs and combination therapy as ways to get smokers to quit. A reminder to listeners to have your patients check out QuitNet.com, a website where people can interact with peers who are also trying to quit smoking, and where patients can get expert counseling and advice via email and chat rooms. Isn't it awful? Yeah. Oh, yes. Oh, it's awful. Yeah. It's talking about you. On the street smoking cigarettes. Lord have mercy on such a woman that's living this day. Other articles in this issue include a large industry-funded trial comparing high-dose IV isomeprazole to placebo for patients with bleeding gastroduodenal ulcers. That demonstrates that isomeprazole reduces recurrent bleeding and the need for endoscopic retreatment and blood transfusions. Thank you. whether or not the patients had significant comorbid illnesses. That's significant because recent updates of screening guidelines emphasize the need to account for life expectancy in decisions about whether or not to screen. So the data from this study suggests that healthy older patients may be underscreened, perhaps because their life expectancy is being underestimated, while less healthy patients may be overscreenscreened, perhaps because their life expectancy is over-estimated. In our January 20th issue, we published a study looking at the association between HDL subfractions and cardiovascular outcomes. This issue were going low with a systematic review of LDL subfractions and cardiac outcomes. The authors of the review describe an extremely heterogeneous literature consistently suggesting that higher LDL particle number is associated with an increased risk of cardiovascular disease. But they couldn't find any evidence showing consistent associations between any other LDL subfractions, such as small dense LDL and cardiovascular risk, nor was there any evidence that any measure of LDL subfractions improves cardiovascular Thank you. in renal insufficiency who took metoclopramide, another about QT interval lengthening in 20 patients on starvation diets, and the third about the onset of transient apical ballooning syndrome, or takotsubo cardiomyopathy, in a patient undergoing dobutamine stress testing. This print issue has the healthcare reform articles I summarized last month in our March 3rd podcast, and if it's getting hot in here, get some vasomotor stability with this month's In the Clinic supplement on menopause. Well, that's it for today. Our closing credits remain the same. Theme music by Fiction Friends. The interlude you heard earlier was Smoking Woman in the Street by the Reverend J.M. Gates. That one's available on Volume 9 of his complete recorded works on Document Records. Technical support for this summary was provided, Thank you. Thanks for listening. It ain't cause that I don't smoke myself, and I don't reckon they hinder your health. I've smoked them all my life, and I ain't dead yet. But nicotine slaves are all the same at a petting party or a poker game. Everything's got to stop while they have that cigarette. Smoke, smoke, smoke that cigarette. Puff, puff, puff it if you smoke yourself to death. Tell St. Peter at the Golden Gate That you hate to make him wait But you just gotta have another cigarette
Hello and welcome to the podcast for the June 2012 issue of the Lancet Infectious Diseases. Richard Lane here and I'm joined this month once again by John McConnell, although not for the whole of the podcast as we are now introducing monthly author interviews which is terrific. John, walk through some of the highlights from this month's issue for us. Well Richard, this is an issue which we're taking to the International Conference on Infectious Diseases in Bangkok, which is taking place in the middle of June. So we've got something of a global health focus and also a couple of papers which look at particular issues for Southeast Asia. So you will be hearing from the author of a paper which we have on poor quality antimalarials in Southeast Asia and in Africa. And then, as I say, we've got some other papers which also address developing world issues. Thanks, John. Do you want to just go through some of the titles of the content? Yeah, well, we've got a randomised trial which looks at giving acyclovir to people who are co-infected with HIV and HSV. We've got a systematic review and meta-analysis on treatment outcomes of children with multi-drug resistance tuberculosis. Children tend to be neglected when it comes to tuberculosis treatment and particularly to MDR-TB treatment and this meta-analysis shows that you can get as good treatment outcomes with children as you can with adults. And then accompanying that paper in the review section, we've got a review of the management of children exposed to multi-jug resistant tuberculosis. The final paper in the research section looks at the impact of haemoglobinopathies. So these are things as such as the thalassemias on the epidemiology of malaria. And I think as a sort of the general take home message here is that the haemoglobinopathies Thank you. is a systematic review of community-acquired bacterial bloodstream infections in the developing countries of South and Southeast Asia. Many thanks indeed, John. And now let's hear more about the very important issue of poor quality antimalarials. Earlier, I spoke to one of the authors of this review, Gauravika Nayar. Gauravika Nayar, many thanks indeed for talking to the Lancet Infectious Diseases. You're one of the authors on a very important review paper in the June issue of the Lancet Infectious Diseases. This concerns the troubling problem of drug quality in relation to malaria treatment. Can you just remind us, summarize the actual global burden that malaria is taking on the world stage? Malaria is an enormous problem. 3.3 billion people are at risk of contracting this disease and up to 1.2 million die from it every year. This burden is enormous and can be prevented if drugs available to treat malaria were effective, of good quality, and used correctly. While there are no global estimates on the exact scale of poor quality medicines, our study highlights that the problem is widespread and needs immediate attention. Apart from the obvious increased morbidity and mortality from these medicines, they promote drug resistance, which has dangerous public health implications, especially for malaria. Poor quality drugs often have lower than the recommended levels of active pharmaceutical ingredient, which will kill some parasites but allow for resistance to develop and select resistant parasites. The global burden of malaria in the last decade, you know, we've had a lot of progress. It's gone down significantly, but this progress has been dependent on the long-term availability of effective anti-malarial drugs, especially artemisinin. And as we have reports of artemisinin resistance surfacing on the Thai-Cambodian border, it's imperative that we safeguard our artemisinin combination therapies because there are only hopes to maintain progress towards global malaria eradication and poor quality medicines are putting this goal at a major risk. Thanks very much indeed and yes of course one of the papers documenting the rise of artemisinin resistance on the Thai-Cambodia border was reported in the Lancet not so very long ago. In terms of the source of these poor quality antimalarials could you outline what you think the main origins of the source of these problem drugs are? There have been many factors that lead to the existence of poor quality antimalarials. Could you outline what you think the main origins of the source of these problem drugs are? There have been many factors that lead to the existence of poor quality antimalarials. So first, it's important for us to understand what poor quality antimalarials are. These drugs include counterfeit medicines. These drugs include degraded medicines. These drugs include substandard drugs. For counterfeiting and falsification, which has really been the focus of our paper, it's essential to note that the economic incentives that cause for falsification of antimalarials far surpass the risks involved in their production and sale. With that, antimalarials are widely self-prescribed. They have an erratic supply and frequent stockouts. And with that said, they make up about 25% of the drugs consumed in malarious countries. In short, the demand for antimalarial drugs is enormous. Overall, the large profit margins coupled with the lack of drug regulation systems and the absence of punitive measures makes these medicines very attractive targets for counterfeiters. And in this particular review, you've basically reviewed published and unpublished documentation, haven't you, about the quality or rather the poor quality of antimalarials. Can you give us an insight into how you went about doing that? I would like to mention that our findings here are not estimates of the prevalence of poor quality antimalarial drugs. Our findings were purely a snapshot of the data available, the only estimates we have as of now on this issue. We reviewed published literature and we got some unpublished literature from the period of 1999 to 2012. We looked at studies that provided us with sample numbers that gave us information on chemical analysis and packaging testing of the drugs themselves, particularly in Southeast Asia and Sub-Saharan Africa where the burden of malaria is the highest. We looked at data. We got our data from PubMed, WHO documents, anti-counterfeiting networks online, and confidential data from the experts. Our findings were, to some, quite shocking and to others, you know are large proportions, aren't they, when you think to the health of the most vulnerable populations with malaria and children who are at the most at risk of dying from malaria. So it's an urgent concern. It's extremely important that some action be taken. I think there's been a lot of lip service on this issue, but not much action. So we're hoping that this paper gives evidence to support that this is a problem and it requires a change in the way we're thinking about it. Related to a question earlier, but specifically the issue of counterfeit drugs, this is something you have covered, haven't you, which you've just mentioned. Is the situation with counterfeit antimalarials similar or different to poor quality overall? Do people know where these counterfeit drugs are being made and where they're coming from? We do have some information on where these drugs are made and how they are distributed, but the current data available don't suggest any definitive sources or supply chain entry points or countries as leading producers or distributors of these drugs. We do know that they're widely available and can be bought at local shops, at health facilities, at pharmacies, at grocery stores, and most popularly online. Our study shows that poor quality medicines were available in seven countries in Southeast Asia and 21 countries in Sub-Saharan Africa. But again, this is a snapshot of the problem, a tip of the iceberg, as many of cases of counterfeiting and falsification go unreported or reported to the wrong agencies or kept confidential. The Interpol does track these drug distribution networks, and so do sometimes pharmaceutical companies that might have noted their product being counterfeited. But that's sort of the essence of the information we have on drug distribution systems for counterfeit medicines. And can you tell from your data, given that it is a snapshot, is this sufficient data to have a clear core fraction? What needs to be done, do you think? There's no quick solution to address the problem of poor quality drugs. It's a complex problem and it requires a multifaceted solution. First, there's a need for a global consensus on the definitions of poor quality medicines because if we don't have a clear definition, taking any action is difficult, especially internationally there is a need for consensus on this issue. There's also a need more specifically on cheap and portable point of care and pointurchase diagnostics that help us test for medicine quality. Such a diagnostic would empower medicine inspectors, healthcare providers, and the general public to ensure the quality of the antimalarial medicines that they're receiving. In this light, it's critical that routine national surveys of the drug supply chain and public markets be conducted to ensure safety of the national drug supply. While these interventions sound great and something that we can do right away, these interventions will all converge upon the national medicine regulatory authorities.
And this is an immediate and urgent concern and needs to be addressed. Thank you. And a final question, a corollary to the one that you've just answered, actually. What would the consequences be if action is not taken on this issue? Clearly a reverse in a positive trend that we've been having in tackling malaria over the past few years. Yeah, absolutely. If poor quality medicines are allowed to continue to flood the markets that we trust, more people will suffer from malaria and die, but the public will lose confidence in these medicines. They will lose confidence in their healthcare providers and the financial implications to pharmaceutical brand companies are also enormous. But most importantly in all of this is that the underdosing which can lead to drug resistance can put decades of progress at risk and ruin investments made in the last decade to eliminate malaria. If we lose the ability to rely on artemisine combination therapies due to drug resistance, it would be a huge setback, not only jeopardizing any progress we've made so far, but also costing scores of lives in the future. And we will be all researchers scrambling to find a new effective drug against this deadly disease. Indeed, well, it's a fascinating and obviously a very important review review. Govika Nair on the line from the National Institutes of Health in the United States. Many thanks indeed for talking to the Lancet Infectious Diseases. Thank you so much. See you next month.
Hello, and welcome to this JAMA Editor's Audio Summary for our March 28, 2017 issue. This is Howard Bauchner, Editor-in-Chief of JAMA. Starting with the research reports, the first, hysterectomy for stage 1 endometrial cancer. Endometrial cancer is typically treated by removing the uterus and performing a bilateral Sao Ping oophorectomy. Compared with abdominal hysterectomy via laparotomy, laparoscopic hysterectomy has lower morbidity and results in better recovery. In a randomized clinical trial by Jada and colleagues of 760 women with treatment-naive endometrial cancer, the operations resulted in equivalence disease-free survival at 4.5 years, laparotomy 81.3% versus abdominal hysterectomy 81.6%, and no difference in overall survival. In an editorial, Wright cites this trial as evidence that laparoscopic hysterectomy is the preferred surgical modality for women with early-stage endometrial cancer. The second original research report, vitamin D, calcium, and cancer. Some studies have reported an association of low vitamin D status with an increased risk of cancer. To determine whether dietary supplementation with vitamin D and calcium can reduce the risk of cancer, Lappe and colleagues conducted a randomized clinical trial of over 2,300 healthy postmenopausal women and found that supplementation compared with placebo did not result in a significantly lower risk of all-type cancer at four years, 3.89% versus 5.58%, a P equals 0.06. Interestingly, a number of exploratory analyses did show benefit for the vitamin D group. In an editorial, Manson and colleagues note that many participants in this trial had baseline vitamin D levels in the range that has been hypothesized to provide protection against cancer, and they suggest that the potential benefits of vitamin D supplementation may be limited to individuals with vitamin D insufficiency. The third original research report, Childhood Blood Lead Levels and Adult Cognitive Function. Young adults with history of childhood lead exposure have been reported to have limited intellectual function and altered brain structure. To learn whether the adverse effects of lead exposure persist until later in adulthood, Rubin and colleagues followed a cohort of just over 1,000 participants for 38 years. Mean blood levels at age 11 years was 10.99 micrograms per deciliter. Lead exposure during childhood was associated with declines in IQ and downward social mobility. After adjusting for maternal IQ, childhood IQ, and childhood socioeconomic status, each 5 micrograms per deciliter higher level of blood level in childhood was Thank you. reasoning and education section. There's three papers, two from the U.S. Preventive Services Task Force. The first, screening for celiac disease. Celiac disease is caused by an immune response to dietary gluten, a protein complex found in wheat, barley, and rye. This recommendation statement of the task force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. In an editorial on this article and a systematic review in this issue of JAMA, Chung and Murray acknowledged the lack of evidence to support screening for asymptomatic individuals. However, they recommend testing for individuals with symptoms that may be caused by undiagnosed celiac disease, especially in high-risk populations such as those with an affected family member or those with type 1 diabetes mellitus. To inform the U.S. Preventive Services Task Force deliberations on screening for celiac disease, Chow and colleagues synthesized findings of a systematic review of 56 original studies and 12 previous systematic reviews, along with primary studies of 62, 158, and 40 participants. The authors found little or no evidence on the benefits and harms of screening for celiac disease in asymptomatic individuals. Overall, I would say these two papers are fascinating reading. They provide a great deal, a great deal of clinical information about celiac disease in general, approaches to screening, and approaches to diagnosis. The third article in the review section. This article in the JAMA Performance Improvement Series explores the case of a patient with a retained lumbar catheter tip. A root cause analysis identified a lack of clarity about which specialty service was responsible for catheter management and insufficient training and supervision of residents in the procedure of catheter removal. Delancey and colleagues discussed strategies for improving clinician education, communication, and delineation of task responsibility. And let's wrap it up with the viewpoints, and there are two. The first by Adashi Krishna and Gruposa, for-profit medical schools, a Flexnerian legacy upended. And the second by Gostin and Hodge, reforming federal public health policies, responding to national and global threats. Thanks for listening. This is Howard Bauchner with JAMA. For more podcasts, visit us online at jamanetworkaudio.com. You can also subscribe to our podcasts on iTunes and Stitcher.
Welcome to the monthly podcast presented by JAMA Health Forum. I'm Dr. John Iannion, the Director of the Institute for Healthcare Policy and Innovation at the University of Michigan and the Editor of JAMA Health Forum. And I'm Dr. Melinda Bunton, Chair of the Department of Health Policy at Vanderbilt University and the Deputy Editor of JAMA Health Forum. JAMA Health Forum is a peer-reviewed, open-access online journal focused on health policy, healthcare systems, and population health, and one of 12 specialty journals in the JAMA Network. Our podcast each month presents highlights of new content from the journal, including timely interviews with authors of research studies and commentaries. Follow us on jamahealthforum.com, on Apple Podcasts, or wherever you get your multimedia, and on JAMANetworkAudio.com. Our guest author today is Dr. Rishi Wadhera. Dr. Wadhera is section head of health policy and equity research at the Smith Center for Outcomes Research and Cardiology, an assistant professor of medicine at Harvard Medical School, and a Cardiologist at Beth Israel Deaconess Medical Center. He is the senior author of a paper in JAMA Health Forum titled Association of the Medicare Value-Based Purchasing Program with Changes in Patient Care Experience at Safety Net versus Non-Safety Net Hospitals, written with colleagues Nicholas Chu, Rahu Agarwal, and Yang Song. And in fact, I think this is one of two papers you submitted to JAMA Health Forum in February, for which you submitted revisions within a week of each other in April, and they were both accepted. Isn't that correct? That is correct. Thanks so much for giving us an opportunity to revise both. Yes, and they're both going to come out in July. So Rishi, to get us started, what was the motivation for this new study that you published in Gemma Health Forum? And what data did you analyze to conduct this study? Well, we know that patients often interact with health systems during what can be a very vulnerable period in their lives. And so it's important to ensure that those experiences are positive. And in 2011, the Centers for Medicare and Medicaid Services, or CMS, really made this a policy priority when they rolled out the Value-Based Purchasing Program, or the VBP, nationwide. And this program basically began financially rewarding or penalizing nearly 3,000 hospitals in the U.S., in part based on how they performed on measures of patient care experience. And early evidence three years into the program suggested that it had not meaningfully improved patient care experience, which was a little disappointing. But proponents of the VBP argued that it just takes time to meaningfully invest in an improved care delivery, which I agree with, and that we might expect to see meaningful improvements over the long term. They also argued that incentives in the program were weak and that as the maximum potential financial penalty increased each year, hospitals would be more likely to respond. In contrast, critics of the VBP really raised concern about the fact that the program, at least in the early years, seemed to be disproportionately penalizing safety net hospitals, which we know tend to care for minoritized racial and ethnic populations, as well as patients with a higher burden of medical and social risk factors. And so they worried that the regressive nature of this program would unintentionally widen disparities between patient populations at safety net and non-safety net hospitals. And so we basically used publicly available data from the CMS Hospital Compare website to perform a long-term evaluation of the value-based purchasing program, really to understand how measures of patient experience changed at safety net compared with non-SafetyNet hospitals eight years into the program's implementation. Great. So can you fill us in on what were the main findings of your study? And did any of your findings surprise you? So our study had three key main findings. The first finding was that SafetyNet hospitals performed worse than non-safety net hospitals on overall measures of how patients rated their experience, as well as measures of doctor and nurse communication, clinical processes like staff responsiveness, and hospital environment, like cleanliness, throughout the study period, so from 2008 to 2019. The second key finding was that measures of patient experience were actually improving at both safety net and non-safety net hospitals before the VBP was implemented, but that these gains appeared to slow down at both sites after the program was implemented. And third, and probably most importantly, we found that the VBP did not narrow or widen gaps in patient care experience between safety net and non-safety net hospitals eight years after its implementation. And I have to admit, we were more relieved rather than surprised to find that disparities between safety net and non-safety net hospitals didn't widen under the program. So we've seen that a number of researchers are using the CMS quality data that you drew on. Are there lessons you learned in your study that other researchers should be aware of that may be interested in using the same data? At first, I think it's just fantastic that CMS makes so much data about health systems, whether it be 30-day mortality rates for heart attack or patient satisfaction scores publicly available to researchers. And I think there's just a lot of opportunity to better understand how health systems in the U.S. are performing, particularly in response to policy interventions. I think like all data sets, researchers just have to be aware of what the limitations of these data are. For example, some measures that CMS posts have large margins of error around the point estimates of performance. And so when we're doing research, we can't simply just pay attention to the point estimates when comparing health system performance. Great. Well, I know we're starting to see more papers come in and we'll be well aware of those things when we review them. So I was also wondering that given that you were in effect sort of relieved that the program didn't increase the gap between safety net and non-safety net hospitals, what additional policy options do you think should be considered if we want to improve safety net performance? Well, I think over the last decade, we've learned through many, many studies that this measure it and stick a financial incentive on it or carrot and stick approach that's been mostly employed by value-based pay for performance programs like the VBP hasn't really worked. And if anything has been incredibly regressive, and this is my personal opinion. I don't think there's really a sound theory of change that I at least can point to, to suggest that financially penalizing already resource-constrained safety net sites that are caring for the sickest and poorest patients in the country will magically lead to improvements in care delivery and health outcomes. So I think we need to move away from this approach. It's always easier to identify problems. So the question is, what's the solution? And I think one alternative strategy would be for CMS to start focusing solely on identifying hospitals or health systems that are true outliers, maybe in the bottom 5%. That struggle year over year, whether or not they're safety net hospitals, rather than spending so many resources and so much time to tease apart who's performing at the 48th percentile versus the 70th percentile nationally across so many measures. And I think that CMS needs to support rather than penalize outlier health systems that consistently struggle, because we could make significant progress from a health equity perspective if we spent more time trying to understand the local challenges that a small number of poor performing outlier institutions face and dedicated more resources to helping those sites develop tailored strategies to improve care delivery. So we have much more to gain by bringing those outliers up into sort of the normal range of performance. That's a really interesting idea. It almost sounds like another JAMA Health Forum piece to identify how stable that low-performing group is and how many resources you'd need to bring them up, as you say. Yes, it very well could be. And I'll just add that, you know, when you focus on outliers, you sort of mitigate all of these issues that have been raised over the last decade about how fairly can we truly compare hospital performance without concerns about inadequate risk adjustment, along with other issues that impede our ability to fairly compare health systems performance. So I think focusing on outliers, which is a group of health systems that I think we can reliably identify using these measures, whether they're perfect or not, might be the better approach. Well, I feel like John and I were just about to ask you about the risk adjustment question, but you anticipated it and answered it. So we'll move on because towards the end of our podcast interviews, we also like to ask a couple of questions of our guest authors on the Thank you. I think multiple people have given me this advice, including John, actually, when I met with him many years ago when he was in Boston. But it's generally just work with colleagues who inspire you, make you think differently, and are just really fun to be around. And I'm just very lucky to work with colleagues here at the Smith Center for Outcomes Research who really do that.
And another question we ask of our guest authors is, what's the biggest change in health policy you expect over the next five years? Yeah, I think as we emerge from the pandemic, we're going to see a tsunami of acute and chronic illness due to disruptions or deferred care that occurred during the pandemic. And I'm already starting to see the adverse collateral effects of these disruptions in my clinic and at the hospital where I work. And so we know that going into the pandemic that the U.S. already performed poorly compared with other higher income countries from a health outcomes perspective. And I think that things may only get worse in the years that follow the pandemic. And so there's going to be no single solution to address this issue. But I think there are policy levers that we can pull, like closing remaining gaps in insurance coverage, whether it be through Medicaid expansion, enhanced premium subsidies in the ACA marketplaces, which the Biden administration had proposed, or even by lowering the age of eligibility for Medicare, just to make sure that people have access to the care they need during this vulnerable period. I think that as we move forward, equity needs to be front and center of state and federal policies and care models that aim to improve care delivery quality and outcomes because we know that historically marginalized populations have disproportionately borne the burden of the pandemic. And I'll just finally add that the increased burden of illness that we expect after the pandemic will inevitably lead to increased healthcare spending. And so while many initiatives over the last decade have focused on addressing our healthcare spending problem by reducing the use of unnecessary or low value care, I think we hopefully will see greater policy focus on addressing the high unit prices of healthcare services in this country, whether that be through greater monitoring and policy regulation of health system consolidation, which we know leads to higher prices without often meaningful improvements in quality. Thanks. I think you've really crystallized the health policy agenda that we all should be focusing on for the next five years and beyond. And I think we'll be seeing many of those topics covered in the issues of JAMA Health Forum. So I want to thank you, Dr. Rishi Wadera from Beth Israel Deaconess Medical Center and Harvard Medical School, our guest author on today's podcast. This episode was produced by Daniel Morrow at the JAMA Network. The audio team here also includes Jesse McQuarters, Shelley Steffens, Lisa Harden, Audrey Foreman, and Mary Lynn Furkelup. Dr. Robert Golub is the JAMA Executive Deputy Editor. Thank you.
This is the New England Journal of Medicine COVID-19 update for March 15th, 2023. I'm Stephen Morrissey, Managing Editor of the journal, and I'm talking with Eric Rubin, Editor-in-Chief, and Lindsay Baden, Deputy Editor. Eric and Lindsay, today I'd like to talk about the changing landscape of science in COVID-19 as it's been reflected in scientific and medical publishing. During the beginning of the epidemic, we were deluged with manuscripts. At this point, though, that slowed quite a bit. Eric, what do the metrics look like at this point? Steve, I don't have the numbers in front of me, but I know at the height in the spring of 2020, we were receiving more than 200 COVID-related manuscripts each day, seven days a week. Now that's slowed to a trickle with no more than a few daily and many days where we have none at all. Of course, we're only able to publish a small percentage of what's submitted. I think it's difficult to measure interest, but I suspect that we're publishing an even smaller percentage of what we receive at this point. So Steve, three years ago, as we faced this emerging pathogen that we knew so little about, we as a community were responding as providers, as researchers, as public health authorities to rapidly understand what was emerging and what was the significance. That required different types of evidence or information to guide us, particularly given the need for information rapidly. And case reports, case series, cohort studies, and then finally, more formal research in the terms of randomized trials emerged. But those all took time. And so, Eric, as you point out, we received a large number of manuscripts in part due to the imperative to inform the community to be able to respond, protect themselves, and care for patients. And unfortunately, not all of that information was as insightful, directive, or even correct in how we as a community interpreted it. But it was needed to guide the response given the overwhelming nature of the illness three even if it wasn't the gold standard time of evidence. But of course, as time has gone on, the standards have changed, and we're requiring more and more high-quality evidence for what we recommend that people do. I guess I'd modify a little bit. I'm not sure our standards have changed. We always want to publish the best evidence available to help providers take care of the patients in front of them. And what's different about COVID, SARS-CoV-2, was the speed with which it spread, how little we knew, and the overwhelming need for individuals to protect themselves and providers to care for their patients. And so we published, as you point out, the best evidence available at the time, much of it incredibly weak, but timely given the decisions providers had to make. Fortunately, over time, better evidence can be generated and therefore provided, and we have the opportunity to help publish and disseminate the highest quality evidence that's available, which is what we continue to do today. Obviously, there have been a lot of changes in the COVID epidemic. While there continue to be new cases, the number of deaths has fallen dramatically. Physicians have become far more comfortable with advising patients and treating disease, and the knowledge of COVID in the general public has improved considerably, even though there's still a good deal of circulating misinformation. So I'd like to ask about what you'd like to learn about COVID-19 and how we should be managing the outbreak today. Well, let me start with a bit about what we know. What kinds of submissions are we seeing now that we're not publishing? Let me start by saying that, of course, we welcome any submissions and we continue to try to give feedback to authors very quickly. There's certainly a lot of important research going on. At this point, though, a good deal of it is not of general enough interest for our pages. Just to name several categories, we continue to hear about interesting or unusual manifestations of COVID, though largely at the case report or case series level, where it's difficult to establish causality. So we've published fewer of these case reports and descriptive case series, although we understand these remain helpful for clinicians and they are still useful, particularly in specialty journals. We continue to receive manuscripts describing serologic responses to vaccination, but since we don't fully understand how well these correlate with protection against disease, particularly against severe disease, we're publishing fewer of these. Even the large studies of treatment and protection are difficult for us because by the time they're submitted, they're describing the responses to viral variants that are no longer circulating. But let me end where I began. There is still a lot of interesting work out there, and we are happy to evaluate any manuscript in any area of COVID. Eric, I would like to say that we're done with COVID, but unfortunately, COVID is not done with us. And as you point out, insights which advance critical aspects of our understanding of the disease and the consequences of the disease are of great interest. However, given that science in this area has advanced so much over the last three years, we want the highest quality evidence to guide our understanding of the problem that's being unraveled and the treatment that's being developed. A real challenge with treatments, as you point out, Eric, is that prospective clinical trials take time. Fortunately, in the context of COVID, these trials are now able to be done in months, which is quite an advance, not only for COVID, but also for science in general and how we think about doing clinical trials to advance our understanding of the disease or problem in question. The problem with COVID is the virus is evolving in weeks to months, so faster than these trials can be done. So the insights that are able to transcend a given viral variant and allow us to understand principles of the biology of this disease or the response or the countermeasure development are of great interest because they can transcend the variant of today. But high-quality data will likely have studied the variant of yesterday. So we in science need to make sure that what we learn can transcend the transient nature of the given variant. And we know there are studies going on out there. We get to see them. And we encourage continued research in this area because this will allow us to get ahead of the virus, even as it mutates faster than our studies can be completed. So we've talked about what we're not publishing much of, but what kinds of things would you like to be seeing? And what are the major challenges that we're facing? Eric, I'll start with you and then we can alternate. Well, let me throw out something here, and that is it would be great to see vaccines that produce broader protection. This is a difficult area, both technically and logistically. Technically, we don't know what will produce broader protection, and our only measures of protection that are available in the short term are serologic. We don't fully understand the correlation between serologic responses, especially for new viruses, and protection. That being said, there has been evidence that infection with distantly related viruses may produce broader protection, and perhaps that some vaccines can induce protection that is somewhat broader. Essentially, what we're looking for are vaccines that anticipate the future instead of the continuing to evolve variants that can escape. Perhaps we could get vaccines that produced protection against something that might evolve in the future. It's a tall order because evolution is probably smarter than we are. Nevertheless, it would be great to see some more work coming out in that area. Eric, I think you raised two important concepts. How to develop a vaccine immunogen that could be, for example, pan-coronavirus or to an epitope that's invariant and cannot change over time because it's required for viral success. Whether or not these are achievable are unclear, but being able to approach that may allow us to develop a vaccine that is more durable through time. Speaking of more durable, we do want our vaccine-elicited immunity to be more durable and to be relevant where we contact the pathogen, in this case, the respiratory mucosa, and how best to augment the immune responses brought out in these arenas. What is tricky, and you allude to this, Eric, is how do we know that a vaccine brings out an immune response that we care about? The holy grail in vaccinology of a correlate of protection. And can we discern what the correlate of protection is for a given vaccine, which may be dependent on the delivery system as well as the immunogen that's being delivered? And it may depend on the variant that's circulating and that tomorrow's variant may not be as susceptible to today's vaccine. And therefore, we need to better come up with in vitro laboratory parameters, correlates of protection, that allow us to better understand if the new vaccine is likely to be effective. We do this for influenza, where each year the influenza vaccine is qualified based upon immunologic criteria that have been established over decades.
And I know scientists, public health authorities, and companies are all working hard in this area, and we look forward to the insights that can allow us to more effectively and efficiently develop the new vaccines that we'll need. Lindsay, your mention of mucosal vaccines brings up another thing on the wish list. At the beginning of the epidemic, when vaccines were first introduced, they were amazing because not only did they prevent severe disease, as they continue to do now, but they really prevented any disease at all and probably limited transmission as well. Now, that largely ended as the virus continued to mutate, and current vaccines have a limited ability to prevent infection and prevent any disease. But it would be great if we had vaccines that could do that again. Clearly, the approaches we're taking right now are unlikely to provide strong protection against infection. But perhaps the kinds of approaches you're talking about, a mucosal vaccine, might increase protection against infection. Now, there are many caveats to that. Such protection may not be long-lasting. It may require frequent exposure to antigen, something that just won't be practical. But it's worth a try. And I'm hoping that we see more work in that area. And what about treatments? What would you like to see there? So Steve, I think that there have been tremendous advances in treatments, such as the development of monoclonal antibodies and the iterative technology, as well as antivirals. And I think on both of these fronts, we need more advances. On the monoclonal antibody side, we need to better understand which targets are likely conserved through time and therefore worthy targets to develop MAVs, monoclonal antibodies for. Because the big weakness in this approach has been the selection of a singular or perhaps two targets that an antibody or a pair of antibodies may go after that allows the virus to evolve around because it's so focused. Very attractive technology, very scalable. However, it is limited by the ability of evolution or viral escape. The antiviral side is incredibly attractive, and we have several agents that are effective. However, they have substantial limitations. Remdesivir requires intravenous administration. Nirmatrovir, ritonavir has significant drug-drug interactions. And these medications have largely been studied, or at least the initial efficacy, in an unimmune, unvaccinated population. So we need better agents that have favorable pharmacokinetic properties so they can be used more easily and earlier in illness, often with an outpatient positive test in an outpatient setting. And we need to better understand their strengths and weaknesses as the virus changes and the immunity in the population changes. But it is terrific that these agents have been developed and are able to be used widely, at least in certain circumstances. And as we've also seen, agents with novel mechanisms of action, such as molnupiravir and early studies on oral forms of rindesivir analog have also emerged and are very attractive to better understand their activity and therefore where they may fit in in our response. Lindsay, I agree that it's great to see the progress that's been made and we know that there's work continuing. One of the issues with the antivirals, of course, is accessibility. In this country, initially, the antivirals were made freely available. As the public health emergency expires, it's not clear how available these things will be, particularly for those with no insurance. And of course, there is a larger equity issue which pervades all of the approaches to preventing and treating disease, and that's the global availability of these agents. They're expensive. They're going to be too expensive to use in much of the world. So it would be great to see something that is widely available and inexpensive enough to be used in parts of the world where it's just not feasible to be spending a lot of money on these agents. So Eric, I think you raised several very important points. We need the community to do the critical studies to demonstrate where the maximal benefit is of these agents. And these studies need to be done in all communities affected, both domestic and international, especially in those communities that have less resources. That will allow proper policy to be able to be made to then push the global community to deliver these therapies to all who need it. So I think the equity issue is tremendously important, and it permeates all stages of the scientific endeavor. But I do believe that through the best data, the best policy can be made, and we can push government leaders, public health leaders, financial parts of the economy to do what is right and to provide the support needed to treat all who could benefit from treatment. And that is an area I think we have a high level of interest in wanting to promote healthy discussion to improve the equity of all who could benefit from these therapies. So before we go on with treatments, I want to ask about public policy and social measures. That's been evolving. Is it going to continue to evolve? Will we get to a point where there'll be no further need for masking, for example, differ in different countries, and therefore the weaknesses are different in different countries. But Lindsay was just talking about the equity in healthcare delivery and how we have not done a very good job of that. And certainly I'd love to see us taking lessons from COVID and applying them and seeing some advances being made for health in general and not just for COVID. For the very specific question of social measures, you know, that's been a difficult issue. Masking, for example, remains controversial. And there has been, I think, a misinterpretation of some of the studies that are out there in the popular press that suggests that masking doesn't work at all. Of course, that's not true. Masking works if you wear masks. However, broad government policies that require or recommend masking won't work if people don't wear masks despite the policy. So it's not that simple. It's important to remember that there is a large group of people who are particularly susceptible to disease or more importantly, particularly susceptible to getting severe disease if they contract COVID. For them, these sorts of social measures, distancing and masks remain critical, very, very important. So at the very least, it's going to be important to have a society that allows people to take the steps that they think are necessary for their own health in order to protect our most vulnerable populations. Eric, I think you raise a very important point where, again, we need more data to guide us. But as tools emerge that are effective in preventing certain types of COVID-associated problems, be they masking, physical distancing, be they vaccines, be they monoclonals or antivirals that can be used to either prevent infection or treat very early infection. We need to develop strategies that can apply to those who will most benefit. And whether it's the neonates who have not yet been vaccinated, or as you mentioned, our growing population with a weakened immune system, either from cancer chemotherapy or organ transplantation or a variety of the biologic agents that are being heavily used to treat different autoimmune diseases, we need to understand who does or doesn't respond to a given preventive intervention, and then how the menu of prevention strategies can be used to protect those who are most vulnerable during their most vulnerable time periods. And there, work could be very interesting in helping us understand how to optimally deploy strategies that have emerged that have clear value in certain settings. Speaking of strategies that work in certain settings, I want to get back to the therapeutics question for a moment and talk about hospitalized patients. Certainly, enormous strides were making in improving survival of patients who had severe disease early on. And the measures varied considerably from really simple measures like prone positioning, which made a surprisingly enormous difference in caring for patients, to corticosteroid therapy, which also has had an impact, to more elaborate anti-inflammatory drugs. We've published quite a bit in this area. Of course, people continue to die and it would be nice if we could do better. Not sure we can do better because we enter into the area of the therapy for ARDS, which is problematic after many, many years of study. However, one potential benefit of working on COVID is perhaps we can have more insights into therapies that would be more effective in ARDS. And I'd love to see some of that work. Eric, I agree. I am just hopeful that with broad population immunity, we will continue to see low levels of hospitalization due to COVID so that we do not have enough illness to be able to study COVID hospitalization questions. Having said that, for those who are hospitalized with COVID, improving these therapies, as you mentioned, is of great interest. Okay, another topic. What are your thoughts about long COVID? Steve, I think that long COVID has been an area that has been extraordinarily difficult. Many people are suffering from a variety of symptoms after they recover from the acute illness of COVID.
People have symptoms all over the map, and rather than a single syndrome, this is likely to be multiple syndromes that may have different causes and different therapeutic approaches. I think we are disappointingly still very early on in understanding long COVID, and I think we really would like to see some better insights followed by better therapies for this group of people. I completely agree, Eric. I think long COVID is a significant problem for many who have had COVID. However, without a definition, so we can begin to understand the myriad of associated syndromes, which very likely, as you point out, have different pathogenesis. It makes it very hard to care for these patients and to plan appropriately targeted interventions, which are of high interest to all. I think that this conversation, Lindsay, has really pointed up the fact that there's much to learn. This is a disease that's affected likely billions of people in the world with all kinds of manifestations, with varying severity, and with consequences like long COVID that we really don't understand. So we started out by talking about the kinds of manuscripts that we're seeing and not accepting at this point. But we really do welcome more work and would really appreciate the opportunity to be able to review some of the outstanding research out there. So please keep sending us stuff. Thank you, Eric. Thank you, Lindsay.
Welcome to the Radiology Review Podcast, your on-the-go source for radiology education with your host, Dr. Matt Covington, a board-certified radiologist. Please follow the podcast on Twitter at RadRevPodcast. Send emails to theradiologyreview at gmail.com or visit the website theradiologyreview.com. Welcome back to the Radiology Review Podcast. On this episode, I will cover a non-interpretative skills subject of periprocedural care. On the surface, this may seem straightforward, but as with many things in the non-interpretative skills portion of the examination, there are details that you may not be aware of that are highly testable, and I will try to focus on these highly testable details on this episode, again in question and answer format. The questions and answers from this episode specifically refer to information that is presented on the 2021 version of the American Board of Radiology Non-Interpretive Skills Study Guide that is available online at the ABR website. I will make the study guide for this episode freely available for download on my own website, theradiologyreview.com, and this episode is a reminder for all of those who have the core exam in your future that the non-interpretative skills portion of the examination should not be overlooked or necessarily underestimated. Even though you are provided with a fairly comprehensive study guide from the ABR, there are details in these questions that can be tricky. Let's go ahead and get started. After one plug to follow at RadRevPodcast on Twitter or Instagram, where I am currently posting on a near daily basis tips for the physics portion of the ABR core exam, and I occasionally have other board-relevant material that I present there as well. Let's get on with this episode. First question, how many patient identifiers need to be confirmed during a timeout prior to a procedure? According to the Non-Interpretive Skills Study Guide, at least two patient ident that are discussed in the Non-Interpretive Skills Study Guide include patient name, medical record number, telephone number, date of birth, government-issued photo ID, or the last four digits of a patient's social security number. Again, you need to confirm at least two of these prior to a procedure. So that is two of the following patient name, medical record number, telephone number, date of birth, government-issued photo ID, last four digits of a social security number. Next question. True or false? A patient's current room number can be used as a patient identifier prior to a procedure. The answer here is false. Something like a patient's room number in the hospital is considered a, quote, transient factor, end quote. A transient factor, according to the Non-Interpretive Skills Study Guide, is something that is not permanent but could change, such as a patient's room number. So something like a room number that is a transient factor cannot be used to identify a patient prior to a procedure. Next, true or false. If you are unable to verify patient identifiers with the patient because the patient is unable to verify their own identity, such as an unconscious patient, a relative, guardian, domestic partner, or healthcare provider who has previously identified the patient can be used as a source to identify the patient. The answer here is true. The Non-Interpretive Skills Study Guide also states that if there is a discrepancy between patient identifiers of any variety, the procedure cannot be completed until additional information is obtained to confirm the patient identity prior to proceeding with a procedure. And again, this question states that it is true that if the patient is unable to verify their own identity due to something like altered mental status or loss of consciousness, you are allowed to use a relative, guardian, domestic partner, or healthcare provider who has previously identified the patient to confirm the patient is who you think they are prior to performing a procedure. Next question. To be approved for sedation, an accredited practitioner must assess for the following. Recent oral intake, adequate pulmonary and cardiac status, vital signs to include pulse oximetry and capnography if available, EKG if available, baseline level of consciousness, and any recent illness. Next, can you list the four levels of sedation according to the Joint Commission and the American Society of Anesthesiologists? The four levels of sedation according to the Joint Commission and American Society of Anesthesiologists, are 1. Minimal sedation or anxiolysis, 2. Moderate sedation slash analgesia, 3. Deep sedation slash analgesia, and 4. General anesthesia. So again, minimal sedation, moderate sedation, deep sedation, and general anesthesia. Those are the four levels of sedation. And that leads us into the next question. Can you define key features for each of these four levels of sedation? First, let's talk about minimal sedation. Minimal sedation is a medication-induced state that causes reduction in anxiety. Minimal sedation is not too deep for a patient to respond to verbal commands. There may be impairment of cognitive function and coordination. The patient is breathing on their own, and a patient has stable cardiovascular function. Let's move on to moderate sedation. With moderate sedation, consciousness is minimally depressed due to pharmacologic agents. The patient is able to maintain their own airway, the patient has protective reflexes, and the patient can be aroused by physical or verbal stimulation. Next, deep sedation. Deep sedation involves a deeper sedation state in which consciousness is depressed due to administered pharmacologic agents. The patient in a deep sedation state cannot be easily aroused but does respond purposefully after repeated or painful stimulation. The patient may not be able to maintain their own airway or maintain adequate ventilation without some sort of intervention. With deep sedation, cardiovascular function is usually okay without intervention. Finally, general anesthesia, and this is a controlled state of unconsciousness. With general anesthesia, there are no protective reflexes, a patient cannot maintain their own airway, and the patient is not able to respond appropriately to pain. Let's move on. True or false? Minimal sedation patients do not require monitoring. The answer here is false. Next question. How many classifications are there in the American Society of Anesthesiologists' physical status classification? And can you name some details about each of these American Society of Anesthesiologists' physical status classifications? First of all, there are six levels of classification within the ASA physical status classification, and these are as follows. Class 3. Class 4. Class 5. And finally, class six, patient with brain death undergoing organ removal for donation. I do think it's important to know details about each of these. You can imagine it is relatively easy to write a multiple choice question on this topic. You can review this on the source from the ABR non-interpretative skills study guide, or you can also review it on the study guide I will make available on my website for free download. Next question. True or false? Class V ASA physical status classification patients may be sedated by a non-anesthesiologist? The answer here is false. As a reminder, a class 5 patient is a patient who is not expected to live without the operation or procedure at hand and is a moribund patient, M-O-R-I-B-U-N-D. And to make sure it is completely clear, a moribund person is a person who is at the point of death. The answer to the question is that class 5 ASA physical status classification patients may not be sedated by a non-anesthesiologist. These patients require specific skill that non-anesthesiologists simply do not possess, and class V patients should only be sedated by anesthesiologists. Next, what ASA physical status classification classes require at least a consultation with an anesthesiologist or anesthetist prior to performing an operation. At what levels do you need to first consult with the anesthesiology specialist? The answer here is class 3 and class 4 patients. These are patients that require a radiologist overseeing sedation to first at least consult Next question. The answer here is true. Continuous monitoring includes things like level of consciousness, respiratory rate, pulse oximetry value, blood pressure, heart rate, and cardiac rhythm, and that is a lot to keep track of while the radiologist is also performing a procedure. Therefore, you do need a separate qualified healthcare professional who has a primary focus on monitoring, administering medications, and care of the patient while under sedation. Next, patient monitoring must continue at least how many hours following administration of a reversal agent? The answer is that a patient must be monitored for at least two hours after administration of a reversal agent or else the patient may risk relapsing into a deeper level of sedation. Remember that a reversal agent for anesthetics may have a shorter half-life than the sedating agent and therefore may wear off and the sedating agent is still on board and the patient falls into a deeper level of sedation.
So if the patient does enter a deeper level of sedation, you will be alerted and can respond appropriately. Next, what is the universal protocol that must be followed prior to each procedure? The universal protocol refers to three steps prior to a procedure. First, pre-procedure verification. Second, marking of the procedure site. And third, pre-procedure timeout. Next, what are steps to perform during the marking of a procedure site? This is a great example of a question that seems very simple on the surface, marking a procedure site. In your mind, I'm sure you all think simply marking an X on the skin over the surgical site. However, the procedure site should be marked when there is more than one possible location at which the procedure could be performed, and performing the procedure at a different site may harm the patient. So there are certain scenarios when the site may or may not be marked. Additionally, a licensed independent practitioner who will be present during the procedure must mark the site. In certain cases, this task of marking the site may be delegated to residents, PAs, APRNs, and so forth. The mark must be visible and made in a manner that won't easily wash away when prepping the skin. Additionally, some areas are difficult to mark, such as mucosal surfaces and so forth. In such cases, follow your organization's written alternative processes that determine how to proceed. Note also that marking on premature infants can potentially cause a permanent tattoo, so in such cases alternative processes should first be established by the institution and subsequently followed. Last and final question for this episode. What are steps to perform during a pre-procedure timeout? Hopefully the answer to this question is second nature because you are in the habit of performing high quality timeouts in your clinical practice. However, let's go ahead and review to make certain that we get these questions right on radiology board examinations. First, during a pre-procedure timeout, this should be conducted immediately prior to starting an invasive procedure all immediate team members, including nurses, techs, the anesthesia team, and so forth. During the time out, all relevant members should actively communicate and voice agreement or dissent with the following, correct patient, correct site, and correct procedure to perform. Follow your organization's policy regarding how to document the timeout. That is enough for now. I hope these questions and answers will be helpful for many of you. Remember, if you are listening to this episode in a future year, that the ABR may have a more updated version of the Non-Interpretive Skills Study Guide, and I would encourage you to check this information with the newly updated study guide, as this study guide does tend to change, at least in minor ways, from year to year. If you want to review these questions and answers in written form, you can download the free study guide on this topic available on my website, theradiologyreview.com. If you would like more non-interpretative skills topics, please let me know. You can reach me through email at theradiologyreview at gmail.com. You can also send me a message through Instagram or Twitter at RadRevPodcast. Thank you for listening to this episode. Keep up the good work. Study hard. Remember, you have to study really hard to succeed on radiology board exams, so prepare to succeed. I will catch you on the next episode. or recommending any course of treatment. This podcast should not be used for self-diagnosis or self-treatment and is not a substitute for independent professional medical care. Please consult your own physician regarding any diagnosis, imaging interpretation, or course of treatment.
Hello out there. This is Dr. Kathy DeAngelis, the Editor-in-Chief of JAMA, the Journal of the American Medical Association. And this week I'm going to tell you about the September 1st, 2010 issue. And as always, I will begin with the art on the cover, which this week features Tibetan altar, that's a Buddhist altar, with domestic motifs. This was from the late 19th or early 20th century. It is Tibetan, and it's possibly from the Kam, that's K-A-H-M region. And the dating of this is only estimated, and the judgment comes from the colors used in this painting. And the first article deals with risk-reducing surgery for BRCA1 and 2 gene carriers. Women who have inherited mutations with the BRCA1 or BRCA2 genes have elevated risk of breast and ovarian cancer and may elect to reduce their risk by undergoing prophylactic mastectomy and salpingofrectomy. In an analysis of data from a prospective multicenter cohort of 2,482 BRCA1 and 2 mutation carriers, Dr. Susan Domachek from the University of Pennsylvania School of Medicine and her colleagues assessed cancer risk and mortality reduction. In an analysis stratified by mutation and prior cancer status, the authors found that mastectomy was associated with a lower risk of breast cancer and salpingofrectomy was associated with a lower risk of ovarian cancer, first breast cancer, overall mortality, and the breast and ovarian cancer-specific mortality. In an editorial, Dr. Laura Esserman from the University of California, San Francisco School of Medicine discusses the importance of identifying women with genetic predispositions to breast and ovarian cancer and advances in risk-reducing surgery. And the second article is the clinician's corner, Cerebral Palsy Among Health and Insurance Registry data, Dr. Dag Moster from the University of Bergen in Norway and his colleagues assessed whether timing of birth in the term and post-term period is associated with risk of cerebral palsy. The authors report that compared with delivery at 40 weeks gestation, delivery at 37 weeks or at 42 weeks was associated with an increased risk of cerebral palsy. And the JAMA patient page has information for your patients about cerebral palsy. And the third article deals with home-based intervention for patients with dementia. Professor Laura Gitlin from Thomas Jefferson University School of Medicine and her colleagues report results of the care of persons with dementia in their environment, or COPE trial, in which community-dwelling patients with dementia and their caregiver were randomly assigned to either a home-based, non-pharmacological, biobehavioral intervention or a minimal contact control condition. The intervention involved up to 12 home or telephone contacts by health professionals who identified and targeted modifiable sensory, physical, and cognitive stressors in the patient's home environment and sought to enhance caregiver skills. Patient-caregiver dyads assigned to the control group participated in up to three scripted telephone conversations with the research staff and received informational brochures. The authors report that compared with control, the biobehavioral intervention resulted only in better outcomes for the patient-caregiver dyads at four months, but no difference in the patient outcomes. And the fourth article deals with perinatal regionalization for VLBW infants. To maximize access to and the capacity of neonatal intensive care units, it is recommended that perinatal services in the United States be regionalized and that very low birth weight, that's VLBW infants, receive care at highly specialized Level 3 hospitals. However, significant percentages of VLBW infants are born in lower-level hospitals, which may have implications for infant survival. In a systematic review of the published data on the relationship between hospital-level at birth and neonatal and pre-discharge mortality, Ms. Sarah Laswell from the CDC and Prevention and her colleagues found that birth outside a level 3 hospital was associated with higher rates of neonatal and pre-discharge mortality among VLBW and very preterm infants. And we have a commentary from the Archives Journals. It's an abstract and a commentary, and it deals with what to advise patients about hernias. And this one was written by Dr. Edward Livingston from the University of Texas Southwestern. And Dr. Livingston is a contributing editor to JAMA. And we have four others just straight commentaries. The first, a new research and development policy framework for the biomedical research enterprise. This one by Dr. Howard Federer from Georgetown University School of Medicine and Dr. Rubin. The second, a national strategy to improve sexual health. This is by Ms. Andrea Schwarzengruber from Johns Hopkins University School of Public Health and Professor Zenennelman. The third commentary, Improving Access to Healthcare Data, the Open Government Strategy. This is by Dr. Patrick Conway from the University of Cincinnati School of Medicine and Dr. Van Lari. And the fourth commentary, Societal Perceptions of Physicians, Knights, Knaves, or Pawns. And this one is by Dr. Sachin Jain from the Office of National Coordinator for Health Information Technology and by Dr. Chris Castle from the ABIM. And the medical news and perspectives. Resting heart rates above 80 per minute, considered within the normal range and often discounted in physical examinations, increase the risk of cardiovascular complications and may be associated with poor renal outcomes. New rules call for more oversight and fewer hours for first-year residents. Obstetrics group relaxes the guideline for trial of labor after cesarean delivery. Screening misses high LDL in many youths. And estrogen spray poses risks for children, pets through contact with treated skin. And the lab reports blocking HIV transmission, sweet treatment, memory regained, and regulating addiction. And from the Centers for Disease Control and Prevention, Emergence of Cryptococcus Gutti from the Pacific Northwest, 2004 through 2010. And an update, Influenza Activity in the United States, 2009-2010 Season. And A Peace of My Mind. This one is written by second-year medical student Jordan Godovich from Philadelphia, Pennsylvania, and I quote, I was at a loss for words to respond to my patient's tearfulness. Instead, I took his hand and held it firmly. He gently squeezed my hand in reply. And the title of this is Holding the Hand. I'd say that was a very valuable lesson learned by Mr. Godovic. Sometimes all a physician can do is hold a patient's hand. And the author in the room teleconference, we invite you to join Dr. Matthew Winnia Wednesday, September 15th from 2 to 3 p.m. Eastern Time when he will discuss the role of professionalism and self-regulation for detecting impaired or incompetent physicians. And that's it for this week. Thank you very much for listening. Please let me know if you have suggestions to make this podcast more educational or interesting to you. This is Dr. Kathy DeAngelis, Editor-in-Chief of JAMA, speaking to you from beautiful downtown Chicago, where the wind is still blowing mightily, but the patients are always the top priority.
From the JAMA Network, this is JAMA Internal Medicine Author Interviews, conversations with authors exploring the latest clinical research, reviews, and opinions featured in JAMA Internal Medicine. Hello and welcome to this author interview from the JAMA Network. This is Deanna Balandi with JAMA Internal Medicine. with communication and resolution programs after medical injury. Their work included interviews with patients, family members, and staff at three U.S. hospitals that operate communication and resolution programs, also known as CRPs. They join us to talk about their work. So, Dr. Mello, first tell me how common are CRPs, how do they work, and what's the objective of a program like this? CRPs are increasingly common, but still the exception. The traditional approach to managing patients after a medical injury occurs is to hope that they go away and stay as little as possible. These programs do the opposite. They try to meet patient safety goals and liability cost reduction goals by disclosing adverse events and errors to patients, rapidly investigating, even where the patient's not complaining about the care, offering an explanation of what was found, forwarding the case on to the insurer for consideration for proactive compensation instead of waiting for the patient to sue, come forward and pay a fair compensation for the event. The objectives are several. They are to improve communication and transparency around adverse events, to improve patient safety, to reduce lawsuits and promote reconciliation by trying to proactively meet patients' needs, and to support clinicians in their journey to disclose medical injuries effectively. So, Dr. Moore, the study included interviews with 27 patients, 3 family members, and 10 staff at those hospitals. Can you tell me about the design of the study? Sure. So we undertook semi-structured interviews deliberately so that we could give patients and family members in particular a really good opportunity to tell us how their experiences were. And we knew from prior research that this kind of work is challenging to do. IRBs, for example, worry that if you do this kind of research you'll re-traumatise patients and hospitals worry that you might provoke legal action on the part of patients and family members. But we actually managed to surmount those challenges and undertake these interviews and I think it's fair to say that there was surprise expressed by some of the institutions at the number of patients and family members who agreed to participate in the study. So now let's talk a little bit about what you found with regard to aspects of a CRP. Among the 30 patients and family members who were interviewed, 27 patients experienced injuries that were attributed to error and they received compensation. Were they satisfied? 16 out of the 27 said that they felt satisfied overall with the compensation portion of the program. What's interesting is when we talked to them about the reasons for being less than fully satisfied, some of it was about the amount of money that they received. But what we also heard was dissatisfaction with the process that led to that compensation offer. The hospitals really felt that they'd been very proactive and assertive in trying to anticipate and meet patients' and families' needs. The families didn't feel that way a lot of the time. They felt that they had to wait longer than they should have to get compensation and that hospitals hadn't done a particularly good job of anticipating things like the mortgage coming due at the end of the month. Finally, they felt that some of the collaborative, meaningfully emotional conversation that started out in the process when the error was being disclosed did not continue into the compensation phase. As one patient put it, the gloves came off sometimes, and it really started to feel adversarial to them. So those are some of the leading reasons for dissatisfaction. So how many patients regarded the CRP experience as overall positive, and when were they generally the most satisfied? We had about 18 people overall in our judgment say they were satisfied overall with their experience. And we really connect the differences in overall satisfaction to how they were communicated with during the process itself. I think it had something to do with the amount of money they received, but again, much more to do with how they were treated during the process. In particular, hospitals that really achieved this goal of authentic, empathic communication with the patient, providing the information that patients needed, in particular information about patient safety improvements, and really being proactive, not just in offering compensation, but in thinking thoughtfully about what this family is going to need. Those were the types of things that communicated to patients, this is still an institution that cares for us. Something that was really interesting was that we found 18 out of the 30 patients and families were overall satisfied, as Michelle pointed out. It was also really interesting that 18 of those patients continued to receive care at the hospital, think it was helpful to have the plaint attorneys. But we found that patients reported they were useful and there are a number of reasons for that. One was that the painless attorneys could provide support. They could also assess whether the offer, particularly the compensation offer, for example, was fair. And indeed, hospital representatives also noted that plaintiff's attorneys could add value in that respect as well. Another really interesting finding was that plaintiff's attorneys can also have a role in achieving reconciliation, restoring trust between the interpatient and family and also the hospital staff. That was particularly interesting. So an example of that was a patient who said, look, after the injury, I thought that the hospital staff were, quote, evil. But when my lawyer said to me, look, how do you view the relationship going forward? What do you want to happen going forward? They actually noted that the lawyer helped them to restore that trust with the hospital. So that was really interesting and quite surprising, really. So, Dr. Mello, the results of your study indicate that patients and families express a really strong desire to be heard. So I'm curious, that said, how did they expect attending physicians to behave during a CRP? What we heard loud and clear is that the most important thing attending clinicians can do during these conversations is to sit back and listen to patients express what's important to them about what has happened to them. And in particular, patients wanted the attending physician to listen attentively without taking notes, without interrupting, and without asking the patient to confine herself to clinically relevant information. The patient wanted to narrate a story about what happened and what it meant for them and their family. And clinicians too often are there in their usual role to elicit information and figure out how can I help. But in this case, the conversation has to be different than a typical clinical encounter. The good news is that even if you're not particularly skilled at having difficult conversations, anyone can listen. Dr. Moore, did patients care whether the hospital had done anything to prevent recurrences of a similar event? Yes, they absolutely did. And this was consistent with prior research that has found that patient safety efforts is really important to patients and family members. And indeed, our group of participants really clearly noted that they didn't feel they could move on or achieve reconciliation if they weren't notified of efforts to prevent recurrences. And what we found was that the hospitals reported that they had done this, they had communicated the patient safety efforts, but unfortunately about 24 out of the 30 of our participants receive no information about patient safety efforts. So again, they said this are the takeaways from the study? the institutions actually listen and it may involve listening for a very long time and letting the patient's priorities lead the conversation. For example, if a patient hears that the injury has prevented her from doing housework and she likes a clean house, it's really important to hear that and not dismiss it as something that's not clinically relevant. The second thing is that plaintiff's attorneys can actually add value to the process and may also have a really important role in restoring trust and encouraging the patient to continue to receive care at the hospital. And then the third thing is around the patient safety efforts. It's not enough just to actually take the action in the hospital. It's really important that that effort is communicated to the patient and the family, and it's important to do that if it takes a very long time to fix the issue. The hospital should still reach out to the patient and family. Otherwise, they still feel that they can't move on. So what do you think, Dr. Moore intimated, that has traditionally been something that hospitals have been very afraid of. I think this study demonstrates that you can ask patients about hospitals' performance in this area without provoking ire and lawsuits, and that patients are really, really hungry to give feedback about what was often one of the most difficult experiences of their lives. Well, thank you both for talking to us about your work. This is Deanna Balandi with JAMA Internal Medicine. For more author interviews, please visit us online at jamanetworkaudio.com. You can also subscribe to our podcast at Apple Podcast or on Stitcher.
I'm Stephen Morrissey, Managing Editor of the New England Journal of Medicine, and I'm talking with Susan Occhi, a medical journalist and clinical assistant professor of family medicine at Georgetown University School of Medicine. Dr. Occhi has written a perspective article about the ongoing evolution of the primary care physician. Dr. Occhi, you trained in family medicine. Why did you choose that path and what kind of advice put you on it? Well, I graduated from Harvard Medical School in 1978, and at that time, family medicine as a specialty was relatively new, and it was getting a lot of attention among medical students and generally in the country, the whole idea of bringing back the general family doctor, but with better training, more extensive training to see both children and adults. And there were no Harvard or Boston training programs in family medicine, but there were a number of people in my class who were interested in it, and I chose it because I liked being a generalist. I always have liked that and didn't really want to narrow in on a specialty, and I knew that I preferred outpatient medicine to hospital medicine. But I would say that even at that time, the advice I received was that the best programs for family medicine training were in the West and in the South and in rural areas of the country because in hospitals, particularly in the East where there were multiple residency programs, there was competition between the internists and the family doctors or between the internists and the pediatricians for getting to manage patients. So you saw this sort of competition, and I think it has played out a bit in the marketplace, too. Family doctors really are needed and probably most appreciated in rural areas and in places where there is a doctor shortage. Despite what we sometimes hear, you cite survey data in your article that indicate that primary care physicians are no less satisfied with their work than specialists are in the United States. Do those data jibe with what you've seen and with what medical students say they're hearing about primary care? Well, the data are collected over time, and they do compare populations of physicians in one era with another. So they do show that doctors, for the most part, people that go into medicine remain satisfied with medicine generally. They enjoy it and they are happy to be in it. But I certainly hear primary care colleagues complaining about being overwhelmed with all the demands of documentation, the demands of quality assurance, and trying to work fast, work efficiently, and fulfill all of the expectations that they have about what needs to happen during a typical primary care visit. Patients come in with more expectations, more questions, and there are many different measuring points in terms of what should happen, vaccinations and preventive care and so forth. So I think there's certainly a lot of pressure on colleagues that I see doing primary care, and it's probably a higher pressure specialty than in the past. If the Affordable Care Act is upheld, there'll be an additional 32 million patients in the U.S. healthcare system, potentially. Given what you say, can that kind of number be accommodated by the existing pool of primary care physicians? I don't think that it can by primary care physicians alone, not by the number that we have right now. I think that we will need the involvement of nurse practitioners and physician's assistants and probably the involvement of some specialty physicians to meet the rising demand for primary care. And I believe that's part of the reason that health systems and large medical practices are putting so much emphasis on team care, and you see a lot of them hiring nurse practitioners and PAs as well. And given the unpopularity of primary care among today's medical students, would it even be feasible to produce more primary care physicians to meet that demand? Well, during my research, I talked a lot with Dr. George Thiebaud about these kinds of questions. He is president of the Macy Foundation, which looks particularly at ways to reform medical education and training. And he suggested that it may require efforts to adjust the number of residency slots in various specialties so that the numbers of doctors that we're training in different specialties more closely match what the nation is projected to need. Right now there isn't really national control over how many members of certain specialties get trained versus how many primary care physicians. And I think that to change the minds of medical students, it will also require some changes in the financial incentives. We know that students come out of medical school with huge debt today, and this is a factor in what they decide to do. And doctors in most other specialties make more money than primary care physicians. Sometimes they make much more. So if there were a way to either equalize the income landscape or have financial incentives that would reduce the debt of graduates who went into primary care, that would probably shift the balance. And I would say that at Georgetown I mainly work with first-year medical students, and I do meet students who come to medical school with the goal of going into primary care, very excited about going back to their home communities, whether it's their own ethnic group or whether it's to a rural area or to the town where they grew up, and doing primary care and taking care of those patients. But at the same time, the medical students that I meet with are very excited about providing clinical care, and they often work in a student-run clinic which takes care of indigent patients or uninsured patients. And they get quite overwhelmed by how complicated the health system is and how many financial and social barriers there are to providing good care. So I'll hear students say that they really want to be able to fix a problem. They really want to be able to take care of a problem for a patient. And they get quite discouraged at the idea that disease is chronic and that it's an ongoing process. And those students who say that they really want to be able to fix somebody and make them better are very often the ones who say they want to go into surgery or into specialty care. How has the scope of practice of the primary care physician changed in recent years? Well, the scope of practice has narrowed. One interesting source of information on this is periodic surveys that are done within family medicine, and they are fairly exhaustive surveys because family physicians who are board-certified have to fill out these surveys as a condition of remaining board certified. And they show that right now most family physicians are not doing preoperative, postoperative, or maternity care. More than half of them are not doing any in-office surgery. About 55% say, surprisingly, that they spend no time in mental health care, and a quarter of them don't see children. The mental health care data, as I was told by the head of the Family Medicine Board, may not include... It's possible that physicians don't interpret that question as including the prescribing of antidepressants, which I think is a common practice that probably most primary care physicians do. But part of what we're seeing is there is competition with other specialists for patients, and particularly the issue of not caring for children may reflect the fact that a lot of family physicians are hired these days by large health systems or HMOs, and they're often asked to see primarily adult patients because there's a serious shortage of general internists and there's not a shortage of pediatricians. So another big change, too, is that with the growth of hospitalists, very few primary care doctors, whether they're internists orrasinski, who observed a number of primary care internal medicine practices, that there is more of a tendency among internists these days to refer patients to specialists for problems that they might have treated in the past. So I think you can say that there's a general narrowing in the scope of practice among primary care docs. What do you see as the pros and cons of team-based care? You mentioned physician assistants and nurse practitioners. What are the appropriate roles for them on a team? I work with nurse practitioners and physician assistants in a safety net clinic, and my observation is that they can do very well on a lot of the routine problems that we see. We tend to see many of the same diagnoses time after time, chronic illnesses like diabetes or hypertension. And they particularly do well explaining and counseling patients, sometimes talking about lifestyle changes and keeping track of preventive care measures that need to be done at intervals. And they can work really well on a team with physicians, and in the process they can give the physician more time to focus on diagnosis or on discussing different treatment options with the patient or on deciding what to do when a decision is complicated. At the same time, there's been a kind of emphasis on team care because it allows other team members to share in the paperwork and documentation, so it kind of helps with the paperwork burden that physicians have these days. And nurses and medical assistants and other members of the team can also provide a lot of care coordination between visits when patients call, when they have questions, when they need a prescription filled, and so on. But I think the challenge is that there has to be really excellent communication on a team and trust among the team members in each other's skills. And as physicians or as nurses, we really aren't taught how to do all this during our training.
So a lot of focus now is being placed on the whole idea of interprofessional education. That's another goal of the Macy Foundation, and I've heard about it from deans at medical schools and public health schools and nursing schools, the idea that these different professionals are going to have to be educated together more if they are going to be learning how to be very effective team members in the office. And I guess I think the last challenge is maintaining a consistent quality of care, standard of care within a practice, and trying to ensure that if a patient has an uncertain diagnosis or if they have multiple illnesses or their case is otherwise complicated, that that case would get triaged to a doctor rather than always being seen by another professional. You quote Dr. Sinskey as saying that the electronic health record is a disruptive innovation. What's been the effect of the EHR on the patient-doctor relationship in primary care? I think in some ways it's improved care because it provides better availability of clinical information and test results and so forth at the time that you're seeing a patient, so it's able sometimes to reduce the unnecessary duplication of tests and improve communication among different providers. But that all depends upon having a system that is coordinated so that different doctors in different sites can get access to the information and talk to one another so that they can look up something that happened at the hospital. And we're really in so much the infancy of this new technology that I think doctors and other professionals are dealing with systems that don't always communicate with each other, that aren't always user-friendly, that are full of glitches. So it involves a huge amount of learning on the part of doctors and other professionals, and at the same time working out the glitches and entering the data manually. So it's hard to say how this is all going to turn out, but right now there's just, I think, great frustration that kind of goes along with everybody having to learn this new technology at the same time that they're trying to do their job. The other dilemma, Abraham Verghese particularly pointed this out during my research, is that young physicians and physicians in general can get so focused on interacting with the computer that they forget to look at the patient. And they have to get things done during the visit, including getting data entered. So the most efficient way for them is often to ask the patient questions and then type the answers into the record while they're conducting the visit. But as a result, there's less eye contact quite often between the doctor and the patient, and there may be less in the way of a physical exam in some cases, according to Dr. Verghese, because lab results are there on the screen and the doctor is checking the lab results, and sometimes the physical exam can get neglected. So those are all challenges that I think the electronic health record is posing that we are going to continue to be working through. Given that list, do you think the positives outweigh the negatives? I think they will outweigh the negatives, but I can't say if they're outweighing the negatives right now. I mean, I'm not in clinical practice five days a week, and this is a huge technology change that's changing the whole profession in every setting within the health care system. So I don't know. Good question. What do you think primary care will look like in the United States in 10 years or 20 years? I think that we will see, we're already starting to see bigger practices, a lot of consolidation. Here in the Washington area, we're seeing a lot of health systems moving in and buying up primary care practices or taking over primary care practices. And those practices are looking more diverse in terms of having both doctors and nurse practitioners and different kinds of professionals. There's kind of an economy of scale involved in having, if you have a bigger practice that is connected to a health system, it's easier to really provide team care and have additional professionals like health educators or nutritionists. And I think that's the direction that things are going in. I think that more of us will probably go to the doctor and not always see a doctor every time. Maybe we'll be more apt to see a nurse practitioner or a PA for some kinds of issues. I think the electronic records will get better and probably get better at communicating with one another. And all of us will probably get more used to using the computer as a portal to look up our lab results or to ask questions or to renew our prescriptions. I mean, that's the ideal, and hopefully things will get smoother as the changes go on. But I don't think we've answered the question with any of this as to how we're going to take care of underserved populations. We still are going to have people in rural areas who are seriously underserved and many populations even within the cities that don't have good access to care. We still have a lot of undocumented immigrants in the country who don't have good access to care. So these kinds of disparities are going to continue to haunt us and still need to be addressed. Thank you, Dr. Oki.
Hello, and welcome to this author interview from the JAMA Network. This is Jim Michelski with JAMA. Many anticoagulant strategies are available for the treatment of venous thrombosis, yet little guidance exists regarding which drug is most effective and safe. Dr. Mark Carrier of the University of Ottawa conducted a study to summarize and compare the efficacy and safety outcomes with various anticoagulation options for the treatment of venous thrombosis. Welcome, Dr. Carrier. Thank you. First of all, why did you choose to examine this particular issue? Well, Jim, a few weeks ago I was in clinic and I was counseling a patient with a new diagnosis of deep vein thrombosis and I was reviewing the different treatment options with him. I discussed with him that obviously the standard of care was Lomacrid, Heparin in combination with vitamin K and Tagnes, but I also touched base with him that in the past couple of years, there's new direct oral anticoagulants that are available that could be used to treat deep vein thrombosis and pulmonary embolism. He asked me after counseling him, he asked me a question that I couldn't answer. And basically, he told me, Dr. Carrier, you talked about different directorial anticoagulants. How are they comparing to one another? And I couldn't answer him because all the different trials that compared or assessed directorial anticoagulants always use low-molecular weight heparin, vitamin K, and tagnus as the comparator. And therefore, we don't know how they compare to one another. And therefore, in clinic, he identified an important knowledge gap Tell us about how your study? Well, we used lomacrate heparparin and vitamin K antagonists as the comparator, and all the management options, with the exception of intravenous unfractionated heparin and vitamin K antagonist combination, were associated with similar clinical outcomes. What was interesting is management strategies using rivaroxaban or apixaban without preceding parenteral anticoagulation appears to be associated with a reduction risk of major bleeding episode. However, clinicians need to keep in mind that although it might be leading to a reduced risk of major bleeding, these products don't have antidotes at this point in time, and bleeding management might be more challenging than with vitamin K antagonists. Dr. Carey, what do you believe are the implications of your findings? I think it will help clinicians, it will help policymakers, and it will help government agencies. It will help clinicians because it will help clinicians to tailor the different anticoagulation options for their patients with acute venous thrombosis. For example, if a patient is presenting with a new acute venous thrombosis and it's high risk of recurrence but low risk of bleeding, clinicians, by looking at the results, might be able to pick the most effective drug. Whereas, for example, if another patient presents with a lower risk of recurrent event but high risk of bleeding, then based on their findings, the clinicians might be more likely to pick the drug with the best safety profile. Regarding policymakers and governmental agencies, I think the findings will be important because they can be included in a cost-effectiveness or cost-utility analysis to determine which treatment option is the most cost- effective, and that might help to decide on funding and reimbursement. Dr. Carrier, in your opinion, what additional research is needed? Well, obviously, we did indirect comparisons of the different treatment options. What needs to be done now is trials comparing the direct oral anticoagulants, so trials randomizing patients to receive rivaroxaban, dabigatran, or apixaban or edoxaban. However, these would require lots of resources and be very expensive. Thank you for talking to us about treatment strategies for venous thrombosis. This is Jim Michelski with JAMA. For more podcasts, visit us online at jama.com.
Welcome back to the Curbsiders. Oh. Yeah, that's right, Stuart. That was surprising. I didn't know we were doing a second one. That's right. We are doing a second one. Like you said, Stuart. This, like you've said. Oh, hold on. Where did you come from? Thank you. that we had to spill over into another episode. This is the Curbsiders, the internal medicine podcast that uses expert interviews to bring you clinical pearls and practice changing knowledge. I'm Dr. Matthew Watto, here with my co-host, Dr. Stuart Brigham and Dr. Paul Williams. Stuart, you're so surprised that we were recording tonight. You literally just went right into it. After two hours of recording, it's just a little bit shocking. Well, we're back for part two with Dr. Joel Topf. On this episode, we talk about kind of medication management, which medications to avoid during chronic kidney disease, and also trying to dispel some myths. Thank you. Bactrim, SGLT2 inhibitors. A lot of interesting discussion here with Dr. Joel Toff. Just to remind you, Dr. Joel Toff is best known as atkidneyboy on Twitter. He is one of the creators of the Nephrology Journal Club and is well known for his blog, Precious Bodily Fluids, Musings of a Salt Whisperer. Dr. Toff is a board certified nephrologist and partner at St. Clair Nephrology. He holds academic appointments as clinical assistant professor at Oakland University William Beaumont School of Medicine and academic faculty for the St. John Hospital and Medical Center Nephrology Fellowship. And he's back for this part two on CKD with some random clinical pearls. I hope you enjoy it. I will. That was your best one yet, Stuart. Well, from what I wanted to do from here, I think there's some really interesting stuff, Joel, that I know you gave a recent talk on contrast-induced nephropathy. So I want to get into that. I do want to make sure we touch on medications that may or may not be safe in CKD because I know that some of those are also controversial. So maybe we can talk about medications and then we'll get to the contrast nephropathy next. So patients with CKD3, CKD4, everyone says never give these patients NSAIDs. Be very careful with Bactrim. Definitely no metformin. Well, now those recommendations have changed a little bit. So can you talk about some of those medications that primary care doctors maybe place that we make mistakes or where maybe we believe things that aren't actually true? Yeah, let's go through them. And then they looked for people dying of sudden cardiac death within a couple of weeks of filling that prescription. And they found three excess sudden cardiac death per thousand prescriptions. And these people were outpatients, and they were probably getting treated for sinusitis and pretty mild diseases. And that, to me, and the control was amoxicillin. And to me, that sounds like a placebo, right? If you can treat it with amoxicillin, it wasn't that serious of an infection. And so how much sudden cardiac death are you willing to accept as you're in your placebo grip or for minor URI symptoms or maybe UTI symptoms? And man, that number is very close to zero for me. Presumably, this was due to hyperkalemia because Bactrim is a combination of trimsulfa, trimethoprim, and sulfamethoxazole. And trimethoprim is an antagonist at the epithelial sodium channel. So if you visualize the nephron, we're going to go to the distal nephron, so the cortical collecting duct. And this is the site where potassium secretion happens. And this drug acts exactly like a potassium sparing diuretic, and it'll block potassium secretion. So hyperkalemia is a known and expected complication of this drug. Additionally, it will compete for creatinine secretion at the proximal tubule. And so we talked about the difference between GFR and creatinine clearance. We didn't go into the details, but the reason that creatinine clearance does not equal GFR is some creatinine makes it into the urine, not by being filtered at the glomerulus, but by being secreted at the proximal tubule. Since Bactrim will compete for that secretion at the proximal tubule, you'll get decreased creatinine secretion. That means your serum creatinine goes up a little bit, about 10% or so. And that means that the creatinine clearance now actually better approximates the GFR if you're on Bactrim. No, it does. Another drug that does this is Cimetidine. And when I was a fellow at the University of Chicago, we kept getting enrolled volunteering army style for these different studies. And a lot of them required to do creatinine clearances as part of the study. And they usually would load us with Cimetidine so that our creatinine clearance would more better approximate our GFR. But the same thing happens with Bactrim. So you'll get a bump in the creatinine when you take Bactrim, but that has nothing to do with, it doesn't mean any change in the GFR. That's just, it means it's just an affecting, serum creatinine goes up a little bit, your GFR hasn't changed at all. But the rise in potassium is significant, and it can be serious, especially in CKD. So that's a drug I to put those patients on Bactrim and see their creatinine. Like if you happen to check labs, their creatinine's up, their K's up. You're just like, oh my gosh, this looks like a terrible basic metabolic panel I've just created here. So I've just stopped doing that after learning it the hard way in one or two patients, I'm sad to say. Right. And then the other one that the conventional wisdom to avoid is the NSAIDs. And so again, the NSAIDs, it's the same pattern of stuff, right? It's going to bump your creatinine and it's going to bump your potassium. The NSAIDs work by antagonizing prostaglandins. And a lot of these patients, as they get to lower and lower GFRs, become dependent on those prostaglandins to maintain dilation of the afferent arteriole so that their GFR is somewhat dependent on maintaining prostaglandins. When you give them an NSAID, you block those prostaglandins and you'll get a drop in your GFR. And then when you have decreased sodium delivery, that's going to result in decreased potassium excretion. And so these drugs are considered a no-no. And all the guidelines recommend avoiding them completely in chronic kidney disease patients. But these drugs aren't given for no reason, right? These patients usually have significant pain. And the alternative has always been just to give them opioids. It's not clear to me that those drugs don't have toxicity also. And so to me, I'm not in love with the guidelines saying just not use them. I mean, I have these patients in my clinic. They say they can't get out of bed without taking their Celecoxib or their ibuprofen in the morning. And taking those away really affects their lifestyle. And I'm not sure if that's the best thing. And I think there's some interesting data came out in last year. A study was called the PRECISION trial. This came out of the fact that there was some concern that Celecoxib may have some cardiotoxic effects, right? Because Vioxx had significant cardiotoxicity. It had been pulled from the market. And the question was, did Celecoxib have a similar thing? So the FDA mandated that the manufacturer, I think it was Pfizer, had to do a post-marketing study where they looked for cardiotoxicity. And this is how you do a study, an N of 24,000 patients. And they were randomized to Celecoxib, ibuprofen, and naproxen. Now, the average creatinine in the study was 0.9, average age was 63, 75% Caucasian, and 75% female. And when you get that type of advanced age, and you get white female, and a creatinine of 0.9 with a standard deviation of 0.23, you actually have a significant number of patients with chronic kidney disease that are randomized there. Now, take a look. The doses were Celecoxib, 100 milligrams BID, and if their pain wasn't controlled, they titrated up to 200 BID.
And this is every day for 20 months, right? And then naproxen was 375 BID, titrate up to 500 BID. Again, every day for 20 months. And their kidney events, their kidney outcomes after that, ibuprofen 1.1%, celecoxib 0.7%. And I'm telling patients they can't ever take 400 milligrams of ibuprofen. It just felt like we were slamming these patients with very high doses of the drugs and there were not many kidney events. It's because the GI bleed happened before that. Well, GI events, so the primary outcome was major adverse coronary events or GI bleed. Oh, great. Okay, so those doses, 20 months, follow-up for 34 months, 2.7% with ibuprofen, 2.3% with celecoxib, no significant difference between the two. Yeah, and GI bleed was 1.6% for ibuprofen and 1.1% for Celebrex. Really? You'd expect it to be better than that, right? Yeah, that's for GI bleed. That's serious GI bleed. Clinically significant was even less. So 0.9% ibuprofen, 0.7% for Celebrex. I don't know why there's clinically significant and serious. What's the difference between clinically significant and serious? I'd have to look at the definitions. I wonder if one of them was a transfusion. Yeah. Usually major bleeding is usually the drop of two grams hemoglobin or they need two units of blood. That's usually what they define it. It says definition is provided supplement, whatever. Oh, you've got to be kidding. It's not even in the primary literature? It's not even in the supplement? Yeah, it's not even in the, yeah. You know what? I'm going to pull that up just for you. Well, let's get out of the gut and back to the kids. Yeah, let's get back to this. So we're talking about NSAIDs here. And basically this large study showing that like 1% or less of patients are actually having problem. Patients who presumably could have had CKD. At a dose you would never consider, you know, 800 milligrams three times a day for 20 months. I would think their kidneys would shrivel and die. The problem is the lawyers would eat you apart, though, if something happened to them. And I think you'd have to be careful. Right. You know, I think it's a situation where there's always risk. And once I've read this study, I've been a little bit more liberal with the use of NSAIDs. Maybe not quite as toxic as we thought. And then, of note, I also... So when I read this, this was the first thing that popped in my mind. I was like, well, what's the rest of the data look like? So it's surprisingly thin. There was a study in JAMA in 2001, which is 22,000 male physicians randomized to aspirin and beta carotene for primary prevention of heart disease and cancer. And then they had 14 years of follow-up. And the primary outcome was a bump in creatinine or GFR less than 55. They asked patients about use of acetaminophen, aspirin, or NSAIDs. And in the end, 4.2% of the patients had elevated creatinine. And that bump in creatinine or that rise in creatinine, the development of chronic kidney disease, essentially, whether they took aspirin, acetaminophen or NSAIDs made no difference. So the people that took ibuprofen weren't at higher risk than the people that took NSAIDs or whether they took aspirin. And if you looked at their, they did, they did an estimate of their dose exposure. There was no dose response whatsoever. But the crazy one was the same study, but this is done for nurses, the nurses' health study. This is 32,000 nurses. And then they looked at women that had more than 1,500 tablet consumption of these pain medications. And here, the risk of chronic kidney disease was largest in the acetaminophen group. Don't tell me I can't give Tylenol to people now. I'm just telling you what to do. I know it doesn't work, but I'd like to be able to give it to people. You're like, you want your placebos to be safe, damn it. But the only signal they found, and it looks like there's a little dose response, was with the acetaminophen. Oh, geez. And this was backed up in a study with patients with rheumatoid arthritis. So this link between NSAIDs and CKD is not nearly as brightly lit as we would think. And certainly not as well lit as NSAIDs causing acute kidney injury. There's no doubt. Everybody's seen that a number of times. You take NSAIDs, especially if you're a little dehydrated, a little volume depleted, boom, you'll pop the kidneys. So I want to segue for you here. So if the person's taking a PPI along with that NSAID, maybe that's the more dangerous thing. What do you think about that link between PPIs and CKD? Yeah. The PPI with CKD link, that has emerged. That's interesting. I think the data consistently shows that link to be there. What we're missing is kind of a mechanism. I think that's a lot of what's so appealing to the NSAIDs causing CKD is we can go right to the physiology. We can say, hey, we can go right to the afferent arteriole and the prostate glands and be like, see, this is how it works. The PPI story, this one started with one of the things that's emerged over the last 20 years is the causes of acute interstitial nephritis has changed. So when we first discovered acute interstitial nephritis, it was due almost entirely to beta-lactam antibiotics. And you put people who, especially if they have osteomyelitis, they're going to be on weeks and weeks of a beta-lactam antibiotics. You put people who, especially if they have osteomyelitis, they're going to be on weeks and weeks of a beta-lactam antibiotic. Three, four, six weeks into treatment, they start to have P blood and their kidney function goes down. They get a rash. They get renal failure. This is something that was a very stereotypical finding. They would get white cell casts, they would get eosinophilia, they would get fevers, and they would get a rash and the renal failure. And you take away the beta-lactam antibiotic and they would generally get better. So once we defined acute interstitial nephritis, we actually saw that it wasn't only with beta-lactams, that other antibiotics would also cause this. In the last 10 years, proton pump inhibitors zipped up the chart and became one of the most frequent causes of acute interstitial nephritis. So this is a cause of an AKI, and we would pull the proton pump inhibitor once we knew that that was the cause, and their kidney function would kind of get better, but it really wouldn't go all the way back down to normal. People started scratching their heads like, well, why isn't it going back to normal? And what emerged was that this was actually a cause of chronic kidney disease. And again, this is looking at databases and looking at exposure to proton pump inhibitors and development of CKD and seeing that those two correlated. Yeah. So, I mean, in my practice, I've definitely started to put people on these for the minimal time possible. You know, I'll give them six weeks worth and I'll say, okay, you know, you need it right now for six weeks, but after that, we're going to try to pull you off of this, see if you still need it or not. And any patient who was able to tolerate coming off them, I was taking off of them. Right. Same here. Yep. And then I've been using a lot, I've been going more to the H2 blockers, see if we can, if they're dependent on the PPI, well, could we get by with some ranitidine or some thimotidine instead? How about some cimetidine? You like that one? Sure. And Joel, we've been talking about the efferent arterial and NSAIDs, something that I was always taught. So if you have someone on an ACE or an ARB, because I do want to talk a little bit about an ACE and an ARB.
But then also, is it a big no-no to use an NSAID along with an ACE or an ARB because then you're kind of dilating both the afferent or you're constricting the afferent arteriole and you're dilating the efferent and dropping their GFR? Yeah, you're totally setting them up for AKI. And the last piece of that puzzle is to add the diuretic in. No, I'm serious, right? I told you to put everybody on a chlorothalidone, so I've already set them up. And they got to all be on an ACE inhibitor. And so they got two pieces of that, and then you throw on the NSAID, and that doesn't actually... That study was done in great britain where they were looking for risk factors for aki and if you just use the n said they didn't find it or if you just use the n set and the ace inhibitor they didn't find it but if you used all three the ace inhibitor the diuretic and the n said then you then you found a real signal for aki right and so yeah i mean the physiology, the physiology works out nicely. And so you could extrapolate, if you are going to use an ACE inhibitor and an NSAID, make sure the patient stays well hydrated. Otherwise, you know, they're going to be in trouble. This is the thought behind the sick rules that are popular in Great Britain and in Canada, where patients are given these little pocket cards that it's a list of drugs that they should stop if they get sick, where they might get dehydrated or have a decreased PO intake, and it includes metformin and the ACE inhibitors in their diuretics. It's the type of thing that makes sense, but whether it hasn't prospectively been shown to be beneficial. Yeah, you know, it's interesting. So I pulled up a study. It's from the British Medical Journal 2012. It had 487,372 participants. So large, right? Because it's probably using their database. They had 2,215 cases of acute kidney injury in that large cohort. And looking at the co-treatment with these three agents had the highest predisposition to acute kidney injury. But just looking at the numbers, it was seven per 10,000 person years. Joel, I want to bring it back to our case from earlier in the show. And let's say that this guy, he has diabetes. Let's say he had a little bit of proteinuria. So we want to start him on an ACE or an ARB, what bump in his creatinine is acceptable? How do you interpret that? So the traditional rule is anything less than a 30% bump in creatinine is acceptable. And if it's more than that, you probably want to stop the drug. And then if you listen to lectures, the subtext there was actually, if you look at the people that get the most benefit from the ACE inhibitors, it's the patients that get the largest bump in creatinine, actually get the most renal protection. And this was a post hoc analysis of some of the ARB studies that looked at diabetes early on. But this past year, there was a study by Schmidt, Mansfield, and Tomlinson in the BMJ. This was March 2017, serum creatinine elevation after renin-angiotensin system blockade and long-term cardiorenal toxicity. And they kind of threw this whole theory under the bus that any increase in creatinine, the greater the increase in creatinine, the greater the future risk for mortality. And there was no threshold effect. There was no protection, no magical number of 30%. The more the creatinine rose after you added the ACE inhibitor, the worse these patients ultimately did. The problem is this was just comparing it to, this is just what happens to their craniotin. It doesn't give you any guidance, right? Because it doesn't say what happened if you stopped the drug. Right? Because presumably these patients have an indication for the drug, and the indications for ACE ACE numbers are pretty compelling. And so, you know, it's almost like this is laying down the groundwork for a very interesting randomized controlled trial where if you get patients that get a significant bump, where it looks like they're going to have bad outcomes going forward. And, you know, I'm looking at the people that had a bump in their creatinine of 40% or more, and they reached 25% reaching mortality at less than three years. That's a study that's doable with that type of outcomes. Hopefully, this will lead to a randomized controlled trial where we actually know whether it's better to stop the drug or not, but this doesn't answer that question. It just shows that these people are at risk. And it also kind of debunks the threshold argument that 30% is some kind of magic number that below that's fine. But it's one of those things that got written in somebody's discussion and then became kind of dogma that's been repeated a thousand times later since then, right? Right. I love that people are going out and testing this dogma and finding out what the truth is. Let's say that we start this guy on it and he bumps 15%. I think most people would just let it ride and keep him on the drug. If it bumps 35% or 40%, it's kind of got to be a shared decision-making, maybe close follow-up. I don't know how you would handle that. I'll tell you what. If somebody bumps 40%, I have a hard time keeping around the drug. That's just a lot of loss of GFR. I probably would stop the drug. It wouldn't be a shared decision-making. I'm not sure if it's the right decision, but the data for increased creatinine is not a good thing. Let's flip this around. You take a look at the ARB studies, Rinal and IDNT. These are the landmark studies from 2002, the reason that we use ARBs and type 2 diabetes. And they provided somewhere around 16% protection from a composite endpoint of doubling the serum creatinine dialysis or death. Well, over five years, a 16% reduction of this relative risk versus a 40% bump in creatinine. I mean, it's not like what you're getting with this drug is nirvana. You're slightly loading the dice in these guys' favor, right? Right, right. And so I would probably stop. Great. And a question we had on Facebook was, okay, I put a patient on an ACE or an ARB, and let's say it's at a maximum dose. Is there any point to keep checking their albumin creatinine ratio? What are we going to do with that information? I can't think of a compelling reason to continue to check that. I would get, you know, I guess the argument, you know, you're going to get their blood pressure down already, right? You have a compelling reason to already control their blood pressure. That's another way you can lower their proteinuria. There are some other agents that you can add, right? You can add the non-dihydropyridine calcium channel blockers, and they will also lower the proteinuria a little bit. What you're missing there, as far as I'm aware of, there's no outcomes data that shows that reducing the proteinuria with that mechanism, with the calcium channel blocker, has a beneficial effect. The other thing you can do to further lower the proteinuria is you can add an aldosterone antagonist, but the history of adding additional agents to further lower the proteinuria is rather speckled. We first tried it with endothelin antagonists in the altitude study, which did a beautiful job of lowering proteinuria, but those patients had excess heart failure. And then we did it with ACE and ARBs again, did a beautiful job of lowering proteinuria, but they had excess acute kidney injury, excess hyperkalemia, and no signal. Even in the few patients or the patients that didn't develop those complications, they didn't see any signal that they lowered their progression of kidney failure. And the combination of aldosterone antagonists and ARBs, we know they lower proteinuria further, but no one's done the study to say if it has better outcomes. And man, the history doesn't look good. And so I would not, I won't tell you that I never do it, but it's not something I certainly wouldn't advise other people to do it. Yeah. Paul and Stuart, I think one of the only other topics, I mean, we could go on forever. Another topic that we haven't got it into yet is contrast nephropathy, which I think we can touch on in the last little bit here.
I mean, we've been recording for like 90 minutes. Yeah. Like I said, it's probably only two episodes. Who knows? I kind of want to talk just briefly about Empically Flosin and your position on using that for renal disease. And so we have two outcome studies, one called CANVAS and one called EMPA-REG. One of them looking at impagliflozin, the other one looking at canagliflozin. And these were studies designed to look at cardiovascular outcomes. And both of their cardiovascular outcomes were positive. And they also looked at renal outcomes, but as a secondary endpoint. And that does compromise the study to some degree. And the reason it compromises the study, actually, let's back up a little bit. Let's make sure we know what we're talking about. These drugs are the inhibitors of SGLT2. And this is the molecule that allows the kidney to reabsorb glucose. And so these are drugs designed to treat type 2 diabetes, and they block the kidney from reabsorbing glucose. So even though your serum glucose might only be 120 or 80, you're going to spill glucose in the urine. So normally you won't spill glucose till your glucose gets over 200. This drug lowers that threshold down to, I think it's about 140. So you'll start peeing out glucose at a much lower glucose. That peeing out that glucose is going to lower your A1C. It's going to lower your energy intake, right? You're going to start peeing out glucose. So these patients lose weight. It acts as a diuretic. And so these patients actually will, their blood pressure reliably falls about five points systolic. They lose about two kilograms of body weight and their A1C goes down by about a half a point. These studies looked at renal endpoints. Now, again, it's not a great population to study. They were looking at people that were at high risk for cardiovascular disease, but they didn't have low GFRs. Their average GFR was in the high 70s. I think it was 77 in one and 80 in the other. And some of them had diabetic nephropathy, but not a lot of them. It was about 10% of the people had heavy proteinuria when you did a dipstick or a measurement of microalbumin to creatinine ratio. That said, they were able to cross a threshold. Both the studies kind of created somewhat unusual renal outcomes. So the Empirex, if I get this right, their renal outcome was development of new macroalbuminuria, albumin greater than 300, plus or in addition, another composite was a doubling of serum creatinine, another one was development of renal failures requiring dialysis, and another one was death due to renal disease. So that is a composite that has, on the one hand, two things that are super important to patients, death and dialysis, and on the other hand, doubling the serum creatinine and development of proteinuria, things that most patients really wouldn't worry about. Sounds like something the doctor worries about more than the patient. True. Right, so that's a problem with those composite outcomes. And then the CANVAS study, they had the doubling of, they had, no, not doubling the serum creatinine, GFR dropping by 40%, which is something they seem to have created out of thin air. I've never heard of that before. And then new macroalbuminuria, and then death and dialysis in addition. And using those thresholds, the drugs were effective. But that's not a threshold that's going to be adequate for the FDA, and neither of them have an indication yet for preventing diabetic kidney disease. And I know that mPagliflozin is now recruiting and may have already started a trial of patients with diabetic nephropathy to see if this drug works in a population that looks more similar to the studies that we did with ARBs, Rinal and IDNT. I want to circle back one last thing about these drugs. These drugs did prevent these outcomes. And even though nearly 80% of their patients were on ARBs or ACE inhibitors, so these patients were really getting state-of-the-art renal protection, and yet these drugs were still able to add additional renal protection. Nobody's been able to show that before. Even though it's not a perfect study and there's a lot of questions about it, it is an impressive result. To me, I think these drugs are real game changers. Very interesting. Well, the last thing I want to ask about is the contrast-induced nephropathy. There was a study, I think it was in the emergency medicine literature from earlier this year, kind of questioning whether contrast-induced nephropathy even exists at all. And I think you have some other studies in your recent talk that I had seen as well. So where are you at on this contrast-induced nephropathy controversy? Right. So this has been simmering for a long time. It's been a pretty popular question in the radiology literature. And I first saw a couple of meta-analysis back in, I think it was 2013, where these things emerged. And there was a definite signal, or there was a lack of signal, that administering contrast caused any problem. Now, this way these studies are done is they get patients that received contrast, and they try to match them up with similar patients that don't receive contrast. And they try to see whether there was an increased risk of contrast nephropathy. This is sophisticated statistics, and every time those statistics get sophisticated, you start to question, what are we really looking at? Is this measuring what it purports to look at? This became real hot in nephrology about a year ago when a gentleman named Glenn Chertow published an analysis that really showed the same thing, that there was no signal that receiving contrast during hospitalization was associated with developing acute kidney injury during that same hospitalization. And now it was no longer trapped safely in the radiology literature. This was now front and center in the nephrology literature. And we were really forced to answer that. Most people that I talked to, it was hard for them to believe. But the data looked, to me, there should be a signal, right? If the contrast causes acute kidney injury, when you look at everybody getting contrast, we should see more acute kidney injury. And he just couldn't find that signal. And then later, early in 2017, I think it was in February 2017, there was a trial, I believe it was posted in The Lancet, called the AMACING trial. And the AMACING trial is kind of the logical progression here. It says, well, if there's no such thing as contrast nephropathy, why do we even give prophylaxis? Why would we give saline to patients that are about to go for cardiac cath? And that's the question that Amacine asked. They randomized patients to either placebo or saline, or not really placebo, no IV fluids versus IV fluids. And they protocolized the patients and they got significant fluids if they were on the fluids protocol. I think it was like 800 before the cath and 800 after the contrast versus nothing. They only enrolled people with GFR down to 30. So CKD stage three is what they were looking at. And they found absolutely no difference in the risk of this contrast nephropathy. And that, you know, to me, that's the classic, that's the study you need to do to show that this doesn't, this might not exist. Now, again, it's not the sickest population. It's not the people with a GFR of 22 where there's really risk, significant risk of dialysis GFR drops at all. But these are patients that normally we would be very concerned about the risk of contrast nephropathy. We would be very proactive in giving them IV fluids and trying to do everything we could to prevent it or even avoid the test completely because we were worried about the risk of contrast nephropathy. And there was no indication that the fluids helped at all. That said, I believe there is an entity of contrast nephropathy. I've definitely seen patients that are stable as a three-legged table. They're moving right along, and they get exposed to contrast, and their kidney function deteriorates, and I can't point to any other event that happened. But I think the vast majority of patients that we call contrast nephropathy are not such straightforward cases. They're patients that are in the hospital and they're acutely ill and they have sepsis or they the hypotension or it could have been the sepsis or it could have been the aminoglycoside that did it.
And so it's impossible for this disease not to exist because I've seen it dozens or hundreds of times in my career. And I think that a lot of these cases may not be as clear cut and that the real rate of contrast nephropathy patients that, like I said, were completely stable and have no other explanation is actually much rarer. And a lot of the conclusions we say were, well, how do we figure out the people that have risk factors for contrast nephropathy, or how do we find that, how do we protect people against contrast nephropathy? We're really just trying to protect against these random variations in creatinine or these developments of acute AKI from other etiologies. I'm not sure that we're actually protecting against contrast. Okay. I guess that part never occurred to me is we tend not to do radiographic contrast driven studies on patients who are doing terrific. Well, certainly something else going on too. Yeah. It just, that's a great point. Yeah. You just, did you just thank yourself? Oh, nevermind. I don't think you did. I think I did not. Okay. It sounds like something I would do. Stuart is having auditory hallucinations. We might have time to call it. Yeah, I think it's about time to call it. I'd also like some take-home points just for we discussed a lot of different drugs. We discussed contrast nephropathy. Okay, I'll roll through those. Okay. So in CKD, you want to be careful with the medications that you're using. So the ones that you always think about, metformin, you can use down to a GFR of 30 now. Bactrim is a no-no. It's going to make your metabolic profile look lousy. It's going to bump their creatinine. It's going to bump their potassium, and it increases their risk for sudden cardiac death. You want to avoid that drug. NSAIDs, this is a drug that's on everybody's no-no list for CKD. There is some evidence, especially in mild CKD, that it might not be nearly as dangerous as we had once feared. So that's something that at least something that you should be able to consider and think carefully about stopping their NSAIDs and giving them an opioid because you may not be doing them a favor if you do that. Contrast nephropathy. This is an area of intense controversy. The recent data really looks like this disease is not nearly as common as we had once thought. And especially in patients with GFRs over 30, the use of IV fluids didn't prevent any episodes of contrast nephropathy in the one study that looked at it, though that's something that needs to be repeated before we can really call that gospel. But it is really surprising that it's even a signal at all. And I'd keep your ears open about that. You know, I'd love to keep talking. I have more questions, but we got to let you go. And you're a chief of nephrology, so you're still working at Cashlack. We can get you back another time and people can hit you up on Twitter for questions that we missed from social media. So thank you so much. Thank you. Thank you, Joel. This has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole. Delicious. You can find show notes along with links to any articles, books, websites, or apps mentioned on the show at thecurbsiders.com forward slash podcast. You should also sign up to receive our weekly mailing list where you'll get our expertly done show notes at thecurbsiders.com forward slash knowledge food. And please send an email to thecurbsiders at gmail.com. Tell us what you love or hate about the show. And follow us on Facebook, Instagram, and on Twitter, at The Curbsiders. Until next time, I've been Dr. Matthew Watto. And I'm Dr. Stuart Kent Brigham. And good night. And I remain Dr. Paul Nelson Williams. Good night. Well thank you, Annie, Kate, and Justin for all your hard work.
Yeah, and Dr. Colburn, by the way, was a fantastic guest host, which made me entirely uncomfortable. I don't like that he was cracking jokes. I don't like how capable you seem without me and Stuart. Right. I feel like a slippery slope we're on here, Wado. I wasn't going to do this on air, but you guys are both fired. It's okay. All right, we're going to go start the, what was it, Schmerb Ciders? Schmerb Ciders. The Schmerb Ciders, yeah. Schmurbsiders. I promise not to take you to court over that. Wonderful. Hello, and welcome back to the Curbsiders. Hello, Matthew. Hello, Stuart. Hi. Very formal tonight. That made me real uncomfortable. Actually, it made me a little uncomfortable, too. Yeah. The internal medicine podcast that uses expert interviews to bring you clinical pearls and practice changing knowledge. I'm Dr. Matthew Watto, here with my co-host, Dr. Stuart Brigham. I am Dr. Stuart Brigham. And Dr. Paul Williams. Hey guys, how are you? Hi Paul. I'm doing well, Paul. I actually wanted to start off the show. We've probably not done enough of this, but I did want to read a nice email that we got from a listener, Shelby. Shelby says, Hello, I am writing the team to thank each of you for the amazing podcast you present. I commute to work, two-hour round trip, and recently lost my carpool partner. Two-hour round trip. It's a long one. We've got a problem here already. So she goes on and she says, Anyways point of this, all this jabber, the podcasts are great to listen to on my drive. They are interesting and comical. So I'm not snoozing like many would imagine listening to medical updates and news. I also want to let you know that your target audience is not just physicians, but pharmacists as well. Keep up the excellent podcast and I look forward to hearing more. Thank you. And this is Shelby from Kansas. You know, what I got out of that is that she shouldn't move anywhere closer to work because then our podcast would be too long. Yeah, that's true. Yeah. Well, she could split it between the morning and the afternoon. That's true, but at least this way she can listen to us twice a day. Yeah, I like that better. Me too. Or maybe the same episode. Thank you, Shelby. That's very nice of you. We appreciate the feedback. Sorry that we're micromanaging your life. Anytime. Okay. If you need any parking tips, please, by all means, let us know. Paul, as always, I'm fascinated by this quest of yours. How are we doing there? Or how are you doing? I'm not part of it. I mean, spiritually, I feel like you are. No, I'm trying to catch up. It's slow going, but I'm going to recommend one out the gate, even without you asking me. And I'm not breaking any new ground here, but I finally sat aside three and a half hours of my life and watched Lawrence of Arabia. Ooh. Yeah. The 1962 epic that everyone's heard of, but almost no one's actually sat down and watched. There's a reason for that. It is easily in my top five. It is one of the best movies I've ever seen. There are pieces of cinematography that literally sort of made me catch my breath. So if you consider yourself a big film fan, it's one that you should watch just to say that you watched it, but also because it is just a beautiful movie that is sort of breathtaking in scope and um and the score of course is is justifiably acclaimed so if you're even a minor fan of movies you should watch them yeah i i can't say i know anything about lawrence of arabia i've heard of it though yeah i only watch movies when i'm like stuck on a plane i'm forced to watch one if a movie looks like it's more than like 20 years old at this or i guess 30 years old it's before my childhood, I'm just like, nah, I don't think so. I'll be weirdly sincere for a moment, but you can just see how it's influenced just tons of movies. The one that springs right to mind is Raiders of the Lost Ark, which I guess was still made before many of our viewers are born at this point. I just depressed myself. I can't even remember what I'm saying anymore. I've seen Raiders of the Lost Ark, Paul. Me too. I'm a huge Indiana Jones fan. I'm not that young. I guess it was before Matt was born. Okay. We probably should just introduce the episode. I feel like we've gone off on a tangent here. Okay. Sure, why not? The point of this episode, it's titled The Pseudoendocrine Patient, and our guest was Dr. Michael T. McDermott. He is a professor of medicine at the University of Colorado. T stands for thyroid, right? I think so. Okay. Yes. Thank you for that interruption. Professor of medicine at the University of Colorado Denver School of Medicine and the director of the endocrinology and diabetes practice at University of Colorado Hospital. He spent 20 years in the U.S. Army, where he served as the chief of the endocrinology service and also the director of the endocrinology fellowship program at Fitzsimmons Army Medical Center, and also was the endocrinology consultant to the surgeon general. His clinical research interests include the treatment of type 1 and type 2 diabetes, the treatment of osteoporosis and related metabolic bone diseases, and the pathophysiology of disorders of the thyroid gland. He is also the author of the book Endocrine Secrets, which we will talk a little bit about. It's now in its sixth edition. And we asked him on the show to kind of teach us what is a pseudoendocrine patient, how can we help these people and maybe avoid an endocrinology consult. Excellent. Yes. I found it helpful and I hope you will too. That's right. And Shelby, don't fall asleep. I heard it's a zinger. Hello and welcome back to the Curbsiders. This is your host, Dr. Matthew Watto, here with my co-host for the day, Dr. Jeffrey Colburn. And groupie here following. Jeff, thank you so much. We're here at ACE again. And today we have with us, we're so excited to have Dr. Michael McDermott from the University of Colorado, Denver School of Medicine. And he is also the author of the very popular book, Endocrine Secrets, which is right now in its sixth edition with the seventh edition in the works. And we have him on the show today to talk about the pseudo-endocrine patient. And we will have him tell us exactly what that is. But as you know, we always like to start asking our guests a little bit about themselves. And Dr. McDermott, I kind of prepped you in the pre-interview. I wanted to know what is your one-liner, kind of giving the audience a flavor about yourself? Well, I'm an endocrinologist. I've been an endocrinologist for 40 years. I'm married. I have four children, four grandchildren now. And I am an avid outdoor person. I like to fish and golf and bike and ski. So Colorado is a great place for you to live. Yeah. I imagine that's why you've been there for 20 years. That sounds awesome. It probably kept the kids busy too, right? Yeah, sure did. I also have four kids. Jeff has two. And keeping the kids busy is a big part of my life, big mission in life every day. I agree. I wanted to ask you a little bit about when you were coming up as a learner and when you were cutting your teeth as an educator, what is some good advice that you got that you can pass on to our audience? There's a lot of advice I think I got over the years, and so to say what's the best is difficult. But I'd say if we go to the top of the list, it's really listening to patients as they describe to you why they're there and what their symptoms and concerns are, and being interested in that and pursuing it, not trying to make up my mind too quickly about what the main issues in their life are.
And I went to your talk yesterday. I was very intrigued by the title, not knowing exactly how to define that. Can you give us the definition of the pseudoendocrine patient and a little bit about what your talk was about? So it's a new term. I was asked to give this talk, and I think the people who asked me to do that made the term up. And so I'm really giving you a definition sort of on the fly, but I think we all who see patients would recognize that we have patients that would fit this description that they either have symptoms that could be due to endocrine disorders, nonspecific symptoms that could be endocrine-related or other things, and they've had some degree of endocrine testing and their tests are normal, but they still have their symptoms and they come to you and you're left with, how do I evaluate and help this person who does have symptoms that have an endocrine disorder, a thyroid disorder that's already being treated, but they still don't feel like they're back to normal. And even though you're giving what is the standard of care, are you doing enough? So that would be another. Another type of pseudoendocrine disorder is that there is some misinformation that people get from the Internet or from some alternative providers who might diagnose them with some conditions that sound plausible but have been proposed without any proof that they ever exist. And so people have been labeled as having one of these conditions, and we really don't have any validation that there really is such a condition. But people believe they have that because someone has told them or the Internet has told them they have that, and they would like to seek treatment for it. Well, I want to get into the case you gave yesterday. It's kind of the painful appointment that you get. It was a 30-something female. She was maybe eight months or so postpartum. She had ordered her own endocrine tests off the internet based on, I think you said she had read on the internet, and she thought these tests might be be useful for her and she was checking her growth hormone or IGF-1 or thyroid reverse T3 and all the tests were for the most part normal. Some things were just like lower limit of normal or slightly abnormal. She was a young woman and to repeat her symptoms, she had chronic fatigue that had been going on for about 10 years and was progressive. And she was having difficulty losing weight. She wasn't overweight, but she was heavier than she had been in high school and still wasn't in the overweight category, BMI of about 24.5, but wanted to lose weight and was unable to do that. So I would say those would be the two main complaints would be just fatigue and difficulty losing weight and frustration about that. And so as a young woman, she really didn't have significant other history. I did ask about all other medical conditions and surgical conditions. She didn't have any of those. She took a multivitamin, but she didn't take a lot of supplements in it. She took one multivitamin. Physical exam, completely normal. All of us in endocrinology know that you can feel a thyroid gland, and if the person has Hashimoto's thyroiditis, for example, which is the most common cause of hypothyroidism, it feels a certain way. And most of us who have been feeling thyroid glands for a long time can tell when a person has that condition, regardless of their test. But she had a normal thyroid exam. She had a normal general exam. At that point, I would have recommended some tests. However, she had gone online, and a lot of people are not aware of this, and I don't recommend it, but she had gone online and found one of the online sites where you can order your own lab tests. I mean, as a disclaimer, people have to know insurance doesn't cover this, and these tests cost a lot of money. And interpreting tests really isn't a matter of just looking at the number and is it in the normal range. You have to interpret every test in the context of the patient and what their symptoms are. And every hormone in relationship to every other hormone is important. So she came in with her list of tests and had highlighted in yellow the test results that were at the lower end or upper end of the normal range, so not frankly abnormal, or were frankly a little bit low or a little bit high. And this is really common. I mean, she has been suffering with her symptoms for 10 years, and she is looking for something, and she didn't find anything overt. So I think it's perfectly logical for her to say, so do these abnormalities mean anything? So I think she had a perfectly logical approach and that has to be respected. And yeah, I get that sort of thing all the time. Somehow the patient saw their labs before they got to the office with me and they said, oh, it said my MCHC is low or something like that on the CBC that I don't even remember what that means for the most part that I don't think is relevant to their care. So this lady had a reverse T3 that was abnormal. And can you talk about the reverse T3 syndrome, what's out there on the internet and how we can dispel that? Okay. So the reverse T3 is not really a test that endocrinologists order except in people who are hospitalized and may have what we call euthyroid sick syndrome or non-thoroidal illness. When people get very, very ill with a hospitalized illness usually, their body decreases conversion of T4 to T3. Their T3 levels drop. And instead of T3 being made, they make reverse T3. So it can help you in the hospital sometimes distinguish somebody who has a real thyroid problem from just the thyroid function abnormalities that occur from being sick. So I don't want to say there's never a reason to order reverse T3, but in an outpatient setting, it really doesn't have value. On the internet, however, you'll find multiple sites that talk about a reverse T3 syndrome, which is a hypothetical condition hypothesized by someone who says, you know, if your reverse T3 level is high for whatever reason, that will compete with T3. T3 is the active thyroid hormone that binds to thyroid hormone receptors and causes thyroid hormone action. And if your reverse T3 is high, it competes with T3, and therefore you don't get T3 into your tissues and you feel hypothyroid even though your tests are normal. A nice hypothesis. I mean, I believe that we all ought to be thinking outside the box, but if we have a hypothesis before we tell people it's a real disease, we should test it and validate it, and that's the weakness here is that's never been validated as a disease. So there, in my opinion and the opinion of the American Thyroid Association, the Endocrine Society, and ACE, is that there is no reverse T3 syndrome. And you even presented a slide that said that T3 has 100 times the affinity for the thyroid receptor as the reverse T3. So it shouldn't be out-com moderate increases in reverse T3 couldn't compete with native T3, which, as you just pointed out, has a 100-fold higher affinity for the thyroid receptor than reverse T3. So that not only means that the condition isn't validated, but there's good scientific evidence to refute that it does exist. It's interesting how complex it is. Like going back to your example of the admitted inpatient, the rare instance when somebody might order that reverse T3, giving active T3 cytomel products to those youth thyroid 6 syndrome patients actually increases their mortality. And so it's interesting. This may be a marker, not necessarily a cause of disease. It's just very complex. So just going back to your point of you can't just look at a lab in isolation, Yes. who are given thyroid hormone because their thyroid hormone levels are off due to their illness, actually do more poorly. They have worse outcomes if you give them thyroid hormone. So clearly that's an adaptive response. I'm glad you pointed that out. Now for this young lady to go back to the case, normal thyroid exam, we're not worried about the, she had I think a normal TSH and free T4, her reverse T3. I think I misspoke. Was it slightly high, but we're not worried about that? It was at the upper end of the normal range, so it was just like one-tenth below the upper end of normal. And for the reasons we've stated, that is not of concern and shouldn't have been ordered in an outpatient anyway. So we've kind of put thyroid off the table. One other thyroid test, she had a free T3 that was the low end of normal.
And free T3 is a very difficult assay, and there's a lot of questions about how accurate it is. So we don't actually recommend measuring free T3. When you want to assess somebody's T3 status, we still recommend a total T3, even though it doesn't tell us what the free level is, but the free assay is not highly accurate at this point. We hope someday it will be. And having said that, her free T3 wasn't frankly low. It was in the normal range. It was just at the lower end of the normal range. And I think that's an interesting aspect of endocrine tests in that, like, for example, an internist that orders a hematocrit, the hematocrit's not dynamic. It stays pretty stable unless the patient's bleeding, whereas hormones fluctuate on certain patterns. And then also, like you'd mentioned with the free hormone, it's like 1%, I think, of the hormone content. It's less than 1%, yeah. So it's, you know, measuring this, like, picomolar, like, tiny amount is very challenging and difficult. And I think patients see labs as it's either in the range or not. And I think the complexity of lab testing really, I think, warrants having someone with that expert mind to look at it. It's one of the core features of endocrinology is to interpret every lab test in the context of the entire patient, you know, how they feel, and in the context of what their other labs look like. A low normal T3 in the presence of a high TSH is different than a normal TSH. Estradiol, all of those, there's a picture that's being painted that you have to look at as a whole. And moving on to the other glands, so we kind of said, all right, we're pretty sure this lady, thyroid's normal. You also talked about pituitary and adrenal. So how did you reassure yourself that there was no pituitary problem or adrenal problem? You can pick whichever you want to go to next. So she had a normal cortisol and a normal ACTH. Adrenal insufficiency, when it's chronic, can cause fatigue, although it typically is associated with weight loss, not weight gain. And when people are acutely ill with the flu, they typically will get very sick because they don't have the ability to make cortisol in stress amounts. Cortisol is a stress hormone, so it typically doesn't present with 10 years of just progressive fatigue. And when it does, most of those people are darkly tanned and they've lost a lot of weight. In this case, she was having trouble losing weight and her skin was normal. So her clinical picture didn't really look like adrenal insufficiency. Certainly didn't look like Cushing syndrome either, which is the opposite where you make too much cortisol. She had no features of cortisol excess. And that's a very distinct look that people have. And so a normal cortisol and a normal ACTH, I mean, you could probe that axis more with some additional tests, but I don't think there was really any clinical indication. And she was satisfied that those tests were okay. Okay. And then the pituitary, which tests reassured you it in pulses. And in between those pulses, we actually don't make it at all. So a good bit of the day, every single normal person may have a growth hormone level that's zero. And then if you happen to sample that blood test when they're making a pulse, and that pulse might be made every three hours. Then you might have a growth hormone level that's in the normal range, or it might actually be high. So a growth hormone level in a person is not an adequate way to diagnose growth hormone deficiency, and growth hormone deficiency generally in adults occurs only because of a significant pituitary disease. It is a cause of growth failure in children, but this was an adult. But growth hormone goes to the liver, and these pulses of growth hormone cause the liver to make a protein called IGF-1, insulin-like growth factor 1. And it's not made in such a pulsatile fashion. It sort of reflects the total daily exposure to growth hormone. So a person with a growth hormone level of zero at any point in time could have a normal IGF-1. Now, we don't recommend testing growth hormone and IGF-1 except in people who have known pituitary disease. It's not a valid test or even a good test to do in people with chronic fatigue. And I would say there might be an exception to that, and that's people with head trauma. And in the session I did, and I did the second session later on, at least five people asked, has this person ever had head trauma? Because we know that soldiers that have gone to war and have been in the vicinity of blast injuries or people who've had head injuries from motor vehicle accidents may have some pituitary damage and they may have some subtle pituitary defects. And we're just starting to learn that. So, you know, it may be that someone who has a chronically progressive case of fatigue who had significant head trauma, that we will learn someday that there is a better indication for ordering growth hormone studies and a better way to interpret them. Growth hormone deficiency, however, in an adult without any known pituitary disease is extremely rare if we ever see it. Because if they had true growth hormone deficiency from a genetic cause, they wouldn't have grown normally. So acquired growth hormone efficiency in the absence of pituitary disease is very, very rare. And when it occurs, the IGF-1 level is not usually minimally low. It's usually quite low. And because hormone levels vary throughout the day and because hormone assays are not entirely reliable, to have a level that that the accuracy may be questionable for some labs. And this lady had gotten a lab, not at my place, but someone that she mailed off to a lab that I don't even know what kind of quality control they had. So to interpret a level of 57 when normal is 60 or above as being low would be highly questionable. And certainly without any physical features of pituitary disease, it would be unwarranted to say that represented growth hormone deficiency. So once you untangle this patient from Dr. Google a little bit, and we have lots of patients that get tangled up by Dr. Google, what evaluation or what low-hanging fruit are there that probably should have been the initial evaluation of her complaints, which now if you've successfully been able to comfort her about the endocrine labs that she's had come back you're focusing the patient's attention away from what might really be the root cause of what's going on. And if you look at fatigue, for example, which was her main complaint, I think if we look at what is the most common complaint in the population of all, what do people complain about when they go to a doctor? Sleep is a big one. Well, the most common complaint is pain in some place. And the second is fatigue. And that's well known. And then so sleep might be a cause of the fatigue. But fatigue is probably the second most common and it may be the first. And if you go across the board and look at fatigue, the most common causes are not actually medical conditions. They're usually disorders where people don't get adequate sleep. They don't get adequate exercise. They don't have a well-balanced diet. They have too much stress in their lives. They have depression or they have another medical illness. So that's six different causes that actually are more common than endocrine disorders. Now, endocrine disorders are low-hanging fruit, as you said. I mean, you wouldn't want to miss hypothyroidism. You wouldn't want to miss true adrenal insufficiency. You wouldn't want to miss deficiency of vitamin D or B12 deficiency or anemia or kidney disease or liver disease. So a good set of fairly inexpensive lab tests can diagnose the vast majority of medical causes of fatigue. But I think you also have to keep in mind those top six causes of fatigue. And so you really need to go into sleep, not just do you sleep okay, but do you snore? Does your husband or wife say you snore? Does your husband or wife snore and keep you awake? Do you have a baby that wakes you up all night? You know, what time do you go to bed? When do you wake up? Sleep hygiene. I mean, ask them good questions. I don't think anybody, well, ask them about their exercise habits. Many of us don't have the best dietary habits, and I think it's good to go through, you know, what is good nutrition? You know, the fruits, the vegetables, the whole grains.
Stress reduction is a big challenge. If I had the secret on how to reduce stress, I'd probably start my own business because I don't know how to reduce it in myself or anyone else. I do think there are things like sleep, like exercise, you know, meditation, yoga. There's things that you can do to help yourself relax. And like one of the people in the audience said yesterday, maybe advise the patient to take a vacation. Well, that may not be something that patient really like to hear the first time, say, go take a vacation. But nonetheless, the advice that maybe you need to give yourself some time out where you relax and just some me time. This lady had a very significant family commitment to two children and a husband who was a full-time worker and a triathlete who trained all weekend, every weekend. So her me time was very low. I think, and I'm smiling because one of the audience members said, I like to ask a patient like this the question, when is the last time you had fun? And I just thought that was kind of a novel approach. Like it might light bulb the patients. Like if they can't answer that question, then, you know, that's their stress. They're all that kind of stuff. I'm having fun right now, man. That's very good. I'm having fun. Start a podcast that will make it fun for you. I thought it was a great point that that person made. I've never asked somebody that. But, you know, when it comes to a term we call anhedonia, it means I never have fun. I mean, that's a key symptom of depression. Many men won't admit to depression. And women sometimes are more willing to, but not always either. So I think it's one way to get at that, and I don't think it's appropriate to suggest to somebody the very first time you see them that, well, I think this is all due to depression. But I think you have to keep that on the table, that maybe after we've established a relationship and we've worked together for a while that we might want to touch on, do you think that maybe depression isn't the whole thing, but do you think their depression may be playing a role as well? Too much stress, not enough exercise, all of these things I think can play a role. And I think probably fatigue is multifactorial. And if you just focus on sleep or one of those six things, you're probably not going to fix fatigue. And I think like many other conditions that I think are chronic ailments, it's a multifactorial symptom that requires a multifactorial approach and patience and time. If you slept well and exercised and ate well for one day, you're not going to relieve your fatigue. It's a long haul. Your comments here remind me. So I do medical education as you do, as Dr. Colburn does. And I'm just thinking about the poor residents. They all have stress. They're all probably not sleeping as much as they want to. And they're not getting as much physical activity as they probably did when they were med students or in college. And so doctors and other healthcare practitioners struggle with this too. And so you gave six. I have a similar variant that I do for my fibromyalgia morning report or my back pain morning report. I say if the patient's not sleeping, if they have mood disorder or stress, I just kind of lump that together. Or if they're not physically active, then you're really fighting an uphill battle for any kind of pain or fatigue complaint. I was going to say, no matter what that ultimate cause is, this lady has symptoms that are frustrating her and that are reducing the quality of her life. And no matter whether she came in with the diagnosis that, or that she has the diagnosis now that she thought she came in with or whether it's an endocrine disorder or not and whether I'm an endocrinologist or something else, it doesn't mean I can't help. And I think that just human kindness and concern, listening to people as I brought up to begin with, goes a long way. And I think that there's a lot to the interaction between the provider and the patient that has more therapeutic value than a pill or any other prescription that we have. I'm not saying that being kind to someone just relieves every symptom they have. But I think that it starts the ball rolling. And this lady actually may never, you know, in the next few years feel all the way well. But what if she feels a little better? You know, that's a victory. And we've contributed to that by listening and trying to track down and admitting that I don't have every test. And maybe five years from now, I will. And I'll say, here's what you had. And we can fix it now. But if we can't, because we can't fix everything with a pill, we need to try to go about this the best way possible, which I think lifestyle interventions, just like for treating overweight and obesity, lifestyle interventions, but they have to be done chronically. They have to be done over a long term, not a short term that results in frustration. We need to set expectations that you need to do this for a while. Well, I know we're, and Jeff, I see you have a comment here. I know we're taking a lot of your time. The other two conditions that come up on the internet that you had mentioned in pre-recording that I think we should just sort of dispel a little bit, adrenal fatigue and the other one was thyroid or Wilson's T3. It's one that I'm not even, I can't even recall the name because I had never heard of it before. You just mentioned it. So adrenal fatigue is also a disorder that is not validated by any scientific evidence for existing. So it's a disease, or let me say it's a condition that is diagnosed by a test. I mean, the disease came about as a result of a test. It's a salivary cortisol profile that people get salivary pledges that you chew on. You turn in a salivary sample every hour all day, and the salivary cortisol levels are plotted along a line. And if you fall below a certain line, it's called adrenal fatigue. And it's been actually advertised or discussed by Dr. Oz. It's been refuted by the president of the Endocrine Society, Bob Vigorski, in a very educated and well-stated way. There's no validation, there's no evidence at all that adrenal fatigue exists. And my concern with that is more maybe with the other, more than I have with some of the others, because if one were to treat that, say, with an adrenal steroid, those are dangerous medications that can in the long run hurt people. And I also think it focuses people away from what their real problem is. So there are many patients that are being diagnosed by alternative providers with adrenal fatigue. And they do come in to their endocrinologist and then say, and I want you to manage this now. And it does frustrate their endocrinologist because there is no such condition as adrenal fatigue. And it's hard to take that diagnosis away from somebody who's been told by somebody else they trust that they do have it. So it's a difficult situation and that physician-patient relationship of building trust is important. The Wilson's Low T3 Syndrome is the oldest of these. This was popularized over 25 years ago. A big website and the theory behind this is that for a variety of reasons, stress might be one, different nationalities might be one. Scottish heritage, for example, was one for some reason, that people might have a chronic inability to convert T4, the inactive hormone that the thyroid gland makes, to T3, which is the active hormone. And therefore, that lack of T3 is what was responsible for their fatigue. But the way that it's advertised on the Internet is you don't measure any of these hormones. You do a body temperature with an axillary temperature. And if it's below a certain level, then you have Wilson's Low T3 Syndrome, which is preposterous. And there's no validation, first of all, that there is such a condition that T4 to T3 conversion is reduced and that causes fatigue. And furthermore, that you can diagnose any thyroid condition with a body temperature. And the treatment for that is actually quite dangerous. There's accelerating doses of T3 or Cytomel to sort of, quote-unquote, reset the thyroid stat, which is quite dangerous. And it's caused some problems with some serious side effects. But that's still on the Internet, too.
I don't blame patients at all for seeking help from alternative providers or for going on the Internet. They're just trying to take care of themselves. They're trying to get information as well as they can, and I think it's difficult for patients to know what's a valid site, what's a good medical site, and what is not. And unfortunately, there's no marker on the Internet that says this one's really not a very good site. You kind of take your chances when you go. So I would like to find a way to educate patients on what are good Internet sites, where can you get good information, and where do you get misinformation. And that misinformation can be misleading, but in some cases it can be harmful. I think the Mayo Clinic has some really good patient resources on their website. And I know University of Michigan has some pretty good stuff, especially the GI department there, which we've plugged on some other episodes. I think this is a good time. I wanted to ask you for your take-home points. Before you get to those, I just wanted to see, so it sounds like if you get a patient that comes to you with fatigue, it's reasonable to check probably a CBC, you want to check, make sure they don't have anemia, a CMP, which you'll check the liver, you'll check the kidneys with that, and then a thyroid test potentially if there's reason to suspect it. Any other ones you would add? I think vitamin D, 25-hydroxyvitamin D, vitamin B12, those are reasonable, even if the CBC is normal. We could argue that, but I think that's reasonable. And I think that people should be at least questioned about the possibility of a sleep disorder. I don't think fatigue should automatically trigger a sleep test, but at least question people about that. And if there's any suggestion of snoring or poor sleep, people don't have to undergo a full overnight sleep study. They can do an overnight pulse oximetry. There's plenty of companies that do that. And if your oxygen saturation drops below 90% multiple times, then you probably should have a full sleep study. And there's the stop-bang questionnaire that's been validated that you can use, which way back on our insomnia episode, Dr. DeGromge had mentioned. So that's great. We talked about sleep, but we forgot to mention the sleep study potentially as part of this if the patient suggested. At this point, I'll ask, and of course, the big six that we talked about or the big three, whatever you want to call it, those definitely take that good history and ask about those. I wanted to ask you for your take-home points for the audience and if you have any asks or anything you'd like to plug. I think anytime a patient comes to me or any of my colleagues, the first thing to keep in mind is it's a distinct honor that they have entrusted you with their health care. And that has to be taken very seriously. And if they are giving you complaints of symptoms, nobody really wants to have symptoms. So these are things that are frustrating them or decrementing the quality of their life. And so I think we need to take them very seriously and't able to diagnose what is causing your symptoms with our currently available tools. And we may be able to do that someday. And maybe everyone wouldn't agree that the next part is appropriate, but for me it would be, is that I'm willing to work with you on this, and I'd like to see you back and see how you're doing on this. And I've had validation about that part from a psychiatrist who's a friend of mine who has shown me evidence from the psychiatry literature that many nonspecific complaints will resolve if you're willing just to see the person on several occasions and work with them, whether it's depression or whether it's fatigue or stress. And anecdotally, I can tell you I've seen that in my practice where a really challenging patient, they have these kind of vague complaints and I'm working, I'm taking them seriously, I'm seeing them back every one to three months, something like that. And sometimes if I get lucky, they'll come in and they won't even mention the complaint. And I'll be like, how's that going? They're like, oh yeah, that got better. And I don't know what I did other than take them seriously, try to rule out the bad things. So that's a really great point. And I can say at least one patient I've seen it with. So Jeff, anything you'd like to add? No, I'm fatigued now. You're fatigued? Okay. No, I think this was a great discussion. I appreciate your thoughts. Yeah, this was awesome. This will definitely be really helpful. I know that everyone listening is struggling with this kind of problem in their practice. So thank you so much. And check out Endocrine Secrets. And that's, yeah, that's it. Thank you. Good. Thank you. And we're back. Hi. Hi, guys. I really startled you. Sorry, Stuart. Yeah, you kind of did. I'll start with you since you're so excited. Stuart, you had a chance to listen to the conversation with Dr. McDermott. I did. I did. Anything you wanted to highlight for the listeners? Yeah. I just wanted to thank him so much for explaining to me why I should be ordering reverse T3 on all of my outpatients. It was very stimulating. I'm going to make sure that they all get a free T3 and a reverse T3. And I hear that adrenal fatigue is real. So we're good. I think, I hope our listeners get sarcasm because in the last, Paul did this similar thing last week. I may have stolen it from him. No. It's a solid bit. That's right. And I was like, I hope people know he's kidding here because, yeah. But anything, so other than don't order reverse T3 and try to convince your patients. Have you ever ordered a reverse T3? No. I mean, honestly. I haven't because I don't really know what to do with it. Paul, have you? No. I will be honest with you. I've ordered it three times. I'm completely unsurprised by that. Thanks. Twice was inpatient was to verify the sick uthyroid. The third one, and this is an interesting patient, came in with a tsh of 40 okay okay and so uh started patient on about 100 mics of uh synthroid and the patient came back was having palpitations sweating was having insomnia loose stools it sounds like hyperthyroidism right and so i decreased this Synthroid dosage to 75 mics, and this patient was still having symptoms. So for this patient, I checked a reverse T3 and a total T3. And the idea behind this is that when you have a longstanding hypothyroidism, the type 1 and type 2 diodenase activity changes. So you're going to make more of the active hormone, less of the inactive for negative feedback. So if you put them on a high-dosage Synthroid, they may have symptoms. And so the levels of reverse T3 in this patient were actually suggestive of that. So it was actually relatively low, reverse T3, and high total T3, suggestive that they were converting a lot of that Synthroid to the active metabolite. So for this patient, and realistically for any patient like that, when they show up, you don't have to get a reverse T3 and a total T3. It's completely overboard to get that. But to know that for someone with a longstanding history of hypothyroidism, if you start them on Synthroid, they may have symptoms because of this type 1, type 2 deiodinase activity. And the goal in that case is to counsel them, take your Synthroid, consider a beta blocker if they're having symptoms. And this patient's heart rate was in 90s to 100 range, but it wasn't like in the 120s, 130s, or anything like that. And you may have to back off on the Synthroid dosage and slowly increase it to a goal dosage to get their TSH back down. Going back to reverse T3, in the euthyroid 6 syndrome, all the levels are going to be low. The total T4, the free T4, the total T3, and the TSH, they're often low. The TSH might be low normal, but the reverse T3 level is high. And that is just what happens in acute illness.
Realistically, that's the only reason to check a reverse. That's the only reason. Right. And because if the reverse T3 is also low, then it's central hypothyroid and it's not euthyroid 6 syndrome. Right. So that is something you can, there's a nice table on UpToDate that sort of, or a nice graph up-to-date that kind of highlights that. But basically in euthyroid 6 syndrome, reverse T3 is high, everything else is low. In central hypothyroidism, everything would be low, including reverse T3. And this is hard to think through, so we'll have to put a link to this in the show notes so that you can see this visually. Paul, so that was kind of the discussion of euthyroid sick syndrome. Are you totally lost or do you have any follow-up points? Anything you want to make more confusing for our listeners? No, that was great. I think I went transiently blind for some reason. I feel better now. I actually thought Dr. McDermott's sort of broader philosophic point, he actually made a couple of really great points. Like it can sometimes be frustrating as a provider if a patient comes to you with sort of, you know, this constellation of constitutional symptoms, you know, sort of fatigue and I just don't quite feel right. And I think his point that you do your due diligence, you sort of order your thyroid test, your CBC, your vitamin D levels when clinically they seem semi-indicated. But if they all come back stone cold normal, don't keep chasing them down. Start to look for sort of alternate things and just talk to your patient and listen to your patient. And oftentimes, I think you guys discussed that, that can be sort of the most therapeutic thing. I think, Matt, you've made the point sometimes just by doing that and taking the concern seriously, the patient will come back and actually just feel better even without any actual intervention. So I thought, I know this is not quite so fun as sort of graphing out changing reverse T3 levels, but I think it's a really important point for our listeners and something I think about a lot. So I like that you guys talked about that. I think one of the most profound things that he said, and this is something that I've said to residents whenever I'm on the inpatient ward, is to start when they're normal and walk up in their lives, walk with them until the time that they show up with you. And if you can take that time to obtain that kind of a history from patient, you can oftentimes find the answer for whatever's causing their fatigue, whatever's causing their symptoms, whatever's causing the reason why they're coming in to see you or being admitted to the hospital for that matter. Yeah. And Stuart, I have to give you credit. We had this conversation. It was, I think we were talking about a different, it wasn't in relation to this podcast, but it was in relation to maybe something happened in clinic and you, we were talking about how important the history is. And you were telling me that point there where you say, when was the last time things were normal? And I was, I had the pleasure of doing some nighttime admissions at Cashlack Memorial. And so I was testing out that question on a patient in the emergency department. And I had coming in with multi-system complaints, had a history of a lot of supertentorial illnesses. And I said, when's the last time you felt good? And she said, it was when I moved. She said, oh, just last month. And then she told me how all her family was there and she just moved here. And so it sort of broke the case wide open for me by just asking that simple question. I didn't really have to ask a lot of follow-ups. She just kind of went on this thing. It's pretty telling whenever I'm on the inpatient wards and I've got this bug-eyed intern or even resident or medical student sitting in front of me and they're just like, Dr. Brigham, I have no idea what's going on. I'm like, all right, walk with me to the patient and watch how I talk to the patient. Just watch how I interact with the patient. I'm not the most, I mean, let's be honest, I've got some Asperger-ish autism going on upstairs. So I'm not the best at connecting with patients when it comes to connecting on a personal level. But having said that, I'm able to recognize patterns and groups of behaviors that lead to certain issues. And so when I ask them that question, oftentimes they give me those patterns of behavior that lead to the diagnosis. That's just the way that I think. But having said that, you can come up with that answer, even if you don't think like the way I think. I mean, it's a huge, it's not, I don't want to say one of my favorite things, but you know, we've all run into this patient who, you know, is admitted for probably an exacerbation of a chronic medical issue, but sometimes their left nostril bleeds, and then their eye hurts sometimes, and one time their toe hurt, and every so often they get this funny feeling in their left chest, and you're like, God Almighty, what is happening here? And if you just take a moment and be like, and how are things at home? And then they start crying and everything kind of unspools from there. Like it's just to show interest and actually have that conversation. I feel like we're way off the path on this, but I think it's an important conversation to have. And there's something to be said about getting down to the patient's eye level, sitting down, or even like getting below their eye level. And you'll notice that their tenor changes, their voice changes, their ability, Right. The last point that I wanted to make, because I think this is a good time to wrap up, Dr. Colburn, who was helping me out with this interview afterwards, said to me that in his endocrinology clinic, they have a questionnaire that is very targeted to the big six that Dr. McDermott talked about, the sleep, activity level, diet, stress level, mood disorders, and other medical illnesses. And Jeff was saying that a lot of the times the patient will have filled it out and he'll say they sleep four hours a night, they drink four beers a night, they never exercise. And he has that information in hand before. So I was going to put a link to that in the show notes. And I think that would be helpful. We can certainly look at implementing it at Cashlack in the internal medicine clinic. But I think that sort of thing can really help save you some time because when the patient's waiting for you, they can fill out some of these questions and kind of give you this big picture, kind of way back to the functional medicine episodes where they talked about that matrix that they fill out, where it sort of takes in all the factors in the person's life that feeds into their symptoms. Yeah, and Dr. Colburn, by the way, was a fantastic guest host, which made me entirely uncomfortable. I don't like that he was cracking jokes. I don't like how capable you seem without me and Stuart. Right. I feel like a slippery sloper on here, Wado. I wasn't going to do this on air, but you guys are both fired. Okay. All right. We're going to go start the start the, was it Schmerb Ciders? Schmerb Ciders. The Schmerb Ciders. Yeah. Schmerb Ciders. I promise not to take you to court over that. Wonderful. Okay. Don't worry, Paul. He's not as loquacious as you or as autistic as me. This has been another episode of the Curb Ciders. Schmermerbsiders. Bringing you a little knowledge food for your brain hole. You can find show notes along with links to any articles, books, websites, or apps mentioned on the show at thecurbsiders.com forward slash podcast. You can also sign up to receive our monthly newsletter, video newsletter, summarizing the key tools, tips, and tricks for your practice at thecurbsiders.com forward slash knowledgefood. Stuart, are you going to make some appearances in the video newsletter? Maybe I'll like paste my head into the video. Okay. Possibly featuring a floating head of Dr. Stuart Brigham. Wonderful.
I've been Dr. Matthew Watto and I'm Dr. Stuart Kent Brigham and good night, Shelby. And I remain Dr. Paul Williams. Oh, hi, Paul. And good night. you you
Welcome to Deep Breath In, the podcast for GPs from the BMJ, sponsored by Medical Protection. Get out your stopwatches. Today we're racing the clock to cover everything you need to know about the time needed to treat, or TNT. It is a huge challenge for GPs to balance the need to address individual concerns of each patient while also acting on the slew of relevant clinical recommendations that largely operate on a population health level, all in the space of a 10 or 15 minute consultation. It's as if guideline making bodies assume GPs and other clinicians have unlimited time, even though we all know this is far from true. In a recent BMJ analysis article, Mina Johansson, Gordon Gaya, and Victor Montori argue that guideline setting bodies should explicitly consider the time clinicians need to implement the host of relevant preventive care guidelines or the time needed to treat. I'm Jenny Rasanathan, family medicine doctor and clinical editor for the BMJ, here today with Tom Nolan while Navjoy is out. Hi, Tom. Yes, hi. Yeah, I'm still here. I'm Tom Nolan, a GP near London and the clinical editor for the BMJ. Hi. And hi, Mina. Can you introduce yourself for our listeners? Hi. Yes, so I'm Mina Johansson. I'm a general practitioner working for 13 years at a healthcare center in a small town on the Swedish west coast. I've been working within Cochrane since 2017, and I'm also leading a new global center for sustainable healthcare. And I'm very happy to be here. Thank you for having me. Fantastic. Well, thank you so much for joining us and congratulations on your article. It's been making quite the splash. Yes, it's been fantastic. It's been quite overwhelming with a lot of attention and people reaching out to me. So that's been absolutely fantastic. Great. So can we start by just asking you to describe the concept of TNT here, the rationale for the concept, including kind of a little bit about your thinking on how GPs currently make decisions, and just giving a little bit more depth on the concept to our listeners. Sure. So the time needed to treat is a new method or a new concept aimed to help guideline panels to consider clinician time as a finite resource that they need to carefully prioritize when they issue guideline recommendations. And the reason that this is needed is because currently there is a massive mismatch between what is being recommended by clinical practice guidelines and the time clinicians have available to provide the recommended care. For example, there's a recent study from the US which estimated that for primary care physicians to follow the guidelines that apply to their patients, they would need to work 27 hours per day. There's an older study from Norway, which estimated that if general practitioners would follow the European guidelines for hypertension, they would not be able to do anything else. It would take more general practitioners than available in Norway to follow just the hypertension guidelines. So the time needed to treat concept is like a suggestion to find a way out of this, to start finding a way out of this, a constructive way to help guideline panels consider this issue. Because I think, I mean, we're all in the same boat. We want able to take care of their patients. of the population eligible for the intervention as a proportion of the clinician time available in the relevant context. Tom, I wonder how that kind of lands with you and whether you've ever felt like you're staring down a tsunami. Yeah, I mean, it seems to be addressing one of the things that as GPs we see every day is this overwhelming demand and increasing demand and yeah that tension that you feel like we've always been asked to do more from every direction and knowing that you can't do it but probably not having the I suppose knowing you can't do it not doing Like we, none of us all follow the guidelines all the time. In fact, you know, rarely do we follow them at all, perhaps. And this is perhaps just giving us a branch to hold onto and say, well, maybe there's, maybe this is the way out because there needs to be, it's a problem that needs to be solved, doesn't it? Addressing this real problem. But I think that, I mean, it's a balance there because what happens now, I think that many people, many of us general practitioners become so desolutionized. Like it's no point in following the guidelines at all. But there is. I mean, we should work evidence-based. So I think it's this balance between questioning how it is now and not become nihilistic. Yeah, definitely. It's true because if you start to say, well, I can't follow the guidelines, it's just impossible, then where does that leave you in your practice? Yeah. Absolutely. Exactly. Yeah and Mina I wonder if you could say a little bit more about this kind of how you think about balancing population health needs and kind of the care that we understand is evidence based on a population level with that kind of nuance of individual patient care? And maybe even drawing on some of your recent thoughts in an editorial about the Nordic trial. Yeah, so I think, I mean, this is a very complex question, and I want to be careful with my wording to not get misinterpreted in this. But I think, I mean, what's happened during the last 50 years or so is that the medical territory has sort of expanded to primary prevention for a larger and larger proportion of the population at quite low risk. And this is intuitively appealing because it seems much better to prevent a disease before it has happened than to wait for people to suffer. But the consequence, I think, as soon as we go to primary prevention for people with low risk, we end up including a large proportion of the population and the time cost of that will be massive. And I think one of the problems with guidelines and the whole evidence ecosystem from primary research, evidence synthesis, guidelines, policymaking, quality metrics, financial incentives, and so on. This whole ecosystem is very, we are very poor at consider opportunity costs. We're very poor at thinking about resources as finite. We are very poor at understanding what we do in medicine through a lens of sustainability. And I think this contributes to it. So like, as one example, another example of this, it's, I mean, everyone was talking about the obesity epidemic. And I agree that it's probably a big, big problem from a public health perspective. But I read this USPSDF guidelines on behavioral interventions for weight reduction for people with obesity. So everyone above BMI 30. And they recommended these really, really intense behavioral interventions. It's between 12 to 24 sessions the first year, between 15 minutes to two hours each. And that's only the first year. And they were multiple years. And this is for 40% of the population in the US have obesity. And the effect was after one year, the effect was a weight reduction of, I think, 2.5 kilos or something around that. And that lowered to, after two years, it was 1.5 kilos weight reduction from these behavioral interventions. Very, very resource intense. And then that was with the intervention. So we don't even actually know what happens when the intervention stops and follow up after. And I think that what happens is that we believe that, okay, so maybe this doesn't have a huge effect, but it doesn't hurt. And it's a good thing. It's sort of, it just, it feels good. But if we take a step back and consider the opportunity costs of this, it would be massive. I mean, imagine 40% of the US population undergoing these interventions. It's just massive. So I think that the problem lies in this inability to consider the opportunity costs of what we recommend. This development within medicine, the expansion of medical territory to include primary prevention of low-risk populations, it has had major consequences for healthcare and for societies at large. But there's been no sort of deliberate process where the community has been included in, is this what we want or not? I mean, as you hear, I'm sceptic to this, but I am not the one who should decide if we should do this or not. It should be like the community should come together and say, is this a good use of our common resources? Is this a good way to do it or should we best. Can I ask you two questions? I want to make a case. I'm going to try and be the kind of nice guideline or other guideline group kind of, you know, arguing against you. But also, I want to ask you first, is this public health? What's your view on public health? And, you know, are you sort of against the current kind of perceived wisdom in public health? And should we just have less public health and more healthcare?
So this is a complex topic. But I want to say that my general view is that I think that healthcare should not expand more. Probably maybe we should do less. But public health is crucial and important. But the only way for prevention is not to go one individual at a time within healthcare. In fact, healthcare is not that good at primary prevention. To give one example, I read that the best case scenario, screening for lung cancer in the US is estimated to save about 12,000 lives a year, best case scenario estimates, and interventions at the societal level to decrease smoking is estimated to save 160,000 deaths per year in the US. So it's more than 10 times as many lives to a much lower cost and without the harms of overdiagnosis and overtreatment and psychosocial consequences. So I think that, I mean, we, in our culture, we have a very, very deeply rooted tendency to think about all solutions at the individual level. That's sort of our lens to everything. But in this case, I think we have mountains of evidence that this is probably not the best approach when it comes to primary prevention of low-risk populations. So I'm not against public health, rather the opposite of what you said. I think that more money should probably go to public health and less to healthcare, but it's what you do with it. Thank you so much for bringing that in, because I think that was the second piece of discussing the concept of TNT, which is that if we reframe the effectiveness of our interventions relative to the time costs and other opportunity costs, it might change the strength of an overall recommendation. And I wonder if you could say a little bit about that before, Tom, you represent the guidelines. Nice. That's great. It's good with some critical questions, I think. Well, I think it's important to make clear that the time needed to treat estimates would be only one piece of the puzzle. So there could definitely be recommendations where the TNT estimates are very high, so it takes a lot of clinician time, but it would still be worth it to recommend the intervention. And the opposite, it could be instances where the time requirements are very small, but it would still not be a good idea to recommend the intervention. So it's only one piece of the puzzle. So I'm going to try and make the case perhaps that NICE, certainly I'm sure other guideline groups already do this to some extent. So they have on each NICE guideline, they have the rationale and impact on their website on each guideline. And against each recommendation, they do make a comment about the impact on current practice. So there is something, and perhaps the argument it's it's perhaps false to try to put a number on it because it's so variable like for one patient it might be a two minute thing or they could do it themselves they don't need to see a gp whereas for somebody else they might need um you know quite a long relatively long time and so um isn't it good enough to have experts on the committee including those in primary care sort of making a judgment and feeding that in in this way um yeah so first first of all i have the highest respect for that this is an issue that many people are working on and have done like great a lot of of really good work on this issue already. So it's not, I don't think that the time needed to treat concept is like the golden key to solve this problem. I think that it needs a lot more work. And for us, it's basically just like a first, this is an idea. What do you think about it? Like, do you want to develop it? Do you want to help us test it, try it, criticize it, find new ways? I mean, we don't feel like we own this idea. We want people to use it or develop it and change it in any way they want. So first, I wanted to say that. And then, like, for example, in health economy analysis, there's also some work around how to help prioritize between different guidelines in a better way. But obviously, I mean, we still have a problem because this study from the US saying that primary care physicians would need to work 27 hours a day, that was from last year. So,, this, even all the stuff that we have done hasn't helped enough. Like we still have this problem and it's massive. And I think that, I mean, many guidelines, NICE, for example, they have the resources to make very advanced analysis, health economy analysis and impact analysis together with the guidelines. But in a lot of other areas, like for example, the region where I live, there's no health economy analysis tied to the guidelines that I work with. So basically what I'm saying is that I think that all initiatives to solve this are fantastic. And it's really great that NICE is working on this too. I think that there's still more work to be done. And I think that a very simple method that could be applied very easily, that is very concrete and sort of make you get it, what's this about, can be helpful, even if there are more advanced analysis that do similar stuff. Does that make sense? Yeah, yeah. I mean, I wonder if it's... As a GP, I often feel that the time that I would spend with a patient if they brought something up isn't perhaps valued by the system as much as patients do and I do. And I think it's important to try to go into the appropriate depth and with a patient for any anything they bring up and um and perhaps some of the some of the guidelines to go well it wouldn't take that much longer so we'll you know it won't really make a difference whereas you have to do things properly in a in a way that we want to with patients and to have to have a shared decision making and all those sort of principles that we aspire to takes time. And perhaps what you're suggesting with time needed to treat is to put maybe more realistic time on those things, as well as trying to quantify it. I'm not sure it's a more realistic thing of what actually happens in practice, because I think that it would not be a good idea to sort of get into, like measure exactly how long time things take in practice and use that to micromanage what happens in the consultation. I think that would be a terrible idea. I think, in my view, what TNT would help with is to help the guideline panels understand what would happen if the clinicians actually did what we are telling them to do. Then, of course, that will never happen. Even if the number of recommendations were cut down by 50%, I mean, all guidelines wouldn't be fully implemented anyway. So it's not a realistic number of what TNTs are not sort of realistic estimates of what actually happens in clinical care. It's more of helping the guideline developers, the panels understand like, so if what we're telling people to do, if they would actually do it, what would that cost in terms of opportunity costs i guess it reminds me this concept with we we talk often on the podcast about the role of the gp and maybe the expanding role of the gp or maybe ill-defined role does this help us to to move that forward a little bit yeah i think this relates a lot to the what we talked about before, about the expansion of medical territory during the last 50 years, which in some way has been positive, but in some way also have now this really complex negative consequences for the population. I know that in the UK, you're suffering a crisis for GPs, that patients can't get access to their GPs, even when they have really, really strong care needs. And that's a crisis that we see everywhere. So I think that TNT can help in helping us take a step back and reflect on what is it that we are doing and what do we want to do? Because this, I think, should be a decision that we make together as a community. How do we use these resources? I mean, I'm working in a very high resource setting, yet I don't have time to care for my patients. And how can we solve that? I mean, we could hire taxes by 50% and spend all of that on healthcare and educate many, many more GPs. That could be one solution. But do we want that? Do we as a community want that? Or do we as a community see, can we see that if we put all of this on the plate of the GP, then we will have problems. Then when, if I go to my, if I get, if I sort of get this and this and this and this according to guidelines from my GP, then when my neighbour has a really serious problem, maybe symptoms of cancer or other serious diseases or suicidal thoughts or something really serious, then they won't get access to the GP to discuss it. So I think it's, like I said, I don't think that individuals should decide what's right or wrong in this.
But I definitely think that the role of GPs need to be reconsidered. The role of healthcare needs to be reconsidered. And the pandemic has shown that, but we had the problem a long time before that. That is really interesting. Thank you. Our conversation GP is part of who you are whatever the time of day. So when it comes to your indemnity you need someone you can turn to at any time. Medical Protection is always here for you with expert medico-legal advice including 24-7 in an emergency. We don't just cover patient claims we're also here to provide support and legal representation when it comes to GMC inquiries, coroner inquests, criminal investigations and more. Online, we offer risk prevention courses and webinars to keep you up to date with current news, risks and legislation. We also go the extra mile when it comes to your wellbeing. With a free counselling service and eCare app, we're helping members take positive steps to better mental and physical health. It's the protection your career deserves, all in one place. And if you're about to qualify or have recently qualified, we can help you take the next step in your career with savings on membership for newly qualified GPs. To find out more, visit medicalprotection.org. And now we're back to Deep Breath In, talking with Mina Johansson about the time needed to treat. I just wanted to pick up on something we started to get into before the break. Thank you. kind of consciously think in advance of, you know, an encounter with their health care provider about how there's going to be limited time. And they, you know, I'm not sure how many people are really conscientiously prioritize things to discuss in any given appointment or even over the course of months or a year. And I wondered kind of what time needed to treat begins to mean for patients. And if people had more awareness of the kind of competing guidelines, whether it would change the way that patients think about their kind of 20 or 30 minutes of time with their GP each year? Well, I think to start off, I just want to say that the whole point with the time needed to treat is to improve care for patients. I mean, this idea or this thinking for me personally comes from working as a GP for 13 years in the same health care center, being extremely frustrated every day that I don't have the time for the stuff that really matters for my patients. I don't, some patients, I mean, in some consultations, we spend a lot of time on stuff that is of very limited importance, while the patient actually has something of much more importance that they want to share with me, but we don't have the time. And some patients, many patients don't even get to see me. And unfortunately, that's a higher proportion of those patients that are living with disadvantage, facing disadvantages. So it's a cruel system that we work in currently. So this is a massive frustration that I think that many of my colleagues experience and the patient experiences it. So I think, as you say, the TNT concept might be abstract and not really fit with the feelings of patients. But I mean, the feeling of not getting time in healthcare, that's, I think, many patients feel that. Very difficult to access care, very difficult to get an appointment. When they are there, they can only say one problem, even though they have five, or they are interrupted very quickly from the agenda of the clinicians. They don't get the unhurried conversation that Victor Montori talks about. They don't get listened to. So I think that, I mean, this is the idea with, as I said before, I think it's very important that the TNT concept is not used to micromanage the consultation because what happens in the consultation should be sacred. It's between the patients and the clinician, and it's a dance. And it shouldn't be, we have a huge problem with this micromanagement of what happens within the consultation that really counteracts patient-centeredness. And I think that's terrible. So, like, again, one of the reasons that I got very frustrated about this was that I feel in my work that I could, I mean, I serve about 1500 people as a GP in Sweden, and I could easily spend all that time discussing pros and cons of different screening interventions of treatment, pros and cons of the different pharmaceuticals for mild hypertension, or very relevant in the UK now, the pros and cons of treating with statins for people at low risk. I could easily spend all the time, all my time on that. And to some degree, I do spend a lot of time on that. But I mean, I don't have time to, the consequence of doing that is that I don't have time to listen to the patient carefully to see maybe some of my patients have suicidal thoughts. And I go on with this screening intervention stuff, but I don't have the intention to listen to the patient. Or if I have patients with really severe depression, I don't have time to see them again soon enough to care for them properly. And, or other, I mean, there are so many examples of things that I don't have time for. And it's a bit, I mean, it's so strange because we have never spent more money on healthcare as a society. And yet all healthcare personals that constantly feel that we don't have time. That's so contradictory. And there's something fundamentally problematic with the way we understand time. I guess it feels like what you're talking about is, you know, this is the product of a very medicalised society where a few years ago, I read in a newspaper, a quote from somebody from a cholesterol charity saying you should definitely have a conversation with your GP about cholesterol every year and I was like you know obviously tearing my hair out at that idea and thankfully most people don't do that but if they did then like you say that would be almost the whole system flooded but everywhere you know you're right you can never blame somebody for coming in and just doing what society tells them to do which is to get that mold checked or see you about that cough or um get your cholesterol psa all these other tests that you're constantly told you must do or you you might die prematurely or end up like that person off the telly. So, yeah, I feel like... Yeah, sorry for interrupting. But I think exactly. I mean, it's so easy that we sort of blame the patients for this, but it's not strange that you ask for this because the guidelines tell us and the quality metrics and the financial incentives for clinicians oftentimes. So I think that we need to rethink this. We need to think about a new way of thinking about this. And I think one step in that direction is for guidelines to consider clinician time as a finite resource that needs to be carefully prioritized. But the whole idea with that is to improve care for patients. And I think this idea that Victor Montori and his team and the many different teams work with is of unhurriedness in the conversation is, I think, really crucial. And we have gotten so far away from that in healthcare today. And this elegance of the conversation between two people, where you try to understand each other and try to understand what matters in the consultation, that's really important. I very much agree. And also, I mean, it was fantastic to have Victor Montori along with Dominique Allwood contributing an essay on this in our most recent Christmas issue, which I would recommend to everybody. But as I was listening just now to both of you, I was thinking, you know, there's also an element, and maybe this is just me, but there's also an element, you know, when I see like red that I meant to click and turn green in my EHR or when I am going through you know patient encounters at the end of the day and realizing oh I didn't talk to this person about about you know pap smear I I didn't do this person's cardiovascular risk screen like I personally feel guilt like I am not doing a good job by these patients, because I'm failing to implement all of these evidence based guidelines. And I, I'm not sure if that's something that has come up in any of the reactions that you've gotten to TNT. Absolutely. I mean, there's been, like I said, in the beginning, the response has been almost overwhelming. There's been like from such a broad range of people that lots of patients have contacted me, clinicians, many GPs, of course, but also different kind of organ specialists, nurses, physiotherapists, policymakers, politicians. There's been such a massive response, which is fantastic. But I think this guilt, and it's also so strange. I mean, you could have the most really, really good consultation where you really listen to the patient, you understand what matters, you help them solve the problems that they come to you with.
I mean, what is that? It's strange, right? But that said, I think it's always important to have the balance because some interventions we have to accept that we have an agenda that is probably good for the patient too. So it's a balance between it. Like, for example, if someone comes in and talks about some problem and then they say in a byline that, I mean, I also have gastrointestinal bleeding, then of course I, as a doctor, need to have the agenda to discover, like, what is this and do we need to investigate it further? So there's a balance in it. But I think this, I mean, this really goes back to the importance of being patient-centered, like starting every consultation with how are you or like an open question to put the power back to the patient, what we're going to discuss. I keep saying oh how are you and they're like oh I wouldn't be here doc if I was all right. Okay. But I keep saying it anyway. Yeah I think think also like many i think patients are not sort of used anymore to to being free to talk about what they want to or having there and that's also a bit sad but yeah i mean different i think it's nothing is universal it's it different things works in different contexts and for different personalities but it's it's just to have a discussion that how do we actually work patient-centered? How do we have these unharried conversations? And how do we have a system that facilitates that instead of hinders it? I think that's very important. I guess we've talked before, haven't we, about because you can't measure it, you't incentivize it and I think there's probably some cleverer people than me could make a similar case about things that you can make pop up onto an electronic health record you can't say did you have an unhurried conversation no you can't say you didn't discuss the risks of ibuprofen and you haven't documented this and that. Yeah. I mean, and we should be really careful to measure unhybridness too. I think we shouldn't go there. But I mean, that's a general problem in society, isn't it? I think teachers have, I was actually interviewed for Teachers Magazine around time needed to treat in Sweden because they said, well, we have the same issue for teachers. So I think it's a cultural movement where we don't trust professionals anymore. We think that we need to micromanage everything that is happening, control everything and measure everything. And as you say, the stuff that we can measure is absolutely not always the most relevant stuff. And we don't consider the opportunity costs of what we choose to tie to financial incentives or quality metrics. Like, for example, in my health care center, I don't get funding. I don't get money myself for doing the stuff in the quality metrics, but my health care center do. So if I don't follow it, we might have to fire a nurse. So that's what I'm dealing with. So we have to, I mean, it's very difficult. Like, for example, some of the guideline people in response to TNT have said like, well, I mean, you don't have to follow the guidelines. It's only guidance. Well, if they're tied to quality metrics and financial incentives, it's very difficult to not do it because either you have to, it doesn't become financially viable. I have to fire one of my colleagues or you get the quality metrics saying that you're a very bad doctor. You don't want that either. So it's not that easy, I think, to ignore it. Yeah, I definitely hear that. And I'm curious about some of the other reactions that you've gotten. Well, to my sort of surprise, it's been like 99.9% has been extremely positive. And I think, like I said before, or I really want to make clear that, first of all, to give credit to my co-authors, Gordon Guyatt and Victor Montori, this was really a team thing, writing this piece, this analysis piece, but also to the many, many people that have worked really hard on these issues for decades, like, for example, the papers that we cite in the paper. So this is, in a way, really not something new. It's more like a slightly new way to communicate the problem. And I think that I've been thinking, because the method is also very simple. So I've been feeling a bit guilty for all the attention around it. But of course, it's fantastic that this issue gets so much attention. But I think one of the major reasons for that is, I think that it is a clear way of communicating the problem. Like you get it. Like, okay, so if this guideline on brief advice for physical activity would take 15% of GP's time to implement, and there's no evidence of any benefit, then maybe we need to take a step back and think, is this really worth the time? So the opportunity cost becomes very clear and up on the table. But I think that it could definitely be misused. I think what you're asking is, could it be misused? I think one reaction that has been a bit negative is that the things that take time is the lifestyle interventions or the more complex behavioral interventions. And TNT will sort of make them less tempting and instead will be more medicalizing. Like, okay, so it's much easier to give a pill than to make people lose weight or whatever. But I think, and I can understand that reaction. And I think it needs to be carefully thought through how to use it. But I mean, if we have great behavioral interventions that are not implemented, it will still be a massive problem. Like, because we don't do, yeah. I suppose one reason. Sorry, I've lost my thought, yeah. I guess the thing that takes the least time to do as a GP is prescribe or, you know, refer or... Is there a... I haven't worked this through before opening my mouth, but... I love that. Is there something around that? We need to say more things before we... You know, like the prescription for antibiotics, which often the patient isn't actually there for, but if they are, and you say yes to that quickly, then in theory you've got a bit more time to talk about other things, or as inevitably the person might be, oh, by the way, can I talk about my mood or something else? Could this principle have these kind of maybe slightly unwelcome consequences in that way I think if it would be applied without any thought it might have but that's what we do in medicine isn't it we just say this is now the rule we almost do that until we realize but like I really want to stress that this the tNT estimates is one piece of the puzzle. Like it has to be, it has to be understood in relation to the benefits, the harms, the priority of the problem, the financial costs and acceptability, feasibility and all that other issues. And I think like, if we take the antibiotic example as one example, I think that really shows our understanding of everything through the individual lens. Like when I started as a GP 13 years ago at my health care center, it was really difficult to convince people not taking antibiotic for viral infections. Now it's not hard at all. It's like kicking in an open door. It's almost difficult to convince people that they need antibiotics when they have a serious bacterial infection. And why is that? I mean, it's not because I have had a discussion with each individual of my 1500 patients. Like that's not the reason. The reason is the understanding in the community that we need to have a common responsibility for the antibiotics that we have. So it's been like mass media campaigns. It's been like a democratic process in the community that has led us here. So I think that you could say that, okay, so it's easier for GPs to just prescribe the pill. Yes, where do we have this problem and where is the solution? For example, MRIs for low back pain, we know that we shouldn't do them. We know it's a low value care, yet I do them quite often because it's very difficult to take that discussion with each individual every time and the time pressure. So we need a bigger discussion around this. We need de-implementations. We need strategies that are not focused on the individual. I think that's the solution. And maybe go back to the, that it might nudge a guideline recommendation from a strong recommendation to a weak recommendation. It's another nudge to take with everything else. Yeah. And I also think that TNT shouldn't be used for the fine discussion. It's not like, is it a 2%?
And where's the cut up? That's not the kind of decisions that it should be used for. There's so many low hanging fruits in guidelines, I think. I mean, when we talk about primary prevention, it's usually a lot of discussion on like the exact risk reduction, for example, in colorectal cancer screening in the Nordic trial. There's a lot of discussion on like, is it a 0.2% absolute risk reduction or is it 0.3% absolute risk reduction? Or is it like, it's a lot of discussion around that uncertainty around the exact estimates. But the uncertainty of, is this worth the human resources that we put into it? And what are the opportunity costs? Is it worth the opportunity costs in our community? The uncertainty around that is like exponentially larger, but we don't deal with it. So it becomes like a focus on the exact estimates around the evidence, which is a minor issue in the context, I believe. more about the time needed to treat, have a look at bmj.com or check out the link in the show notes to this podcast. You've been listening to Deep Breath In, the podcast for GPs brought to you by the BMJ and sponsored by Medical Protection. Deep Breath In is available on Apple Podcasts, Spotify, or wherever you get your podcasts. Subscribe to hear more nuanced conversation about the thorny issues in primary care. Until next time, bye from all of us.
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That's patreon.com slash curbsiders. You know, Paul, ever since my son started swallowing money, I've noticed some real change in him. I like that one. Okay. The Curbsiders podcast is for entertainment, education, and information purposes only. And the topics discussed should not be used solely to diagnose, treat, cure, or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of the host and should not be interpreted to reflect the official policy or position of any entity, aside from possibly cash, like more hospital and affiliate outreach programs. If indeed there are any, in fact, there are none. Pretty much we aren't responsible if you screw up. You should always do Matthew Watto, here with my great friend, Dr. Paul Nelson-Williams. Tonight, a show about dysphagia, dysphagia. You be the judge. We have a great guest, Dr. Diana Snyder. And Paul, how are you doing? I'm great, Matt. Thanks for asking. How are you? I'm good. It's been a month since we recorded. I feel like I forgot how to do this. Yeah. I think you did very well tonight, Paul. The audience is in for a real treat, but would you tell them what is it that we do on the show and can you introduce our wonderful co-host? Sure. Happy to, as always, Matt. As a reminder, we are the Internal Medicine Podcast. We use expert interviews to bring you clinical pearls and practice changing knowledge. As you alluded to, we are joined by your fave and mine, Dr. Elena Gibson, who is also the writer and producer for this episode. Dr. Gibson, how are you? I'm lovely. How are you? I'm good. Thank you for asking. I'm going to leave the space open for you to tell us about who we talked to and maybe even a little bit about what we talked about. Yeah, happy to. So tonight we have a conversation with Dr. Diana Snyder. Dr. Snyder is currently an assistant professor of medicine at Mayo Clinic in Rochester. She attended medical school in residency at Loyola, and she was chosen as a chief medical resident there as well. She completed her gastroenterology fellowship at Mayo Clinic Arizona, where she was also a chief fellow, and she was the first Mayo Clinic Arizona advanced esophageal disorders fellow. Her research is focused on esophageal disorders, including motility disorders and eosinophilic esophagitis. She is principal investigator for multiple EOE clinical trials and has completed several high-impact studies evaluating opioid-induced esophageal dysfunction as well. So in this episode, we talk about quite a few things, including how to differentiate esophageal and oropharyngeal dysphagia, when to think about eosinophilic esophagitis, which is more common than we think, and then what to do as far as next steps in evaluating dysphagia, including EGD or additional imaging. So let's get to it. And before that, a reminder, this and most episodes are available for CME credit through VCUHealth at curbsiders.vcuhealth.org. Diana, thank you so much for joining us on the show. Back by popular demand, we wanted to know a one-liner. Tell us a little bit about yourself and tell us a hobby or interest you had outside of medicine. Thank you so much, everyone, for having me today. So I'll have to tell you, my favorite hobby is actually going on hikes and walks with my husband, but as well with my adorable Cavapoo puppy. I have a one-year-old dog, Duke, who's very spunky and adorable and looks like a little teddy bear, but he also likes to go hiking with us. So that's how I decompress from the hospital. Fantastic. Fully support that. That is, we get a lot of hiking answers, Paul, and I don't hike, Paul. Do you hike? I don't hike or garden. So I remain poorly adjusted. Paul, I challenge you with your upcoming move that you need to start doing both of those things, or at least one of them. I think one's going to be more of an option than the other, but we can talk about it later. All right. Well, did you have any questions for our wonderful guest? Sure. I'll ask my usual. I am almost caught up in some of the pop culture I want to be caught up with, but I do wonder if there is like a TV show or book or a piece of music that you would recommend that you think our listeners might enjoy. Yeah, there's actually one I just started watching. It's called The Lost Kitchen. It's on a few different streaming services, but it's really interesting. It's this self-taught chef, Erin French, who's from this very small town in Maine, but she developed her own farm-to-table restaurant. So she goes to all the small farmers and basically shows you how she learns to find the best produce or fish or whatever entity it is and then brings it to a restaurant and goes through the steps of building farm-to-table meals. It's very soothing and another kind of nice thing to do after a long day and taking care of patients. This sounds very much my jam as someone who only watches Food Network and The Cooking Channel. So this is exactly the thing I'm going to do. I've been watching it on HBO Max is what it's on right now. It may be on other things too, but it's great. And there's three seasons to catch up on, so you can binge it too. Stellar recommendation. Elena, how about you? Any questions for our guests before we start getting into some cases here? Yeah. Could you tell us some meaningful advice or feedback you've received during your career training? Yeah, one of the most important pieces I received was actually from my esophageal mentor from fellowship, who is also my program director for my extra esophageal fellowship. And we were doing our last meeting before I was going on staff. And he said, Diana, it's really important that you pay it forward. All of the mentorship, research mentorship, sponsorship, all of these privileges that we gave you, you need to send it down to the trainees that are working with you. That's the one thing I ask of you. If you do that, we'll be proud of you. So it's really important to pay it forward to your trainees. Nice. Yeah. And here you are. So good. Good example. All right. Well, that's a great transition to let's pay it forward by helping us through a case from Cashlack. And Elena, if you would start us off. Our first case is Quinn, a 28-year-old with six months of trouble swallowing associated with intermittent chest pain and feeling like some food is getting stuck. She has a past medical history of hypothyroidism on levothyroxine, and she takes some daily loratadine for allergic rhinitis. So before we get into the details of Quinn's case, can you review the definitions of some of the common terminology, so dysphagia, odynophagia, and globus sensation? I'm really glad you asked about this because often there can be overlap and it's difficult to distinguish, so it's important to define this. So dysphagia itself is really the subjective sensation that a patient has that something isn't moving from the oropharynx into the stomach, whether it's solids, liquids, pills, saliva, whatever it is. A dynophagia, though, is when you're having pain when you're swallowing. So that's pretty distinct. What gets a little trickier to delineate is globus.
And how I distinguish it from dysphagia is typically when they're actually actively swallowing, globus gets better. It's something they notice more at rest. So if they're swallowing, it gets better. It's probably less likely dysphagia and more globus related. That is a simple but very important distinction is better with swallowing. I think I could remember that. So I think you get so many complaints in primary care about people having swallowing difficulty. When I was reading about a lot of the causes of dysphagia, it seems like there's like a delay in diagnosis for people getting an actual diagnosis. You think that's because we don't know how to take a good history when someone comes in complaining of dysphagia? And can you tell us how you go about that? So it's not that we're bad at taking histories. I think a lot of it's our situation, right? We have limited time. So we do the best we can with limited time to ask the detailed questions. But the biggest issue we see with diagnostic delay is actually with eosinophilic esophagitis. That's very common. The incidence and prevalence are going up even beyond us doing more endoscopies on patients. And a lot of that is because of compensatory mechanisms. So a patient that has had difficulty swallowing solids basically since childhood practically with EOE learns how to drink a lot of liquids, learns how to be the last one to leave the table, choose well, eat slowly. And so often they don't even realize that they're different than everyone else sitting with them because they're so used to compensating. So we really have to tease out some of those details in order to figure out what's going on. I feel like I would, well, I know I would get tripped up by this case too. I think based on age alone, and then you gave what looks like maybe some post-nasal drip in there, like I think I would anchor pretty hard on the globus. I'd be chasing down heartburn maybe, or trying to diagnose this poor patient with an anxiety disorder they don't have too. So I can see some diagnostic delay just based on patients looking overall benign too. Yes, especially as you point out younger patients that are pretty healthy overall. The big trigger to me actually was seeing that in the case there was allergic rhinitis. So I do like to hear about other allergic conditions or atopic conditions. So patients who have atopic dermatitis or eczema or asthma or even asthma as a child that now is in remission or allergic rhinitis, There is quite a bit of overlap for that with esophageal disorders like EOE. sent off, Memorial Day sale. It's coming soon. They have all the home essentials that you know and love. And guess what? Wirecutter and Good Housekeeping have called Brooklyn and Sheets the best around. And customers agree because they have like over 100,000 five-star reviews. Paul was a Brooklyn and customer before they were even a sponsor on the show. And my wife and I were so excited to get our Brooklyn and Sheets. And as I've said, sleep is really important to me. And I'm sleeping really well with my comfortable and luxurious Brooklinen sheets. Their most popular are the Luxe sheets. They're buttery soft with a luxurious finish and great for all types of sleepers. So what are you waiting for? Your Memorial Day sale is coming soon. Shop 20% off in-store or online at brooklinen.com. That's B-R-O-O-K-L-I-N-E-N dot com. Can't wait until the sale? Visit brooklinen.com today to sign up for emails to be kept up to date with exclusive offers, new products, and much more. So we've kind of heard about her past medical history and what would make you concerned there. Do you find it helpful to ask things like pointing to where people feel like food is getting stuck or whether or not they're having any vomiting, kind of other questions you might ask to try to figure out what the next best step for evaluation would be? Yes, I do ask them to point, but there are caveats to that. So the neural pathways in the esophagus cross over extensively. So sometimes I'll have a patient that points right to the suprasternal notch, and actually the issue is the Schatzky ring at the lower esophageal sphincter. So it doesn't always correlate, but if they do point up high more to the throat area or the suprasternal notch there, then I will ask further questions to try to delineate is this oropharyngeal dysphagia versus esophageal. And that's when I start asking things like, is there nasal regurgitation? Do you see liquid coming out of your nose? Are you coughing or choking when you start the swallow? Do your family and friends tell you you have bad breath? Or do you notice a foul odor? Or sometimes do you wake up and find some food on your pillow? So it's important to ask some of those things that trigger me to more oropharyngeal dysphagia because pointing to the higher part of the chest or neck alone doesn't tell me if it's esophageal or not. And then as you mentioned, other associated symptoms are important. So before I go through the associated symptoms, I also ask about what types of items they're having dysphagia with. Is it solid foods? Is it the trickiest solids like dry bread? Is it meat, rice? Those are usually more difficult. Is it softer solids like oatmeal? Are there issues with liquids? Because liquids are important to ask about. When solids progress to liquids, then we're more worried about things like malignant causes. When solids and liquid dysphagia is occurring simultaneously, we start worrying about motility issues. And then also, are they having difficulty with pills? Often pills are challenging. We're really not designed to swallow pills. That's a human invention, right? So those are very challenging. So I do ask about that as well. And then with the associated symptoms, once I further delineate the actual dysphagia component, I like to ask about alarm symptoms. So I do ask about weight loss as we do for many areas of internal medicine, right? Are we worried about something more alarming like a malignancy? Is there bleeding? Are they having aspiration pneumonia? Those are the big alarms or vomiting. And then after that, I like to ask about common associated things. So it's important to remember erosive reflux alone can give a patient dysphagia, even without a peptic stricture there or a Schottky ring. So it's important to ask, are you having heartburn? Are you getting sour liquid regurgitation up to your throat? Also, it can overlap with dysphagia and rumination. I realize I see a bit more of that because I'm a subspecialist, but I think it'll even come to your internal medicine clinics where a patient will be swallowing food and thinking they're having dysphagia, but really, oh, it's just effortless. The undigested food comes back up and they're reswalling and don't realize they're not nauseated. They're not retching. They're just ruminating. So I do try to ask about that too. And then the other thing, what I mentioned before is I do ask about all those EOE compensatory mechanisms and atopic overlap, because that's another common thing not to miss. Faithful listeners will know I'm the guy who just asked like the most basic questions just because I want to make sure I'm understanding stuff. But you'd mentioned sort of differentiating oropharyngeal versus esophageal dysphagia. I wonder if you wouldn't mind just taking a minute just to make sure that I understand the terms exactly what you mean when you say those things. Like what, if you can just sort of talk about what goes in each of those, because I feel like that would be helpful in terms of thinking about pathologies too. So when I talk about oropharyngeal dysphagia, I mean everything above the upper esophageal sphincter. So once you're below the sphincter, the top muscle of the esophagus, then we're talking about esophageal dysphagia. So oropharyngeal dysphagia has numerous buckets. You think about the common structural problems like ENT issues. Is it a cricopharyngeal hypertrophy or BAR? Is it an older patient that has that plus a Zanker's pseudodiverticulum or outpouching there where the bar is? Or is it more of a neurologic problem?
So I think of those areas within the mouth and throat and pharynx, whereas everything else below the upper esophageal sphincter is esophageal. And so you already told us we can't necessarily assume it's upper if they're just pointing to that upper throat. We can ask those type of questions, but it's not 100%, which is a shame because, Paul, we're always looking for that just like, that one thing, just make it easy for me. Just tell me what to do. I wish. Yeah. For a simple, a simple pipe system or a simple bag of, you know, muscle, the esophagus, the neural pathways are actually super complicated. So sadly we can't just point. I wish it would be a lot, make my job easier and yours. And there's a lot, there's a lot that can go wrong here. So I guess, why don't we read the next part of the case, Elena, and then we can ask some follow-up questions. Sure. Yeah. So Quinn describes a progressively worsening sensation of solid food getting stuck around her sternal notch. Symptoms do improve whenever she drinks liquids. They did not change when she was started on a PPI trial three months prior to the current appointment. So the PPI was discontinued. So thinking about what we now know about Quinn and her history, how would you determine what the next best step for evaluating Quinn's dysphagia would be? And within that, which patients should be evaluated within EGD versus barium esophagram or a modified barium swallow? So really, almost any patient with progressive dysphagia, including Quinn, as she's described with that here, really warrants an upper endoscopy because dysphagia alone is considered an alarm symptom, right, that requires endoscopy. The caveats to that would be certain other clinical comorbidities that would limit someone to undergo moderate sedation or monitored anesthesia care. So as long as the person is healthy enough to undergo the procedure and the dysphagia is progressive, they should really get an endoscopy. So what to do in terms of imaging studies? So there's not a lot of guidelines on what to do with esophagrams and modified barium swallows. So for run-of-the-mill solid food dysphagia, technically you don't have to do those. You could just go right to endoscopy. We use them quite often, of course, because as an esophageal specialist, we like to have that roadmap because sometimes we're seeing complex strictures and things where it's nice to have that delineate on the esophagram before going in with an endoscopy. So, but generally speaking, the modified barium, which is really a video fluoroscopic swallow study, that's really for those patients I mentioned earlier where we're thinking there's an oropharyngeal problem going on, meaning they're having the coughing, the choking, the liquid regurgitation out of their nose, the halitosis. Those are the ones where we need to do the video swallow. The esophagram is looking more at the body of the esophagus and relaxation of the lower esophageal sphincter. It can also look at the mucosal lining of the esophagus, whether there's a diverticula, whether there's a stricture, whether there's a ring or a web, and really a low threshold to order an esophagram. It can be done at every hospital. It's cheap and it's not harmful to the patient. So, and there are some patients where maybe you're worried about starting with an endoscopy because of some of those anesthesia risks, but being able to do an esophagram that's non-invasive is a good starting point. There are specific things that we look for in addition to those general principles, and there are patients that, you know, I see a lot of patients with achalasia, and that's always something we learn as a med student, but there are specified barium protocols we use for that where they actually give the patient a huge 200 milliliter bolus of barium, and then they measure the column up from the lower esophageal sphincter to wherever in the mid to higher esophagus it flows and how high that column measures at five minutes. And that's really important for us to see before and after we treat achalasia and watch that column go down. The other thing we use is we have a special EOE protocol where our radiologist knows how to put the patient in different positions and measure the max and minimum diameter of the esophagus so that we can track strictures because even esophageal specialists like us can miss strictures endoscopically that are subtle and we can pick them up on esophagram and then know to look for them and target informative source like locumstory.com. You'll learn all the ins and outs of locums, details on travel and housing, assignment coordination, tax information, and more. You'll also learn firsthand stories from locum's physicians from all walks of life, so you get a bigger picture of the diverse options. Get a comprehensive view of locums and decide if it's right for you at locumstory.com. Once again, that's locumstory.com. I wanted to just recap a little bit about the barium. So you said the modified barium or the video fluoroscopy, that's really for if we're thinking pharyngeal, like oropharyngeal dysphagia, and those are the patients you said, like the nasal regurgitation, they're choking, aspiration pneumonia, bad breath, those people. And then the esophagram, which is often not the first study for dysphagia, but it can be a good study. Maybe if you already know someone has a problem and you're looking, you said use it as like a roadmap. That was an interesting way to look at it. And that there's all these various protocols that can help for specific diseases. So that's something that I didn't know about at all. And we were talking about this ahead of time that sometimes I'm waiting three months for someone to see GI for an EGD. So I'll end up getting the barium swallow, even though if you look at a lot of algorithms, it seems like it's always not the first line test. I'm often getting it just while I'm waiting sometimes, depending on the situation. I like that strategy because you can rule out some larger malignancies and significant stricturing disease that would prompt if they're found to get an expedited consult. So I like that strategy. That's a good way to do it. So for our patient here, you said you would be looking for an EGD for her. And you gave us a little bit of the differential already, but I guess, can you tell us, like, what would you be thinking as you are, you know, as you're approaching this? Like, what would you be looking for and what would be done on the EGD to try to help figure out what it is in the differential? So when we're talking about esophageal dysphagia, there's a lot of buckets of things we can think about. So in this case, it was progressive solid food dysphagia and progressive solid food dysphagia or even intermittent solid food dysphagia in a young person is EOE until proven otherwise because it's so prevalent. So you really need to do the endoscopy to look for that. But the other buckets of things, so we think about inflammatory conditions. So those are going to be things like EOE or erosive esophagitis and reflux or pill esophagitis. Then we think about primary motility issues. And again, cue that more for patients that are having solid and liquid dysphagia. And the classic primary one we think about is achalasia. There's a lot of other nuances to those motility disorders. And if it's not achalasia, trying to delineate those, you can always talk to a specialist like us. And then there's the secondary motility problem. So those are patients who have other conditions like autoimmune conditions, like scleroderma. They get absent distal peristalsis and motility problems. And then finally, we think of the usual structural or mechanical issues like peptic stricture, Schottky ring, those types of etiology. So those are the big buckets. But here, young person, solid food dysphagia, EOE is differential diagnosis one, two, and three. I was going to ask what you made of the strategy of the trial of a PPI, even in the absence of like overt reflux symptoms. Is that something that would be reasonable to do in a patient like this? Or is that you're just wasting time and they should be scoped to be looked at?
It would be reasonable to do it after the endoscopy. So do the endoscopy, you see endoscopic features of EOE, you get confirmation on the histology, and we can talk more about that if you want to as well. And a pre-PI trial to treat EOE would be very reasonable. Roughly 40 to 50 percent of patients are histologic responders to proton pump inhibitors for EOE. So we're not just treating reflux, we're treating EOE directly. Proton pump inhibitors work on the EOE is basically a TH2 mediated immune reaction. And so there's certain factors in their EOTaxin-3 that the PPIs directly target. So they're not just treating reflux overlap in EOE, they're directly treating EOE just in that flip of a coin percentage of a population. PPI trials are okay when you're dealing with someone who's presenting with heartburn, regurgitation, classic reflux symptoms, no alarm symptoms, no dysphagia, no weight loss. That's reasonable to trial for eight weeks. Progressive dysphagia, you need to go to some kind of endoscopy or imaging. We have this broad differential, and you mentioned achalasia and EOE. You told us this ahead of time. Can you tell people the prevalence of EOE compared to achalasia just in general? Yeah. So EOE is one of the most prevalent conditions we have. So now it's up to one in a thousand or one in 2000 patients, which is a huge magnitude compared to the prevalence of achalasia, which is one in a hundred thousand. So achalasia is much rare. It's that classic thing we learn. You have to learn the bird's beak on the esophagram as a med student, right? But EOE is what you're going to see a lot in clinic. Yeah. You know, when people have this non-cardiac chest pain, I'm like, could this be distal esophageal spasm? Because sometimes it just feels like people are, they're kind of describing, oh, it felt like my, something was spasming in my chest. And I'm like, but it seems like that is also pretty uncommon, especially compared to something like EO primary to make sure they get the EKG or the stress or whatever they need. As you mentioned, this is non-cardiac chest pain. So that already happened, which is good. That should happen before they come to me, but sometimes it doesn't. So once I think it's non-cardiac, then we really have to delineate what this spasm type symptom is that they're having. And there's a lot of different things that can cause that. So usually I need to do an upper endoscopy with esophageal biopsies to make sure it's not an atypical presentation of EOE. In addition, we'll often do pH reflux testing because acid reflux alone can present a spasm pain, which is kind of an atypical form, but it is possible. And then way down the list is true motility disorder, distal esophageal spasm, where we see spasm on a high resolution esophageal manometry study. And if you really find that, you need to send the patient to me or one of my colleagues, because it's very rare. It's less than 1% of all manometry studies. So pain that feels like spasm, very common. We all see it all the time. Whether it's really distal esophageal spasm, very unlikely. Look for reflux. That's usually the biggie. And three-month trial of PPI, let's say we have that three-month window before they're going to see you and they're having some dysphagia, is a PPI trial often a reasonable thing to do? And is three months too long or too short? What do you think about that? Yeah, usually we say about 8 to 12 weeks for a PPI trial. If you have high pretest suspicion for EOE, we have to be a little careful with the PPI trial because 40% of those patients will respond to the PPI. So by the time you do the endoscope, it may be normal. And we won't know if they ever had EOE or not. So I actually am in the business often of peeling off medicines for people and then objectively defining, do they have EOE? As long as I'm not worried about them having a food impaction or something in the meantime. So often I'll have to take them off medicines. And that's another important point we can talk about. We do see a lot of patients where they get the kitchen sink thrown at them with EOE. They're on a PPI, they're on some kind of topical salt, swallowed steroid, and some form of a non-systematic diet elimination. So they come to me on all three. So I have to peel everything back, scope their native esophagus, get accurate scoring systems where we look for all those EOE features, meaning the rings, the furrow train tracks, the swelling, the exudates, get the eosinophil counts. We consider it, as many of you know, above 15 eosinophils is abnormal. And then I figure out what line of treatment I want to go on because we like to streamline to one treatment if we can. The one caveat to that is there is a high overlap between EOE and reflux. Sometimes EOE is secondary to reflux. The initial mucosal hit that the patient gets is reflux damaging their mucosal barrier, and then the EOE food antigens go in and create the allergic response. So in that situation, if the PPI isn't going to put them in histologic and symptomatic remission for EOE and control reflux, then I have to have them on two therapies, one for EOE and then a low-dose PPI for reflux. Paul, do you know what they call the EOE rings? I see you have a friend recording with you there, so I thought you'd enjoy this. Don't tell me. You're dying to say. I think they call them a feline esophagus, right? Isn't that one of the things? Because it looks like the rings on a cat's tail, Paul. I thought of you when I was reading that. I appreciate that. Paul's going to love that. And he has his cat in his lap right now. All right. Alayna, what is next here for Quinn? Yeah. So Quinn gets an EGD. And as many of us might have suspected, she has some esophageal rings and pathology of her distal esophagus shows increased epithelial eosinophils with a peak of 100 eosinophils per high power field. Overall findings consistent with eosinophilic esophagitis. She has started on topical steroids and her symptoms improve. So I think very quickly, just to recap, I know we've talked a lot about EOE, but is there anything else needed beyond the pathology to make the diagnosis, or is that enough? So it's a clinical pathologic diagnosis. So they have to have the symptoms. So they need to have dysphagia. In addition, they need to have endoscopic findings. So we have a scoring system that you may see, the endoscopic reference score when you get the reports from us. And so that's where we're looking at the rings, furrows, edema, exudates, and strictures. And then in addition, histologic confirmation. So more than 15 eosinophils from the lower and mid or upper esophagus. And you told us that prior asthma, food allergies, ATP, those are things that would maybe key you in on this. So people that give you a history of food impaction or just anyone who doesn't respond to a PPI, are there any other things you listen for in a history that make you think of that besides any other high-yield ones for us to think about? Yep. Young, food impaction, chasing meals with liquids, last to leave the table. Those are all important ones to think about. All right. And so we treat this patient. She feels better. We are conquering heroes. What kind of follow-up is there at this point? Are we done with the patient, or do need kind of serial monitoring or sort of what do we do from here after they're feeling better? Yeah, critical question. So I'm glad the symptoms are better, but we're not done there. So whenever you initiate treatment for EOE or change treatment, you need to define histologic response. So she has 100 eosinophils.
And so repeat endoscopy with biopsies. So it depends. So in this case, topical steroids. So most of us, when we put our patients on topical steroids, we'll start at a higher dose. And so that's to get induction into remission. And then after 8 or 12 weeks, repeat endoscopy with biopsies to make sure the eosinophils are under 15. Getting patients into remission is in a lot of our guidelines. What to do once they're in remission and on maintenance, we don't have any guidelines. It's all patient and provider dependent. Do we follow them with an esophagram in a year? Do we follow them with repeat biopsies? Do we just do a clinic visit? And you'll ask several GIs or esophagologists and we all have a different answer. Since sometimes endoscopic features can be subtle, you can have very subtle furrows or rings. And it's really important for us as GIs when we biopsy to target those, to look carefully and target them because EOE is patchy. So I could biopsy on the normal segment in between the line or the furrow, and the eosinophils will be normal or under 15, and you won't know what's going on. So it's really a close, careful endoscopic look. But there are cases where a patient has dysphagia, they don't have clear endoscopic features, and they do have EOE. That's less common, but we do have a low threshold to biopsy, even if it looks normal, if our pretest probability is high. Or they may have a stricture. That may be the only feature you see, and it may not be reflux. A Schottky ring or a stricture that looks like a peptic stricture may just be with EOE. Paul or Elena, any other things with this first case that you wanted to go over? Not feeling good. No, yeah. Okay. And I think some of the take-homes were most people with dysphagia, I mean, dysphagia itself is an alarm symptom, so an EGD is warranted, but low threshold to get an esophagram, there's a lot of information you could potentially get from that. And the big buckets we talked about, there's like inflammatory, that could be like an esophagitis from a pill or erosive esophagitis, EOE, motility, that's if the person's saying like dysphagia for liquids and solids, you think about that. And then structural stuff is also in the differential. And ultimately, you have to take a look. You're not going to just diagnose it just by history, especially not where they point to, which is a shame, Paul. Yeah, I know. You're going for it. I'm lament checking with no ATM fees nationwide, 24-7 customer service, and loan options custom made for physicians and trainees at every career stage. Instead of running up credit card debt, try their PRN Personal Loan designed to give you a better way to cover expenses like relocation, board exams, home renovations, or even consolidating high interest debt. Panacea's PRN Personal Loan is funded in as little as 24 hours Thank you. So the next case, we have Jack, who is a 73-year-old gentleman coming in with history of coronary artery disease, hypertension, does have a history of GERD and recurrent falls. He has progressively worsening dysphagia. He describes difficulty swallowing while eating about five times per meal, and he feels like the food is getting stuck in the back of his throat. And he does have symptoms of coughing after swallowing. He kind of points the level of his pharynx as the location of where food frequently gets stuck. So comparing Jack to Quinn definitely has some more of those symptoms that we might associate with oropharyngeal dysphagia with the coughing and feeling like food is stuck as he's eating it very early. So what are some of the common etiologies that you would think about for this patient and any medications that might worsen oropharyngeal dysphagia as well. So the common buckets then for oropharyngeal dysphagia, so we have sort of the structural ENT type issues. So particularly in older patients, they can have cricopharyngeal hypertrophy or BAR. Sometimes they can have an outpouching there too, like a Zanker's diverticulum and malignancy if they're a smoker. Low threshold to send patients to ENT if they're a smoker. I have had patients that have come to me as the initial physician with dysphagia. They were a smoker. Remember on our endoscopy, we don't see the oropharynx well. We do everything we can to get through that area as fast as possible so we don't go in the larynx, right? We're going right into the upper esophageal sphincter. We don't see any of that. So ENT with their laryngoscopy and clinic, they have found, I've sent patients and they've found squamous cancers for me, even ones that were missed outside by ENT. So I have a low threshold for that. Next bucket are neurologic issues. So common things being common, like this guy is high risk for stroke that can cause oropharyngeal dysphagia. Other neurologic things like Parkinson's, myasthenia gravis, and then other myopathies can do that as well. And then I think Elena had asked about medications too. Like do you, like especially the ones with anticholinergic type side effects, I imagine would, you know, like anything that causes dry mouth would do it. Are there any other like big buckets or medications that we should ask about when someone presents like this? Yes, definitely. So one area I have to point out, because it's one of my areas of research and it's becoming more known, is chronic opioids are a big trigger for dysphagia. So we all know about opioid-induced constipation. Even our patients know about that. But now we've learned that opioids actually cause dysphagia, chest pain, heartburn, and they can cause esophageal motility problems, including certain types of spastic achalasia or type 3 achalasia. So that's really important to ask about. We're trying to study this more prospectively, but our retrospective data does show that potentially weaning the dose to reduce the morphine equivalents or weaning them off may help, but we don't have any reversal agents for opioid-induced esophageal dysfunction like we do for, you know, opioid-induced constipation. And then the other things are what you alluded to, like tricyclic antidepressants, SSRIs, especially the TCAs with dry mouth that can really cause dysphagia. And then the other thing we always have to remember, too, is meds that cause pill esophagitis. So you have common things like NSAIDs or potassium pills, certain antibiotics, bisphosphonates, those all can cause dysphagia too from the pillosophagitis. Yeah, doxy is one of the antibiotics, even though it's my favorite. I think it's one of the ones that can do that. Yep. I had no idea about the opioids. And is this, are we seeing this in people on opioids for chronic pain or is this like illicit, like fentanyl use or all of the above? All of the above, but mainly chronic opioids prescribed for pain. If they're on it, usually for at least three months, we've seen a higher rate with oxycodone, hydrocodone, mainly because it has higher morphine equivalent dosing. Tramadol, less likely what we've seen because it's weaker. But we are trying to study this more. So it's something that I'm trying to publicize more because your patients will come to you with dysphagia or reflux symptoms at some point on opioids. And they don't realize it's from the opioid because they're used to focusing on the constipation. So I do like to let people know that we're studying that. Yeah, because Paul, I know you're doing a lot of addiction medicine, buprenorphine. And are you seeing any of that? Or I guess maybe now you'll be peaked. Yeah, I'll probably be a little bit more diligent. I will say that in that space, there's, this is probably a side note that I don't really need to include necessarily, but there's so much comorbid tobacco use that if someone would come to me with dysphagia, I probably would still, I'm not sure I would leap right to the opioid as a possible cause.
But so it's not, but it was nowhere on my radar. Now that we've kind of talked about what are some possible etiologies for Jack's dysphagia, what would be the next best step in evaluating his difficulty swallowing? So like we talked about, and as you mentioned, he was having more difficulty transferring the food in his throat and he was coughing, so we're worried about oropharyngeal dysphagia. So that's when you need to send the patient to the speech pathologist to do what is either a modified barium slash video fluoroscopic swallows, really the same thing, whatever. It's just a different name for it to evaluate further what's going on. Because the endoscopy, as I mentioned, we can't see that area very well. And on esophagram, you can get some information about the cricopharyngias, but you get better information with the focused swallow up top with the speech pathologist. Yeah. And so let's say Jack also doesn't have any smoking history. So we send him directly to speech therapy. He does get a modified barium swallow. The results are really notable for one, silent aspiration with a large bolus of thin liquid and two, severe pharyngeal dysphagia marked by near absent pharyngeal stripping wave, which prevents full epiglottic inversion. So they recommend a modified diet and speech exercises, and he is going to follow up with speech therapy. I think, you know, there's quite a few results in that. So is there anything that we should be more concerned about or that would require additional evaluation or is going forward with speech therapy appropriate? So I'm definitely concerned about the aspiration. That's always the most concerning thing that we can see. So basically his epiglottis isn't covering the larynx properly when he's swallowing. So that's why the barium is getting back and aspirating into the larynx. You'll also see other terms on there. Sometimes they'll use the term penetration versus aspiration. So penetration is basically just a little flash, a little flash of the barium going at the larynx, but aspiration is going all the way in. So we definitely worry about aspiration. So being able to retrain the muscle motions there, and if it is from a stroke, usually over time, as well as the exercises, that can improve. But trying to retrain the muscles there because we don't want them to have an aspiration pneumonia is important. And it's important to work with your speech pathologist, but also a dietician. Because typically it's not exercises in isolation. They need to do the strengthening exercises. They also need to do certain chin tuck and maneuvers to help protect the airway. And in addition, modifying the consistencies of food and liquids to those that the speech pathologist can see are less likely to go into the larynx. This may trigger some of our geriatric, geriatrician listeners. Yeah, I was worried about that. Yeah. Now, have you seen the UCSF geriatrician group, Eric Widera and his friends? They did a thickened liquid challenge for the geriatricians that were prescribing thickened liquids to a lot of their patients. But the one thing he was a fan of, though, I think it was the puree, Paul, right? It's some sort of, one of the modified diets he said is actually quite delicious, which I think it was the puree. I think that's right. I can't remember if we had talked about this in the episode or not, but I used to work in nursing home kitchens for like a decade before actually going to a career in medicine. And I prided myself on the quality of my pureed food. So that sounds right to me. They've got little molds and things can like, if you're serving fish, you can actually like, it's in the shape of a fish, even though it's all pureed up. So it's a lot of great options for texture modification if you're interested in that kind of thing. They help with pills too. Like I mentioned earlier, we're not designed to swallow pills or capsules or things of that shape. Have them put their pill in applesauce and it really spreads the pharynx and the pharyngeal tissue nicely and it's much easier for them to swallow it. Yeah, in primary care, metformin, the higher tablet strength metformin is one of the ones I've had a lot of patients complain about and sometimes potassium tablets too. Classically, I was going to say potassium is invariably complained about as a gigantic pill. Yeah, that's a big one. I do feel like I see a fair amount of people that just like, they have some chronic swallowing dysfunction, but they're not losing weight. There's no major alarm symptoms and they seem to be just like getting by. I'm not sure I always send every single person to where sometimes people just seem to have these transient complaints of dysphagia. And then there'll be like a few months later, they'll be like, oh no, it's better now. I don't know, Paul, if you seem to see that too, but it's not like every person that tells me they have dysphagia is getting an EGD. It just doesn't happen because it's such a common complaint if you're seeing them in primary care. So I hope that's okay, Diane. Yeah, it's okay. I see that too. Sometimes it goes away. I mean, even all of us, let's presume the four of us have normal swallowing. If you eat a giant hamburger and I don't chew it well, you know, you get that tight thing stuck in there every once in a while. We all do that. And sometimes patients tell us about that because they're hypervigilant and want us to know, but I really teased through it. And if it went away, it was one time and they don't have alarm symptoms. It's fine. That happens. So it's okay that you're not sending everyone for testing. Yeah. Okay. So the weight loss, bleeding, recurrent aspiration, pneumonia, you told us those are, those are definite ones that we should, we should think about. So Elena, what else? I know we're kind of coming, coming towards the end. Are we, are we doing anything else for, for Jack, ouryear-old man here? No. Jack goes, he gets some exercises and does pretty well overall and feels like the coughing is improving. And that was really his biggest concern too. And so I think the only other question I had, and we did kind of touch on this, but speaking of patients who maybe have this dysphagia and then they get an EGD and it's normal and they come back to primary care, when is it helpful to think about then getting a motility study or like which of those patients should you send back for a motility evaluation? Yeah. So if the endoscopy is normal and they're having the solid and liquid dysphagia, then I would say you should get the manometry. If they're not having liquid dysphagia, the likelihood it's a motility issue is unlikely. And again, you can rule out achalasia pretty well on an esophagram. So you should be able to see dilation of the esophagus and a narrowing at the lower esophageal sphincter. The gold standard is still manometry to diagnose it, but you can pretty well exclude it with the esophagram if they're not having liquid dysphagia. So that's usually what I would do for that. Paul, fun fact that I was reading about achalasia. Apparently they have trouble belching. Diana, is that because the upper esophageal sphincter is just also tight and just not, they just can't get the air out once it's in there? Yeah, we don't really understand those mechanisms very well. I do see that sometimes. We don't see it quite as often with achalasia. I mean, the ones that we really see it with are the patients that come to me that had anti-reflux surgery. Those are the ones that really can't belch because they had a fundoplication, right? So their stomach cardia is wrapped up tightly and so they can't release the air. So they have a hard time belching. From their stomach. Yeah, from their stomach. So with achalasia, they can still technically belch, but I have seen a little bit of what you're talking about, but we don't really understand all those mechanisms because we still don't understand the etiology of achalasia as well. Okay.
Yeah, no, it's good that we spent a couple of minutes discussing belching specifically on this incredibly rare condition that we're probably not going to make the diagnosis. Yeah, belching's tricky. And remember, there's gastric belching and there's supragastric. And so they're either, you know, air swallowing and then releasing it, that's supragastric versus gastric, which is physiologic. They should be belching because the fundus should be venting the stomach fundus. So if you're not sure about that, just send them to us because we can do impedance testing to figure out what kind of belching it is. And if it's super gastric, we do basically psychotherapy, cognitive behavioral therapy, and diaphragmatic breathing. So those nuances, send them over to us. But when in doubt, diaphragmatic breathing treats a lot of esophageal issues. It treats reflux too, because it helps you contract the diaphragm and keep reflux down. So I think unless Paul and Elena have other questions, I think we're ready to get some take-home points on this. Paul, Elena, last chance, any favorite questions you wanted to ask? Sneezing in yourself like esophagitis? No, I think I'm good. Thank you. All right. So Diana, can you give us a couple favorite take-home points for the listeners from what we talked about this evening? So first, when you ask them about their swallowing, just start open-ended. So when they come to see me, ask, what brought you to come see me? Why are you being referred? And then I'll ask them, tell me about your swallowing. Sometimes in that clip of one minute of what they tell you in a nice, concise story, you actually get a lot of the info. Then I'll go into the granular details we talked about. Is it solids, liquids, pills, multiple things? Is it progressive? Is it intermittent? And are they having alarm symptoms like weight loss, bleeding, aspiration, pneumonia? And then we keep hammering this home, but ask about questions for EOE. Are they compensating? Are they chasing with liquids, last to leave the table? Do they have atopic overlap conditions? It's just very good to hit things that are common. And EOE is very common, like we talked about. So it's something to really make sure that we're not missing. Do you have anything that you would like to plug, any websites, resources related to dysphagia or any work you're doing that you wanted to just make the audience aware of? We have a program at Mayo that's pretty unique. It's a self-dilation program. I'm one of the directors of it. So if you have any patients where they're getting endoscopy after endoscopy after endoscopy for refractory strictures, usually patients that had radiation or the biggies, especially the head and neck cancers, send them to me because we can teach them how to sword swallow. Essentially, I teach them how to pass a bougie dilator in and out one second in the morning. Then they don't have to get an endoscopy sometimes ever again, sometimes maybe in a year instead of every week. And then I have these patients that survive cancer and now they can have their spaghetti and meatballs who are on a feeding tube before. So any refractory stricture, send them our way. Oh my gosh. These people must love you. It's one of the most rewarding parts of my practice. They go from a cancer patient on a feeding tube to eating what they want. So it's initially scary for them, right? It's mind over matter, learning how to pass a tube through their mouth while they're awake. But when they learn and realize how easy they do it in the morning, when they brush their teeth, it's in and out. And they're so grateful. It's a really important part of our practice. I do have one more question. Go ahead. Now, I'm just wondering, like, is this accomplished in one clinic visit? Like, it's pretty fast to teach them or? So we have a video that they watch ahead and then they meet with my nurse and they meet with me. We have dedicated esophagus nurses that help teach them. So yeah, basically over a video and two brief sessions, we can get 99% of patients to do it. It's very rare for us to not be able to. Limitations are more anatomic if I don't think they're a candidate ahead of time when I see the outside endoscopy. But in terms of the willingness of the patient, if they're motivated, I can teach them to do it 99% of the time. As an esophagologist, as our expert, it sounds like it's dysphagia, not dysphagia. I just, I feel like that's something that I've debated with for years now. Have I been mispronouncing the entire time? I don't know if there's different regional dialects. I'm from Chicago, so I have a little bit of a Chicago accent, but I say dysphagia. That's what I think most people say, but it's not wrong for you to say dysphagia. It sounds more elegant, doesn't it? I mean, it does. And you're from New York, Pennsylvania. Yeah. All right. This is a great place to end. Thank you so much, Diana, for all your time and teaching. This has been fantastic. Thank you so much for having me. I really appreciate it. And we're committed to high value practice changing knowledge. And to do that, we want your feedback. So please subscribe, rate and review the show. You can find us on YouTube, Spotify or Apple podcasts. You can also send an email to askcurbsiders at gmail.com. A reminder that this and most episodes are available for CME credit through vcuhealth at curbsiders.vcuhealth.org. And I wanted to give a special thanks to Dr. Elena Gibson for helping to write and produce this episode. And our technical production is done by the team at PodPaste. Elizabeth Proto runs our social media and Stuart Brigham composed our theme music. And with all that, until next time, I've been Dr. Matthew Frank Watto. Helena Gibson here. It always delights me. I don't know why. And as always, I remain Dr. Paul Nelson Williams. Thank you and goodbye.
The increased reliance on digital tools in patient care has elevated the importance of digital inclusion for promoting health equity in the United States. The recently passed Infrastructure Investment and Jobs Act, although not focused on health care, could present opportunities to advance digital inclusion. I'm Stephen Morrissey, Managing Editor of the New England Journal of Medicine, and I'm talking with Jorge Rodriguez, a hospitalist at Brigham and Women's Hospital and an instructor at Harvard Medical School. Dr. Rodriguez has co-authored a perspective article about the infrastructure law and why digital inclusion is a healthcare issue. Dr. Rodriguez, could you start by explaining why digital inclusion is important? How did digital redlining and other policies and practices hinder access to health tools in marginalized communities? I think the main point here with digital inclusion is that increasingly we're seeing healthcare systems become quote-unquote digital first. And along with that, I don't think there's been as much of a focus on being digitally inclusive first. And I think that as we've seen throughout the pandemic with the rise of telehealth and patient portals playing an increasing role, we've seen these significant gaps develop in which marginalized populations don't have use or access to these tools. And it really goes back to the communities that they're part of, the broadband infrastructure that they live in, the affordability of the internet, the affordability of devices, their ability to interact with all these tools. All the components that we think about with digital inclusion really drive at the fact that if we're really going to commit to being a quote-unquote digital first healthcare system, we really have to, right along that same path, be digitally inclusive first, or else we're just going to extend the disparities that already exist in so many other places in the healthcare system. What steps have individual health systems taken to try to address some of these barriers and not be sustainable or may not be applicable to certain, for example, smaller clinics that may not have the funding to say, I'm going to start giving everyone a device and internet access and really forces us to zoom out and say, okay, this is clearly a community issue. This is clearly a component of the way we deliver care across the community. And what can we do to better address that? My sense is that interventions like that, that are very healthcare focused, are just not going to be a sustainable way to ensure digital inclusion. You write in your perspective article that the Infrastructure Investment and Jobs Act takes away much of the responsibility for building digital infrastructure from these individual healthcare organizations and makes digital inclusion a public concern. So what components of the law are relevant to the healthcare sector? There's a whole area around digital equity, and the main focus of it is $65 billion for digital inclusion initiatives. There's about $42.5 billion, which specifically invests in actually like broadband infrastructure. So the laying down of wire or satellite, whatever it is to actually build out internet access in communities that may lack it. And then it has $14.2 billion to focus on affordability. So now that you may have internet set up in a community, can patients actually afford it? And it uses those funds to create a $30 a month subsidy term, the Affordable Connectivity Program, which also includes $100 towards a device, which is nice. And then interestingly, it also includes $2.8 billion towards the creation of digital literacy programs. So it seems to show a real good understanding of the challenges that healthcare systems and patients are facing and bridging that gap between we have telehealth and like getting it out to patients. So I think those are the kind of key funding pieces. And then the last point I'll mention, which was very kind of progressive for me to see and exciting to see, was it actually encourages the FCC to look at digital discrimination or digital redlining in the way internet service providers are actually deploying and developing some of these internet services in marginalized communities to make sure they're not either not offering enough speed in certain areas or offering very high cost in certain areas. So I think it takes a multi-pronged approach, what I think is a really nice way for healthcare systems to now be able to be more active participants and also be able to deploy that kind of digital first dream to some extent. Looking at digital literacy, you talk in your article about the role of healthcare organizations in partnering with community-based programs can have to encourage digital literacy. What could those kinds of collaborations look like? I think it really comes down to looking at the healthcare organization as like one touch point or one player in this larger spectrum of digital literacy. If you think about digital literacy, it really sort of goes to the point of being able to interact meaningfully with whatever device or computer technology is in front of you. And that not only affects your health, but also affects education, workforce development, your civic engagement. And so I think some of the things that I imagine working well would be, I've now engaged a patient or talked to a patient about the fact that they had trouble using a video visit, for example. I've been able to support them to do a video visit and now got them interested in technology as a part of their life. Can I now refer them to a local class for English learners who's also doing workforce development and teaching people how to use Microsoft Office to help them apply for jobs, help them sign up to vote? Can I now help them apply for schooling that they may need? So those kind of things where there's a lot of great community organizations that have been doing this for such a long time. And it really helps us promote the fact that like the healthcare system doesn't have to reinvent this. They can go out to the local libraries, the community organizations to make those connections. I really view it as sort of like a touch point to get folks interested in this can also be used for your health, but also for other areas. And can you then say, I'm going to now refer you to this community organization that sort of knows the digital literacy space even better and can impact these broader aspects of your life, which in the end, as we all know, and we think about this context of social determinants of health, then feed back into the patient's overall health. So I think there's a lot of opportunity there that this bill lays the foundation for. You say in your article that healthcare organizations will need to address additional barriers that aren't covered in this new law in order to create an inclusive system. So what steps do you envision them taking? I think the other components here are, one is, I think there's a big opportunity from like a data perspective. One, there's, we sort of know that a lot of the current data around internet access is limited or not granular enough, or just a little bit unreliable. So I think there's an opportunity for healthcare organizations to, as a lot of healthcare organizations are gathering that data, they're asking patients, do you have device? Do you have internet? Can you use it? So that's really powerful data that you can then bring back to policymakers and folks that are administering a lot of the funding that comes with it to say, here's the data that we have as a healthcare organization. Here are the gaps, here are the communities that are really lacking affordable broadband, here's where you should put your efforts. I think there's a component of kind of like data is power that I think that health organizations can bring to the table. The other component that connects with that is really around the impact. A lot of this push kind of goes with some level of a sense that by providing patients better access to technology, we're going to improve their healthcare outcomes. But the only way to be able to look at that is for healthcare organizations to then go back similarly and say, okay, we undertook, you know, as a community, undertook this Broadband Funding Act, and we built out the broadband infrastructure in this area. And we were able to get up and running a diabetes monitoring program. And our diabetes outcomes got a lot better. Look at the impact that broadband had on this community. And being able to kind of feed that back to policymakers, I think will be another key component for healthcare systems to play. The other piece that I'd say it doesn't address is really a lot of the platforms that healthcare relies on. So a lot of the telehealth platforms platforms or a lot of the patient portals that patients see. So it doesn't really address those pieces. So I think healthcare systems going back to like EHR vendors, for example, encouraging them to build kind of culturally and linguistically tailored tools is another component with a healthcare system. Even if you had the best infrastructure in place and the devices and the internet, there is some component where that there's some work to be done there. And then the last part I mentioned goes back to making sure that we're really addressing a lot of the existing disparities that we aim to address with a lot of the digital tools that we're implementing. So I think it's very important. And in the end, going back to patients and saying, is this the right tool for you? And making sure that we have multimodal components.
One patient was like, wow, this is the best thing ever. I love this patient portal. And the other patient was like, I need an email for this. I don't really want an email. I'm perfectly living my life without email. And being able to be flexible in that way is the other piece of this that the infrastructure bill doesn't necessarily address. But I think it's important for healthcare systems to maintain that kind of multimodal components of care. Finally, if we imagine that this new law is a first step, what additional policy changes do you think will be needed to support digital inclusion? And how can physicians and healthcare organizations help ensure that policies most effectively address inequity in this area? I think there's a big component, especially in the telehealth space, around reimbursement and reimbursement across different types of modalities, like video versus audio, as compared to in-person. So there's that component to it. There's other components that a lot of other folks have talked about around interstate licensing laws and kind of simplifying those pieces to it. So I think those are important just from like making sure that the kind of reimbursement and licensing side of the world are addressed. But I think the biggest thing that healthcare systems can do are really be active participants, have a seat at the table in these discussions with the FCC, with internet service providers, with EHR vendors, and really coming together to say, we're taking this kind of digital inclusion as a key component as we're thinking about a digital first approach. And I think this infrastructure bill really encourages that to happen. Thank you, Dr. Rodriguez.
From the JAMA Network, this is the JAMA Editor's Summary, a review of important research, viewpoints, and review articles appearing in the latest JAMA issue. I'm Dr. Kirsten Bibbins-Domingo, Editor-in-Chief of JAMA, and I hope you find this week's issue beneficial. Here's your host, Dr. Christopher Seymour. Hello, and welcome to this edition of the JAMA Editor Summary Podcast for the March 5th, 2024 issue of JAMA. I'm your host, Dr. Christopher Seymour, Associate Professor of Critical Care and Emergency Medicine at the University of Pittsburgh and Associate Editor at JAMA. Let's begin with the original investigations. This week's issue includes three research articles and two research letters. The first research article by Dr. Bakris and colleagues is titled RNA Interference with Zilabicerin for Mild to Moderate Hypertension, the CARDIA-1 randomized clinical trial. Zilabicerin is an investigational RNA interference therapeutic that targets hepatic angiotensin synthesis, a key regulator of blood pressure. This Phase II randomized double-blind study examined the safety and efficacy of different zilobicerin dosing regimens for the treatment of mild to moderate hypertension. Participants with daytime mean ambulatory systolic blood pressure of 135 to 160 millimeters of mercury after antihypertensive washout were recruited from 78 sites in Canada, the Ukraine, UK, and the US, and randomly assigned to receive one of four subcutaneous zilobesarin regimens, 150, 300, or 600 milligrams once every six months, or 300 milligrams once every 3 months, or placebo once every 3 months for 6 months. Among the 394 participants, treatment with zilobicerin at all doses significantly reduced 24-hour mean ambulatory systolic blood pressure at 3 and 6 months. Non-serious drug-related adverse events occurred in 16.9% of zilobucerin-treated participants, principally injection site reactions and mild hyperkalemia, and 8% of placebo-treated participants. Dr. Ernesto Schifrin has an accompanying editorial titled RNA Injection Every Six Months to Improve Adherence and Lower Blood Pressure in Patients with Hypertension. Dr. Schifrin anticipates that if shown to produce sustained blood pressure lowering, treatment with an injection every six months could help achieve goal blood pressure in patients who do not adhere to currently prescribed antihypertensive treatment and represents a significant improvement in outcomes for people with hypertension. The second research article by Dr. Siraj and colleagues is titled Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles. There is clinical evidence for benefit of endovascular thrombectomy in patients with large acute ischemic stroke, but limited data on how outcomes may vary based on the extent of ischemic core or perfusion mismatch. This exploratory analysis of the SELECT-2 trial examined the relationship between imaging estimates of irreversibly injured core brain and at-risk mismatch regions of penumbral tissue and clinical outcomes of endovascular thrombectomy treatment. SELECT-2 was a randomized clinical trial that enrolled 352 adults from 31 global centers who had acute ischemic stroke due to occlusion of the internal carotid artery, or M1 segment, of the middle cerebral artery and a large ischemic core, and randomly assigned them to endovascular thrombectomy within 24 hours from stroke onset versus standard medical management. In this exploratory analysis, non-contrast computed tomography images of the brain were scored to define levels of ischemic injury and volume of brain with severely reduced blood flow was identified on computed tomography perfusion or restricted diffusion on magnetic resonance imaging. At 90 days, endovascular thrombectomy improved clinical outcomes across a wide spectrum of infarct volumes compared with medical management only, although enrollment of patients with minimal penumbra volume was low. In patients treated with endovascular thrombectomy, clinical outcomes worsened as presenting ischemic injury estimates increased. The investigators concluded that large ischemic core volume is an important prognostic factor to consider when individualizing treatment decisions. Dr. Zimberto Pensato, Rhonda Lunn, and Andrew Demchuk have an accompanying editorial titled Thrombectomy in Medium to Large Ischemic Core. Do Patients Still Need to Be Selected? Given the substantial cost and resources required for endovascular thrombectomy, the select two trials' high rates of poor functional outcomes, underrepresentation of patients lacking core penumbra mismatch, and non-significant effect in patients with very large ischemic strokes, the editorialists call for more extensive evaluation of pooled imaging data and additional trials before moving to a simpler imaging paradigm to select patients for endovascular thrombectomy. The third research article by Dr. Case-Macher is titled Time to Treatment with Intravenous Thrombolysis Before Thromboectomy and Functional Outcomes in Acute Ischemic Stroke, a Meta-Analysis. The benefit of intravenous thrombolysis for acute ischemic stroke declines with longer time from symptom onset, but it is unknown whether a similar time dependency exists for intravenous thrombolysis followed by thrombectomy. This individual participant data meta-analysis of six randomized clinical trials examined whether the benefit of intravenous thrombolysis followed by thrombectomy for acute ischemic stroke was modified by the time from stroke symptom onset to treatment. The selected trials compared intravenous thrombolysis plus thrombectomy versus thrombectomy alone among 2,313 patients enrolled from 190 sites in 15 countries who had anterior circulation large vessel occlusion presented directly to thrombectomy-capable stroke centers and were eligible for both treatments. The median time from symptom onset to expected administration of intravenous thrombolysis was 2 hours and 28 minutes. The investigators found that compared with thrombectomy alone, intravenous thrombolysis plus thrombectomy was significantly associated with a favorable shift in functional outcome at 90 days if the time from symptom onset to expected administration of intravenous thrombolysis was within 2 hours and 20 minutes. Thereafter, there was no statistically significant association. The first research letter by Dr. Al-Hairy is titled Delivery Device Patents on GLP-1 Receptor Agonists. Nearly all glucon-like peptide 1, or GLP-1, receptor agonists approved by the U.S. Food and Drug Administration for type 2 diabetes and weight management are drug-device combinations containing active ingredients sold together with the delivery devices. This study analyzed FDA-listed patents on GLP-1 receptor agonists and found that brand-name manufacturers listed dozens of device patents with the FDA that were disconnected from active drug products. These patents contributed to large patent thickets, a situation where many patents are directed towards the same product and served as a basis for litigation against potential generic GLP-1 manufacturers. The second research letter by Dr. Anderson and colleagues is titled Trends in Phenylephrine and Pseudoephedrine Sales in the U.S. Existing data does not show that oral phenylephrine is an effective nasal decongestant, and the U.S. Food and Drug Administration is considering removing it from the market. This serial cross-sectional study evaluated patterns of oral decongestant purchasing in the U.S., including phenylephrine and pseudoephedrine products, and found that between 2012 and 2021, phenylephrine was the most commonly purchased oral decongestant, and sales remained stable during this time. The researchers suggest that if the FDA removes oral phenylephrine from the market, clinicians and consumers could consider oral pseudoephedrine or intranasal decongestants as alternatives. Let's turn to the two viewpoints in this week's issue. The first viewpoint by Dr. Robert Roswell, Erica Johnson, and Rajiv Jain is titled Maintenance of Certification, the Value to Patients and Physicians. Some physicians question the benefits of maintenance of certification, but the viewpoint authors argue that evidence has shown that patients who are cared for by physicians who demonstrate more medical knowledge through certification and maintenance of certification have a better prognosis for a host of important outcomes. The authors propose that by participating in maintenance of certification, physicians can reassure patients, colleagues, and themselves that they are doing what they need to stay current in medical knowledge and practice. The second viewpoint by Dr. Salvatore Mangione, Maria Basil, and Stephen Post is titled Out of Touch. The authors lament the demise of the physical examination for the art of medicine and question if the patient-physician relationship has been hurt by the loss of physical contact and reduced eye-to-eye interaction. The authors propose that in these times of epidemic loneliness and declining empathy, touch may have enormous benefits. In this week's clinical review and education section, Drs. Frederick Ruberg and Matthew Maurer review cardiac amyloidosis due to transthyretin protein. Systemic amyloidosis from transthyretin protein, known as ATTR, is the most common type of amyloidosis that causes cardiomyopathy.
In the U.S., up to 150,000 people have heart failure due to ATTR amyloidosis. The diagnosis can be made using serum-free light chain assay and immunofixation electrophoresis combined with cardiac nuclear scintigraphy. Loop diuretics are the primary symptomatic treatment for patients with ATTR heart failure. Tifamidis is the only currently approved ATTR-directed therapy, and compared with placebo, its slowed progression of ATTR amyloidosis improved survival and prevented hospitalization. Thank you. In an editorial titled Communicating Medicine, a new JAMA series, JAMA Associate Editor Dr. Ann Coppola and JAMA Editor-in-Chief Dr. Kirsten Bibbins-Domingo launched the new JAMA Insights series titled Communicating Medicine, a forum to introduce strategies for the clinician to improve communication of medicine and health-related topics to patients. JAMA invites submissions for this series. This week's Insights by Dr. Joseph Capella and Richard Street Jr. is titled Delivering Effective Messages in the Patient-Clinician Encounter. The authors discuss four strategies for clinicians to share credible and clear health information with their patients. Uncover patient beliefs and knowledge, provide accurate and understandable information, promote the credibility of information, and check for shared understanding. In an Associated Author Interview podcast, Dr. Coppola interviews Insights authors Capella and Street. A JAMA patient page covers the topic of childhood leukemia, the most common type of cancer that JAMA. A link to this issue can be found in the episode description. This is JAMA Associate Editor, Dr. Christopher Seymour. And for more podcasts, please visit jamanetworkaudio.com. You can also listen and follow wherever you get your podcasts. This episode was produced by Daniel Morrow.
Hello and welcome to the Annals of Internal Medicine podcast. I'm Dr. Christine Lane, Annals Editor-in-Chief, with highlights from the June 18th issue of the journal. But first, a few words about some articles that we published online first since the last podcast. The first is the U.S. Preventive Services Task Force recommendation on preventing child maltreatment. Child abuse or neglect affected more than 680,000 children in the U.S. in 2011, and an estimated 1,500 died as a result of maltreatment. Survivors of abuse face potentially significant health, emotional, and behavioral consequences. Physicians and other health care providers who care for children and for families are uniquely poised to identify children at risk for abuse and neglect during well checks and other visits. Thank you. which is generally considered to be a community-based service provided to at-risk families. The evidence for interventions in primary care is limited and inconsistent, and therefore the task force concluded that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. Thus, the task force cannot recommend either for or against these interventions. These recommendations apply only to screening children without signs or symptoms that indicate possible maltreatment. Of course, if a physician or other health care provider has reason to suspect child maltreatment, they should investigate further. The next online FIRST article found that diabetes patients on Medicare Part D were two to three times more likely to be prescribed brand-name drugs than comparable patients receiving care within the U.S. Department of Veterans Affairs, at an added cost of about $1 billion per year. Of the four medication groups used by patients with diabetes, Medicare beneficiaries were more than twice as likely as VA patients to use brand-name drugs in almost every region of the country, Since strong evidence shows similar effectiveness of generic and brand-name drugs among the diabetes drug classes included in the study, switching to generics would improve efficiency without harming the quality of care or access to effective medications. On April 15, 2013, the U.S. Supreme Court heard oral arguments to address the question, Are human genes patentable, and is expected to deliver its ruling by the end of June. The case centers on patents held by myriad genetics that underlie testing for inherited risk of breast and ovarian cancer attributable to two genes, BRCA1 and BRCA2. On June 11th, we published an online first, Ideas and Opinions Commentary, by Robert Cook-Deegan of Duke University. He reviews the history of this case and predicts how the court will rule. Go to annals.org for his prediction. You can also view a video of Dr. Cook-Deegan discussing the case. Now on to the June 18th issue. The optimal management of men with low-risk localized prostate cancer is a topic of great debate. The first article in the June 18th issue is a cost-effectiveness analysis that compared watchful waiting or active surveillance with active treatment at initial diagnosis. With watchful waiting, physicians observe men without monitoring and provide palliative treatment if the disease becomes symptomatic. Active surveillance follows men closely with serial PSA tests, rectal examinations, and biopsies. The researchers conclude from their model that observation is more effective and less costly than initial treatment and that watchful waiting is the most effective and least expensive approach over a broad range of clinical scenarios. Sensitivity analyses showed that treatments would need to be markedly more effective than current options for this conclusion to be overturned. Go to annals.org to read the article. You can also test your knowledge and earn CME credit by completing the associated quiz. For patients with a new diagnosis of atrial fibrillation, anticoagulant therapy options include warfarin, a vitamin K antagonist, or one of the newer agents, dabigatran, apixaban, or rivaroxaban. For those with atrial fibrillation already receiving warfarin, options include continuing warfarin or transitioning to one of the newer drugs. The second article in the June 18th issue is a subgroup analysis of a trial that found rivaroxaban non-inferior to vitamin K antagonists for anticoagulation in patients with atrial fibrillation. The analysis report in this issue compared patients already receiving a vitamin K antagonist at randomization to those who were vitamin K antagonists naive. Patients receiving rivaroxaban resulted in more bleeding events in the first seven days of therapy, but fewer events after 30 days of therapy. These findings may be useful to clinicians considering a transition to rivaroxaban for patients who are already receiving vitamin K antagonist therapy. Some antibiotics increase blood values of commonly prescribed statins by inhibiting the liver enzymes that metabolize them. The next article reports a population-based study that used linked healthcare databases in Ontario, Canada to measure the frequency of statin toxicity after co-prescription of a statin with clarithromycin or erythromycin. The researchers found that older people taking statins who were prescribed clarithromycin or erythromycin had more hospitalizations for rhabdomyolysis and acute kidney injury and higher all-course mortality than those prescribed azithromycin. These findings suggest that clinicians should consider prescribing an antibiotic other than clarithromycin or erythromycin for older patients taking a statin. Next in the issue is a group of very interesting articles, two systematic reviews with meta-analyses and four editorials related to a very unique project. The clinical issue under study is the effectiveness and safety of recombinant human bone morphogenetic protein 2, or RHBNP2, an orthobiologic agent used to promote bone growth in spinal surgery. RHBNP2 is widely used to promote fusion in spinal surgery. However, in 2011, a review of publicly available data suggested that the risk of adverse events with RHBNP2 was 10 to 50 times higher than reported in trial publications. In this issue, we published two independent reanalyses of data on RHBNP2. These analyses used patient-level trial data provided via an unprecedented data release by Medtronic,porated, the medical device company that manufactures RHBNP2. Medtronic provided the data to the Yale University Open Data Access Project. Rather than analyzing the data themselves, the Yale researchers identified two teams of systematic review experts, one at Oregon Health and Science University and the other at University of York in England, via an open competitive process to perform two independent analyses of all RHBMP2 trial data. To maintain the independence of the two reviews, Annals of Internal Medicine used two separate teams to review the manuscripts, and neither team had access to the other manuscript or associated materials until after both articles were accepted for publication. While there are few differences in the reviews, both have the same bottom line, that in spinal fusion, RHBMT2 does not result in clinically significant improvement in pain or function at 24 months and was associated with an increased risk of adverse events. The researchers cited lack of blinding of surgeons, patients, and outcome assessors and conflicts of interest as the main sources of potential bias in the initial trial reports. Along with both articles, Annals has made available materials related to our review process, including the initial and all revised versions of the manuscripts, reviewer comments, and correspondence between the editors and authors, providing a unique view into the peer review process. The trial data used in these reviews is available through the Yale Open Data Access Project, and the link to obtain these data is available in the articles on annals.org. There are also four editorials that provide perspectives on the systematic reviews and the data sharing that made them possible. Thank you. and the systematic reviews. Even if RHBMP2 is not of particular clinical interest to you, the project is a historic event in data sharing, and I'm sure that you'll find it interesting. This issue also includes an update that summarizes studies published in 2012 that the authors consider highly relevant to the practice of endocrinology, a commentary on planning for acute unscheduled care, and an on-being-a-doctor essay. And as always, the second issue of the month includes ACP Journal Club. Go to annals.org for summaries of a dozen recent studies that your internal medicine colleagues judge to be of high quality and high clinical relevance. And if you haven't yet registered for ACP JournalWise, go to journalwise.org to do so. This service will send alerts to your smartphone on topics and from journals that you select at a frequency that you set. That's all for this issue. Thanks for listening, and I'll hope you'll return on July 2nd to hear about the next Annals issue. Thanks to Beth Jenkinson, Neil Cole, and Andrew Langman for their technical support.
Hello and welcome to the Lancet podcast. I'm Richard Lane on Friday, September 3rd. Did you know, and I didn't, that 2010 is the year of the lung? Well, this week's issue of the Lancet, which is dated September 4th to the 10th, is rich in pulmonary content relating to asthma and other respiratory diseases, ahead of the European Respiratory Society meeting taking place in Barcelona between September 18th and 22nd. The World Health Organization estimate that 300 million people worldwide are affected by asthma, and vulnerable groups, particularly young children and elderly people, can be especially difficult to treat. Two reviews in this week's issue focus on these groups, for which asthma is associated with considerable morbidity and mortality, and is characterised by scarce data from research. With an ageing population, the prevalence of asthma is set to soar among older groups over the next few years, yet diagnosis is often overlooked because of comorbidities, the underreporting of symptoms, insufficient use of lung function testing, and also often the overlap between asthma and chronic obstructive pulmonary disease. In a review in this week's issue, Peter Gibson and colleagues take a close look at asthma in ageing populations, and they take an integrative approach to the understanding and management of asthma in the elderly age groups. One of the main problems being that elderly people are nearly always excluded from research into asthma because of the age restrictions for trial entry, comorbidities and smoking history. At the other end of the age spectrum, Andrew Bush and Seija Siglani focus on the management of paediatric asthma that is not receptive to treatment. One of the main issues concerning asthma in young children is that severe asthma is often misdiagnosed and adherence to treatment is difficult. Also in this week's issue relating to respiratory disease, a research article which details how a simple questionnaire could reduce the impact of anaesthesia in young children. Also research about whether oxygen or room air should be given to patients with dyspnea, in other words severe breathlessness, in end-of-life care. Look out for an interesting comment by Richard Beasley calling for the withdrawal of monotherapy for long-acting beta agonists. Such therapy is only effective when used concomitantly with steroids. Why not a combination inhaler containing both the beta agonist and the steroid? And talking of inhalers, this week's profile written by my colleague Tony Kirby is about Heather Zahr who is a leading respiratory paediatrician in South Africa. Here's a short clip of her describing a novel approach for producing an inhaler from plastic bottles which is suitable for young children. That inhaler that you've got, that asthma inhaler, as you know you've got to push it and breathe in, synchronise your breathing in with depressing the... Children can't do that. Also anyone who's tight from an asthma attack can't do that. So they need to attach what's called a spacer to the end of the asthma pump. And there are a whole lot of commercially produced spacers, but they're relatively expensive. So what we developed is we took a 500ml plastic bottle and we melted a hole in the bottom exactly the same size and shape as the asthma pump. Put the asthma pump into that bottom and then either the child can hold the bottle in their mouth, the other end, or you can put a mask on the end of the bottle and put that over the child's face for a smaller child. And so it enables children to effectively use asthma pumps. And to show that this was effective, we had to do quite sophisticated studies, although it's a very simple device. We had to do aerosol deposition studies, we had to do clinical studies and lung function testing, and so on. In fact, one of the major articles is published in The Lawns, which was the clinical trial in older children. Very low-cost, simple device that has enabled inhaled therapy for children widely. And do read the full profile in the Perspectives section. She is a fascinating person. And there is plenty of other content relating to asthma and respiratory diseases in other parts of the journal. Though just to sign off with a non-asthma item, this week's case report details an unusual case of Legionnaire's disease caused by exposure to garden compost. It's well worth a read. Well, that's all for this week. Many thanks for listening. See you next time.
Hello, my name is Shelly McGill and I'm a medical officer in the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention in Atlanta. Inappropriate antibiotic use contributes to adverse effects in hospitalized patients and other complications and it also contributes to the emergence and spread of resistant organisms. In order to know how best to improve antibiotic use in hospitals, we need to understand the epidemiology of that use. So we need to get a better understanding of the types of drugs that are being used, how common that use is, and the reasons why different antibiotics are being used. For this particular survey, we wanted to understand the prevalence of antibiotic use in a large sample of acute care hospitals in the United States. We wanted to understand the distribution of the different types of antimicrobial classes and specific antimicrobial agents that were being used. And for those different specific drugs and classes, we wanted to understand the different reasons why they were being used. In addition for those drugs that were being administered to treat infections we wanted to describe the types of infections they were being prescribed for and the settings in which those infections had their onset whether they were community onset or healthcare onset infections. So it was a cross-sectional survey of patients in the hospital. We did point prevalence surveys. So these were one-day surveys that were done in each of the participating hospitals. We worked with the Emerging Infections Program to conduct the survey. And the Emerging Infections Program, or the EIP, is a CDC network of 10 state health departments and their academic and other partners. Our colleagues in the EIP sites recruited up to 25 hospitals within their specific catchment area and in each of those 25 hospitals we surveyed a certain number of patients depending on how big the hospital was. So overall we ended up with 183 hospitals across those 10 EIP sites participating and a total of 11,282 patients. The surveys were conducted between May and September of 2011 so each of the 183 hospitals participating selected a specific single day during that time period that they would conduct the survey. Of the 11,282 patients that were surveyed, 5,635 patients were on antibiotic therapy at the time of the survey. So that's about 50% of all of the patients. And when we looked at those patients who are on antibiotics at the time of the survey, about half of them were getting a single antibiotic drug and about half of them were getting two or more antibiotic drugs. We also looked at the different reasons why antibiotics were being prescribed and we found that the vast majority of antibiotic use, approximately 78%, was for treatment of infections. Smaller proportions of the antimicrobial drugs were being used for surgical prophylaxis and for medical prophylaxis and then very small proportions were being used for either non-infection related reasons or for reasons that just weren't documented in the medical record. When we looked at those drugs being given specifically to treat infections, we found that the most common drug overall was parenteral vancomycin and then following parenteral vancomycin, the most common drugs were ceftriaxone, piperacillin, tezobactam, and levofloxacin. Those four drugs were commonly used for both healthcare facility onset infections and for community onset infections. They were also among the most commonly used drugs for patients in the intensive care unit and patients outside of the intensive care unit. So those broad spectrum drugs and drugs that we typically think of as being used to treat more resistant pathogens are being used in settings where resistant pathogens are not perhaps quite as common as they might be in the ICU and in infections that have their onset in healthcare settings. We think that the data from this survey serve as a foundation for assessing opportunities to improve antibiotic use in hospitals. One of the things that we did not attempt to do in this particular survey was to assess the quality of antimicrobial prescribing for individual patients. That's a very complex undertaking and it's something that we would like to understand more about. This survey provides us with a foundation that we can use to then develop additional tools that hospitals can use to evaluate whether antibiotic use is correct or incorrect in specific patients. And that's really our next step is working with the information that we now have for those common drugs and those most common infection syndromes for which antibiotics are prescribed to develop tools that can be used to assess the appropriateness of use in specific circumstances.
From the JAMA Network, this is Conversations with Dr. Bauchner, interviews featuring researchers and thinkers in healthcare about their publications in the latest issue of JAMA. Hello and welcome to this author interview. This is Howard Bauchner, Editor-in-Chief, and I'm joined by David Naylor, who is a Canadian physician, a medical researcher, and was president of the University of Toronto between 2005 and 2013. David is also a member of the National Academy of Medicine, having been elected in 2005. David, welcome. Thank you, Howard. Delighted to be here and to be speaking with you again. Before we start, I just want our listeners to understand that David used to be on the editorial board of JAMA, and then a few years ago, he joined the Journal Oversight Committee. And the Journal Oversight Committee provides an evaluation of my performance each year, although because of my relationship with the American Medical Association and my contract, even though the JOC evaluates me, I continue to have editorial independence. Before we start, I just want to reflect a bit on my relationship with David. First, David is a remarkable writer, and even his emails are erudite. So if you ever get a chance, you really want to have an email exchange with David. He's also one of the preeminent physicians in the world. He's had a remarkable career, first as a physician who trained both at the University of Toronto and then at Oxford, then Dean of Medicine and Vice Provost at the University of Toronto, and then as President of the University of Toronto. But David had a very interesting experience in 2003, which I think would be interesting to just spend five or ten minutes on before we get to the viewpoint. Now, the viewpoint is entitled The Evolution of Schools of Thought in Medicine, and we'll return to that. But David, in 2003, you were chair of the National Advisory Committee on SARS and Public Health. And given the coronavirus outbreak currently in China, can you talk a little bit about what that was like and how you think the SARS outbreak compares to the coronavirus epidemic. Howard, it was a very unsettling time with tremendous uncertainty. In sharp contrast to where we are now with the virus sequence quite quickly and the sequence available for replication of serological testing all over the world, it took a considerable period of time before we had the genetic code of the virus. So a lot of the guesswork about case identification is now being vitiated by that advance. At the same time, I would say that this virus is spreading faster than we saw with SARS, and the case counts are already way up compared to a similar period of time with SARS. Again, uncertainty in both counts as to when exactly this epidemic started. Let's acknowledge that. The case fatality rates look pretty similar, but it's too early to tell. And again, case identification uncertainty adds to some clouding of those numbers, but certainly lower than Middle Eastern respiratory syndrome, which had very high case fatality rates. So there's a real sense of deja vu on some levels and real uncertainties on others. Certainly in Canada and in Toronto, SARS paralyzed our medical system. Hospitals were largely on lockdown. All elective surgery was cancelled. We more or less suspended a lot of the medical education activities of the medical school. And then the review afterwards, when the outbreak abated, really led to a lot of soul-searching about how municipal, provincial, and federal authorities had worked together, or not work together in all honesty to combat the outbreak. And a big overhaul ensued. We had creation of a health agency to deal with public health issues in Ontario. But most importantly, we had the creation of the Public Health Agency of Canada. And for the first time, a public health officer who would be the chief advisor to the National Minister of Health. So a lot of changes in process, in politics, and a real wake-up call in terms of clear communications. And I'm seeing a lot of that play out on an improved basis with this outbreak. We've had a couple of cases in Canada now that are being confirmed. I expect more will come. So we seem to be in better shape. I think the world is in better shape. But the last thing I'd say is, despite the advances in science, we still don't have a magic bullet for this virus. We're still using a couple of antiretroviral compounds with some uncertainty as to whether it'll be useful. And by the same token, we're still relying on old-fashioned public health, quarantine, tracking cases, isolation, all those measures, including protective gear for health workers and families to make headway in containing the outbreak. So 21st century science and 19th century public health measures combined, but we seem to be further ahead. And I hope we get a vaccine in the next three months or so, which again was unthinkable 16 years, 17 years ago when SARS hit. So some progress, some similarities, lots of grounds for concern, but I think we are further ahead and I'm cautiously optimistic. Yeah, it's interesting. I spoke to Tony Fauci for about 25, 30 minutes the other day. We did a live stream and then it's now on a podcast. And I think he had similar feelings. You know, he's lived through HIV, SARS, MIRV, and then a number of the more malignant flu outbreaks. And he's guardedly optimistic about a workable vaccine in three to four months, although there was an announcement today that one of the larger pharmaceutical houses thought closer to a year, but that we can sequence so quickly. The offending organism is remarkable, and it's really a tribute to scientists around the world that it was made publicly available for people to begin to use so that they could try to develop a vaccine. Yep, it's encouraging, but I think we're all chastened a bit by how fast this has spread, by the rapid rise in case counts, and by the mortality toll to date. And certainly, I think everyone understands that this is a real nightmare for our colleagues and fellow citizens of the world in China. So let's turn to a different story, which is your viewpoint. As I've already mentioned, it's entitled The Evolution of Schools of Thought in Medicine, Healthy Tensions. And I wanted to read the subtitles so that people will be able to follow the discussion for the next 20, 25 minutes. The first is Scientific Medicine as a unifying force. The second is 20th century challenges. The third is epidemiology-based medicine rises. The fourth, more new medicines, biology bites back. And then the conclusion, back to the future. So David, why did you write the viewpoint? I think it's so important in a time when there's a lot of churn in the world, a lot of feelings of this being an unsettled period in human history, and for us to think about where we are and where we've come from. And for a profession like ours, which has global reach, and where we're immersed day to day in very busy lives of clinical care, education, research, whatever it is, I think it helps to have that sense of where we actually have traveled over the last century where so much has happened to us. And of course, we're in an incredibly exciting period of transition in medical care with technology and science burgeoning at a breakneck pace. So this was really a kind of exercise in mapping where we've been more or less in the last century. And I think that helps particularly for younger physicians who have grown up in this period and may not know how it relates, but for all of us who are very busy to reflect a bit on how we got here. It's interesting because, you know, we've had so many conversations. I've often said that there's been more changes in medical publishing in the last decade or two than there were in the previous 100 years. I hadn't thought about that. The same may be able to be said about medicine and science, that they're very in that regard. So, you start with scientific medicine as a unifying force. You acknowledge three prominent time periods, the 1830s, then of course the really famous book by Osler in 1892, Principles and Practice of Medicine, and then of, Flexner's now famous 1910 review of U.S. and Canadian medical schools. Can you take us through this time period, scientific medicine as a unifying force? Certainly. You know, medical history is often written as, you know, great men, great ideas, great discoveries. And unfortunately, it's almost always men. And that kind of punch biopsy of centuries is really not a good way to understand how slow things were. Lewis Thomas called medicine the youngest science for a reason.
And really the emergence of bacteriology and the glimmerings of basic science that started in that century began to change the way people approached medicine. Osler's great epoch was really based very much on skepticism more than anything else. He was accused of being a sort of terrible skeptic by some of his colleagues. Because what he did was he looked at the available practices with a critical eye and concluded that for most of them there was no real basis, no real evidence as we would call it today. So his landmark textbook in 1892 was in so many ways just a listing of the need to provide supportive care, a dose of doctor, and an acknowledgement that the conventional wisdom actually had very little to it. And that period was also notable because the new sciences meant that his school, what was called the New School at that time, also rejected what had been caricatured as allopathy. Remember, homeopathy was popular at the time, the notion of dilution of medicines to extraordinary degrees, treating like with like. Not a lot of science there, obviously. But it was popular because mainstream medicine really was tremendously harmful. There was bleeding, there was purging, there was surgery without proper asepsis and without proper anesthetic. It was not a pretty period. So the founder of homeopathy, Hahnemann, called that allopathy, treating things with different medicines, whereas homeopathy was like with like. And so that terminology was really used to pigeonhole the prevailing or conventional wisdom. Oster rejected allopathy as strongly as he rejected all the various what were called sectarian modes of practice at the time and embraced the new sciences, called for medicine to become scientific, called for teaching at the bedside. It was a revolution in thinking with more and more medical schools realizing they had to be connected to science, connected to universities, and they had to be connected to hospitals. So it was a huge transformation, and people lose sight of the fact that until really the early 20th century, there was no profession in medicine quite as we know it today. There is no unification, except as occurred in those years around science. And the basis for medicine was profoundly unscientific. So this was a period of shaking of foundations. Klebschner comes in at a critical period when a lot of the groundwork, a lot of the skepticism has taken hold, a lot of mainstream practitioners and academic experts, they are rethinkingthinking medical practice and says, you know, it's time for everyone who practices on this sort of dogmatic basis, including mainstream allopaths to down tools and for us to get together and focus on a much more scientific basis for medical practice. And if you haven't read his book, I'd say to any listeners, go through the Flexner Report. It is a spectacularly written report. It is still timely. It's called for thinking critically for a scientific outlook on how we do things. And it's also absolutely scathing in its assessment of some of the practices of the day and very brave and bold. So that really was the kickstart of the modern era of medicine. And after that, we had the new school often called not only scientific medicine, but modern medicine really had its roots then. And the modern profession really is quite young. Do you think the Flexner Report, which I have read and was in part sponsored by the AMA, something they're quite proud of, do you think that sense, yes, I think Osler's work was catalytic. I think the emergence of Hopkins as a center for bedside teaching was catalytic. But I think there were a lot of players who contributed across many schools, particularly in the U.S., to a lesser extent in Canada, to that catalytic moment that Flexner seized when he toured and visited so many of the schools on both sides of the border, and frankly pronounced in very scathing terms on almost all of them. Well, after the Flexner Report, you've already talked about the new school, and then you jump to the 1960s and the 1970s, describing it under the title 20th Century Challenges, with a number of different issues, prevention versus care and cure. And then interestingly, in the 60s and 70s, a plea by Osler and Peabody for medical care to stay humane and person-centered. We could say we're returning to that in 2020 because of machine learning, AI, and technology, but we'll leave that for another day. So what's worth commenting about regarding the 20th century challenges, the early or the mid-20th century challenges? I would say, Howard, that from about 1915 to the mid-60s, there was something of a consensus around scientific medicine. A lot of the thinking was grounded in physiological and biochemical research. Molecular biology was just gaining momentum at the time. The first randomized trials of real substance were not done by Hill until really the mid-40s. So much of what would eventually shake the foundations of medicine was still pretty vestigial. And there was a very strong consensus around what I would call a pathophysiological model. The 60s, of course, were a period when everything was challenged. Everything was up for grabs. And so we had criticism of medicine and its misuse of resources for poorly validated treatments. We had the early emergence of clinical epidemiology and its critique of practices that were not evidence-based. We had health economists arguing that medicine was not well organized and healthcare required an overhaul. So from many streams of thought, there came this criticism of how medicine was organized, but also the scientific foundations for how physicians did their work. In that period, one of the themes, of course, was why not more prevention? And quite intriguingly, even in the 60s and 70s, you saw that movement split in two streams. There were those who said, let's do more clinical prevention. And there were others who started to talk about what we now call the population health model, which was looking at broad determinants from a social standpoint, an environmental standpoint, to understand how we could, through broad social policies or environmental policies, address the causes of the causes. So it was a tremendous time of churn. And in that period, I think we saw the glimmerings of what has become epidemiology-based medicine, as I've termed it, which we often refer to as evidence-based medicine today. So a tremendous transition, but really molecular biology was still very much in its infancy and epidemiology-based medicine was just taking hold. It was interesting your comment about the causes of the causes. Periodically, you know, we get a lot of viewpoints about social determinants of health, and I try to point out repeatedly, it's not a very new concept. It's certainly been articulated somewhat differently in the last maybe five or eight years. But, you know, my training was at Boston Medical Center, then Boston City Hospital. And, you know, that was in the 70s and early 80s, and social determinants of health were quite prominent three or four decades ago. You then turn to epidemiology-based medicine. And all the familiar names that I grew up with. I think I've mentioned to our listeners, I was a pediatric clinical scholar at Yale. But then there's Archie Cochran, David Sackett, Alvin Feinstein, the birth of evidence-based medicine that really starts in Canada, interestingly enough. But JAMA gives it light because of the JAMA EBM series, although it's all written by Canadians, which I always felt like JAMA got the benefit. We didn't really introduce EBM. We just published the papers. That's a Drummond Rennie gift to JAMA. But can you talk about epidemiology-based medicine in the 60s and 70s? Sure. It was a very exciting time, and I graduated from medical school in the 70s, so I remember just how, even at a fine medical school at the University of Toronto, how the bedside teaching was really about eponyms and memory work and syndromic descriptions. What a joy it was to begin to have attempts to understand these phenomena in a more quantitative and rigorous way and to think about treatments that actually had been tested experimentally through randomized designs. It was a very exciting period, particularly obviously in Canada where there was so much churn, but no shortage of activity in the UK or the US. What was intriguing is that the reaction of mainstream medicine was not particularly favorable. There was a lot of resentment. The argument one heard was, we've been practicing evidence-based medicine. We've been doing science-based medicine. Why should we be doing this cookbook stuff and wedded to numbers? And what's intriguing when I fast forward 25 years is some of the response today of clinical epidemiologists and EBM adherents feels a little bit like the way the mainstream responded to us all those years ago when we become the mainstream. These things do change over time.
Herman Rennie, as you mentioned, was a tremendous champion. The series which Gord Guyot spearheaded was great fun. You'll remember also evidence-based physical examination or rational clinical examination had started then with Dave Simmel. So JAMA really was at the forefront of moving all that along. And many of us got a lot of great exposure publishing in JAMA as young faculty members back then, thanks to that nurturing environment that JAMA created. As I said, I was always struck when I read the series because it wasn't JAMA, but it was largely written by Canadians and people from the UK. So I always thought that was interesting. I mean, the McMaster group has been the center and the focus of EBM now for four decades. It's an extraordinary group led by many different people. But then you move on, and I love the title of the next section, More New Medicines, Biology Bites Back. So part of what prompted me to write was this sense of churn. We have this 50-year sweep of scientific modern medicine, and then the renegades come along talking about evidence-based medicine or epidemiology-based medicine, perhaps more accurately. And then suddenly people start to realize that medicine based on averages and measures of central tendency more generally, the effect sizes of one type to another with uncertainty, are not necessarily easy to apply to individuals. And of course, when you look at the literature right from the start, everyone acknowledged that epidemiology was the science of populations. And much of medicine, not all of course, but much of medicine is about treating individuals. So this question of how to apply evidence derived from populations to individuals has been one of the challenges that evidence-based medicine faced really from the outset, and it was never really fully resolved very happily. Once you have more detailed characterization of patients, enabled by advances in genetics, growth of all the biomarkers, and then, of course, digitization of everything so that we have an enormous proliferation of data sources to begin to make sense of health and illness. Then we have this rapid emergence of what are, to some extent, counter forces, all focused on increasing individuation. So we've had evidence-based medicine based on epidemiology and populations, then we hear about molecular medicine, then we hear about personalized medicine, then we hear about precision medicine, and suddenly we have this proliferation of medicines. The fun thing about this, Howard, is that through these decades, there's always been what I'll call humanistic sentinels. Back in the early part of the century, it would have been Cabot and Peabody. Before that, of course, Osler bridged both humanities and sciences beautifully. In the 50s and 60s and 70s, it was sometimes ethicists like Paul Ramsey and Stanley Joel Reiser. a British psychiatrist named Michael Belant also championed the patient as person. And then we move through, and in the 90s, Tricia Greenhalgh was very influential with narrative-based medicine, which is still a stream people pay attention to, reminding us that the patient has a narrative. These are not passive physiological constructs. These are people who are living an experience of illness, not just a disease, and their families live it with them and their friends live it with them. So those streams all are part of this attempt to remind us continuously of humanism. And of course, today we have people like Abraham Berghese, who's been so eloquent, some of Adil Gawande's writings, and latterly, deep medicine, Thank you. deep learning using data science to individualize care, we have to have a bond to patients. We have to connect with them, build deep personal relationships, and of course that's Eric Topol's contribution. So there's been this other stream, this counterforce to science and technology that is so important, and that really is a lovely thread that I think runs through a lot of these periods with the sentinels, I'll call them, who keep reminding us that ultimately it's about the patient as a person. I was so fortunate in 2011 to come to JAMA. And I think my predecessors at JAMA have really tried to hold and I've tried to continue to hold that balance. So clinical trials are very important to me. Evidence-based medicine is very important and how that continues to evolve. But JAMA's had a peace of my mind series for 40 years. And I won't tell everyone about what's planned as a 40th anniversary, but there's a unique issue of JAMA coming in the spring that I think will please many people who love the series and really want to make sure we retain that balance of humanism and how it's expressed in narrative medicine. You conclude the viewpoint with the statement, these developments lead to consideration of several important tensions in medicine, all arguably healthy. You list six of these. I may add one or two, but do you want to talk about the tensions that you clearly are quite comfortable saying are healthy that exist in medicine today, David? Yeah, one of them is that we're seeing with all these currents of science, and I would add the admixture of social science, and of course the humanities, that medicine has really become a tremendously convergent field. You have people in the UK and the US talking about 4P medicine with this sense that we now have personalized preemptive or preventive participatory medicine that is really pulling a variety of disciplines together to make sense of health and illness. So I think we have to understand that this convergence also means that there's going to be some churn as regards what medical truth is, that no one really is going to be able to claim they own evidence in quite the same way given how things have changed and that's healthy. The people who focus on personalized medicine may say, well, those of you who do clinical epidemiology and I'm one of them and I'm an apologetic clinical epidemiologist, you're doing range finding. We do the really precise work. The clinical epidemiologist may say, well, you know, very little that goes on is actually that personalized. Someone has to figure out whether this stuff works. So there'll be lots of positive tensions, and I think they're healthy. The other thing is that this is a very different type of sectarianism than we saw in the 19th century and early 20th century. That was based on ignorance. This proliferation of different types of medicine in schools of thought is a byproduct of amazing progress. I think it's exciting, it's positive, and I really believe the people who are able to navigate these different paradigms, who can be the Rosetta Stones who translate modes of thought back and forth We're going to be very positive contributors, not only to practice and education, but some of the greatest researchers will be capitalizing on this period. So it's all positive. I do think that we are going to find that making decisions is not any easier because there'll be so much evidence, and a lot of it will not change the fact that uncertainty is Malthusian. I don't describe it that way in this paper, but elsewhere I've talked about the fact that when you have so many different tests and treatments, that combining them, the order, how to use them together, creates not arithmetic but geometric uncertainty. We can't test all of them. We can't test the sequences and combinations. The same is true for different types of evidence. So we're going to have to be a lot more humble about what evidence is and how it drives things. And I said basically that we're going to be less able to talk about evidence-based decisions and we're going to have to talk more about evidence-informed decisions because values and trade-offs and patients' preferences and even political perspectives are going to come into things. The fourth tension that I think is important is to acknowledge divergence. And I think having honest disagreements is healthy. It's sort of epistemic pathfinding. And the example I give, as you know, Howard, is that if we think about the determinants model, where we're getting to grips with environmental and social and behavioral factors that make some people healthy and others unwell, that's one mode of thinking that is very promising still. And yet I see a lot of talk about so-called precision prevention. Well, that's going to be pretty expensive. It's almost at cross-purposes with the notion of doing things on a broad population scale to have maximum impact. So that conversation needs to happen about what we mean by prevention in an era of molecular medicine. The fifth element is simply a bit of a caution about the move to personalization and precision medicine. I'm a fan. I believe firmly that we have to go that route, that the imprecision of epidemiology and evidence-based medicine has to be tempered by much more precise characterization of individuals. And at some point, we're going to find more and more of our diseases break down into an array of specific biomarker-driven subtypes with different treatments. So things are going to get complicated.
We can grumble a little bit about whether evidence-based medicine needs a bit of a tune-up, but these quantitative tools, particularly some of the new data sciences and machine learning methods, are going to be invaluable. And last, back to what I said earlier about this enduring core of medicine, the humistic core. Now I'll simply read what I wrote, and that is, whether they construe disease as an abstract pathophysiological, biomolecular, epidemiological, or algorithmic construct, future physicians will need to understand illness as the lived experience of patients and their loved ones. I have just two additional comments and then a closing point to make. The tension that we see at JAMA in original investigations as well as in viewpoints is this notion of population health versus individual health. Certainly precision medicine in the realm of cancer has led to substantial gains. I think sometimes those gains are somewhat overstated, but certainly in certain cancers, certain fields, you know, the molecular basis of treatment has really advanced dramatically over the last five to 10 years. But at the population level, as people know, as we've written in our pages, life expectancy has declined in the United States. You know, that's an enormously sad comment. And 40% of individuals in the U.S. who are hypertensive are either unrecognized or not treated. So if you really wanted to make great gains in population health, it wouldn't be the genes of cancer. It would really be to understand more common diseases and ensure that people are treated. And then, of course, there's the entire field of nutrition and exercise and healthy living. The other more contemporary issue is the politicalization of health in the United States. And I don't think it's only in the United States. I think in decades past, health, health care, health policy somewhat walled off from the politics of a country. I think that's no longer true. And I'm frightened by that. I'm not entirely sure where it will lead. It's always been around the margins. It's possible that it's more stressful now in the United States than it has been in the past, but I am concerned about that. And then to reflect on your sixth point, which is so beautifully written, for me, the core, the atom of being a clinician, physician, is that remarkably intimate and personal relationship that a clinician creates with a patient and their family. It is the emotional center of being a clinician, and we have to ensure that it's never lost, despite all the technology and the devices and the drugs. Because if we lose that, I think we will lose the trust that patients have in clinicians. I think that's very eloquently put. And part of this is a dose of doctor, that time-honored concept. And to maintain that, it does require being present in the clinical encounter. And I really respect the way Abraham Berghese has talked about the eye patient and the insidious role of some of the electronic health records and the head down on the keyboard rather than connecting with the patient. We have created some conditions that are not winning for the next generation to really enjoy those connections with patients and family. I also have a lot of confidence in them. They're the digital natives and eventually I think they will rediscover not only the joy but the value, not just the patients but themselves, of that kind of narrative construction done jointly. One of the things I emphasize to young physician leaders is that part of being connected is to learn about yourself, to have your own narrative, to build your own resilience've been talking to David Naylor, who often describes himself to me as a country physician from Canada. I would say David is much more than that. He's the former Dean of Medicine and Vice Provost at the University of Toronto, the former President of the University of Toronto between 2005 and 2013, international member of the National Academy of Medicine, and a remarkable individual. David, thanks so much for jamanetworkaudio.com. You can listen and subscribe wherever you get your podcasts.
From the JAMA Network, this is JAMA Otolaryngology Head and Neck Surgery Author Interviews. Conversations with authors exploring the latest clinical research, reviews, and opinions featured in JAMA Otolaryngology Head and Neck Surgery. Hello and welcome to this latest JAMA Otolaryngology Author Interview from the JAMA Network. I'm Dr. Michael Johns, online editor for JAMA Otolaryngology Head and Neck Surgery. Today, we have Dr. Alfred Iloretta with us. He is assistant professor in the Department of Otolaryngology at the Eichen School of Medicine at Mount Sinai in New York. He is senior author on an interesting study entitled Association of Surgical and Hospital Volume and Patient Characteristics with the 30-Day Readmission Rates in Otolaryngology Procedures. Look for it today in this week's JAMA Otolaryngology Online First. Welcome, Dr. Iloretta. Thank you for joining us today. It's a pleasure to have you with us. Thanks for having me. Okay, I really enjoyed reading your study published this week in JAMA Otolaryngology. Your work is particularly salient given our society's collective need to manage rising costs of delivering healthcare in a resource-limited environment. Would you mind giving the listeners some background? How did you become interested in the topic? Why is it important to look at readmission rates in general and otolaryngology specifically? So I have the privilege of training in a major urban population such as New York City, practicing here and doing residence here. We had experiences in a variety of settings, including major tertiary care center like Mount Sinai, multiple community-based practices, as well as city hospitals that had incredibly diverse patient populations from each other. For example, Elmhurst, Queens is the most ethnically diverse urban area in the world. In anecdotally, throughout training, we noticed that there were differences that we thought in our post-operative outcomes from area to area or hospital to hospital. So as an attending or once I've developed my practice, we decided to look in these differences using multiple large databases, patient-set databases. And we started on looking at the epistaxis population and the pituitary surgery population using the SPARKS database or the NISQIP database. From our experience there, we've kind of taken that to look at essentially otolaryngology as a practice in general and as well as subspecialties. The importance of third-day readmissions is really a marker of a quality of care. It's been shown in several other publications, New England Journal and The Lancet, within the general surgery population. So we wanted to look at this in otolaryngology or ENT specifically. So in our practice, you know, a lot of us do quality of life surgery. And unfortunately, we don't have a large database that reflects these patient reported outcomes that we need. So the best that we can do right now, I feel, looking at a population in general is looking at 30-day readmissions. And this has been done previously in some other papers, looking at parotid surgery, for example, or acoustic neuroma surgery. Got it. So when we reflect about adverse outcomes in surgery, usually more than one factor is involved in these. So what do you do in this investigation to dig into the details? So there are volume associations that have been seen with high volume surgeons on high volume centers or centers of excellence that have been shown to have a significant effect on surgical outcomes. In this study, we looked at a variety of variables. So surgeon in hospital volume is something that we looked at, and it's been found to drive positive surgical outcomes. In addition, we looked at the patient level characteristics, such as age, sex, socioeconomic status, income, insurance, private versus Medicaid, race, ethnicity, and other existing medical comorbidities. What we did is we used what's called the SPARCS database. It's a New York state-based database. It's a comprehensive all-payer data reporting system that is required by all Article 28 facilities in New York. So this includes essentially any public or private institution with inpatients. All inpatients are required to be reported within this system. And taking that database that we had, we used the procedural codes, also known as CPT codes, to identify the otolaryngology procedures, kind of index procedures. And we looked at this data set between the years of 1995 and 2015. And then we took those CPT codes and we put them in silos according to otolaryngology subspecialties such as head and neck cancer, laryngology, rhinology, pediatrics, etc. That's what piqued my interest in your study is that you not only looked at surgeon volume, but you looked at hospital-level factors and patient-level factors. You can imagine there's scenarios out there where there's very high-volume surgeons who are taking care of really high-acuity patients, and despite their volumes, they still may end up with adverse outcomes for factors that are perhaps outside of their control. So tell us about your findings in general in each of those domains, the hospital level factors, the surgeon level factors, and the patient level factors. So what we did is we broke up the surgeon volume and hospital volume into three categories, high, moderate, and low. So high volume being 100th to 75th percentile, moderate 75th to 50th, and then low 50 and below. And then what we did is we used a univariate logistical regression to look at the relationship between all those independent variables and the 30-day readmission. And then the variables that we found significant within that analysis, we plugged into a univariate analysis that takes those multiple variables and put in a multivariate logistical regression to associate their interplan, their association with 30-day readmission. So what we found is surgeon volumes have a significant relation to a readmission. So high volume surgeons for all procedure types had a significant correlation with improved outcomes or a lower admission rate. So it was 8% readmission rate on the low volume surgeon versus the high volume surgeon having a 5% readmission rate. And that was further enhanced in the multivariate analysis, which showed a 24% increase or chance of them having a patient coming back with a 30-day readmission. Got it. And that seems clinically significant too. Absolutely. Interestingly enough, we did not find a significant correlation with hospital volume, but we would like to think that surgeons with significant experience do take advantage of the optimized perioperative care. So that's something that we would likely roll into having an effect on the decreased readmission rates. At the patient level, we saw higher odds of readmission were associated with male gender, a higher comorbidity score, and lower income. In addition, Medicaid and Medicare insurance increased the likelihood of readmission relative to private or commercial insurers. And then we also saw several comorbidities such as alcohol abuse, anemia, CHF depression, hypertension, presence of metastatic cancer, and renal failure, which increased their likelihood of readmission. Got it. So these are individuals who are sicker, who have less financial resources, presumably. which kind of alludes to these are overall just sicker patients in general. Then what we did is looked at the readmissions within the subspecialties, and we found that the subspecialties, including laryngology, head and neck cancer, and rhinology, had a higher preponderance of patients requiring readmission. And looking at this even further, the reason it's already been published, or someone has also described this in rhinology, but the patients having inpatient surgery for laryngology, which is a largely outpatient-based practice, as well as rhinology, tend to be sicker. So these patients that are admitted or taken to the hospital for surgery, you would think that they would have a higher chance of coming back for remission because of their systemic or other comorbidities that they have at that point. And that kind of makes sense too. And then, so then how does otology fit into the equation? That's a specialty that runs the gamut from really straightforward procedures we'd expect to know readmissions or any admissions to very invasive procedures at high risk. Where did otology stand in the mix? For their patient population, it was mainly CPA-angled tumors or lateral skull-based tumors, which were patients that were readmitted. For the most part, they were on the lower end of the spectrum in terms of readmissions for the procedures, like they do a decreased complexity of the patients. Their patients really didn't need inpatient surgery.
So this kind of tells us that there is a critical pointer screening that could be potentially done to improve the readmission rate specifically in this patient population or within the specialty. Yeah, so tell us more about that. What is your kind of summary of the data, maybe in general and perhaps for specific subspecialties, and what recommendations can you share based on these findings? So we found that overall socioeconomic factors, patient comorbidities, surgeon volume were significant predictors of 30-day readmission. In this study, and looking back, there are multiple system-level changes that need to occur to improve our outcomes. I think it's important that we implement development of practices that can identify, monitor, and coordinate early postoperative medical care for these at-risk populations by identifying them and then diverting their care or enhancing their care to reduce these readmissions and improve overall outcomes, such as the allocation of additional resources and incentives to hospital to treat these at-risk populations. Something that we've actually done in our group specifically, we actually rewarded a grant recently, and what we've done is developed a program to optimize our perioperative care for our skull-based patients in general. So what we've done is essentially created a perioperative pathway, kind of analogous to Google Maps or kind of ways that we all use to drive around in our cars for navigating the steps before and after surgery. Our program's kind of tailored to these at-risk populations by being multilingual. So right now we have Spanish, Mandarin, Cantonese, and Arabic. Yeah, it includes essentially reminders. So initially, the second the patient is scheduled for surgery, even before that right now, they get a video of what anterior and lateral skull base surgery is very, very basic. It's almost at the fifth greater level is what we kind of trying to aim the videos towards using illustrations, nothing too grotesque. So we can ensure that everyone kind of understands or maximizes the opportunity for them to understand because, you know, the main job that we do in preoperative counseling is really education. In addition, it includes reminders for them to go get clearances from cardiac or pulmonary, for example. And even more importantly, what it is includes videos on the importance of postoperative instruction. So for anterior skull base, for example, irrigations are very critical to their overall outcome. So we've shown videos on their proper technique and also educational videos to tell them why it is important for them to do their irrigations post-operatively. And within this program, we've also enfolded an infrastructure to kind of monitor how they're engaged. So we can track how many times they've clicked on the video, as well as we've enfolded patient reported outcomes, such as the SNOT 22 score to show how severe their postoperative disease is. And ideally, this program would kind of red flag any patients that weren't being compliant or maybe flaring up so that we could optimize them before they require an ER visit or admitted for a postoperative infection or anything like that. Well, that's pretty interesting. That's a nice example of how you can take data that you've synthesized and presented here and create practical application to better our patients. Leveraging process, leveraging technology, I think that's pretty neat. I look forward to hearing more about that. Any final messages for our listeners? Yeah, and I think your work can be a model for the rest of us to apply in our own institutions. Absolutely. Dr. Iloretta, thank you so much for your time today and an interesting discussion on readmission rates and otolaryngology procedures and their relevance to our specialty. Thanks for having me. It's been a privilege to be able to discuss my research and the work that we're doing. And thank you for listening to this JAMA Otolaryngology Author interview podcast. To subscribe and listen to more podcasts, go to jamanetworkaudio.com.
From the JAMA Network, this is JAMA Pediatrics Author Interviews, conversations with authors exploring the latest clinical research, reviews, and opinions featured in JAMA Pediatrics. Hello again, podcast listeners. This is Dimitri Christakis, Editor-in-Chief of JAMA Pediatrics. With me, as always, my colleague, dear friend, and associate editor, Dr. Allison Galbraith from Boston Medical Center. Hi, Allie. How are you? Hi, I'm good. How are you? I'm great. And this is going to be, I think, our fourth or fifth podcast in the new format. Yes, new and exciting. That hopefully everyone has come to appreciate. And in this format, we bring on an expert to discuss with us an important pediatric topic using an article we've recently published as a springboard. And today's expert is Dr. Melissa Gilkey, who is a social and behavioral scientist on faculty at the University of North Carolina Gillings School of Global Public Health. And she is one of the leading HPV vaccine researchers in the United States. And we've brought her on to talk about HPV vaccination. Hi, Melissa. Good to have you here. Hi, thank you for having me. I'm really pleased to join. Great. So, Allie, what made us think of bringing Melissa on this month? Yeah, so we have two papers that actually touch on HPV vaccination from a little bit different perspectives. So the first one is called Multi-Level Implementation Strategies for Adolescent Human Papillomavirus Vaccine Uptake. It's by Vinnie Rutten and colleagues from Mayo Clinic in Yale. And so we'll talk about this, but HPV vaccine uptake is suboptimal. And so in this study, they used a cluster randomized controlled trial with a step wedge factorial design to test the effect of two evidence-based interventions on vaccination rates among more than 9,000 11 to 12-year-old children in six primary care practices that are part of the Mayo Clinic. So they did the intervention in steps. So they had no intervention and then one of them and then both. And so basically the two interventions were one was a reminder recall to the parents after the child's 11th birthday. And then the other was an audit and feedback for providers about their own personal success with vaccine uptake. I think it was through the mail to them. So what they found is for usual care, there was only 22% of the kids who got a dose of HPV. The reminder recall, there were 35% who got a dose and the provider feedback alone was 30% and both together were 40%. So the odds of HPV vaccination were significantly higher for reminder recall and also for the combination, but not any different for just the provider feedback alone. And not very good overall anyway. to look at both initiation and completion of HPV vaccine series before age 13. And so they just documented the rates, which are also like not ideal, although they have been improving. Basically, the initiation rates and the completion rates have gone up between 2018 and 2021 in both males and females. But they're still the majority of 13 year olds did not complete the series. Melissa, let's start with the elephant in the room. the question you probably get asked all the time, why are the rates so low? I guess I would start with kind of a qualifier that they are low. They have been getting steadily better over time. So when we look at older kids, 13 to 17 year olds, about three quarters start the HPV vaccine series, which is much better than it was 10 years ago. Less than two-thirds, I think it's 63%, actually complete the series. So we have been steadily getting better over time. And I think that's due to a really huge investment by CDC and AAP and others. But we still really do, as we saw in the White Study, have an issue with guideline consistent HPV vaccination or completion on time. So I just want to note that it's not a totally bleak picture. Like things have been steadily getting better. You're a glass half full kind of person. A glass half full. Yeah. I mean, this is an issue that as a country we've really been working on. There has just been really strong support, especially from CDC, for a long time. And so I think that's important. It has been working more slowly than we would like, but it has been working. But in terms of what makes HPV vaccination harder than Tdap or meningococcal vaccination, which are also delivered to that same age group, but much higher in terms of coverage, I think of a couple different things. One is suboptimal or weak communication by physicians and nurses when it comes to recommending HPV vaccination. Parents do turn HPV vaccination down more often than other vaccines. They tend to go on to get it later if they have another opportunity, but that creates a kind of snag in the system. I would say we have a not very supportive policy environment since not many states require HPV vaccination to get into middle school. And then there's some more structural issues around inaccessibility of vaccination data and that kind of thing. What role do you think vaccine hesitancy, and especially now in the post-pandemic environment, you know, anti-vax sentiment, how much does that play into HPV, do you think? I would say that it is definitely a factor, but not always in the way that people imagine. I think when people think about vaccine hesitancy, they tend to think about what some people call anti-vaxxers, people who are really dead set against vaccination, who have really deep-rooted concerns about it and just are really going to be hard to convince. There is certainly some of that with any vaccine, but what's much, much more common is that parents may just be a little ambivalent about it. They're not sure that their kids really need it. They're just not sure about it. And then that's really compounded if the physician or nurse doesn't seem sure about it either, right? If they're not recommending it with the confidence that they recommend with other vaccines. But I think what's really interesting about HPV vaccination is that if you look at parents who initially decline it, the majority of them go on to get it for their child or plan to do so. So we did a survey, this has been a number of years ago, with parents who said the first time they were offered HPV vaccination, they declined it. And over two-thirds of them either had gotten the vaccine by the time that we surveyed them, or they plan to get to it in the next year. And so I think that's different from how we sometimes conceptualize vaccine hesitancy. Is this really, again, like this really deeply felt fear or concern? It's more about ambivalence and sometimes parents just need more time. I think of it as maybe potentially cognitive dissonance. I mean, I think the idea that HPV vaccination has associated with it, the transmission route, which is, you know, sexual, is something that puts front and center in the parent of an 11-year-old, something that they just don't even want to think about. You know, I mean, it's funny because the hepatitis B vaccine, which we give to infants, is also transmitted through sex. And when you have that conversation with a parent of an infant, as I do in the nursery, it's so far away, right, that we even make a joke of it. We say, well, you know, they're not going to be at risk for this for a long time unless they get a transfusion between now and then. But it's just best to do it. And I mean, is that the distinguishing thing here? It's kind of like, okay, and now we do the hep B vaccination. I think, Melissa, you did work on this, right? If you announce something versus if you have a conversation. And so I think people think they should have a conversation about HPV and maybe people are more ambivalent. Whereas if you're just like, this is what we're going to do. This is what we always do. Or if you just say it's a cancer vaccine and don't tell them how it protects against cancer. Yeah, I would say it's both things. Pediatricians definitely say that that 11 to 12 year old age is tricky, right? Because there's just such a diversity in how their patients are presenting, that some of them seem much more mature and that others are kind of still coming in with their American Girl doll or that kind of thing. That's what I've heard one pediatrician say. So it's not a uniform population at all. But I do think that some of it is also physicians and nurses being overly concerned that the parent will have a bad reaction or that they'll be implying something about their child needing the vaccine.
So it might sound something like, oh, you know, your child needs Tdap and meningococcal vaccines for school. And then there's HPV vaccine. And it's not that they didn't believe in it. And it's not that they ever said anything bad about it. But it was that kind of damning by faint praise, right? They just talked about it differently in a way that if you were a parent, you could understand thinking, well, what's wrong with that vaccine, right? Why is there that long pause? And why is it offered as an optional thing as opposed to what it is, which is part of routine care? That presages the next question, which you alluded to before, which is why, and maybe the answer is the same, but why is it not mandated? I mean, it's a communicable disease. It's obviously communicated in a different way. Is that the pushback? Is it that it's a sex vaccine and school districts can't even bring themselves to suggest that it needs to be done? So it does have to do with because those school entry requirements are enacted at the jurisdiction level by states, for example, part of it is just what the priorities of that state are. There are some jurisdictions that have enacted school entry requirements. Rhode Island, which has always done really well in terms of vaccination coverage, but now has the highest coverage in the U.S., enacted them a few years back. Also, Virginia, Washington, D.C., and then more recently, Puerto Rico and Hawaii. And did they see the rates become comparable to everything else then? I mean, did it really work? So it's interesting, the early evaluations of school entry requirements didn't look that great. And in part, people suspected that they had such generous opt-out provisions within the requirement that they just weren't really doing their job. And then you can also imagine 10 years ago when rates were really low, that would be a lot of work, right, for a school district to actually enforce the requirement. However, more recent studies, especially in Rhode Island, show some promise. So I actually feel really optimistic about school entry requirements, and I hope to do a little bit of research in that area myself. Although the mandate issue, I think, is hard because of COVID vaccination and mandates about that too. Those requirements were one of the few interventions that really work, but there can be a political cost and an implementation cost to making them happen. And so you have to balance those two things, which is going to vary a lot by state. You talked about implementation costs. This study that we just saw, that was a lot of work to do reminder recall. It's a lot of work to do audit feedback. Where do you think is the most bang for the buck with those kinds of interventions at a practice level or at a parent level or provider level? I think definitely at the practice and provider level. And I think we're in this interesting moment in which primary care has consolidated so much, right? Even in the time that I've been working in this field, there aren't really private practices anymore in pediatrics the way there used to be. The health systems are getting kind of bigger and bigger and bigger. And I think there are opportunities there. My hope is that with those bigger systems, that practices will have better QI infrastructure, that they'll have better data, that they can do audit and feedback, for example, and that they have people whose job it is to help them. I think the downside is the other shift that I've seen in the time I've been doing this work is just the kind of fee-for-service model. You know, the culture of these systems differ a lot. In the past couple of years, we've definitely heard a lot of physicians say, I can't participate in a quality improvement project. I can't do your training because I'm worried about my RVUs and my system won't give me the permission that I need to do this work outside of my role in patient care. So there are pluses and minuses, but my hope is that the infrastructure is really going to help. And I think it's such an exciting study and it just demonstrates what a really high functioning healthcare system can do if they put their mind to it, right? Like they did three years of intervention work. That's really great and unusual and probably what it takes, right? Well, I'm curious, maybe we can go out on this because a lot of our listeners are frontline pediatricians. You suggested that they are part of the problem, or at least that they can be part of the solution in terms of how they present this. So aside from the practice level and structural changes, what can an individual provider do to sort of overcome the hesitancy to immunize their children in a timely manner with HPV? Yeah, well, Allison alluded to the idea of it's sometimes called a presumptive recommendation, which refers to a way of recommending HPV vaccine that really normalizes it, that puts it in the context of other vaccines and other routine care by starting out with just a very directive approach. Your child is now 11 years old. He's due for three vaccines. We can give these at the end of the visit. So instead of parsing HPV vaccination out and making it something other, it's really including it in that package of routine care with the expectation that the default will be to get the vaccine. If parents do have questions or concerns, it's obviously really important to slow down, right, and answer those. And we do a lot of training about ways to do that effectively. And then the third really important step is if a parent declines to not take that as a forever answer, but to really take care to bring it up again at the next visit. Because all of our data suggests that, again, it's just a longitudinal process, right? Some parents just need more time. And if they have a second opportunity, a lot of them will say yes. Thanks again, Melissa, for your time and sharing your expertise with us and with our audience. I certainly learned a lot. And I hope that the information has been helpful to everyone else. Great. Thank you so much for having me. This episode was produced by Shelley Steffens at the JAMA Network. To follow this and other JAMA Network podcasts, please visit us online at jamanetworkaudio.com. Thanks for listening.
From the JAMA Network, this is Conversations with Dr. Bauchner, interviews featuring researchers and thinkers in healthcare about their publications in the latest issue of JAMA. Hello and welcome to this Conversation with Dr. Bauchner. It is Howard Bauchner. I'm here with Francis Collins. Francis, welcome. Nice to be with you, Howard. We can have quite a conversation here, I think, about what's happening with research and COVID-19. We can. For our listeners, Francis is director of the National Institutes of Health, probably the most influential, research-intensive biotechnology group in the world. It has a budget of $42 billion. Just remarkable science, lab-based, preclinical, clinical. Francis has been director since 2009. He came to the NIH in 1993. But Francis, before we get started, we're going to talk about the viewpoint that we released yesterday and you've written with Paul Stofels from Johnson & Johnson entitled, Accelerating COVID-19 Therapeutic Interventions and Vaccines, Active and Unprecedented Partnership for Unprecedented Times. But before we get into the viewpoint, Francis, you had a life before you came to the NIH. Could you tell people what your life was before you came to the NIH? Oh, sure. It does seem like a while back, but I'm a physician. I went initially into physical chemistry was my calling, and then I got excited about life science and went to medical school at the University of North Carolina. I trained as an internist and then got my research training in molecular biology and human genetics at Yale and then ended up at the University of Michigan on the faculty for nine years in Ann Arbor, a place I loved. And my lab at that point was focused on trying to find the causes of genetic diseases for which we really didn't have any kind of functional clue about what the gene might be that was causing that disease when it was misspelled. So we chased after particularly ones that seemed common enough that you might have a chance of doing this with something called positional cloning. Before there was a human genome project, before you could just go to the internet and read off those letters. And we've co-discovered the gene for cystic fibrosis in 1989 with my good friend Lapji Choi, his lab in Toronto and my lab in Ann Arbor basically fused together to try to do this. It's ironic because now when I think about it, what took us all of those years could be done by a pretty good graduate student with a thermal cycler and some DNA samples in about a week. Yeah, pretty big change. Big change. And we found the gene for neurofibromatosis, which for me is an internist who cares about genetics, about the most common disease that we see in adults that are dominantly inherited, and participated in a wonderful collaborative effort to find the Huntington's disease gene a couple years after that. Yeah, that was my engagement. And yet, when the Genome Project started to be talked about, I was a big fan because I knew we were never going to be able to extrapolate beyond these very difficult gene searching experiences if we didn't have a better map and if we didn't have the sequence to work with. And why not just do it once, make it public, and then empower everybody. And then that was pretty much the argument for the Genome Project. And it got started and Jim Watson was the director and then all of a sudden he wasn't. And then they asked me to come and serve in that role. I do recall that invitation as one of those things where I had very mixed emotions. What? Give up Ann Arbor? What? Become a federal employee? What? My mother always told me, son, you can be anything you want and I'll support you, but don't ever become a federal employee. Oh, well. When you come to the NIH in 93, what were the early years like, Francis? You know, it was pretty intense because I was charged not only with getting the Genome Project up and going, but starting an intramural program in genomics and genetics because there really wasn't a lot of that going on at NIH at the time. So I had a lot of recruiting to do, a lot of building of programs. But for the Genome Project, I mean, we were just this baby in the crib at that point, trying to imagine growing up and actually succeeding and reading out all those three billion letters of DNA. It was a push. And it seemed at many times like we just were never going to get there. The technology was woefully short of what was going to be needed. So a lot of the effort had to be building new technologies for doing DNA sequencing and mostly focusing on simpler organisms where you could show progress, but you didn't have to tackle such a huge target. It was a good several years before I believed this was not going to be a disaster. And it really finally sort of once it picked up, like with most large scale projects, most of the real sequencing got done in the last 18 months, even though it was a 13-year project. Yeah, I'm sure when you first arrived after the first few years, you were wondering if your mother was right, but we'll put that aside. So we'll talk about the viewpoint, which is this private-public partnership, which was announced a few weeks ago. But Francis, what's the role of the NIH in a pandemic? Now, this pandemic is very different than Ebola or even when we've had very, very difficult flu seasons. But what's your vision of what the NIH role is? Because up front initially is the CDC, the FDA, less the NIH. So what do you think of as the principal role? Well, we are the major supporter of biomedical research in the world, but that's the important term, research. We do not go out and do healthcare delivery. We don't do surveillance of what's happening across the country like the CDC would be doing. We don't do regulatory oversight of whether something is good enough to be made available to the public, whether it's a diagnostic test or a therapy. But we are partners in every way. We work extremely closely with CDC and FDA, and I have joint leadership meetings with their leadership. NIH's role in this pandemic, as it has been in others, but this time with particular urgency, is to try to figure out how can we accelerate the development of treatments and preventions like vaccines and better diagnostic tests that we're going to acquire new technology. All the things that you want researchers to do to really rise to the occasion and see what we could do to shorten what otherwise is going to be a painfully long process of death and suffering from people getting infected with this unexpected new coronavirus. So it very much all hands on deck. I mean, beginning at the very first moment in our vaccine research center, when it became clear this might be a threat to the world and the viral RNA sequence was made public within a day, they had already designed the first vaccine, which was going to be RNA-based. And because of that speed with which that operated, that led to a world record by far of the first phase one trial getting started just 63 days later. That same trial, which just yesterday announced the phase one results, which look very promising indeed. And remember, this is May and that was January. And we are now hearing about phase one results that are strong enough to say we're ready to go on to a phase two and three, maybe combine those two together into a phase two slash three trial. That's NIH at its best. That's NIH jumping on a research need and bringing to bear on that all the best technology and capable people that we could, but also working in a collaborative way with the private sector that has its skills. So this is NIH plus Moderna in this case. And I could give you many other examples, but that was what we felt we could do. Maybe not so visible at first, but now right in the middle of trying to be the solution to a terrible global pandemic. So this will flow nicely into the viewpoint, which is this partnership for unprecedented times. About two-thirds, you know the data better than I, two-thirds, three-quarters of your dollars go out, and a smaller percentage kept internally for NIH investigators. Actually, it's about 83% that goes out. 83% goes out. I knew you'd know the percentage. So when you're faced with this new scientific question, how do you begin to think about using those dollars? Are you using those new dollars internally, as you did with the vaccine center, or do you begin to direct external dollars outward, or do you try to create this partnership? You have different options. I'm curious how you think through that. Yeah, I try to think of all the above, because here's a place where if we have resources, let's not worry about exactly what the traditions were about which pothead, which resources.
So what we're doing now in this partnership taps into that 83% that's going out to the extramural community that's going to be running clinical trials and has been and will be doing more. But it's also taking advantage of our own internal capabilities, particularly the Vaccine Research Center, but not just that. But again, let's be clear, as much as we think in this country, we're greatly fortunate and blessed to have all these resources for publicly funded research. And we are fortunate indeed. $42 billion is a lot of money. The industry people are spending twice that every year. And we would be crazy at a time like this not to figure out how to put those things together. And that was really the motivation for assembling this group that ultimately became called ACTIV. Everything has to have an acronym, and it does too, Accelerating COVID-19 Therapeutic Interventions and Vaccines. Now, I just wanted to let people know some of the leadership. The co-chairs are you and Paul Stoffels, who's chief scientific officer at J&J. And then members are Michael Dolston from Pfizer, Tony from the NIH, Gary Gibbons, NHLBI, Bill Paio from Roche, and then John at Woodcock from the FDA. But then you have four subgroups. And I thought we'd walk through each of the four subgroups. Preclinical, therapeutic, clinical, clinical trial capacity, and vaccines. Let's start with preclinical. Francis, what's your sense of what they will work on or that group will work on? So that group is particularly focused on trying to identify whether there are therapeutic agents that were developed for something else that have already been in human trials somewhere. So we know that they're not going to be really toxic, and they've already at least passed through that particular FDA approval process. And maybe, just maybe, somewhere in that pile of compounds is something that would have really strong effectiveness against SARS-CoV-2. So you're talking about repurposing a compound that was developed for something else. And how would you figure that out? Well, you'd need to screen those in a systematic way as possible against various assays, cell-based at first, to be sure that you're not missing something really important. And then for something that's really positive, you'd want to get them tested in an animal model. One of the things that group is doing right now, by the way, is to try to make sure that when it comes to non-human primates, where we need to test therapeutics and we need to test vaccines, and we have a limited inventory of animal model capabilities, let's not squander it on the wrong things. So we're trying to be sure that that priority setting is done properly. That's what that group is doing, trying to feed into the therapeutic pipeline things that you might not have guessed could be valuable, but would turn out to be just what you need based upon all the assays and all the science you can come up with. Is that largely an NIH-focused initiative, or is that NIH with some of the private partners that have been created? Well, the private partners are very engaged in that, and some of them are making available their particular compounds that have never yet been approved by FDA. Maybe they developed them for some other disease, and they didn't look like they were going to work as far as efficacy, but they could be made available in this situation just in case they happen to have the right properties to be effective against this virus. So it's very much a wide-open partnership. Now, the second group is Therapeutics Clinical. We've heard quite a bit about different therapeutics, chloroquine, radesivir, Tosi, some of the other anti-inflammatories. How is the NIH and your private partners thinking about the therapeutics? Well, they have a very busy time indeed. And this group, each one of these working groups is about 25 people, half and half from industry and from NIH and from academia, sort of combining those two together. And they're working oftentimes at least once a day and gathering things in between meetings. They're meeting at night. They're meeting on the weekends. This is flat out. And the amount of dedication is amazing. Their first task was to say, OK, what are all the suggestions that have been made about therapeutic agents that might benefit COVID-19? Well, how many do you think there are? More than 600. Okay, we probably can't put all of those through a clinical trial in the next month or two. So we better figure out which ones have the greatest promise and try to be sure we're prioritizing. So they started with 600. They got that down to 170 by sort of throwing a few aside that didn't have strong arguments. And then they narrowed that further to a little less than 40. And then ultimately, they were asked to come up with maybe six or eight that would be the most compelling and that would have the strongest case for doing a clinical trial now. And they have worked very hard on that. And they put forward their draft proposal just about 10 days ago. And our executive committee will be debating that tomorrow morning or tomorrow afternoon when we meet to see whether they agree with those highest priority proposals, which is about six different therapeutic agents. And if they do agree, those will then need to go quickly into large-scale clinical trials. Don't want to wait. This is time to find out. I think about 100 of those ideas have crossed my desk and submitted viewpoints. I regret not having kept a list because it would have been great to publish at the end. We haven't published many viewpoints about speculation about which drugs people should try. You know, you might have fun because we are actually compiling a list of the 10 worst ideas. Right, that may be a more amusing list for people to read. Amusing, but a very stiff competition, I must say. It'll be hard to narrow it down to 10. It may be. Clinical trial capacity, this comes up repeatedly in part because of basket designs, adaptive designs, what's happened repeatedly in the past. You start a clinical trial and then the cases disappear. A huge problem. So how are you thinking through clinical trial capacity, Francis? Well, again, we want to be sure if we need to do all these therapeutic trials, and pretty soon we'll talk about vaccine trials as well, we want to know where the capacity is between publicly funded efforts through NIH, between such things as PCORnet, which is funded in a separate stream, and then all of the industry capability through CROs to do trials. We want to know what does that look like, that total inventory, and which of those trial networks could be ready to take on a new master protocol in less than six weeks, because we not only want to know they have capacity, but that they're ready to start. That's what that group has been doing, is collecting that information. And it is impressive to see there are substantial numbers of such networks, many of them designed, of course, for other things, some of them for infectious disease, some of them for the lung disease, some of them just sort of general purpose networks. And you put it all together, there is a pretty powerful engine there for doing these kinds of trials. And now we know where they are, and that's going to be helpful in doing the matchmaking between, okay, here's you want to have tested where's the trial network that's best situated to take that on a lot of it though as you say you want to be sure that you're geo mapping this onto where SARS-CoV-2 is currently circulating where the cases are otherwise you have a great trial and you can't enroll and that's a moving target so all that to be sort of fitted together. Nobody's ever really tried to do this before for our entire nation's clinical trial capabilities. It's always been sort of piecework. And this time we're trying to do it all in a much more comprehensive way. And everybody's on board with that. Francis, one of the things that I think is often confusing to the public is prevention trials and then treatment trials. Theoretically, the severe announcement from the NIH was encouraging. It's a 5% mortality benefit, which is really important for that 5%, but it's not a prevention trial. Do you have a sense of the six or eight compounds that you're going to talk about tomorrow? Are they balanced between prevention and treatment, or are they largely focused on treatment? Actually, that group did have a substantive debate about where should their priorities be in setting their sights on what should go next into trials. And they still felt that the number one priority had to be people who are sick.
What's coming, though, pretty soon, Howard, in that regard, in fact, this is now the big focus of that same working group, is what are we going to do about monoclonal antibodies? Many of us, I think, looking at the landscape would say, if there's a hope for something with a big effect size, remdesivir was like, okay, but let's have something that really gives you a big benefit. I think there's evidence based on other circumstances, but nothing you could be sure of is monoclonals derived from people who've survived COVID-19 ought to be our best hope here. Because we know the immune system is pretty good with this particular virus. People get over it and you can't find the virus anymore once they're over it. So that means antibodies and maybe some cell-mediated immunity are pretty darn effective. If you could deliver that passively, you'd probably have something pretty good. Now, that would, of course, be applicable both to outpatients and inpatients. So I will tell you, we're already in the process of designing a master protocol for monoclonals for outpatients and a separate one for inpatients. And there are more than a dozen companies now that are on the process of developing monoclonals for clinical application at various timetables, but some of them are getting pretty close to being ready. And again, we would want, because we're all in this together, to do that in a fashion where you have some harmonization of those protocols, where you can do comparisons across trials, where you have standard endpoints, where you have an understanding about what lab measures you're going to use to decide whether it worked or not. Everybody's pretty committed to that, even though not all of these monoclonals will come along at the same time. That's going to be a big test of whether therapeutics can really rise to the occasion here. And I'm guardedly optimistic we're going to see something encouraging. We've actually solicited a viewpoint from a number of people from the NIH on monoclonals, in part because I think there's been some coalescence in the last couple weeks that in the short run, vaccines are still a longer play, but that in the short run, let's say the fall, when you really want people to go back to school and college, we talked about this. Monoclonals, you could deliver a large number and you could probably get them to the market sooner if they're safe and effective. And so I think we solicited a viewpoint because we feel like our role is partly to educate people about what people are currently thinking. The fourth bucket is vaccines. In the newspaper every day, particularly this morning, controversial about that healthy people challenge. But let's just start with vaccines in general. Then I'll have a few more specific questions. Sure. Well, obviously, everybody wants to see this go forward as swiftly as possible, but also to be done in a fashion where you can be confident that if something does come through the trials, it's not only effective, but it's also safe. So we don't want to cut corners in this space and end up with something that hurts people. And because you're talking about giving vaccines to healthy people, your standard has to be really high about safety. But how do you do that and not end up taking two more years to get to it, which would be a more standard approach, or maybe three or four years? Here again, I think everybody has to figure out ways to accelerate that process without sacrificing the rigor. One of the ways, of course, is to start early. And I mentioned already what was done in terms of this NIH Vaccine Research Center, Moderna collaboration getting started and into phase one trials in just two months. And there are others that are doing that as well. You may have read about the Oxford chimp adenovirus vector vaccine, which also looks pretty good. And there are others not far behind. In fact, I would say there are at least four or five of these vaccine platforms that are looking as if they are going to be ready for a large scale trial in the fairly near future, let's say the next two or three months. And you would want them to have that chance to see how that works. Ideally, again, we want to do this in a fashion where you can learn from each trial things that will benefit an understanding of the whole process. So we don't necessarily want these to be on completely separate pathways, but doing what we might call a harmonized master protocol, again, where you're sharing information about the endpoints and the surrogate measures and so on. And that has pretty much been agreed to. I think we will see the initiation of these trials as early as July. The FDA, I think, being very much on board here with trying to do this in an accelerated pace, sees this as an opportunity to go from phase one to something you might consider sort of a combination, phase two, three. So basically you're watching very carefully at the beginning of a phase three and your DSMB is looking to see is there any signal there of trouble, effectively acting as if it was sort of a phase two, but you're not going to stop. You're just going to keep going if all things are going well. So potentially then, if we can mount that and if we can find, let's say, 10,000 volunteers for each vaccine platform, that's a lot of people. And of course, you have to find them in a place where the virus is actively circulating. You won't know if your vaccine worked unless it protected people. And you won't know that if the virus is not around them. So this means, again, doing this sort of geo mapping of where your capacity is for vaccine trials and where the disease is. I think we can make that work, but it's going to be an enormous challenge logistically. The other thing you got to do is not wait to begin manufacturing. Because if that were your model, you might get to the end of your trial and go, hooray, we're going to have a press conference on our vaccine work. Then everybody goes, okay, now where is it? Well, sorry, we got six months to scale up the production. Just wait. Fortunately, the U.S. is in this situation, particularly of this organization called BARDA within Health and Human Services, to put money into scale-up manufacturing of vaccines even before you know if they are going to work. And I'm sure some of that will be wasted because some of them won't work, but hopefully some of them will. And then you'll be ready maybe as early as the fall with millions of doses of a vaccine that has at least received emergency use authorization from FDA. That's the hope. I don't want to be too over the top in confidence about this. This is white knuckles all the way. There's so many things that might go wrong here. But I can certainly tell you that everybody from the public sector to the private sector to the government is doing what they can to try to make that happen with no letting your foot off the accelerator, not for a minute. Francis, do you worry about the ethics of challenging healthy people with live virus when there's not a cure? I mean, you know, there's been many different opinion pieces written about this. You and Tony and others are at the center of this discussion. I'm just wondering how you think about that. Well, I understand the appeal of it because it certainly could be the case that such a challenge trial could be done in the fairly short order, at least hypothetically, and then FDA might be willing to say that's good enough. If you vaccinated somebody and then you intentionally infected them and they didn't develop disease, okay, that looks like success. But suppose it isn't so successful. And suppose some of your healthy volunteers who were healthy aren't healthy. And suppose you even have mortality. It's very hard to see how that's justifiable for me when you have a disease where you don't have a rescue therapy if somebody gets sick anyway. If our monoclonal antibodies look really good in two or three months in terms of their ability to save lives of people who are really sick, then this could change the ethical circumstance. The other thing, Howard, one needs to say is that even if you thought it was ethically acceptable, don't imagine that this kind of human challenge trial can happen all that quickly. You've got to make a stock of GMP material. You've got to set up a circumstance where you can intentionally infect people, which means you're going to have to have them quarantined with their staff for weeks at a time. You don't want to set off a new episode of infection in the community and do all the measures. Most people would say, we're at least a year away from that, even if we decided right now to start that effort.
Last thing I'd say about the challenge trials is, who do you challenge? You challenge young, healthy people. But okay, so if it works for them, does it really tell you that it's going to work for the elderly or for the people with chronic diseases? Who are the people you most want to be able to assist? Or are you going to fool yourself into thinking you've got a really good vaccine and it doesn't make that much difference in the death rate? That would be horrible. Francis, in these private-public partnerships, I know there's the National Institute of Health Foundation, you know, the issues of financial conflict of interest comes up. I'm wondering, you lead the most important research institute in the world with an enormous amount of resources. But as you said, the private sector in the U.S. contributes $75 or $80 billion, particularly to clinical research. How do you think about the financial conflicts of interest? We have to pay close attention to them because that can compromise everything we're doing in terms of not really having the kind of objectivity that it should and certainly can do great harm to public confidence. I guess I've learned over my 11 years as NIH director that one needs to look closely at that, but you should not let it discourage you from partnerships that can be done in full openness of what's going on. Again, transparency is the best way, I think, to address the potential for conflict of interest because then it's wide open there and people can see whether they think it's at work or not. This active partnership we've been talking about has 18 pharmaceutical companies involved, as well as numerous NIH institutes, FDA intimately involved in that, CDC, BARDA, the Foundation for NIH as a nonprofit serving as a program manager. It is wide open. There's nothing we're doing that I wouldn't want anybody else to know about. And it's certainly not leading to a place where there's any intellectual property that's being generated. But it is making it possible to go faster, which is what I think the public expects of us, than if we were all off in our own corners, afraid to talk to each other. I've done this before with something called the Accelerating Medicines Partnership, focusing on Alzheimer's disease and diabetes and rheumatoid arthritis and Parkinson's disease and cancer. And those projects have been remarkably successful in advancing the field, but have made all their data immediately accessible to everybody. That just seems like the right thing to do when we're waiting for progress to happen. Why don't we bring everybody together and make it happen a little faster? So just a couple other questions. So Francis, when you were at Michigan and you and your colleagues isolate the gene that identified cystic fibrosis, 25 years later, did you think there'd be a treatment? Well, there was a great hope on that announcement in September of 1989 that it wouldn't take long because we now finally had the gene. Gene therapy was looked at as like maybe that was going to be a quick one, if only we knew. And especially because it was a disease of the lungs and the airway, maybe you could just put the normal copy of the gene into a virus, inactivate the virus, have somebody take it as an aerosol and all would be well. And much work was done by a few of us to try to see if that would work. And it was a total frustration. We underestimated the immune system's ability to recognize something that wasn't normally supposed to be there and to wipe it out. And so for the next almost decade, progress for therapeutics really, really was stalled. And then it was really the effort to try to change the paradigm from gene therapy to drug therapy that finally now has paid off. And much credit for the Cystic Fibrosis Foundation for the way in which they took a big risk on that. And to the private sector for Aurora, which then later became Vertex. And now here we are, Howard, in this amazing moment where 90% of people with cystic fibrosis have a triple drug therapy that is phenomenal in terms of what it can do in terms of turning around lung disease and preventing further progression. I get emails almost every week from somebody with CF who has had this experience of getting on these therapies. Some of these people who were pretty much getting close to time for a lung transplant and who are now back at work. It's amazing to see. When it works, what can really happen? That's so inspiring. What was it like to grow up in the beautiful Shendoa Valley and be homeschooled, Francis? You were homeschooled until fifth or sixth grade. What was it like? Oh, now we're really going back, Howard. It was wonderful. My parents were kind of hippies, except the hippies hadn't really arrived yet. Living on this farm in the Shenandoah Valley with no indoor plumbing, starting an outdoor theater in the grove of trees up above our house, which is now, by the way, in its 64th consecutive season, or it would be if they hadn't shut down for COVID-19. It was all about music and the arts and interesting people and literature and science, not so much. That was something I got interested in on my own. And my mother taught myself and my three older brothers at home because she was convinced she was a better teacher than what we were likely to encounter in the local county schools. And she was absolutely right. And so I got inspired by her about the joy of learning things. That was just such an adventure. It never occurred to me that people might find that to be hard work or boring. It was like every day was something new to discover. Finally, when we moved in town to live with my grandmother because she'd had a stroke and needed somebody in the house, my parents decided, okay, you're the youngest. We'll let you go to public school and see how you do. And fortunately, that was good too because public schools were quite good at that point. And I met science in a high school chemistry class that changed me in a very significant way in terms of what I thought I wanted to do with my life. Well, you've done pretty well, Francis. There are quite a few questions. So let me go through a few questions and then I'll wrap it up. Monoclonal antibodies, optimistic when? Do you think they could be available? Well, there are at least two companies, Regeneron and Lilly, who say they're pretty close to being ready to mount into clinical trials. And obviously, then you have to see how long does it take to enroll patients and what does it take to show an effect size. I think we all believe that if this is going to work, the effect size ought to be substantial. So maybe the trials don't have to be that big. So I'll be optimistic and say maybe by August, we'll start to see results. Antigenic shift in the virus has been on the front page of newspapers. It often happens, quite a few articles have passed my desk. Most people have said not dramatic, not substantial enough. I'm just wondering if you can comment on that, Francis, because it is concerning when the public reads, oh, the virus is changing. So could you just comment on that? Well, yeah. First of all, if it weren't changing, that would really be news because this is an RNA virus. RNA viruses change with mutation over the course of time, especially if they have lots of ways to get passed around amongst lots of people. So the total population of viruses gets to be huge. This one seems to be traveling as far as its mutational rate about typically for an RNA virus, not extremely mutatable, but not extremely stable either. So far, what I have seen has not caused me pause in terms of the rate of mutations falling into vulnerable places like the spike protein that might have a big effect either on diagnostics or on therapeutics or vaccines. But you got to watch that. And it's a good thing we now have the capability to do that sequencing of lots and lots of isolates. So we will know. I mean, one of the big parts of this is how long will immunity last for people who've gotten over infection? And a correlate of that is how long will vaccines work? If we generate immunity to today's SARS-CoV-2, what will that look like two years from now or five years from now? Will that require a whole new vaccine strategy? This isn't as bad as influenza. Influenza clearly moves more rapidly than this coronavirus does. But it's certainly possible that this is not going to be something that will be stable over long periods of time. But in the short run, I would say we don't have any major reasons to be concerned that this is changing so fast that our strategies from yesterday won't work tomorrow. and Renee Fleming.
You have two professed loves in your life, music and motorcycles. Why don't we start with music and then you can comment on motorcycles? Well, part of growing up in that Shenandoah Valley farmhouse was an exposure to music. My dad played a really good violin and he could also play a mean hoedown fiddle if he needed to. And all sorts of musicians were popping up all the time to stay with us for days on end when they ran out of money. So music was part of what I grew up with. I play guitar, I play piano. I find this is a way to unwind and relax after a particularly intense experience. And I'm all about intense experiences right now. So I'm playing my piano quite often in the course of one of those very long days and nights. It gives me the sense of sort of being lifted out of the intense details of what's happening in a scientific life into some different plane. And to be able to do this with other people who I greatly admire, like Renee Fleming, has been an enormous gift. Unfortunately, so many of us who love music have been prevented from gathering together. I'm in a rock and roll band. We've lost three gigs already that we were going to be doing during this time, and they're gone forever. We haven't even been able to get together to rehearse. And I miss that a lot. But I know the day will come where we'll be able to bring this all back together. Hey, Howard, I will send you a little video I made for the NIH staff where a bit of a rewrite of John Lennon's song, Imagine, got put together. And I did a little solo video with my wife as the videographer, which has a little bit of a tongue in cheek about exactly what it is that we're trying to imagine. Now, I'll just send it to you. You'll get a bang out of it. Send it along. That'd be great. And motorcycles. Ah, yes. Another indulgence. I started riding in college. I gave it up for a while when my kids were little because it did seem irresponsible and it probably was. And then they got old enough, I figured, okay, I'm going back. And I'm on a Harley Road King Classic, and it is also a wonderful way to unwind when you just want to crank that accelerator down a country road and kind of let the rest fade away for a few minutes while the wind blows and your engine roars, and you take a really nice corner in just the right way. Hard to beat that. This is Howard Bauchner, Editor-in-Chief of JAMA, and it's been a wonderful privilege to talk with Frances Collins, who's Director of the National Institute of Health. It's been a wide-ranging conversation about the NIH, its response to the pandemic, and we've been discussing Frances' piece that he's written with Paul Stoffels from Johnson & Johnson, Accelerating COVID-19, Therapeutic Interventions and Vaccines, Active and Unprecedented Partnership for Unprecedented Times. Francis, stay healthy. Thank you for everything you do for the American and international populations. Thanks, Francis. And thank you, Howard, for everything you do to get the word out about all the things that we're learning and need to learn more. Appreciate your leadership as a remarkable editor. Bye-bye. Be well. Okay. Bye.
Welcome. This is the New England Journal of Medicine. I'm Dr. Lisa Johnson. This week, August 25, 2016, we feature articles on a 70-gene signature in early breast cancer, focused ultrasound thalamotomy for essential tremor, anti-CD22 drug conjugate for ALL, daratumumab combination therapy in multiple myeloma, and obesity and cancer, a review article on the treatment of patients with cirrhosis, a case report of a woman with back pain and a lumbar spine lesion, and perspective articles on the hard work of healthcare transformation, on uncertainty in the era of precision medicine, and on the abyss. Thank you. Clinical Center, Champalemode Foundation, Lisbon, Portugal. In the MINDAC study involving 6,693 women with early-stage breast cancer, the authors investigated the clinical utility of the addition of a 70-gene signature test to standard clinical pathological criteria in selecting patients for adjuvant chemotherapy. A total of 1,550 patients, 23.2%, were deemed to be at high clinical risk and low genomic risk. At five years, the rate of survival without distant metastasis in this group was 94.7% among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen receptor positive, human epidermal growth factor receptor 2 negative, and either node negative or node positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70 gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. Clifford Hudis from the American Society of Clinical Oncology, Alexandria, Virginia, writes in an editorial that these findings provide evidence that the 70-gene signature test can reassign some classically high-risk patients with early-stage breast cancer to a lower-risk cohort in whom any plausible chemotherapy benefit would be modest. The MINDAC trial shows how a well-coordinated and highly collaborative multinational team of investigators can efficiently conduct a potentially practice-changing study. In the clinic today, these results could allow some doctors and patients to choose to avoid chemotherapy if they have carefully considered their own tolerance for toxicity, risk, and uncertainty. On the basis of the MINDAC study, clinicians may consider ordering a 70-gene signature for patients in line for chemotherapy who hope to forego it on the basis of a possibly low genomic risk. What doctors and their patients do with the results of such testing will be highly individualized and will inevitably be finessed by the findings from future studies. Uncertainty in the Era of Precision Medicine A perspective article by David Hunter from the Harvard T.H. Chan School of Public Health, Boston. A National Research Council report on precision medicine explains that the term refers to the tailoring of medical treatment to the individual characteristics of each patient. The report goes on to say, it should be emphasized that in precision medicine, the word precision is being used in a colloquial sense to mean both accurate and precise. In the colloquial sense, precision also implies a high degree of certainty of an outcome, as in precision-guided missile or at what precise time will you arrive. So will precision medicine usher in an age of diagnostic and prognostic certainty? In fact, the opposite will probably result. The new tools for tailoring treatment will demand a greater tolerance of uncertainty and greater facility for calculating and interpreting probabilities than we have been used to as physicians and patients. In the future, we are likely to face a potentially bewildering array of probabilities, estimates of disease risk based on inherited germline sequencing, and, once a disease is diagnosed, of prognosis and therapeutic options guided by OMIC and other analyses. Assessing and acting on these probabilities will require approaches to data presentation, risk quantification, and communication of uncertainty, for which we are largely ill-equipped and that we already struggle with. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor by W. Jeffrey Elias from the University of Virginia Health Sciences Center, Charlottesville. Essential tremor is the most common movement disorder, estimated to affect approximately 7 million persons in the United States alone. In this study, 76 patients with moderate to severe essential tremor that had not responded to at least two trials of medical therapy were randomly assigned to undergo unilateral focused ultrasound thalamotomy or a sham procedure. Hand tremor scores improved more after focused ultrasound thalamotomy, from 18.1 points at baseline to 9.6 at 3 months, then after the sham procedure, from 16 to 15.8 points. The improvement in the thalamotomy group was maintained at 12 months. Secondary outcome measures assessing disability and quality of life also improved with active treatment, the blinded thalamotomy cohort, as compared with the sham procedure. Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%. In an editorial, Elan Lewis from Yale University, New Haven, Connecticut, writes that the results of this study are promising, particularly since this procedure, unlike traditional thalamotomy, does not require entering the cranium with a probe. Nevertheless, there are several important concerns about this study, the first of which is the limited follow-up period, which was 12 months. There are also several important caveats. For example, the procedure is a thalamotomy. Hence, it creates a fixed brain lesion. But even with the concerns and caveats, pros and cons, the procedure will take its place among other surgical procedures for medically refractory essential tremor. Given the perception that it is less invasive than other approaches because it does not involve burr holes and intracerebral electrodes, as well as the evidence that patients with essential tremor are perhaps particularly harm-avoidant, the procedure may allow more patients to avail themselves of a surgical option for the treatment of this often-disabling disease. A head-to-head comparison with deep brain stimulation would facilitate the direct comparison of the two approaches. Inotuzumab Ozogamycin vs. Standard Therapy for Acute Lymphoblastic Leukemia by Hacob Kantarjian from the University of Texas MD Anderson Cancer Center, Houston The prognosis for adults with relapsed acute lymphoblastic leukemia is poor. In this trial, 326 adults with relapsed or refractory acute lymphoblastic leukemia were randomly assigned to receive either inotuzumab ozogamycin, an anti-CD22 antibody conjugated to calikeamycin, or standard intensive chemotherapy. The rate of complete remission was significantly higher in the inotuzumab ozogamycin group than in the standard therapy group, 80.7% versus 29.4%. Among the patients who had complete remission, a higher percentage in the inotuzumab-azogamycin group had results below the threshold for minimal residual disease, 78.4% versus 28.1%. The duration of remission was longer in the inotuzumab-azogamycin group, median 4.6 months versus 3.1 months. In the survival analysis, progression-free survival was significantly longer in the inotuzumab-azogamycin group, median 5 months versus 1.8 months. The median overall survival was 7.7 months versus 6.7 months. Veno-occlusive liver disease was a major adverse event associated with inotuzumab-azogamycin. Both progression-free and overall survival were longer with inotuzumab, Bortezomib, and Dexamethasone for Multiple Myeloma by Antonio Palumbo from the University of Turin, Italy. Daratumumab is a human IgG kappa monoclonal antibody that targets CD38, which is highly expressed on myeloma cells and other hematopoietic cell types. In this study, 498 patients with relapsed or relapsed and refractory multiple myeloma were randomly assigned to receive bortezomib and dexamethasone alone, control group, or in combination with daratumumab. The 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. The rate of overall response was higher in the daratumumab group than in the control group, 82.9% versus 63.2%, as were the rates of very good partial response or better, 59.2% versus 29.1%, and complete response or better, 19.2% versus 9%.
Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone. Treatment of Patients with Cirrhosis A review review article by Philip Gee from the David Geffen School of Medicine at the University of California, Los Angeles. Cirrhosis is the irreversible fibrosis of the liver, the end stage of a final shared pathway in chronic damage to a major vital organ. It is the eighth leading cause of death in the United States and the 13th leading cause of death globally, with worldwide mortality having increased by 45.6% from 1990 to 2013. The major causes of cirrhosis include chronic hepatitis B virus and hepatitis C virus infection, alcoholism, and non-alcoholic steatohepatitis. Chronic injuries to the liver are synergistic. It is not unusual to see patients with cirrhosis that is due to a combination of chronic viral hepatitis, obesity, and alcoholism. In patients with cirrhosis, the risks of medications and the risks of invasive procedures must be weighed against the benefits. Aside from the management of decompensation, the fundamental principles in the management of cirrhosis focus on education, lifestyle modification, protecting the liver from harm, and care coordination. This guide to the practical treatment of patients with cirrhosis summarizes Choi and colleagues. A 28-year-old woman presented with intractable back pain with radiation to the leg. Six months earlier, low back pain developed and then worsened and could not be relieved by ibuprofen. Six weeks before admission, severe pain developed that radiated down her left leg to her ankle. She was seen by her primary care physician, and acetaminophen and hydrocodone were prescribed for two weeks. Her condition did not improve. One month before admission, she was seen in an emergency department, and prednisone was prescribed for four days, with transient improvement. When the pain worsened, she returned to her primary care physician's office. Imaging studies revealed destruction of the fifth lumbar vertebra, L5, and the presence of a large soft tissue mass extending into the spinal canal and paraspinal soft tissues. A biopsy of the lesion in the paravertebral region of the lumbar spine was performed. Examination of biopsy specimens revealed a giant cell tumor of bone. Giant cell tumor of bone is a benign but locally aggressive neoplasm and has been considered to be among the rare benign metastasizing tumors. This patient had an unusual presentation of giant cell tumor of bone. She had a locally advanced lesion of the lumbar spine that produced disabling symptoms due to compression of the spinal nerve roots and adjacent structures. This presentation posed management challenges. Body Fatness and Cancer. Viewpoint of the IARC Working Group A special report by Beatrice Lauby-Secretin from the International Agency for Research on Cancer, Lyon, France. In April, the International Agency for Research on Cancer, IARC, based in Lyon, France, convened a working group to reassess the preventive effects of weight control on cancer risk. Overweight and obesity are the abnormal or excessive accumulation of body fat that present a risk to health. Worldwide, an estimated 640 million adults in 2014 and 110 million children and adolescents in 2013 were obese. Body fatness and weight gain throughout the life course are largely determined by modifiable risk factors, such as excess energy intake, food and drink, and, to a lesser extent, physical inactivity, which are the main drivers of the obesity epidemic. In 2002, the previous IARC working group concluded that there was sufficient evidence for a cancer-preventive effect of avoidance of weight gain for cancers of the colon, esophagus, kidney, breast, and corpus uteri. For the current reassessment, most of the more than 1,000 epidemiologic studies that they reviewed were observational studies on cancer risk and excess body fatness, because studies, including clinical trials of weight loss or weight control interventions, by Richard Bomer from the Nuffield Trust, London. and support of performance improvement activities through education, research, and measurement programs. The financial approaches aim to motivate change in the way organizations and practitioners configure their systems and deliver care. Under the assumption that once they're motivated to seek surplus or avoid sanction, they'll be willing and able to make local operational changes to reduce cost and improve safety, patient experience, and outcomes. Unfortunately, experience shows that although a changed market may be a helpful precondition to local performance improvement, it hardly guarantees effective operational change. However, some organizations have successfully transformed themselves, substantially improving efficiency and quality. How have they done so? Examination of these health care organizations reveals that lasting transformation requires the relentless hard work of local operational redesign, led by multidisciplinary teams. Successful transformers, from Seattle's Virginia Mason Medical Center to the Salford Royal National Health Service Foundation Trust in England, constantly make small-scale changes to their structures and processes over long periods. The Abyss, a perspective article by James Weisfeld Adams from the University of Colorado School of Medicine, Aurora. When James Weisfeld Adams was a 27-year-old resident, his precise, microscopic handwriting suddenly resembled the scrawl of a six-year-old. Suddenly, he couldn't write. His right hand had a peculiar tremor at rest, a vague heaviness waxed and waned in his right arm and leg, and his pupils were unmistakably asymmetric. A nagging uneasiness turned to panic. His basic neuroanatomical knowledge suggested that the distribution, involvement of the arm and the leg on the same side, meant that there was a good chance that the problem had its origins upstairs, in his brain. He knew he needed an MRI. A single area of abnormality glowed conspicuously on one side of his cerebellum. The radiology report ventured that it was most likely inflammatory in origin. His cerebrospinal fluid analysis, clinical presentation, and MRI findings were suggestive of a multiple sclerosis-like process. There was no single confirmatory test for MS. It is a condition that declares itself, or fails to do so, with time. Within a week, the tremor and unsteadiness eased, and his handwriting became recognizable. He started his new residency appointment in New York. He adapted to having pain most days and threw himself into his work and new life. And then a phone call came from his doctor the morning after a routine follow-up MRI, suggesting that he come in to discuss results. Our images in clinical medicine features a 79-year-old woman who presented with a one-year history of gradual neurologic decline involving confusion, memory loss, imbalance, and incontinence. On examination, she was oriented only to self and had mild non-fluent aphasia. CT revealed a large left frontotemporal mass with areas of calcification. CT angiography and MRI also revealed the mass, which measured 3.8 cm by 6.2 cm by 3.9 cm without contrast enhancement or intraluminal filling, which raised suspicion of a thrombosed aneurysm that was likely to have originated from the bifurcation of the middle cerebral artery. Bands of T2-weighted signals suggested previous episodes of layering of blood products. Conventional angiography and three-dimensional reconstruction revealed no residual aneurysm and an occlusion of the anterior division of the middle cerebral artery as a result of compression mass effect, along with retrograde filling from leptomeningeal collateral branches of the anterior cerebral artery. After discussion with the patient's family, a decision was made to conservatively manage the aneurysm and to address the hydrocephalus with the placement of a ventriculoperitoneal shunt and endoscopic transfrontal septostomy. An improvement in the patient's overall neurologic status was noted at a clinic follow-up visit. A human sneeze can eject droplets of fluid and potentially infectious organisms. This image sequence captures, in increments of 20 milliseconds, the emission of a sneeze cloud produced by a healthy person. The sneeze was produced naturally, without the introduction of additives, colorants, or contaminants for visualization. High-speed video recorded at 1,000 frames per second shows a turbulent cloud that consists of hot and moist exhaled air, mucosalivary filaments and drops, and residues from droplet evaporation, nuclei. The ejection lasts up to 150 milliseconds and then transitions into a freely evolving turbulent puff cloud. The largest droplets rapidly settle within 1 to 2 meters away from the person. The smaller and evaporating droplets are trapped in the turbulent puff cloud, remain suspended, and over the course of seconds to a few minutes can travel the dimensions of a room and land up to 6 to 8 meters away.
This concludes the summary of the August 25, 2016 issue of the New England Journal of Medicine. We're interested in your feedback about our audio summaries. Any comments or suggestions may be sent to audio at NEJM.org. Thank you for listening.
From the JAMA Network, this is the JAMA Editor's Summary, a review of important research and review articles appearing in the latest JAMA issue. Hello, this is Ed Livingston, Deputy Editor of Clinical Reviews and Education at JAMA. Today I bring you the Editor's Audio Summary for the January 16, 2018 issue of JAMA. This is a very special issue. It's a theme issue on obesity. It's the third time that we've run a theme issue on obesity in the last 15 years. And in contrast to prior issues, we concentrate on bariatric surgery. And the reason is, bariatric surgery is the only proven method of controlling obesity for very obese patients that actually works in the long run and results in sustained weight loss. Diets, and especially diet drugs, are notoriously ineffective in the long-term control of obesity. The emphasis on obesity surgery is manifested by five original articles summarizing outcomes for bariatric surgery. Three of them are very important because they provide a definitive picture of the outcomes for gastric sleeve resection. There are two randomized clinical trials, both with five-year follow-up with very few patients lost to follow-up, showing that the gastric sleeve resection performs almost as well as the roux-white gastric bypass in resulting in long-term weight loss. There's another observational trial of a very large number of patients from an HMO in Israel that also showed that the gastric sleeve resection had a great deal of durability and sustained weight loss in the long term. These results also showed that the complication spectrum for the two operations is about the same, except for a substantial greater problem with reflux following the sleeve resection. A detailed analysis of the results of these studies was provided in an editorial written by Drs. David Arterburn and Anirban Gupta. I'd encourage you to read that editorial to get full insight into the results of these studies and their significance in establishing the gastric sleeve resection as an acceptable and effective means for inducing weight loss in very obese patients. There is also a JAMA Clinical Reviews podcast with an interview with these editorialists discussing sleeve outcomes in detail. Continuing with our discussion of the original investigations, there's also a five-year follow-up from the Diabetes Surgery Study, the DSS study, a study whose main findings were published in JAMA a few years ago. This study showed that after five years, Roux-Y gastric bypass performed better at diabetes control than a standardized look-ahead diet program. With time, control of the diabetes eroded, but it was still substantially better at five years in the surgery group than compared to the control patients. An important feature that distinguishes the DSS study from other trials of diabetes control for the morbidly obese is that it looked at the ADA triple endpoint, evaluating concurrent control of glucose, LDL, and high blood pressure. When all three of these important endpoints are considered, the results are not nearly as good as if one only looks at diabetes alone, demonstrating that one needs to assess all health outcomes when evaluating the effects of bariatric surgery and not just diabetes or weight loss. Similarly, the observational trial from the Israeli HMO showed that bariatric surgery was very effective in controlling diabetes, had a very small beneficial effect on mortality, and no effect on cardiovascular events. Notably, in this observational trial, where the control patients received routine care, there was no improvement in the utilization of drugs to control hyperlipidemia or hypertension, suggesting that the need to treat these two clinical entities doesn't change much after bariatric surgery induces weight loss. Finally, there's another observational trial from Europe showing that when compared to patients in a specialized weight loss treatment program, where patients received either bariatric surgery or specialized medical care, bariatric surgery still outperformed medical care in the long run. There's also several viewpoints that cover various aspects of obesity. The first is from Mary Burke and Frank Hyland, and it's entitled, Evolving Societal Norms of Obesity, What is the Appropriate Response? Doctors Burke and Hyland posit that one reason that the entire population is becoming obese is that people no longer perceive obesity as being wrong or a problem and are very willing to accept their state of obesity. Doctors Susan and Jack Unosky from the NIH wrote a viewpoint entitled Toward Precision Approaches for the Prevention and Treatment of Obesity. Dr. Eve Guth from the Jesse Brown VA Medical Center wrote a viewpoint entitled Counting Calories as an Approach to Achieve Weight Control, providing a practical approach for how to counsel patients to lose weight. Doctors Pomerantz, Mozaffarian, and Micha wrote a viewpoint about taxation of sugar-sweetened beverages, as did Drs. Lisa Powell and Matt Macheskey. The third article in the obesity theme issue on sugar-sweetened beverages is the effect of price increases of sugar-sweetened beverages in the Philadelphia airport. The Philadelphia airport is so large it traverses two cities, both of which had different rules regarding taxation of sugar-sweetened beverages. As you can expect, when one half of the airport was subject to a new tax, prices went up for these beverages, but they also went up, but to a lesser degree, in sugar-sweetened beverages in the non-taxed part of the airport. All in all, these studies show that even though taxation of sugar-sweetened beverages might reduce their consumption and induce some degree of weight loss, the legal and financial aspects of these taxes are precarious. Taxing sugar-sweetened beverages is probably not the right approach for inducing weight loss in the population, and a more comprehensive approach is necessary to deal with the very large amounts of calories the average American ingests. The final viewpoint is entitled Fitness and Fatness, which is more important from Ann Blair Kennedy, Carl Levy, and Stephen Blair. Dr. Blair is well known for his studies showing that obesity can be tolerated if you have good physical fitness. Thank you. Hubeck and colleagues discussed the societal and cultural barriers to obtaining surgical treatment for listening.
There's something artificial about bringing people into our clinic and into our space, putting them in our gowns, sticking them with different probes and. We have to get out there to really understand how people live their lives, how they explain their lives, how they explain their bodies, their health, their disease, before we can have any real opportunity to start to make inroads into healing. Not otherwise specified has always been one of my favorite phrases in medicine. Not just because it's a fancy way of saying we don't really understand the root cause of something, but also because it captures the human impulse to put tidy labels on things that remain largely unknown. In NOS, I talk with some of medicine's most innovative thinkers to probe some of these messy unknowns behind our healthcare system, its players, and the stories that shape their lives. NOS makes time for the types of in-depth conversations that may not leave us with easy answers, but that shed fresh light on medicine's toughest challenges, as well as the people envisioning its future. I'm Lisa Rosenbaum, and you're listening to Not Otherwise Specified from the New England Journal of Medicine. My guest today is Heidi Beferus, the Chief Medical Officer for Housing for Health at the Los Angeles County Department of Health Services. Heidi's an internist who's devoted her career to addressing the health issues and the life conditions, needs, and humanity of vulnerable populations. During her medical training, she began working with Paul Farmer and the global health organization he founded, Partners in Health. Her current organization, Housing for Health, is a broadly interdisciplinary team that works to provide housing and critical services to homeless and formerly homeless people in LA County and to meet the needs of people with complex health and behavioral health conditions. Heidi recently sat down with me to talk about her early work with Paul Farmer and Maria Contreras, structural violence and social determinants of health, what it really means to be a healer, the role of love in medicine, and how to truly listen to patient stories. Here, we have changed or omitted patients' names or identifying details to protect their privacy. So welcome to the podcast. Heidi, you and I first got to speak soon after Paul Farmer died in February of 2022. And when I spoke to you, I had an experience that I sometimes have as a writer, which is I listen to you say beautiful and wise things for about an hour, and then I had to choose a few sentences that would ultimately get published in a 2,500-word piece. And I remember thinking to myself then, I wish the whole world could hear what you have to say. So I'm really excited to get to sit down and have a conversation with you again. So welcome to the podcast. Thank you. So you went to Harvard Medical School, right? And that's where you first taking a semester and going to Iran and working with a nomadic tribe near where I was born in Shiraz because I had heard that there were health care disparities for that particular tribe just based on their social marginalization, particularly after the revolution when they were somewhat even further dist he's dealing with maybe similar circumstances in his battle to right the wrongs in Haiti. And maybe he would have some advice for me on how to speak to the Minister of Health in Iran. And so I scheduled a time to go and meet with him. And I remember I went in and he very dutifully listened to my story and then said, Heidi, why do you want to go to Iran? Come work with me. And I was like, what? He's like, you don't have to go to Iran to do this work. You know, and in fact, I want to introduce you to this woman who approached Jim, Jim Kim and me a couple of weeks ago named Maria Contreras, who's right down the street from Harvard Medical School in Roxbury. And she kind of told us off because she's like, you're doing all this work in Haiti, but less than a mile away from you, there are disparities that are unconscionable. What are you going to do for your backdoor neighbors? And he said, she's right. And I think you'd be a perfect person to go explore what she. And that's when I started like for you and also how that shaped the work that you would spend the rest of your life doing? Absolutely. Roxbury and Dorchester really are within walking distance of Harvard Medical School and the bastions of healthcare where you trip over a doctor when you walk a square inch in the Longwood Medical Area. And we hadn't been introduced to our neighborhood when we came to the medical school and the campus. We didn't have a sense of our context, where we were working, right? And I remember the first time going into Roxbury, really entering a whole new world that I had driven through, but had never even stopped to look. And Maria introduced me to how disparities and injustice, particularly in the United States in some way, we can easily ignore as we drive from one end of the town to the other. And she taught me that there's a lot that we need to do to open ourselves to the realities of people living structural violence every day. And in Roxbury, particularly in that neighborhood, there were sort of the Dominicans and the Puerto Ricans on one side, separated by Columbus Ave with African-Americans on the other side. Public housing, tenement style for the poor and the disabled. And Maria was a community activist. She was a Dominican woman who had really gotten fed up with the violence in inner city Boston in the late 80s and early 90s with all the gang violence and drive-by shootings. And she had sort of organized her neighbors, gone door to door and said, hey, are you as fed up about this as I am? And she rallied these incredible black and brown grandmothers, really, to come out every evening and stand on the street corner to help kids make better choices, give a sense of resilience and strength, help them get home, provide alternatives, locations or opportunities for participation in community. And something so compelling about her vision of we're not going to get help from the outside. We've got to do it ourselves. And I think it's the first time I really became radicalized, I guess, and started working with her to form what became Soldiers of Health or Soldados de Salud, which was her PIH equivalent program in inner city Boston. And her concept initially was not so much around health and healthcare access, although I sort of helped bring that to the fold. It was really about why do we as poor black and brown people not have the same opportunities that someone does literally a mile down Columbus in the South End or the Back Bay? And what do we need to do? And her vision was expansive, right? It was about creating rotaries to ease traffic burden. It was about looking at air pollution. It was about how do we make sure that kids have access to homework and tutoring support? How do we make sure that kids are hungry, get meals during the summer when school is out? How do we make sure that people get insurance, health insurance? How do we ease the burden of poverty by making sure that people get connected to most fulfilled lives. And it was my second medical school. It was really where I learned about the human condition and what it means to be a true healer, which is to take all of that into consideration. And for me, most importantly, is listen to stories, really understand people's life experiences and how it develops into symptoms that we later label as psychosis or addiction, but really are rooted in that experience and that understanding that and having empathy for that and having the tools that I wasn't learning traditionally in medical school to be able to sit with that and fight it. That's really what it means to be for me a healer. But what I, you know, later learned when I went to Haiti, my favorite term, which is an accompanateur, someone who accompanies and walks with alongside not pushing or pulling, not even necessarily setting the pace or even the direction, but just being there, witnessing and hopefully using our privilege to clear obstacles and to create options and different paths that someone can take and really be part of that healing process, not only for that individual, but their community and the forces that shape them. Why don't we talk about that term accompaniment now and its origin? Because I think there's a story there that involved you that I think also really helps people understand what it actually means. Yeah. So I was first sort of introduced to the concept of accompaniment by community health workers in Haiti. And I remember it was, I think, my second trip to Conj, which was the idyllic healthcare on a hill that Partners in Health had built in the middle of a squatter settlement after the Arbonne Valley had been flooded. And we had brought a whole bunch of NIH researchers and muckety-mucks to this conference to talk about the learnings that PIH had had around creating directly observed therapy for treatment of HIV and tuberculosis using community members.
And I remember I was moderating a conference with the community health workers who were sitting on top of the stage in the church, basically, while all of these researchers and biomedical tacticians were in the audience. And there had been a lot of sort of concern about taking this model and bringing it to the United States. Because in the United States, there's this idea of we're going to give you a leg up, but then you need to figure it out, right? There's no free handouts. You've got to show that you can do this. So we'll help you out for a few months. And then that should be just enough time for you to get your act together, pull yourself up by your bootstraps and keep it going. And someone in the audience actually asked that question. So how long does it take for, you know, this to really work? And at what point do you feel like you could stop and this person would be fine to take their meds on their own? And I remember looking in the eyes of the accompanitors on the stage and they were completely confused. Like, wait, can you repeat that question? And we repeated the question. They said, well, the person has HIV for life. I'm with them for life. This isn't just about making sure they're taking their pills. This is about me showing up twice a day to give them a hug, to make sure they have food, to make sure that their kid went to school, to make sure that their roof isn't leaking, to let them know that they belong and I care. This is for life. And I remember the hush in the audience when they said that. It's such a difficult concept to translate here, right? Because we're all so worried about cost efficiency and sustainability and generalizability and what is the return on investment, right? And it was such a foreign concept in this community. And I think for me, that was my first introduction to the concept of accompaniment. And we had to modify it. I wrote NIH grants. I couldn't necessarily, when we talk about reverse innovation, suggest that this was going to be a model that worked for the United States, even though in my heart of hearts, I know that's what we need. But I learned to push back, right? To fight against that failure of imagination that we sometimes have that Paul talks about in this country around what does it really mean to create a healthy community? It's a lifelong commitment to addressing so many things other than that person's symptoms or eliminating disease. That's not what creating healthfulness is. remember that you think help sort of illustrate for the rest of us who don't do this work, what this actually looks like on a day-to-day basis to accompany people through all of these challenges, including their health, to help them be who they want to be? Yeah. When I was starting my work with Maria in Roxbury, there was this huge building two streets away from Maria that was sort of a housing project for people who had disabilities and the elderly who were poor. And there were people in there who had AIDS and were dying from their HIV disease in the middle of a time when we were like rife with possibilities for treatment, right? People who had mental illness, people who were physically or cognitively disabled, World War II vets who were alone, you know, after careers of PTSD and alcoholism. And Joe was actually a World War II veteran that the social worker introduced me to. She said, you have to meet Joe. I don't know what's wrong with him, but he won't answer his door. And he's usually out here and he's a crotchety old guy, but I'm worried because I haven't seen him in a couple of weeks. So we went up to his room and he was sitting in his chair and didn't look good. He was pale. He was edematous, probably from untreated congestive heart failure. There were cigarette ashes everywhere. He had been trying to eat, but there were food scraps all over the place and infestation. And he was having difficulty breathing. And when we first entered the room, he's like, get the hell out of here. What do you want? And here I am a little medical student. I had no idea what the heck I was doing. And, you know, had been taught inpatient doctor how to sort of talk to someone and approach slowly and just sat down next to him and said, I don't want anything, Joe. I'm just here to be with you. And I want to learn from you. And I want to figure out, like, is there anything that I can do to help? And he started crying. And he said, I'm dying. And nobody cares. I don't have anybody. And he pointed to a picture on the wall of him as a young, you know, shirtless guy next to a tank with his buddies. And he's like, they're all dead. My family won't talk to me. And this is not how I thought I would go out. And that was like the beginning of a relationship that lasted a few months. And we became very close and he was really cantankerous. He was from down East. He was from Maine. And his pride and joy was this beat up old van that had holes in the bottom and he would lay out a mattress in the back. And his favorite thing was to drive up to Maine for the weekend and just go to the woods and just be there because it's where he grew up. And he had a really difficult childhood. He was physically and sexually abused, alcoholic father, you know, sort of ran away to the army and came back and did sort of odd jobs, fell into sort of alcoholism himself. And I think also was like so many children who've grown up in that kind of family also was challenged with being violent to his own children and had become estranged and just sort of now tortured, you know, and alone. And, um, I used to sometimes get into that van with him, Lisa and go to Maine because it was what was meaningful to him. And just listening to his stories of his life and all of his, his hopes and dreams and where he was. And slowly after, I would say about six weeks, agreed to let me examine him. And I remember I brought him into my clinic, which at the time was a women's health center. And he was so pissed off that here I was bringing a World War II vet to a women's health center. And I remember I was examining him and, you know, that point we had sort of like, I had talked to my preceptor at the time and we had figured out what kind of regimen to put him on to help him with his, his fluid overload. And I remember it was my first rectal exam on a patient and I felt inside and I felt a really, really hard, big mass. And, um, after I, I don't know, a month of cajol, went with him to his colonoscopy and he was diagnosed with fairly advanced colon cancer. And the last sort of time I saw Joe in his apartment, I had gone to visit him because he wasn't picking up his phone. And he had given me a key at this point. And I, I opened the door and, uh, there was, there was bloody stool all over his floor. And I tracked it into the bathroom and he was lying in the bathtub and he had his toe in the tub faucet and the hot water had scalded him. He was lying in hot water because the faucet was broken and he couldn't turn off the hot water and he was burning in the tub. And I saw him and I pulled him out of the tub and he was crying. And he said, I knew you were coming and I was just trying to get cleaned up for you. And I couldn't turn off the hot water. And we both kind of just wept. And we got him to the hospital and he died a few days later. But for me, that was my first real accompaniment. And it was a gift to be able to spend those last few months with him. And I think a lot about so many of the people who don't have the opportunity to share their stories and themselves. And what a lost opportunity for those of us to connect with someone like him. And, uh, I had so many of those experiences, you know, working with soldiers of health and I created sort of an offshoot called PACT or Prevention and Access to Care and Treatment to do this sort of accompaniment work. Again, mobilizing community health workers to be the workers, and particularly focused on HIV and AIDS because the highest HIV incidence rates were happening in young people of color. And that was sort of a call to action in thinking about how to form a program to address HIV AIDS in this community.
I mean, HIV AIDS has this remarkable ability to be a mirror that reflects our societal transgressions. And it really did then become a crucible of learning for me personally, but incredible humility about technological advances and what they could do. And over time, seeing it going from a death sentence to now chronic disease, but also how do we make sure that everyone reaps the benefits of that technology, that gap between the haves and the have-nots. And, you know, one Paul often said is, if access to healthcare is a human right, who is considered human enough to have that right? And we struggle with that, right? Does a transgender commercial sex worker who's a meth user have a right to the same healthcare as someone else? But more importantly, how do we ensure that that person gets that healthcare by understanding them and their story and what brought them to that point and accommodating instead of expecting them to be compliant with our rules. And I think that's our big civil rights movement now. How do we close that gap so that everyone can achieve the health to which they're entitled and health defined globally, right? Again, not just the absence of disease or symptoms, but what it means for them to feel like they belong, to have obviously, about structures and systems, but we talk a lot less about love. And maybe that's because our minds are so fixated on what you mentioned in terms of how do you scale it? You know, that's always the question. And I think the thing, if anything changed in me writing about Paul, and I think something did, it was for the first time to appreciate that it's okay to love these people you're taking care of. And in fact, it's not just okay, it's necessary. And we're taught in medical school that that's bad. And I'm someone who my whole life, it's like, if there's something to be felt, I will feel it intensely. And so in medical school, I was really scared that I wouldn't be able to make good judgments because of how much I feel. And then when I talked to you and when I wrote about Paul, I realized that there's this huge distinction between sort of having your judgment clouded in terms of being able to weigh benefits and risks because you're so emotional and then what the role of the physician actually is in so much of what you do, which is to be an advocate and to care and to know. And obviously that's possible without love, but I think love certainly helps. So I guess my question to you is sort of what did Paul teach you about love and how do you think we can begin to bring that back into the way we educate students and trainees? Yeah. you know, Paul was the living example of how you are a steward of love for whom many in the world feel are unlovable because of their, you know, supposed willful self-destructive tendencies or their inability to rise above their circumstances or whatever the issue is. And I think Paul, as a liberation theologist, thought love was the most important thing in his black bag. Because most of us, when we seek healing or comfort, aren't looking for a technician or a mechanic. We're looking for someone to connect with who's empathic, who feels empathy for us and who is willing to accompany us even if we choose to go down the wrong path. And that's what love is. That humility, that empathy, that love, that is the root to building the partnership and the trust and the hope that are that so much of feeling that love and caring comes from, I mean, you called Roxbury your classroom, right? And I think one thing that's sorely lacking, and I'd love to hear your thoughts about this, is that we think that we're teaching people to be empathic without feeling too much in this sort of check the box way, you know, make eye contact, use eye statements, nod your head. And I've always sensed that patients, you know, whatever they understand about the jargon we use or that we don't use, they sense how much we care. Like we can't hide that. We can't fake that. And so it's always felt a little bit like medical education was almost by definition misguided and trying to give us like this toolbox of sort of things that were already made instead of teaching us to learn who these people are in an organic way, which is what you experienced, I think. And I'm wondering if there's any way to translate that experience that you had starting in 1991 to 2023 when we talk more than ever about social determinants and structural violence and addressing some of these problems. But I don't feel in my own experience like we're getting any better. And in many ways, I feel like we're actually getting worse, at least in the hospital setting, in accompanying people. And so I'm wondering how you think, if you could design education, if you weren't in your current role, how would you begin to give trainees some of the experiences that you had? I've thought about this a lot. And I think what's really important first is establishing the paradigm. We've gotten biomedicalized. We talk about social determinants of health, but like you said, it's become very checklist-y, right? They're questions we ask as obligation, but are we really listening? And then do we ask the probing questions to understand what that's like for that person, right? And listening to their story and opening ourselves up to that. We've become so sort of codified and time spent and immediate sort of gain. Listening to stories in an open-ended, nonjudgmental, permissive way takes time and it derails your agenda as a provider. Right? But we have to change the way we think about that. It doesn't. It's an investment. It's a capital upfront investment in a relationship that then can become truly therapeutic. And I think like establishing that as a paradigm is really important. We need to give toolboxes, right? The recovery model, right? Focus on not so much diagnosis of disability, but focus on skills building, right? Focus on the positive forces in that individual as opposed to the things that diminish them, which is a very different approach to medicine, right? I think also talking about harm reduction, people talk about harm reduction, but harm reduction is a principle that I carry with me all the time. I'm not necessarily aiming to get to the person to where I think they should be. They need to help define the path they're willing to go on and what's acceptable for them over time, right? And also letting them direct what's important to them and what their definition of health is, which may not be an LDL of 90 or an undetectable viral load, right? And I'll never forget this with one of my PACT patients. It was a Haitian woman who had AIDS who was dying. And when you think about HIV clinics that were just incredibly resource rich at the time compared to regular primary care, they had social workers, they had educators, they had, you know, um, peer advocates and she still wasn't responding. She still wasn't taking her meds and they would drill into her, your CD4 counts four, your viral load is greater than 750,000. Had no meaning for her. And when you actually listen to her story, which took a long time to build the trust for her to tell you her story of her explanatory model for her illness and where HIV had come from and feeling like she deserved it and that the only redemption was absolution from the church and realizing that she was being ostracized by the church and that my job as a healer was to go with her to the priest, right? Or to talk to her, not about her viral load, but her definition of health was being able to put on her red dress and dance with her husband in the Haitian parade again, but she was too skinny to do that. And how could we change adherence to HIV meds to help her fill out and get strong enough to go dancing in the street? If you don't listen to the story, if you don't understand the context, if you don't open yourself up to that person's life experience,. Because it's very hard on us as people, right? That active witness to suffering. And I don't think we're often taught how to do that as medical practitioners. Maybe we do better in some other fields. But I think that's really important. Trauma-informed care, right? Understanding that our past traumas, particularly when you're working with certain kinds of people who are marginalized, right? Both fiscally and socially disenfranchised. How important that is. And those are some of the paradigms and principles I'm talking about, right? I think the other thing for me is that you only learn that through exposure in the context of the person.
And somehow that's supposed to create an environment where we're learning from them, where it's patient-centered. It isn't. My best learning was done at the bathtub with Joe. Or out walking in the street with those abuelas to keep their kids from getting shot with drive-by shootings. We have to get out there to really understand how people live their lives, how they explain their lives, how they explain their bodies, their health, their disease, before we can have any real opportunity to start to make inroads into healing. And I think the opportunities for that kind of learning in medical school are tremendous, you know, but it comes with a sacrifice of letting go of some things, right? We've just got this amazing wealth of knowledge, all the imamababs and all the checkpoint inhibitors and all the different drugs and all this wonderful, wonderful, wonderful things. But are we also giving weight to this kind of learning and this kind of toolbox? And then I think the other piece for me is for us as educators and instructors is being able to provide the support to the empathic listener and accompanateur, right? It's very, I think, destructive to put someone in a situation where you're saying, open yourself up to the trauma, listen to the story, and we don't help them process that. Right? And that it's okay to not always have an answer. And it's okay not always to be able to fix the problem. But there's beauty in having been there in that moment. And I give you credit for that. Maybe it doesn't show up as a value metric in your score. But you know what? The fact that you were with that person as he lay dying in the bed, it's immeasurable in its importance and value. How do we do that, right? And how do we help deal with building that both end of being vulnerable and resilient in us as healers, which is important because we have to see the beauty in maybe not getting to the LDL of 70, but maybe moving that person to the point where for the first time they call the pharmacy to refill a med they haven't taken in a year. That's huge. How do we celebrate that? I want to go back to this idea of being present with people suffering without breaking. Because I'm actually not sure that I've ever really believed that if you let yourself feel other people suffering, that you break. Because for me, I find that's what almost sustains me is a river. Where we choose to stand in the river, if we choose to stand in the river, as opposed to being sidelined on the bank, whatever comfortable distance away, we choose to stand in the river. And as people come, we take some people out, some we can't save. But the reality is there's always going to be those inequalities for reasons that we could talk about in another podcast. And that it's okay sometimes to get tired and have your legs quiver under you and need a break because it's not a lake that's going to be drained. And it's okay sometimes to feel overwhelmed and need to rest or to just say it just feels overwhelming. But I think what Paul would say is I go back in the river because once I've been in, I can't be anywhere else. I love that. And once you've seen it, you can't turn your back and that there is beauty in la lucha. I want to talk a little bit about what your life is like now in your role at Housing for Health in LA. And maybe we can start by talking about what you mean when you say you're going to end homelessness. Yeah. You know, one of the things I loved Paul talking about was big, hairy, audacious goals. Like don't set the bar low. And I think our commitment to ending homelessness is a testament to that. And that again, the fact that in this country, as wealthy as it is, in LA, which is wealthy as it is, the obscenity of the magnitude of houselessness. And I'm not just talking about the lack of physical structure, but a belonging community integration for so many people who find themselves houseless. But it's also a societal flaw, right? It goes back to the way we're structured and what we value, this idea of individualism and that you're responsible for your own fate as opposed to this concept of us being in a civil society and being measured by the health of all people, not just a certain tier that we value or respect given our sort of bizarre template of judgment. I think that it's not probably a surprise that I do this work because again, it's an intersection of the structural forces in health. And in LA, this is where health advocates and social justice warriors are committed to health as a human right. This is where we work. And one of the things that I think is so interesting when you compare, let's say, L.A. County to New York, when New York is a right to shelter state where it's not as visible, is the homelessness in L.A. is in your face. You cannot deny it. We walk by it, but you cannot deny it. And what's been so compelling, but also challenging is dealing with the politics and personalities surrounding the fight to end homelessness. And I am daily humbled and I have so much to learn in this space. And I'm really excited about the work that I do every day. And I carry Paul with me every day because his lessons resonate here so loudly. And I see him in the face of every person I encounter. Every overdose we try to reverse with Narcan. Every person that we find in their homes in a fetal position after housing them, but we haven't addressed their traumas and their lack of self. In every person who has borne the brunt since childhood of being a poor black male and dying of congestive heart failure at 37 in our country. Living in a van with his family. This is what we're fighting. And it's a good future. It's a tall task, but I think one of the things that I've really learned is we're all in it together. And I think that's one of the things also going back to the idea of medical education is it's not just us as MDs who are going to solve this problem. We have to be able to position ourselves not as lead, but as peers and equal partners, right? APSS worker who's trying to work on the SSI application, the DSFS worker who's coming to visit the family because someone made an allegation of child abuse, you know, with the nurse who's doing dressing changes. All of that is so important in building that community of care. And that's another thing that we really need to learn how to do better in the medical field. How do you help the 37-year-old Black man with congestive heart failure living in a van? What does that look like? Well, I'll tell you a story. So I'll call him James. I met him in my clinic on Skid Row about four years ago. And, um, I had done some reading before he came into clinic and just all through the chart. And you know, this Lisa were, was language around difficult, defiant, challenging, aggressive, angry, non-compliant, non-adherent. And all of these paragraphs of vitriol, really, I mean, tied up in medical lease, right, against this person. And he was in the emergency room every 10 days. He would come in with fluid overload, difficulty breathing. They would give him Lasix. He would pee out like a racehorse, nine liters, and then leave against medical advice the next morning, refusing hospitalizations. Wasn't making any of his outpatient appointments. They didn't think he was a good candidate for an AICD, even though his EF was 10%. And so gave him a vest with a defibrillator device, told him to wear it, prescribed him medications over and over again, which he never seemed to be able to take. And at one point, they just decided, clearly he doesn't care about himself and had referred him to hospice. He was a 37-year-old guy on hospice. And nowhere in the chart did I see a story, even from the social worker. It was unbelievable to me. And I remember I was in my room, I was finishing up with a patient and I heard screaming, shouting. And I went out and James was very upset because I was running late. And I asked the medical assistant to bring him to a back room. And then he started yelling because the blood pressure cuff was too tight and he was cursing and she got scared and she knocked on my door. And I was like, you know, just leave it alone and I'll be there in a second. And, you know, I, I walked in and he was struggling to breathe. He looked scared.
And he started crying. He's like, I'm here because I don't want to die. And he shared with me a story. His mother had died from a drug overdose when he was little. His father was in jail. He'd been raised by his grandmother. He was running the streets from the time he was eight. And he remembers being dropped off by his friends that he ran with at an emergency room when he was 10 years old, when he collapsed and his blood pressure was 220 over 110 as a 10-year-old. And he ended up in juvenile facilities and foster homes and jails. He met his woman, as he called her, and they started having children. And using his words, he said that she was slow and that they had to keep moving. Didn't get into a whole lot of details, but I suspected it had to do with concern for the children's welfare. And he had ended up in LA and he was living in a van in the parking lot of a hospital with his woman and four children aged 10 months to 11. And I asked him, you know, what makes it hard for you to take your medications every day? And he said, where am I going to put them? I have a baby in the car. I leave them with a friend. When I have gas money, I drive and I take them, but that might be once or twice a week. And I said, what makes it hard for you to wear your vest every day? He said, I'm not going to electrocute my kids. What if that vest goes off and it goes through the coils and it electrocutes them? And I asked, what makes it hard for you to stay in the hospital and get the care you need? And he said, the most important thing to me is that my kids get an education and that they're taken care of. And he said, I go into the emergency room and my kids are asleep and I need to get out in the morning to feed them and make sure they get to school. I can't afford to stay in the hospital. And he talked to me about how they were making ends meet by selling his hospice pain meds. And he was paying for his oldest kid to go to a Catholic school because his dream was for him to get a college education. And that he felt bad that he had to sell his drugs, but they didn't have any income. And they did the best they could, you know, and eating fast food. He didn't have access to all these low salt diets that people were applying him with handouts when he left the ER. And when I asked him why he came in today, he said, I woke up at three o'clock this morning and my 11 year old was sitting in the front seat staring at me. And when I asked him why he wasn't sleeping, he said, I'm worried you're going to die. And he said, I can't do that to him. So you have to help me. And none of that was in the chart. If you don't know that, how do you begin to work with someone like him? Right? Everything, all the choices he made were rational and were for his family, which was his most important thing. And we were able to talk about calling DCFS, which was a really hard thing. It took me two weeks to convince him. But they got him into an apartment with his kids. And he was able to get respite care for his wife, for the baby, into the home so that he could get to his appointments. I was able to get an AICD in him. He was able to start taking his meds. His EF went up to 40%. Right. But it's because of that ability to let go of all of our preconceptions of people and really listen and appreciate without judgment the choices that they're making and figure out how do I work within that reality? Because he wanted to be healthy for his kids. And so when I ask, like, how do you ask, how do you work with someone like that? It starts with listening and really hearing and being patient-centered. My guest is Heidi Befroes, a physician and advocate. Heidi's currently working to end homelessness in Los Angeles County by reimagining healthcare through genuine relationships and a deep understanding of both people and the structural forces that shape their lives. It's been such a pleasure to get to talk to you. It actually blew my mind even more than the first time. It's a pleasure. Anytime. And thank you too, Lisa.
Hello and welcome to the podcast for the March 2011 issue of The Lancet Neurology. Richard Lane here and this month I'm joined by Alison Rowan to discuss some of the issue highlights. Alison, welcome. Let's start with the research article. This concerns a way of identifying certain symptoms long before people are diagnosed with familial Alzheimer's disease. Interesting sounding study. What's the background here? So over the last couple of decades, it's been widely recognised that cognitive complaints of varying degrees occur before full-blown dementia is seen. And these are often referred to as mild cognitive impairment, or MCI, and pre-MCI. But because most Alzheimer's disease is sporadic, it's difficult to track disease progression before the onset of dementia. In rare cases though, in about 1% of people with Alzheimer's disease, development of the disease is inevitable because they carry fully penetrant autosomal dominant mutations. People with these known mutations for familial Alzheimer's disease provide a rare opportunity to study the disease course. So in this report, the researchers set out to characterise distinct clinical stages of progression to dementia in the descendants of a family of Colombian patients who carry mutations in the prasannolin-1 gene. Thanks Alison, and tell us a bit about the methodology here and the specific population that we're talking about. So the researchers studied this large Colombian family, half of whom carry a single mutation in the prasenilin 1 gene. They retrospectively assessed the cognitive profiles in about 450 individuals in this family who carried the mutation, and about 500 individuals who didn't have the mutation. The study took place over 15 years, and every two years the participants had medical and neuropsychological assessments, and they completed checklists on subjective memory complaints. Thanks, Alison. How would you summarise the key results here? Do the results show that there are defined time periods for pre-dementia symptoms, such as memory loss, before progression to full AD? Yes, that's right. The authors described two stages of early cognitive decline that were seen before the onset of MCI and dementia. The first was an asymptomatic pre-MCI stage, which they defined as impairments on neuropsychological testing, and the second was symptomatic pre-MCI, which was distinguished from the asymptomatic stage by the presence of benign subjective memory complaints along with the neuropsychological impairment. These early cognitive changes could be seen up to two decades before onset of dementia. The median age at onset for asymptomatic and for asymptomatic pre-MCI was 35 years and 38 years, while median onset was 44 years for MCI and 49 years for dementia. Cognitive changes mainly affected memory and in some cases also involved one or more other cognitive domains. So what do the study authors conclude, Alison? Well, the authors conclude that people known to be at risk of developing early-onset familial Alzheimer's disease should be followed up from the third decade of life. And they also note that identifying similar stages for all types of Alzheimer's disease would be helpful to ensure that these patients can be included in clinical trials and so that any future preventive therapies can be given before there's been too much decline. And Alison, there's a comment alongside this research article, so comment on the comment if you would. Yes, so the author of the accompanying commentary echoes the conclusions of the paper and says that although the definitions of the pre-dementia states are unconventional, this characterisation of the natural history of disease progression does provide a framework for the design of studies of interventions to prevent dementia. Next, Alison, let's discuss a review, and this is looking at apolipoprotein E or ApoE and the way it influences certain neurological disorders. What's the scope of this review? So apolipoprotein E or ApoE mainly exists as a component of lipoprotein complexes and is crucial for regulating lipid metabolism. It's widely expressed in many organs, but especially in the liver and the brain, and various roles for the protein have been proposed, including roles in amyloid beta metabolism, CNS lipid homeostasis, synaptic activity and neuroinflammation. In humans, there are three major forms of the APOE gene. The APOE E3 allele is the most common form, followed by APOE 4 and the APOE 2 allele is the rarest form. Differences in APOE genotype have been shown to affect risk and outcome of some neurological diseases, with Alzheimer's disease and cerebral amyloid angiopathy being the best studied. Because of the effects of APOE in these diseases, and because various biological roles have been proposed, numerous studies have investigated its potential link with other neurological disorders. And the idea behind this review is to assess the evidence for these links and consider potential mechanisms. Thanks very much, Alison. And go on and tell us a little bit more about APOE in relation to Alzheimer's disease. You've just given us some intro there, because am I right in thinking that there are different genetic forms so that sometimes the APOE can be neuroprotective and sometimes the opposite? That's right, yes. So the authors provide detailed discussion of the associations with Alzheimer's disease, and they describe evidence suggesting that the E4 allele is a major susceptibility factor for Alzheimer's disease, and that it reduces the age of onset. APOE E2, on the other hand, seems to confer protection against Alzheimer's disease, and similar links for the E4 allele and risk of cerebral amyloid angiopathy have also been reported. For these two conditions, the authors discuss the potential roles of APOE protein, including its effect on amyloid beta accumulation, as well as how differences in genotype influence response to therapies for Alzheimer's disease. Great, and the review also goes beyond AD, doesn't it, looking at the role of APOE and its influence on other neurological disorders. I'm not asking you to do all of them because there are quite a few, but do you want to just give a couple of examples of other neurological diseases? Yeah, that's right. They discuss the potential effects of the genotype in various neurological disorders. In traumatic brain injury, for example, some studies suggest that patients who carry the E4 allele have an increased risk of developing Alzheimer's disease and that they're more susceptible to poor neurological outcome after traumatic brain injury. And in people with Down syndrome associated dementia, the link between APOE genotype and risk and age of onset of dementia follows a similar pattern as for Alzheimer's disease. There are also some suggestions that outcome after intracerebral and subarachnoid haemorrhage might depend on APOE genotype. Taking all of this together, are there any general conclusions that the authors make concerning the role of APOE? Yes, so the authors note the compelling evidence for links between APOE genotype and Alzheimer's disease, cerebral amyloid angiopathy, and possibly some of the other disorders, and stress the need for improved knowledge of the mechanisms of APOE protein in these conditions, which might help with understanding pathogenesis and treatment. The authors also point out that the jury is still out on whether APOE influences other disorders such as vascular dementia, multiple sclerosis, amyotrophic lateral sclerosis and Parkinson's disease. And as they say, we need further research to understand any contribution of APOE to these disorders. Thanks Alison. Briefly if you would, another review and this concerns processes of neuroinflammation within the context of amyotrophic lateral sclerosis or ALS. Help me here Alison, what is neuroinflammation? Neuroinflammation is a common characteristic of ALS and other neurodegenerative diseases and it's characterised by reactive microglia, astrocytes and T-cells which in ALS contribute to the death of motor neurons. So how is it relevant in the ALS setting? The effects of the neuroinflammatory reaction on motor neuron degeneration and other neurodegenerative processes are now areas of intense research and neuroinflammation is thought to be a promising target for therapeutic interventions. The authors here focus on the mechanisms of glial activation in ALS. From a clinical point of view, studies have so far been disappointing, but an increased understanding of the biological processes of the inflammatory reaction might hold the key to some novel therapeutic approaches for ALS. And finally, Alison, let's end where we started, talking about dementia, specifically dementia awareness, which is the theme of the Leading Edge, the editorial this month, both here in Europe and in North America. What are the key points here? So in January, the US National Alzheimer's Project Act was signed into law and the European Initiative on Alzheimer's Disease and Other Dementias was approved by the European Parliament. Both initiatives promote the creation of national strategies for dementia, and include a range of aims covering prevention, early diagnosis, treatment, care, advocacy and research.
But ultimately, as we say in the editorial, more research is needed for long-term progress in tackling the burden of dementia and what's really needed is biomarkers for early diagnosis and research into basic mechanisms to identify targets for disease prevention. So finally, what are the conclusions? What's the bottom line of the editorial? What are you calling for? So while the goals of both initiatives are very helpful in raising the profile of dementia and creating better coordinated national strategies are important first steps, no extra money has yet been earmarked for the plans. To make real progress in tackling dementia, these plans must be backed up with the much-needed financial resources, and this is especially true for research in dementia. Compared with funding for other major diseases such as cancer and heart disease, the amount currently spent on dementia is a drop in the ocean. Excellent. Great topic. Many thanks indeed, Alison, for steering us through the March issue of The Lancet Neurology. We'll see you next month.
I'm Joan Stevenson, editor of JAMA's Medical News and Perspectives section. Today I have the pleasure of speaking with Dr. Rob Hayward. Dr. Hayward, why don't you introduce yourself to our listeners? Well, hi, Joan. It's a distinct pleasure chatting with you today. I do wear lots of different hats as it concerns evidence-based practice, but I am a contributing editor for the User's Guides in JAMA Evidence and on the advisory board at my home institution at the University of Alberta. I serve as assistant dean of health informatics, and I direct the Center for Health Evidence, which has had a long and very happy and productive affiliation with the user's guides initiative. Well, in thinking in how clinicians can apply this information to their work, what is evidence-based practice, and how can a busy clinician use evidence to make clinical decisions? Well, there's lots of evidence-based words out there, evidence-based medicine, practice, nursing, decision-making, policy, whatever. And there's also a lot of, in my view, misconceptions about what the whole evidence-based movement is all about. If it gets a bad rap, it's usually that it asks us to pay attention only to the results of the highest quality of randomized, double-blinded, controlled trials, whereas those who work in the field, I think, are more convinced that it's about the practice side of things and not so much the evidence side. An evidence-based practitioner is committed to being as aware as is possible of the type and the strength of the evidence that links what we do and why we do it. So it's really about the connection between evidence and action, and that enforces upon us a kind of pragmatism. There just aren't trials out there that address all the questions that we have to ask, but we do need to have good taste in what knowledge is stronger or weaker for the questions that we're asking. So it tends to boil down to having skills in asking answerable questions, asking questions that can be addressed by the kinds of knowledge sources that are available to us, and being very sensible and pragmatic in how we apply that to patient care. But if I was to sum it down to just three things that I tell all of the learners that I work with, it doesn't matter whether you are thinking about evidence that comes from a colleague, something that's in a consultant's letter, or something that you read in a high-quality journal. At the tip of your tongue must always be questions of validity, importance, and applicability. In other words, can I believe what I'm hearing? Even if it's believable, does it promise the impact that my patients would care about? And even if it is of high impact, is it the kind of knowledge that I could use, given my circumstances and my patients' circumstances and values? And so it boils down to the three pillars of validity, importance, and applicability. Healthcare decision makers must consider various sources of evidence to arrive at optimal decisions, and that includes external and internal evidence. What are some of the examples of these? Well, the distinction between external evidence and internal evidence is something that we hear about and we're reading more and more in the literature. It's very simple, and in fact it's a marker of some of the real excitement in the evidence-based movement today. That excitement is the realization that the thinking tools that have been developed to help us decide whether we believe, care about, and can use the results of experiments that are done, clinical experiments, controlled trials, qualitative inquiry, whatever. Well, that inquiry has been conducted usually on patients other than our own, and in that sense is clearly external to our own patient populations that we're trying to help. And so two major sources of external evidence would be the results of clinical investigation, controlled trials, and other forms of investigation, but then also a very large and increasing body of health services research that concerns itself with the cost, the staffing, the processes of how to actually implement knowledge in a way that is efficient, effective, and affordable. But within our healthcare systems, as a byproduct of this digital revolution we were talking about earlier, we have some pretty impressive administrative data systems, electronic medical records, outcomes databases that give us access to higher fidelity information about what's going on in our own population. And the real trick to making good use of the results of research is to see when to apply it in your circumstance and when maybe you shouldn't. That depends upon knowing your circumstance very well. So there's two major sources of internal evidence that we're getting better at gathering, organizing, and understanding. One source is what comes from our various clinical systems, labs, radiology systems, medical records. And another is an increasing access to things like, well, Google Health, consumer-centered information systems that improve the tracking of our patients' experiences and symptoms. The real excitement for evidence-based practice is that those core thinking tools that we've been honing over the years on how, for different types of questions, you can decide whether you believe the research, we're finding that those map very nicely to the kinds of thinking tools you need to use when making sense of internal evidence. And so it's probably more of an answer than you were looking for, but there's a lot of excitement in applying the thinking of EBM to the medical records, administrative data sets, claims data sets that we find within our own internal health care organizations. So I'd emphasize some of the extra things that are part of the online resource that you simply can't get in the book. Interactive calculators, worksheets that help you take a paper you're reading, answer some basic questions, and have more of a sense of its believability, and things like the information cycles attached to many of the chapters. Is there anything else you would like JAMA Evidence users to know about evidence-based medicine? Well, that it's finally coming into its own, and it's going to have a huge impact on the way in which we manage and experience the information flow at the point of care. Impact not only because we finally are seeing the emergence of more and more high-quality, evidence-based systems that make it clearer for clinicians how to guide their practice with the evidence that they are reading in a highly distilled and summarized format, but also because the very medical records and so on that we're using are starting to change in ways that are more sympathetic to the needs of an evidence-based decision maker. So, yes, I'd emphasize that the stuff that appears in JAMA evidence, and particularly the gold that is found in the rational clinical exam series, that's very much of its time. We urgently need it. And for those of you coming up for any kind of assessments, examinations, or certification, it's the kind of thinking that examiners are looking for these days. But if I was to answer that question from the point of view of JAMA evidence itself, the one final thing I'd want folks to know is that this is a dynamic resource. It's not static. There's new stuff being added fairly regularly, and the new stuff reflects not just what the authors think, but what the folks using the user's guides think and give feedback about additional questions or issues in applying that they'd like to have explored. Thank you very much, Dr. Hayward. Thank you.
Thank you. unless so identified. All relevant financial relationships have been mitigated. Information contained herein should never be used as a substitute for clinical judgment. For more episodes, links to CME and MOC, College of Cardiology calls air pollution a modifiable risk factor. Welcome to Annals on Call, a podcast based upon articles from the Annals of Internal Medicine in which we discuss the implications of the article for you, the listener. This is Dr. Bob Centaur. I'm Professor Emeritus at the University of Alabama at Birmingham and former chair of the Board of Regents for the American College of Physicians. This episode of Animals on Call features an article titled Environmental Health, a Physician paper from the American College of Physicians. It appeared October 2022, accompanying it, Environmental Health Translating Policy into Action, printed in the same issue. Joining us on this podcast are the editor of the editorial, Dr. Emily Sine, who's an associate professor in the Department of Environmental Medicine and Public Health at the Icahn. Thank you for listening to our podcast. Thank you very much for joining us on the podcast, Emily and Suja. Environmental health is very important. Some things we can do something about in the short run, some things we can do something about in the long run. But your paper really, that Suja is one of the authors of, really addresses the impact of environmental factors on patient health. And we need to understand what some of those factors are and what can we do at a local level? What do we need to do at a more national level or even a global level? And what I'd like you to do is go over some of these and have a conversation on a particular environmental factor, and then perhaps give us some concrete examples of how that may pertain to people in practice. So, Suja, why don't you start and talk about the paper and then have a sort of a question and answer with Emily. Well, thank you so much, Bob. It's really an honor to be here with you and with my colleague, Emily, as well. I'm really proud to talk about this paper. So as you know, it's our policy recommendations on behalf of the American College of Physicians that went through our usual process of development, which is lengthy and robust. And what we hope to accomplish with this paper and through this discussion and others is to identify and create a common body of understanding around the environmental factors that impact health for our patients, for our communities, particularly focused on our marginalized communities, and understand here as physicians and as a collective body of physicians, we have an enormous opportunity and in fact, a responsibility to address these issues. So that's a lot to start off this conversation, but that's from where I come and from where the American College of Physicians come into this conversation. Environmental health is multifactorial. And so we intend to address various aspects of the environment that impact the everyday health of our patients and our communities that we serve. So we're talking about climate warming. We're talking about water cleanliness. We're talking about other toxins that are present in our environment and other factors as well. So it's the combination of those environmental factors that we recognize have a direct impact on individual patient health. Emily. Thank you, Suja. Thank you, Bob, for inviting me to participate today. I commend the American College of Physicians for digging into this area. We have to remember that somewhere between 70 and 80 percent of the health of our patients is not determined by their genetics, but rather by their environment, whether it be the communities that they live in, the air they're exposed to, the food they're eating, what sort of cultural pressures they might be under. And I think broadening out our history and physical, if you will, of where our patients are coming from to environmental factors is critically important. And that's why I'm a big fan of the paper, expanding these in a much deeper way into the medical community and very supportive of looking at ways that we can understand this better and what we can do in the clinic with our patients directly, in the community, at the hospital level, regional, national, global level. We should be thinking about this because this affects patient outcomes. And it's not as acknowledged as it needs to be. Yeah. And yet, Emily, we see it every day at the bedside, don't we? We see it when we're treating our patients that present with asthma as a great example of the clear impact of the environment on one's health. So we also recognize that the incidence of asthma is disproportionate among certain populations. And again, we mentioned before our marginalized populations that may in fact be more exposed to environmental toxins. And at the same time, we see that they have a much higher incidence of asthma, even at the very young ages. So it really is something that comes to the bedside. One of the things that the committee, your group who wrote the paper went over that I was very pleased to see was a discussion about air quality. And the fact that the current standards, the National Ambient Air Quality Standards, or NACS for short, may not be restrictive enough in terms of particulate matter, if you will. There are many parts of the country that are not meeting safe air quality standards. And when you talk about people with asthma, we need to remember that particulate matter, air pollution, is a very provocative thing to the cardiovascular system. The American College of Cardiology calls air pollution a modifiable risk factor. If it's a modifiable risk factor, we need to be actively modifying it. So I was really pleased to see that. For my own patients, I have patients who have rather severe respiratory conditions. I often advise them to put one of the little air quality apps on their phone and to check it before they go out. There are certainly times of day where they're going to have a problem because the air quality is not good. I was pleased to see a lot of emphasis on air quality as well as water quality in the new recommendations, policy recommendations. Let me ask you a question about that because I really love that because we all take care of a lot of patients with respiratory problems. I've seen apps that would tell me what the air quality was today, and I see it changing. Can you be even more practical about how you actually have that conversation with the patient and what ranges you tell them to pay attention to? And are they able to do it, especially those people who have to work to make a minimum wage, for example? You're right. Sometimes the technology is challenging. There are a lot of apps that are terrific. Air.gov makes an app. That's just one. I don't want to plug any one specifically. But then you advise them that when it gets into the orange range, they need to be very vigilant about their own symptomology and make sure they have all their medication with them. I have some patients who really can't leave the house when the air quality gets bad. I have some patients don't leave during summer months when you have a combination of heat and poor air quality, because then you've got ozone, which brings me to another thing I think we need to discuss. The paper focuses on all these different exposures, right? We talked about chemicals in the environment, heavy metals in the environment, poor air quality, poor water quality. In the environment that we're living in now, we don't have the luxury to focus on one exposure at a time. We have to manage multiple negative impacts on our patients. She mentioned climate change earlier on, and we're going to see more complicated events from climate change. So the environment that our patients are living in has multifactorial environmental exposures that we need to be up on, learn what to do about. So yes, I do advise some of my patients, and they can use the app. You'll be surprised. Once you sit there and download it with them, they get it. One question, because I'm somewhat ignorant here. When you have someone who is concerned about particulate exposure and they really need to get out, does masking help? No. Masks are not recommended unless you are in an area such as a wildfire where PM2.5 would be very, very high. The CDC, as far as I know, I haven't checked it in a year or so, does not recommend masking for poor air quality days. They recommend avoidance. So, for instance, if you know that you're highly sensitized, you might not want to try to do your physical activity during rush hours. You might want to try to do it later in the evening or early in the morning before you have those. So it's really about avoidance of these exposures rather than masking. Great. Well, you mentioned drinking water, clean water, et cetera. Maybe the two of you could discuss that part of the paper also, because I know that there are certain places where it's pretty dangerous to drink water.
So I think that water, and obviously with Flint, Michigan, and the just tragic events that unfolded there and continue to take a toll on those lives, it's heightened our awareness of water quality and the need to ensure clean water in, again, Bob, I have to say, in a equitable way. And that's something I want to underline once more, is when we're looking at environmental health, it's impossible, frankly, to not see the inequities that exist across our nation and how marginalized groups have been historically disadvantaged, whether we're talking about water quality or air quality, particulate matter exposures, etc. There's a real strong theme here that I would be remiss to not to underline. Emily, do you want to expand on that? I'd like to say one thing about that just in addition. The healthcare workforce is the largest workforce in the country outside the U.S. military. And as we saw in the general population, in the health care workforce population, we saw that minority populations were hurt first and worst where the pandemic was concerned. More health care workers of color died of COVID or became sick from COVID than any other two times at least. And, you know, we might want to start with the man in the mirror. Our workforce comes from the communities in which they live. And thinking about it from a health system perspective, that's one area where we can be more active in our local communities, advocating to understand and improve some of these environmental justice issues. We're working in these communities now. Many of our employees come from these communities. Yeah, that's fantastic, Emily. That's fantastic. Thank you for that challenge. And I think, as always, we implore others to consider health equity in every decision. But that's a great reminder that we should be, you know, first and foremost responsible ourselves from that perspective, but also in terms of, you know, our contribution to the environment and healthcare contributes significantly to carbon emissions. So, you know, what are the changes that we can make institutionally and the organizations that we work for, even in our local practices where we can be frankly better citizens. So Bob, you started off like, what can we do, right? What do we do as physicians? We talked a bit about some of what we can do at the bedside, that recognition and direct counseling around air quality, et cetera, for our most susceptible patients. I also want to make sure we talk about the fact that we are strong advocates. We have the potential to be very strong advocates, again, on behalf of our patients and the communities that we serve and that we have this responsibility to, frankly, come up with position papers just like this one and then use these, you know, our positions to inform the advocacy work that we do both locally and nationally. One of the things that I heard you say, Emily, is that we need to be able to talk to patients when we believe that there are environmental factors that are impacting their health. And I know you have experience with that. So perhaps you could talk about how you have that conversation and when you ask and how you ask about their living situation and try to figure out whether they're in an area that has bad water or has more particulate matter and give us some clues as to how we can include that in our social history. Sure. One powerful question that you can ask patients is how close do they live to a roadway? People who live close to roadways have much worse health outcomes than people who don't live close to roadways. Understanding that about patients can tell you about their risk factors. And, you know, we can't move people, but we can recommend lifestyle changes that can help protect them somewhat. Right now, I'm working on approaching patients who need to make lifestyle modifications through health coaching. In other words, looking for ways to choose one or two health goals for patients who are in risky circumstances like living close to roadways that might improve their overall health status. So if it is as simple as incorporating maybe for the first time ever some vegetables or some physical activity away from the roadway, something really simple and helping them improve their underlying risk factors so that the conditions they find themselves in the community are not as able to affect them. That's one way. But the other thing I will say, she mentioned something I wanted to add into, which is our own healthcare footprint, the toxic and carbon footprint of healthcare delivery, which is huge here in this country. And I think maybe we should talk about how we go about reducing our own toxic waste, our own carbon footprint. And I have some thoughts on that if you want to discuss that more in depth, because I think these things go hand in hand. Well, I think that's exactly one of the things that we want to get out of this discussion. So why don't you continue? Right now, healthcare delivery in this country is responsible for about eight and a half, maybe 10% of all greenhouse gas emissions in the country. You know, how do we prepare our facilities for climate impacts? And I think one way we might think about doing that is require that health facilities both measure and manage all their carbon emissions and their waste, and also undertake thorough assessments that use climate modeling that can help determine whether or not there are areas that might in five years, 10 years, not be habitable. A recent study looking at health facilities up and down the Atlantic coast and the Gulf of Mexico identified many, many facilities that are in very risky areas as sea level rise. So I think we need an all-in approach and an acknowledgement that this needs to be part of health care planning, is acknowledging our waste and emissions, managing it, and also looking at threats from climate and the environment to bolster our health care infrastructure. So you stimulated me to ask a question. I hope it's not too controversial, but it seems to me, and I live, as you know, in Alabama, which is a very rural state. And when I go to big cities, I seem to see a lot more smog and things like that. Are there any studies that look at the big city itself as a risk factor compared to a rural environment in terms of environmental? Or am I just making something up? Well, you live in Alabama. Alabama is a hot state. Is that what you mean, that kind of thing? No, I'm talking about when I go to a big city, number one, there are a lot more cars. There's a lot more people driving. When I go over to Atlanta, there are six-lane highways. That cannot be good for the environment to have that much traffic. Are people who live in the inner cities of big cities at more risk than the same demographic who lives out in a rural area? Well, there might be differences there. But one question you might want to ask yourself that might be useful is, what are the health outcomes of Alabama relative to the rest of the country or any particular state? That would give you a good idea. Now, we're talking about environment and climate change. Everybody's going to feel these environmental catastrophes to some degree. It's going to be worse in some places, no question about it. So it's really about localities. But health outcomes, I think we have a pretty good idea about how health outcomes are in different states. Yeah, Bob, I think, you know, you're asking your question, I think, about sort of automobile emissions and other industry emissions that you might see in a big city that are very different from a rural environment. But if we step back, while that might be true, environmental health is also addressing other types of exposures. Again, we've already addressed water, but other toxin exposures. So I think, frankly, it depends. Your experience and your exposures, your overall, the impact of the environment, of all aspects of that environment will vary. But what is not in question is we are all, each one of us, affected by our environment, that collection of exposures. Let's finish up with, I'd like each of you to come up with two or three most important actions that you would recommend our members consider over the next two to five years. Well, I'll go first, Bob. I think, you know, my bent is always towards the macro, tends to be towards the macro, I should say, and our opportunities to be advocates as physicians individually and also collectively. So I think what I would say an important next step for us as physicians is one is recognizing that these effects are real and impacting our patients every day. Second would be to speak about this to one another and to our colleagues, speak openly about this to our patients and begin this conversation. And then I'll end and say that our role as advocates is tremendously important. So I think that, again, collectively and speaking to legislators and other officials that are in positions to ensure safer standards, equitable implementation of standards is key for us as physicians as well. Emily?
They can assess specific risks to their areas and elucidate what local problems might be and address them through learning and through advocacy. Now, in terms of broader issues like air quality and water quality, all those large-scale things need advocacy, which is why I think the paper is so important. But we can advocate from the bottom to make sure that the top down solutions occur. So anything that you can do to, you know, advocate for broad solutions to environmental problems, whether it be at the state level, regional, local, national, will help everyone. Thank you both for joining us on the podcast, shining a light on this important policy paper and your wonderful editorial, Emily. And I hope people learned quite a bit and we'll go back and read the policy paper and the accompanying editorial. Thanks so much. Thank you very much. Now it's time for Bob's Pearls. We had a very interesting discussion about the impact of particulate matter and how one might counsel patients to avoid days with high particulate matter, especially in those areas that have that form of pollution. We also had a very nice discussion of understanding our local water supply and whether or not there might be toxins associated with that. And in particular, there are some cities where there's still lead pipes and patients could be exposed to lead inappropriately. And finally, Dr. Matthew and Dr. Sine urged interested members to advocate at both a local and a national level for policies to improve environmental health. We thank you for listening to our podcast. Information contained herein should never be used as a substitute for clinical judgment. For more episodes, links to CME and MOC, or to view disclosures, visit go.annals.org slash on-call.
This is exactly right. So if you're into home decor, I would suggest looking into Buy Nothing Facebook groups. It's a great way to explore your style all for free. Ooh, we love free stuff. Thanks, Julie. See you next time on the Flash Finds podcast, all about discovering the diagnostic lab that I was working in was adjacent to, when it first opened, the first Ebola patient was an eight-year-old girl who was very, very ill. She actually only survived for a week after that. But she made a special request that she would like some coconut water. It was very easy to get hold of this and it was all arranged. But one lasting image that's like forever burned in my mind after my time in Sierra Leone is a doctor all kitted out in their full Ebola PPE carrying two coconuts into the high containment Ebola treatment tent. One of the stories that really, really struck me was one of our survivor health advocates, Kalako Karoma. She had several children. She was married and they ended up contracting Ebola from a couple traveling into their village from a different village that was affected already. And so they got sick and died and the couple had a baby and Klako had a baby also. And so she took the baby whose mother had succumbed to the disease and breastfed that baby to keep the baby alive. And so the baby, unfortunately, had gotten Ebola from its mother and passed it on to Klako. And then she passed it on to her baby. And so she ended up losing four of her children, including her infants, as well as her husband. And it's incredible to hear someone tell that story and all of the emotion, but then also see how strong she is afterwards and how she's like, she's showing up every day. She wants to be a part of her community. She wants to rebuild her family and just had like so much hope for the future. And so that was pretty incredible. There's a lot of like heartbreak, but there's also a lot of hope that came out of it. People caring for people that they loved were the ones who were getting this disease. And it's like a crazy thing. Yeah, it's vicious. It's vicious. Like passing along this deadly disease through acts of love is really, really hard to imagine. I mean, can you imagine being told that you can't comfort your infant or your toddler or your spouse while they're in like exquisite pain? Just incredible. Hi. Hi. And welcome to episode 11 of This Podcast Will Kill You. Wow, that's exciting. I know. I'm Erin Allman-Updike. And I'm Erin Welsh. In case you haven't figured it out, this episode is all about Ebola. What you just heard were firsthand accounts of the 2014 Ebola epidemic told by three badass women, Lauren Crowley, Nell Bond, and Sarah Page. We're going to let them introduce themselves. So my name is Lauren Cowley, and I'm a postdoctoral research fellow at Harvard P.H. Chan School of Public Health. So I'm Sarah Page. I had a circuitous pathway to my current field. So I work as a global health fellow, and I'm based at USAID. So I'm a senior infectious disease advisor sitting on the health team in the African Bureau. So I work really closely with the global health team that's dealing with the emerging threats division and global health security. Yeah, so I'm Nell Bond. And so I first went to Sierra Leone, part of like a loss of fever lab, which is really interesting and exciting. And then now I'm working on AIDS pathogenesis in an immunology lab. So we'll get back to them and some of their stories a little bit later in the episode. So what are we drinking today? We're drinking the spillover. The spillover. What is in the spillover, Erin? Today it's tequila, kombucha, some lemon juice, and some honey. And don't forget the rim, which is a salt and sugar rim. But the most important part of the spillover, you could really make any drink that you want. Anything. Beer, wine, water, juice. La Croix, for example. Just make sure you fill it all the way to the brim of the glass so that it's about to spill over. Yeah. We're Ebola. Absolutely. One of the scariest. So Ebola virus is, of course, a virus. What? Shocking, I know. Specifically, it's in the family known as filoviruses. I think that's how you say it. They're called this because they're filamentous viruses. Under a very, very high powered microscope, they look like worms. Right. All the viruses in the filovirus family cause hemorrhagic fevers. All of them. Did you know that? I don't know all the viruses in the phylovirus. Do you want to know that? There's only two. Ayo! I made it seem really dramatic, but there's only two viruses in this family. It's Ebola virus and Marburg virus. Oh, okay. Okay. Yeah. I didn't know it was just so limited. I didn't either. So Ebola virus is an RNA virus, which we've seen before, yada yada. It has a fast replication rate. It makes lots of mistakes, et cetera, et cetera. Which means faster evolution. Exactly. Right. There are at least five known species of Ebola virus. Sudan Ebola virus, Zaire, Reston, which is a very interesting... Are you going to talk about it? I am. Yes, I'm excited. And then Thai Forest, which was formerly known as Ivory Coast or Cote d'Ivoire, Ebola virus. And finally, Bundy Bugio, I think is how you say that, which actually wasn't discovered until 2008. Which, that's crazy, an entire new species of virus. Wow. Except that it's not that crazy, since we basically know nothing about microbes and even less about viruses. Not just the ones that infect humans, but overall. Right. Okay, so. There are five strains of Ebola, and they differ in their pathogenicity. So the Zaire strain is the most virulent, with fatality rates of up to 90%. Yep. It's really, that's terrifying. And then the Sudan strain, which is probably the one that we know, Zaire and Sudan we've known about for the longest, so we know the most about them. They've caused the most outbreaks. Exactly. That one has a case fatality rate of usually about 50%. And then the other ones tend to be lower. We don't entirely understand the pathophysiology of Ebola virus. Meaning the way it causes disease in your body. Exactly. So we're not 100% clear on exactly what's happening inside your body. We know a few things. We know that it attacks your immune system, a few different types of your immune cells, and then it causes spontaneous cell death in other cells in your immune system. So basically, it's causing a lot of damage to your ability for your body to fight it off. Okay. We also know that it additionally infects your endothelial cells, which are the cells that line your blood vessels, which is why you can get hemorrhaging, which we'll talk more about later, because it basically makes your blood vessels leaky because it's damaging those cells. So, yeah. So then you have blood leaking out. Little pinpricks. Exactly. Caused by the virus. And one thing that is clear is that those people who survive an Ebola virus infection do so because they have a really good antibody response. Interesting. So somehow their bodies are making a lot of antibody and that's what makes a difference in the outcome of infection. That's really interesting that it has to do with an individual immune response. And I wonder what kind of, whether that's entirely genetic or whether it has anything to do with the number of diseases you've been exposed to in your lifetime. Or just the initial infection dose that you get infected with, like how many viruses you're infected with to begin with. And honestly, from my reading of it, and so someone can correct me if we actually know this, I don't think we really know. It's not really clear what the distinctions are between individuals that end up surviving and not surviving aside from this antibody response. And what causes them to have that response is unclear. And also like high risk groups. Exactly. Right. Yeah. Yeah.
That's between two to 21 days. On average, I've seen about 10 or 11 days. That's what it was, for example, in the last outbreak in 2014, 2015. Okay. Was around 11 days on average. So you touch somebody or you get infected. You get infected. And then 11 days later you start to show symptoms. You start to get the symptoms. And one thing that's important about Ebola virus is that you are not infectious until you start showing symptoms. That is very important. It's very important and you are not very infectious for the first few days of your infection after you start showing symptoms. So what that means is that how infectious you are to other people, meaning how easily it is for you as an infected individual to infect somebody else, depends on how many viruses are in your body. And that number of viruses is going to increase over time. So at the beginning of your infection, you're not very infectious. And so this is different than some of the other diseases that we've covered. Exactly. Where you are highly infectious even before you show symptoms. Right. Something like influenza, for example, you're infectious several days before symptoms start and you tend to be most infectious at the beginning of the course of infection. Whereas with this, you're most infectious at the end of the course of infection, which we'll talk about a lot later, but is really important, was really important in this most recent outbreak. Right. And is really important in general in terms of predicting what diseases might be related to outbreaks or epidemics and so on. Exactly. Interesting. Yeah. So the first symptoms of Ebola virus, Ebola virus disease. So Ebola virus disease used to be called Ebola hemorrhagic fever. It's no longer called that. But the symptoms include a pretty sudden onset of fever and a relatively high fever, fatigue, muscle pain, headache, and often a sore throat. Then this is pretty quickly followed by vomiting, diarrhea, rash, liver and kidney failure, and sometimes, although importantly not all the time, internal and external bleeding. So that's where it got its previous name, hemorrhagic fever, because to hemorrhage is basically just to bleed uncontrollably. So internal bleeding, which is something that we talked about, I believe in yellow fever as well. Right. Ebola virus does exist in basically all of your mucus membranes and things. So anywhere that it exists, you can get bleeding, but you don't have like explosive bleeding. Right. There's no bleeding out. Right. So you tend to die from things like very similar to what you die from in septic shock, which is just your body being overloaded by both immune defenses and the virus itself and then just organ failure. And that's what ends up actually causing death. The virus is transmitted via direct contact with certain bodily fluids, actually most bodily fluids, feces, saliva, blood, vomit, semen. No one said it, but I would assume vaginal fluids as well. And then the virus has to enter the next person that it's going to infect via contact with their mucous membrane. So eyes, nose, mouth, or a break in the skin. So it's not like you can get Ebola just from being in the same room as somebody with Ebola. It tends not to be transmitted via respiratory droplets, but I'm hoping you're going to talk more about that. Just a little bit, yeah. It's really interesting. It's actually really terrifying. That's, I think, the thing that makes people the most scared about Ebola is the potential for transmission via respiratory droplets, which we've talked about before, but again is coughing, sneezing, things like that. Yeah, that's scary. Close talkers. Close talkers. So yeah, so that's how you get infected with Ebola virus. Bodily fluids. Bodily fluids and direct contact. So healthcare workers are especially at risk of exposure because they're dealing with bodily fluids of people who are infected. Now, it's still not what I would call a thousand percent certain what the animal reservoir for Ebola is, but realistically, it's bats. Yeah, probably. Yeah, so more than a few studies have found Ebola virus, at least RNA, naturally in bat populations and without any evidence of infection. So the thing is that we know that Ebola viruses can infect other primates and other animals. They've been found in antelopes and things like that. But they tend to cause similar symptoms and massive mortality in a lot of those animals. Whereas in bats, we don't see that. So that is the evidence that the bats might be their quote unquote natural host. Because if viruses circulate for a long time in a host, they tend to evolve to be less virulent in that host. Whereas when they jump to new hosts, it's unpredictable what the virulence is going to be. But one thing that we do know for sure, and I think that this is going to be the transition to you talking about this, is that outbreaks tend to occur almost exclusively due to spillover events. So the question is, how did we get here? What's up with Ebola and how did it start to be this virus that spills over and kills a bunch of people? That is a question I'm going to try to answer. Our story begins, not in Africa, as you might expect, but rather in Germany. Oh, okay. Yeah. In a sleepy, picturesque little town. In 1967, several people arrived at the hospital with symptoms of extreme headache, internal clotting, fevers, and, most severely, terminal shock. Oof. What did these people have in common? Well, they were all workers at a lab which produced polio vaccine from the kidney cells of African green monkeys. In total, 31 people were infected with this infectious agent and seven of those died. Wow. During the outbreak, no one knew exactly what was causing the disease, but the appearance of similar symptoms and death rates in the green monkey populations at the lab pointed towards an infectious agent. Right. Eventually, researchers isolated the teeny tiny little nugget of RNA that was causing this terrifying disease and named it after the outbreak's location, Marburg. So now we don't have to do an episode on Marburg. How disappointing. I mean, it could still be a future episode. Yeah. But this episode is not about Marburg. No, it's not. It's about Ebola. Yep. So why do I talk about Marburg? Great question. Well, to answer that, let's jump ahead to 1976. Nine years. Nine years after the Marburg outbreak in Germany. In mid-September, a report came in to Kinshasa, the capital of Zaire, which is now known as the Democratic Republic of the Congo, DRC, of a strange new illness causing bloody vomit, bloody diarrhea, bloodshot eyes, and ultimately death in dozens of people. The epicenter of this outbreak was a mission hospital in Yambuku. A few weeks before this report was issued, the first case appeared, a local school headmaster named Mabolo Lquela. At first, the doctors thought malaria and sent him home with some pills to deal with it. But he didn't get any better. Not malaria. No. And saying he didn't get any better is a bit of an understatement. Oh, he died. Yeah. Yeah. About a week after he left the hospital, he died in pain, confused and bleeding from multiple orifices. His body was tended to and buried according to local customs, which include washing the body, clothing it, clipping fingernails, touching it and kissing it during funeral proceedings. Yeah. Yeah. Yeah. And since, as we know, Ebola is spread through close personal contact, it should come as no surprise to you that 21 of his close friends and family members became infected during this funeral. And that's when you're sort of most infectious is at the end of the course. But they had no idea. They had no idea. No idea. And so from there, it erupted, prompting the panicked reports for help. International help did come in the form of epidemiologists, virologists, and physicians. They went to work mapping out victims and tracing contacts. One unusual pattern emerged first. The hardest hit group was women between the ages of 20 and 30. Why do you think that these were the people most likely to suffer from Ebola and have the highest death rates? Were they the healthcare workers? Were they nurses? No. Were they the ones preparing the bodies? Who were they?
Oh. Right. One of the groups at highest risk or highest impact are those who are pregnant or recently given birth. Is that because their immune systems are depressed? I think that's one of the reasons. The other reason is that it turns out that this clinic, this hospital, was used a lot for prenatal care. Oh, no. And the nurses and nuns who were working at the hospital tended to reuse needles. Cross-contamination? Oh, that's so sad. Right. So, yeah, the epidemiologists there were pretty confident that they were tracking an outbreak of an infectious disease, but many questions remained. First, what was the pathogen? Second, how is it being transmitted? And third, where had it come from? Yeah, all good questions. Right. Essential in an outbreak. Tell me the answers. So to answer the first question, which is what was this? Yeah. They sent blood samples from infected people to the CDC to try to isolate whatever pathogen might be in there. Okay. The earliest theory, which is that the cases were yellow fever, was quickly rejected because of the extremely high mortality rate and the different yet equally or even more terrifying symptoms of the illness. Yeah. Next, Marburg, they figured it could be a similar, if not the same, disease. But let's look past the conjecture to some cold, hard facts. I'm talking microscope. Under the scope, the virus in the sample received by the CDC looked very similar to Marburg. It was thin and filamentous. Yeah. So similar. So similar, in fact, that later analysis would put them in the same family of viruses, as we've heard, the filoviridae. But this new virus wasn't quite the same as Marburg. It needed its own name. And for this part, the healthcare workers in Zaire basically walked outside the clinic, closed their eyes, twirled around a few times, and pointed. And their fingers ended up pointing towards the Ebola River. Isn't it the case that they're not supposed to do that anymore? Name diseases after the place that they were discovered because it puts a lot of stigma on them? Very true. Yeah. It hasn't really stopped the trend in Ebola? No, not at all. Like, every different species is named after where it was found. Yeah. Like, come on, guys. Get it together. Okay. So, at this point, the scientists can put a name to the face of this virus. But there are still unanswered questions. How was it being transmitted? Could it be vector-borne? Researchers checked bedbugs, mosquitoes, biting flies, but found no trace of infection. The numbers of infected, though terrifying, seemed too low for it to be airborne. That left close physical contact and exposure through infected bodily fluids. Still, the last question remained. Yeah. Where did this disease come from? Seriously. And that is actually a question that researchers are still struggling to answer. It's probably bats, as we've heard, but to date, no live virus has been isolated from a bat. But why do we think bats? Why are bats the top contender? Well, first of all, bats are incredibly species diverse. Yeah, they are. Did you know that one in every four mammalian species is a bat? No, one in every. I knew there was a lot of them, but oh my god. Yeah, there are over 1100 species of bats. So you go like cat, dog, monkey, bat. Yes. And then like armadillo. What are some other mammals? Dolphin, whale, bat. That's how you do it. That's exactly how you do it. Wow, that was embarrassing for me. What are some other mammals besides? Oh, here we go. Here we go. Rat, shrew, vole, bat. There you go. There's a lot of rodents too. There are a lot of rodents. Yeah. And so if each species of bat carries an equal viral diversity or viral load, that's a lot of bat viruses. Oh, yeah. And to add to that is the fact that most bat species are highly social and live in large groups. Yep. And does that remind you of anything? Yep. Like what happened when humans started living in large groups? I was going to say ants, but... Sorry. Entomologist. Put on your disease ecology hat. Humans, when they gathered in large groups, like during the agricultural revolution, that's when we saw a huge amount of infections. Disease emergence, disease spread, etc. Yeah. Also, many species of bat tend to have lifestyles or natural histories, sure, that bring them into close contact with humans, like roosting in buildings or in fragmented forests. And that's because we tend to destroy their natural habitats. I'll get at that later. Okay, great. Finally, bats can fly. Yep. They can travel great distances, particularly during migrations, up to 800 miles. And so that allows for the exchange not only of pathogens within and among bat species, but also with humans and wildlife. Yep, big time. Many Ebola outbreaks actually have been preceded by large-scale die-offs of primates such as chimpanzees and gorillas. In fact, one thing I read suggested that a third of the global gorilla population has been destroyed by Ebola outbreak. Ebola specifically? One third. Oh my god, that's so sad. It's insane. Wow. Yeah. And so, I mean, overall, the lack of information that we have about the natural history or the ecology of this virus is really pretty worrisome. Yeah. Because it then becomes harder to predict or prevent outbreaks from happening. Definitely. Wow. Oh, my Since there were already researchers on the ground in Zaire, a few of them figured they'd head to Sudan to assess the situation. And once there, they found a village already well within the throes of a similar outbreak. What were the chances? What were they? I have no idea. Infinitesimal. Yeah. These outbreaks had to be related, though, right? Yeah, right. I would assume so. But there was no way that an infected individual could travel the long distance between the two impacted areas without A, dying, or B, spreading infection to villages along the way. In between, yeah. Samples were collected and shipped off to the CDC from the Sudan outbreak, who confirmed that, yes, this is Ebola virus, but a completely different strain. Wow. An apparently less lethal strain, with only, and only here is relative, 150 dying out of 284 cases, which is about 53%. Yeah. So in 1976, two outbreaks of Ebola occur almost simultaneously. That's crazy. Miles apart, alerting the world to this disease for the first time. And two completely different strains. Like, what are the chances that that would happen at the same time? It's really... Wow. Yeah. It's very interesting. Yeah. After making its big debut in the 70s, Ebola goes underground for a while, with a few individual cases popping up here and there throughout the 80s and 90s, and one resurgence of the Sudan strain in the same location as the 76 outbreak. What? Oh, yeah. Hazleton Laboratories, Reston, Virginia. Virginia, United States, by the way. 1989. Yeah. If you've read The Hot Zone, as I suspect many of you have. To be honest, I haven't, but don't hate me for it. I don't hate you for it. This story may sound familiar, though with a little less of the blood and gore that Richard Preston, let's face it, likes to overdo. In these labs, crab-eating macaques, a type of monkey, imported for research purposes, started to show signs of extreme illness, bloodshot eyes, bloody vomit, you know the drill. And then they started to die. Oh. Red flags, right? Yeah, poor babies. Yeah, for sure. Samples of tissue from infected monkeys are sent to the U.S. Medical Research Institute of Infectious Diseases, USAMRID. Wow. Should I have heard of? Yeah. It's a long title. Where initial tests indicate the presence of Ebola virus, Zaire strain. But so far, no human had gotten sick. Very unlike Ebola Zaire. Yeah. Nevertheless, blood samples were taken from a bunch of workers who handled the monkeys, and six of them actually ended up seroconverting.
But they weren't sick at all. No one was ill. No one was sick. That doesn't sound like Ebola to me. So closer examination revealed that this virus, though very similar to Ebola, Zaire, was actually yet another strain of the Ebola virus. Apparently not harmful to humans. Wow. And also transmitted by air. The scariest part of it. This is the thing that when I read it, I was like, oh, now I understand why they were like, oh, we need to do a crap ton of research on Ebola because there is a strain that is transmitted by respiratory droplets because these monkeys in cages that were separated from each other all got sick. It's very scary. And what would happen if one of these very severe strains like Zaire, because it's an RNA virus that mutates so rapidly, just happens to mutate something that makes it possible to be transmitted this way. I mean, that is all these hypotheticals are what, you know, drives our anxiety and fear. This is why I don't sleep. I need a night. I bought two night guards today for my teeth grinding. Oh, my God. It's too much personal information. I live with anxiety. Sorry. Sorry for laughing. It's pretty funny. I bought a two-pack. This is how I measure my anxiety. Yeah. My dog ate the last one. I'm sorry. Getting off topic here. Okay, so. Back on track. Back on track. So in keeping with the geographical tradition of strain naming, this virus is called Ebola Reston. Over three months, about a third of the monkeys who were at the facility died. And at the peak of the outbreak, two or three were dying each day. If you really know your primate natural history, you know that crab-eating macaques aren't from Africa, which is the continent we most associate with Ebola, but rather Southeast Asia. Yeah, dude. Oh. Yeah. This outbreak revealed a few frightening things about Ebola. One is that different strains of the Ebola virus might be a lot more widespread than we previously thought. Yep. Another is that outbreaks could easily occur in places where the Ebola virus reservoir doesn't exist. If the rest and strain of Ebola had been harmful and transmittable by humans, basically, if it had behaved the way we expected it to, it could have been an enormous epidemic, if not pandemic, and in the US, which obviously got a lot more people interested in it. Now that it wasn't just some, quote, over there disease, but one that could happen over here, you know, typical, typical response. That's still true today. I mean, it's basically the only time that any westernized country cares about any of these diseases is if it could actually happen to mostly wealthy white people. Right. Anyway. Anyway. After the Reston outbreak in 1989, Ebola went relatively quiet for another couple of years until 1994 through 1996 when Ebola Zaire caused outbreaks in Gabon and the DRC with mortality rates ranging from 60 to 81 percent. God. Again, scientists deployed to the impacted areas attempted to trace the outbreak to its natural origin, but were unable to. In one outbreak, several of the index cases were workers in mines, inhabited also by bats. In another, it was traced to the consumption of a chimpanzee that had been found dead in the forest. That's not a good idea. Nope. Yeah. Yeah. First, though, let's chat about the evolutionary history of Ebola. Okay. Why has it taken so long to show itself? Or has it popped up many more times, but we failed to recognize it? It's a really good question. Do you know the answer? No one does. If only we could answer these unanswerable questions on this podcast we'd make millions just kidding we'd solve world problems more important i know where your mind first went though and i'm judging you okay so anyway to try to answer this question though viral paleontologists which how cool would it be to have that on your business card? Oh my God. Traced the origin of the family of viruses that Ebola belongs to, the filoviridae. I keep wanting to say filoviridae. I don't know which one it is. Whatever. They traced it back millions of years. Really? Apparently, this family may have emerged as far back as 15 to 23 million years ago. What? And then they continued to evolve and diverge. Interesting. Yeah. are incredible and they also perform a lot of ecosystem functions. Yes. Know that humans really only have ourselves to blame. Yeah. As usual. Urbanization is responsible for, I think it's safe to say, really the majority, if not all of the zoonotic spillover events in the past 100 years. Yeah. Well, plus on top of that, just on top of the fact that you're going to have more spillovers, the more that you're encroaching on forest systems, you also then have humans, like we've talked about, in close contact, which allows for human-to-human transmission. I mean, it has to do with the difference between an outbreak and an epidemic or an outbreak and a pandemic. Or a single case that you might never hear about. Exactly. Yeah. Yeah. And urbanization plays a huge role in the 2014 epidemic that left over 28,000 people infected. Yeah. Until 2014, all of the Ebola outbreaks tended to be limited to Central Africa in rural villages close to forested areas. And the 2014 epidemic started off that same way, with one important difference. It began in the West African country of Guinea, something that would delay its recognition as an outbreak of Ebola. The first person infected with Ebola during this epidemic was a two-year-old named Emil, who lived in a rural Guinean village. He picked up the virus in December 2013, probably when he and a group of children were playing near a hollow tree occupied by a colony of bats. Sadly, Emil died of his infection, and during the burial ceremony, several other family members and village members became infected. From there, the disease spread, eventually jumping beyond this index village, crossing borders and invading large urban areas where it spread like wildfire, infecting and killing thousands. But that is a story that I want you to tell. So please, Erin, tell me about the biggest epidemic of Ebola so far. I'll try. So, like you said, we call it the 2014 outbreak, but it started in 2013 and it continued until well into 2015. Yes. In total, there were 28,616 cases, according to WHO, and 11,310 deaths. Wow. Yeah. That's so crazy. Yeah. So one thing that was really important in this outbreak was being able to diagnose cases rapidly on the ground and trace those cases based on their contacts. So to tell you more about that, let's go back to Lauren Crowley, who was there for five weeks. And we ran the diagnostic lab there. And I came home on Christmas Day. And then I actually went out again. I was deployed six months later in June 2015 to Guinea to provide results and sequencing of new Ebola cases using nano-4 sequencing technology. And this was in collaboration with the European Mobile Lab and the sequencing lab was set up adjacent to an Ebola treatment center in the outskirts of a town called Koya in Guinea. And there we were using RNA extractions from new cases of Ebola that were sent from all over Guinea to be sequenced. And then we used these sequences to look at transmission tracing in epidemiological investigations. Yeah, so we were trying to look at genetic similarities to try and cluster cases that might be part of the same transmission chain based on their genome sequences. For a disease like Ebola, in order to effectively tackle an outbreak, you quickly need to be able to establish very fast diagnostics and transmission tracing and then hopefully chain interception by the epidemiologist. And this, as we looked at with Ebola, you're actually able maybe to be able to use genetic information to help with this. So that's pretty incredible that they were able to do this rapid diagnostic testing, both in PCR, but also with sequencing. So one thing that's important is that this left over 10,000 survivors of the disease. And we've never seen numbers of survivors of Ebola that are that high. So that's something that countries and the world are sort of grappling with at this point is how to best serve these survivors of the disease. And here to tell us about that are a couple of experts, Sarah and Nell, whom you've heard from earlier, and they're going to talk about their awesome project Ebola Survivor Corps.
It wasn't funded, but it did receive a lot of encouragement. So they took it upon themselves to raise funding for this organization. Let's let them share their experience. There was an opportunity to volunteer with Partners in Health or Medicine Sans Frontieres, but once you started going to the volunteer application, first they would say, yeah, we want anthropologists, but then there's no place to actually check off the box. It's like, this is what I've been waiting for. This is what my training is about. But there wasn't a chance to get involved, so instead we sort of helped convene on the lab at University of Wisconsin in this disease ecology group, the lab, together to come up with a proposal to respond to a USAID Gates Grand Challenge to sort of encourage treatment seeking and thought it would be really useful and empowering and obvious to support Ebola survivors or reentry into society and into communities and take advantage of this existing immunity from renewed infection and put them to work as first responders and sort of train them up to do infection prevention control and sort of loop them into the surveillance teams. It became really consuming but also really, really rewarding because we were able to do something to respond within our skill sets and what space there was for us. So we raised $15,000, and during that campaign, we found Nell. And Nell was able to transform the Ebola Survivor Corps concept into a project on the ground. We'll let Mel take over from there. So I went in 2015 and started the project. So the Ebola outbreak at that time was sort of winding down. It was still happening, but it was winding down. And when I got there, our first goal was to identify, I mean, like talk with all the stakeholders and identify people with survivors to work with. And so we went onto the field and we're working in this really remote area of Northern Sierra Leone in Coindigo district. And it had sort of like got the outbreak later and didn't have quite as intense of an outbreak, but that actually worked well for us due to the scale of our project. So we could actually manage the relatively smaller number of survivors. So I went there and met with the survivors and with the chief and everything and started doing infection prevention control training with them and a social mobilization training and got them basically set up to work as initially as sharing the infection prevention control information but also as sort of like a resource like a health educational resource for the community so they're going out and they're talking to different people in their community in the local language and like explaining different health issues, mostly infectious disease stuff on a level that people can really understand and like trying to make that information more accessible. Yeah. There has been a lot of critique of the response to this outbreak. There's actually a really great article that I'm not going to wait to cite because I know a lot of people don't listen to our citations. That's okay. It's a fine, but I want to tell you about this article because it's great. It was called Critiquing the Response to the Ebola Outbreak. And you can find it. It was by Vera Scott et al. in 2016. Google it. So the World Health Organization response to this outbreak was very similar to the response that they've had to all of the other outbreaks. It's what we would probably call a classic outbreak control response, which basically means a whole bunch of technical and medical professionals swoop in and they isolate people and they try to break the chain of infection. And the thing is, in past outbreaks, this has been fairly effective in blocking further transmission. We never saw outbreaks that reached even the thousands before this. What was the biggest one in 2001 or 2002? 450. 450? Not that that's not a ton of people and that really sucks, but it's nothing like what we saw in 2014. So this outbreak clearly spiraled out of control. There are a lot of reasons for this. It's not like there's one single answer as to why this happened. For one thing, when people swoop in and start telling everyone on the ground what to do, there's often resistance. And in many cases in these areas, so the three countries that were most affected by this outbreak were Guinea, which is where it started, Sierra Leone, which is where it spread next, and Liberia, which is where it went after that. So in many cases in these countries, there's not a lot of trust of the government or authorities, and especially not foreign authorities that are just coming in and telling people what to do. Which is exactly what happened. Historical. Right. But that's like that's because of historical reasons. Exactly. Colonization. Right. Yeah. Yeah. On top of that, there's not any good treatment options for Ebola. Right. It's just maintained. Yeah. So if you bring your family member to the hospital and they end up dying, and then you bring your next family member to the hospital and they end up dying, why would you want to keep bringing your family members to the hospital? They're just going to die. So during this outbreak, and especially towards the beginning, hospitals honestly weren't even trying to treat. And there's not any evidence that hospitalization made a difference in terms of mortality rates. So they set up a bunch of these Ebola virus disease treatment centers, but they were basically holding cells. Like quarantine? Yes, they were isolation facilities that were just trying to break the cycle of transmission, which from a public health perspective, I understand you have to try and break the cycle of transmission. But imagine that you're a mother or a father or a child of a person who's infected. Why would you bring your family member to a place where they're not going to be able to touch anyone or see anyone just to die? Like there's not a lot of incentive to cooperate with these people who are just taking your family members away, not doing anything to help them and just letting them die. Right. Plus, healthcare systems in these three countries were woefully understaffed and underfunded and just overwhelmed by the sheer numbers that were coming in. In these healthcare facilities, they also didn't always have protocols in place or they didn't have enough equipment to even follow protocols. So you had a lot of what we call nosocomial infection, which just means hospital-acquired infection. So both healthcare workers and maybe people who were in the hospital, Right. There were a lot of sort of issues that led to this epidemic being as big as it was. Distrust in the authorities, people swooping in and just sort of not being cognizant of local customs in the areas that they were dealing with. One of the biggest things that directly led to a large number of cases were local burial practices. So you mentioned this before, but local burial practices in these areas, because of religious reasons, involve directly touching or washing the body. And it's estimated that at least 20% of new Ebola infections occurred during the burials of people who died from Ebola virus. Yeah. what I gathered reading various sources, the WHO was requiring that all bodies of people who died from Ebola be cremated, which is very much against the normal practices in these areas. Right. So you imagine all of these people coming in and being like, uh-uh, don't do it the way that you've been doing it for generations. Right. Don't do it according to your religion, according to your traditions. Do it my way. How is that going to be well received? We're going to take your family member away from you, not let you give them a burial that is important for their afterlife. It's extremely problematic. And so it took them a long time. They eventually got together a safe burial protocol and they sort of got their ish together in figuring out a way to sort of work within what is normal for that region and still prevent further infection. But yeah, I mean, it's just another example of sort of Western countries coming in or people from Western countries coming in and not being sensitive to cultural practices. And because of that, making things a lot worse. Right. And being like, how don't you know that this is not what you're supposed to do? Right. So a lot of people were not bringing their family members into the hospitals or once they died, not bringing them in to be to because they didn't want them to be cremated. Yeah. On top of that, the infrastructure there, like we said, wasn't very good. So a lot of people couldn't survive the trip from maybe their village to the hospitals because infrastructure, roads, vehicles weren't available to them to even transport their family member to begin with. Right. expected this to be like every other outbreak they had dealt with before. And it wasn't.
And it wasn't until August of that year that they said, hey, this is a really huge public health problem. Are you freaking kidding me? August. I think it was August 8th of 2014 that they were like this is a big problem how many thousands of people had died are you kidding yeah i mean it definitely got worse from there is the thing so yeah yeah so one thing that i'll say that's important to keep in mind is that there's a lot of reasons that these countries weren't able to deal with these epidemics on their own that have to do with former colonization and with the World Health Organization and other international organizations sort of constantly being in these countries taking over, if that makes sense. So like not actually building up infrastructure for public health, but just coming in when needed. Exactly. So the international public health community has a focus on like disease preparedness. Like we have to prepare for the next outbreak, which a lot of people have implicated this in weakening the health systems for day to day life in these areas, where if you're only focused on, you know, what's coming next, then you're not necessarily building general health systems, you're siphoning off these resources that could be used. So then when an outbreak actually does happen, you don't have the resources in place Right. done now that we've sort of recognized this to be able to make it better in the future. Just not only for Ebola, but overall. Yeah, for overall health. But jumping back to Ebola, one thing that I think is really interesting is that initially, both after this 19, the 1976 outbreak, that was the first outbreak, but especially after the, was it 89 outbreak in Virginia in monkeys? Yes. So because of that outbreak specifically, there was a lot of interest in Ebola because of its potential as a bioterrorism agent. Yeah. So for a while, there was a ton of research that was being done about Ebola, not because it was actually causing small outbreaks every year and killing people, but because Western countries were afraid of bioterrorism. Of course. Because they knew that they and other countries were working on Ebola, like engineering it to be an agent of bioterror. So there was a ton of research being done into vaccine development well before this 2014 outbreak. And at some point, I don't know exactly when, but it seems like the money kind of dried up for vaccine development. So at the point of this most recent outbreak, there were a lot of vaccines that had been tested and been shown to be effective in monkeys and non-human primates. That's why in 2015, there was actually a vaccine tested and deployed for the first time in humans. And the good news is it was shown to be extremely effective. 100% of people that were given this vaccine did not develop Ebola. That's awesome. Yeah, it's really exciting. There's definitely still a lot of work to be done. There's a lot of questions as to how long lasting this immunity is. So there's a question as to whether this vaccine could be effective in preventing illness overall, like whether this should be a vaccine that sort of like the chickenpox vaccine now where everybody gets it so that we just sort of try and not have chickenpox be a thing. Or if this is just a vaccine that could be used in the case of future outbreaks, where you do something like they did in 2015 called ring vaccination, where you vaccinate all the contacts of cases and all the contacts of those contacts. But in that case, this has shown to be very effective, which is cool and exciting. It's very cool. So instead of asking how scared we should be about Ebola, what have we learned from the 2014 epidemic? Well, let's actually let Sarah answer that, because I think she had some really nice things to say. I think we've learned a lot, but I think it's the same lesson we've always been learning when there's an infectious disease outbreak of any kind of scale. And that's whenever there's an event or an outbreak, one of the first things that a country will do is set up their national task force and then deploy people to do active surveillance and risk communication. And there's this assumption that risk communication is obvious, that messages are already developed and all you do is blast them over the radio or drive around in the white pickup with the speaker on the back and blast them through the local language and people will just automatically accept the information and change behavior. But it's becoming clearer and clearer that that approach, the very top-down vertical approach, isn't effective. And what ended up being the most effective for stopping the outbreak was communities actually taking it upon themselves to change their behavior in the midst of not necessarily going with the flow of what the outside people who are coming in and telling people what to do wanted them to do. So it took a long time for people to, for sort of the messaging and the behavior change to harmonize. And it required a lot more than just blasting messages. It required a lot of community meetings and one-on-one personal stuff and getting the, you know, the survivor stories out and the affected family stories out and people realizing that Ebola was real. And even if it was a curse from the neighbor, it still could kill you, regardless of where it's coming from. And there's a humongous focus back on Africa now and sort of reinforcing some of the negative stereotypes about the dark continent as being like the heart of disease emergence. So we're neglecting Asia, I think, in this process. So I think we need to not lose sight of the fact that emerging diseases can come from any part of the world and infections like antimicrobial resistance can be found in rich countries too. So I think we need to figure out how to be laser focused and broad at the same time, and then we also need to figure out how to do better engagement with communities and people on the ground and sort of take advantage of all the local experts that exist in all these countries at their universities or maybe even in the diaspora who can be tapped to join that rapid response team. So there's lessons learned and I think we are seeing some changes actually. So while the 2014 epidemic was very scary, it seems like we learned a lot of lessons from it. Yeah, and hopefully things are going to change for the better moving forward. Sources time? Yeah. So because we had such an action-packed episode this week, we are going to, instead of going into detail on our sources, just direct you toward our Facebook and Podbean website where we will list our sources for this episode. You can find them all there. Check, check, check it out. Thank you again to Nell and Sarah and Lauren for sharing your stories with us. Oh my gosh. They're amazing. Yeah. And thank you for what you do. Like you guys are incredible. Yeah. And thanks to Bloodmobile for providing the music. As always. And get real pumped because next week is gonna be awesome. It really is. Get your crying hat on. Is there a hat you wear when you cry? No, I just wear my crying blanket and sweatpants. Okay, so get your crying sweatpants on. You're going to need it for next week. It's true. It's very true. And you know what? Wash your hands. You filthy animals. Just in case.
I'm Stephen Morrissey, managing editor of the New England Journal of Medicine, and I'm talking with Katherine Baker, a professor of health economics in the Department of Health Policy and Management at the Harvard School of Public Health. Professor Baker has co-authored a prospective article on the misguided focus on the creation of health care jobs in the United States. Professor Baker, some aspects of health care reform might tend to increase health care hiring. The expansion of insurance coverage, for example, will increase demand for services. And the focus on team-based care might require new case managers, more physician assistants, nurse practitioners. So is some of the growth in health care employment necessary to better care and better health? Absolutely. And I think the key factor is the goal should be improving health and access to health care. And to the extent that that involves a larger physician workforce, a larger nurse workforce, a change in the mix of people working in the health care sector, that's all to the greater good. But that's a side effect of expanding access and improving the efficiency of delivery, not the goal of the policy itself. In May of this year, only 69,000 new jobs were created in this country, but nearly half of them, 33,000, were in the health care sector. In your article, you cite data showing that over the longer term, there's been steady growth in health care employment as a proportion of all U.S. employment. What are the reasons for that? I think there's ample evidence that we're not getting as much value as we should out of the health care sector right now. We want to get as much health as possible for every dollar that we spend and for every person employed in that sector. And we're spending some money on care that has questionable value right now. That's why I think policy goals should be to improve the value for the system so that everyone has access to affordable care. And that might involve more employment, but it might involve less. You argue that job creation shouldn't be a justification for increased spending on health care. How do you convince people of that during a recession when lawmakers, as we know, are so concerned about unemployment rates? Well, that's a real challenge and was part of the motivation for writing this piece. But I think you have to remember that health care jobs aren't manufactured out of thin air. Higher spending on health care means higher health insurance premiums. It means that workers have lower take-home wages after they pay their share of health insurance premiums. It means taxes are higher as we pay for Medicare and Medicaid and access for the uninsured. The flip side to spending more on health care employment is having those higher premiums and those lower wages and those higher taxes. And I think if you make that argument, people might see that those resources could be better devoted to other important uses like food and shelter and education if we were getting as much health from the health care sector for every dollar that we spent as we could. In a recent perspective article, Steger and colleagues used economic modeling to suggest that the substantial expansion in the nursing workforce is largely a temporary bubble related to the recession and that it will probably deflate over the next several years. Do you agree? And how does that affect healthcare employment growth in general? I think this highlights the challenge of trying to target employment as either a metric of success or as a goal. Really, if we could align incentives so that we were promoting high value care and access for a wide segment of the population, the jobs would work themselves out if we removed the barriers to the efficient allocation of resources. It's very hard to plan ahead of time exactly how many doctors we need, how many nurses we need. That kind of planned economy is destined to get the resource allocation wrong. Rather, we want to set up a system that promotes the delivery of high-value, highly beneficial health care, and then let the jobs flow as they may. You do suggest that in some cases, adding health care workers may be creating value commensurate with the additional spending that would be necessary. How do you measure that value to determine whether any given position is beneficial? That's a real challenge, and that gets back to the goal of setting up a system that has incentives for high-value care. If we reward the provision of high-value care, not just more care, if we promote coordinated care that results in better health outcomes, not just more spending on health, then jobs that are created in the health care sector will be producing high value. You note that a local politician might prefer a larger hospital, which would offer more jobs in his or her district, as long as the people paying for it don't live in that district. And that's possible given our current system of health economics. So does that underlying system need to be changed as well? Absolutely. I think there need to be a lot of reforms in the health care sector from how we pay for publicly provided care through Medicare to how we set up the incentives for value-based insurance in the private sector to how we subsidize employer-sponsored health insurance. A lot of changes would promote higher value care that we've been talking about so that we can get better health outcomes. Remember, we're not trying to buy health care. We're trying to buy health. And if we set up a system that promotes that kind of use, that's certainly going to involve a reallocation of jobs across types of professions and across places in the country. And there are going to be some people who are unhappy about that. And we want to set up systems to help any workers who are displaced and to ensure smooth continuity of patient care. But a byproduct of any reform that promotes efficiency is going to be some reallocation. Thank you, Professor Baker.
Welcome back, Clinical Problem Solvers. We're thrilled to be partnering up with the Human Diagnosis Project again this week. You will hear us tackle three cases of abdominal pain, which will be released on Monday, Wednesday, and Friday. If you've listened to our HumanDx episodes in the past, you'll notice a different format this time around. This time you'll see that a medical student or resident will be sharing the hot seat with a clinical problem solver. Our primary goal will always be to practice and share our clinical reasoning, but we are also heavily invested in promoting a culture that normalizes sharing your thinking and knowledge no matter what level of training you have. So we think that one big barrier to being able to do so in medicine has been this fear of the words, I don't know. We've all been in a situation where the fear of acknowledging our limitation in our knowledge and reasoning has led us to hold back and not share our thinking and practicing these crucial skills. So by tackling cases as a team, we hope to decrease the stress of publicly discussing, normalizing limitations of our knowledge, and also learn from one another in this podcast and hopefully model what happens in real world between all of us. Now I know this sounds lofty, but with your help, we hope to transform the meaning of the words I don't know in medicine from representing inadequacy to opportunity, opportunity to grow and learn. Today, we have Robby and Reza presenting to Charmaine and myself. Hey folks, just a quick reminder that this podcast is not meant to be used for medical advice, just good old-fashioned education. Alrighty, welcome back, Clinical Problem Solvers. We're super excited for Sharmeen and Arsi to take this case on, and I will get us going. So this is a case from Anand Patel. So this is a 71-year-old man with abdominal pain and fullness. So he describes six weeks of abdominal wholeness and lower abdominal pain. He also reports early satiety with a 12-pound weight loss. There's no nausea, no vomiting, and no diarrhea. There's also no constitutional symptoms. His medical history includes CLL, which was diagnosed four years ago, and he's been on ibrutinib since his diagnosis. All right. Thank you, Robbie. I'm very excited to be in the hot seat with Charmaine, who I'm so grateful for. We're going to tag team this. And I'm so excited not to be in the hot seat. Don't let my interjections throw you off. Not at all. I love it. So we have a elder gentleman here with a subacute presentation of abdominal fullness and lower abdominal pain associated with some weight loss. So here, because of the more chronic nature, I don't think this is life-threatening. When I'm thinking about abdominal pain, I love Reza's schema that he taught us a few episodes back to rule out life-threatening causes of abdominal pain, perforation, obstruction, vascular events, and ectopic pregnancies in women. I don't think that's what's going on here just based on the chronicity of it. I would love to know what his fullness really entails. Is it abdominal girth that's a compressive process or is this just early satiety? Given his age and his previous history of having a malignancy, you know, I'm concerned for another malignant process. And with the early satiety, I would be concerned about a gastric adenocarcinoma. I think anytime an elderly patient presents with these symptoms of early satiety and dyspepsia, I think I would have a low threshold to do EGD and pursue that a little bit, more so than I would if a younger person came in and we could do a trial of PPI. The ibrutinib, I would have to look up to see if that's a, I believe it's tyrosine kinase inhibitor. So I don't think there's, there's toxic effects of that, that would predispose to other malignancies because it's, it's, it's a signal pathway and it's not cytotoxic. His CLL makes me think he, he's prone to possibly other malignancies. And with his weight loss, that could be just because early satiety and him not eating, or it could be cytokine mediated from an inflammatory or malignant process. These are kind of my thoughts right now. Charmaine, please help a brother out. This is why I only discuss cases with RC from now on. You guys just heard why. No, I totally agree with you, RC. Just like thinking about his age and presenting with like abdominal pain and fullness, like just thinking a little bit like outside the abdomen as well, like about being at higher risk of BPH just thinking of urinary retention and like bladder scan is an easy thing to do when people hit the door in terms of the things that outside the abdomen can like mimic abdominal pain thinking about like cardiac causes like the fact that it's like more subacute making like acute coronary syndrome less likely as well to keep our differential broad. I love what I learned from like Dr. Dottley Wall down in the ED. And once he told me the only atypical presentation about abdominal pain in an older gentleman is a typical one. So I would keep the differential diagnosis pretty broad. The one thing is like the 12 pound weight loss is something that I'm going to have in the back of my mind going forward. Thinking it's intentional, unintentional, and the time frame that has been going on. And I love the fact that you kind of thought about the medication too. I think tyrosine kinases are associated with some like nausea, vomiting, GI upset. again he's been on it for a long time so it would be odd for it to start affecting his abdominal painfulness. And the other thing that Rez taught us was just like an anatomic approach and the lower abdominal pain thinking the organs involved there as it has abdominal fullness and lower abdominal pain thinking about like left lower quadrant and your right lower quadrant right lower quadrant is big thing is appendix but again six weeks is unlikely and thinking about like diverticulosis and diverticulitis on the left lower quadrant again a six week is a long time I love what was RC focusing on with the Airless Society 12-pound weight loss focusing on that a little bit more. So it would be awesome to get some more information and go from there. You got it, boss. So I just wanted to emphasize it was so awesome to hear you guys really prioritize the time course here. And I think for anyone listening, that is the hearing these guys think through this case and you can really shed light on why we include that in the problem representation. So that was just beautiful to hear you guys think. But as you requested, I will give you the physical exam. So the vital signs are actually completely normal, including a normal temperature. There is no cervical axillary or inguinal lymphadenopathy. There was abdominal firmness noted throughout the lower abdomen, but no hepatosplenomegaly appreciated. The cardiovascular and pulmonary exams were normal. Alrighty. Thanks, Robbie. Whenever we're evaluating patients, vital signs are vitals. So the fact that the vital exams reassuring the patient is afebrile, and that's all good things. There's no cervical axillary or inguillary lymphadenopathy given like the history of CLL that he has. So there's like no buccal lymphadenopathy that is appreciated. The abdominal firmness, it's an interesting one. When I first saw it, I thought about, oh, I wonder if he has a big spleen. And then I saw there's no hepatospinal megaly. but then again like personally I am not good at appreciating hepatospinal megaly on exam at all so I that's something that I would still like have it yeah right I've only probably felt two spleens and they were pretty huge so that's something that I would again like keep in the back of my mind just given the history of malignancy that he has in terms of the cardiovascular exam pulmonary exam being unremarkable that's helpful in thinking about the mimickers that can lead to abdominal pain i don't know if anything is like really going up and down on my differential diagnosis at this point. The firmness is interesting. I'm curious to see how RC is approaching the abdominal firmness here. But just to give us a problem representation, the way I'm putting this gentleman together is a 70-year-old man with a history of CLL on a tyrosine kinase presenting with kind of subacute abdominal fullness and lower abdominal pain found to have a 12-pound weight loss with exam significant for abdominal firmness otherwise pretty unremarkable. Wow, that was awesome. Charmaine, I love your problem representations. They're so much better than mine. I love it. Thank you for putting that together.
That's also good to know. You know, the abdominal firmness, I don't have a good approach to it. But just thinking about it for the first time, I would approach it kind of by layers. Is it something that's subcutaneous, like subcutaneous edema or a little bit lower in the perineum? Is it ascites or is it organomegaly? I agree. I think the physical exam has limitations to that. But firmness isn't something that I typically think about. I mean, guarding and an acute abdomen is a little bit different. This doesn't seem to be that. So I think a CT scan would be helpful or an ultrasound. I felt these masses in one patient before, and we found out that she had a weird reaction to the sub-q heparin. And so it was presenting that way. I don't think this is that, but I think there's different layers that could cause abdominal firmness is what I took away from that case. Dude, I love your approach. That was fantastic, RC. Charm easy partner in crime here. Are you guys ready for more data? Yeah, let's do it. All right. So first some blood work. So the CBC comes back at 13,800 with 73% lymphocytes. The hebolybin is 10.7 and the platelets are 159,000. The basic metabolic panel and LFTs are both within normal limits. The LDH is elevated at 439 and the urinalysis is normal. All right. Excellent. So we have a mild leukocytosis with a lymphocytic predominance. Given that he has a history of CLL, it would be helpful for me to know what his baseline has been. You know, sometimes these patients just ride with these levels. And from cases I've learned from our hematology consultants is that that's perfectly okay. These patients could be at risk for a malignant transformation, like a Richter phenomenon. He has an anemia as well. I can't tell if it's acute or chronic at this point. He could have bleeding that could be causing his abdominal firmness, but it's pretty mild. He doesn't seem like he's toxic appearing on exam or an extremist or really even too uncomfortable, but that's also something that I'm thinking about. His platelets are pretty reassuring. The other thing that's elevated is his LDH. The main organs I think about are the liver, the spleen, and red blood cells when the LDH is elevated. Also, any cell that's lysing, but those are the organs that I've seen as the culprits in cases where I've seen an elevated LDH. Again, with his history of lymphoma, if he didn't have that history, it would raise my concern for lymphoma, but I'm having a difficult time assigning significance to that LDH in the setting of a CLL, maybe they'll become important down the line. If his hemoglobin is far from his baseline, I think a peripheral blood smear and other hemolysis labs could be helpful. But again, tying that to the abdominal pain, maybe a hematoma, we'll see. We'll see the significance of it in a little bit. Sharmeezy, help a brother out again. I really liked how you think through the LDH. That was really helpful. Thanks, friend. No, I totally agree with you. I'm just trying to put this lab work in the context of this patient who's like had this weight loss or this satiety, not eating so she he doesn't have any electrolyte abnormalities make me think he's like able to maybe keep up at least with his PO intake in terms of like medication side effects like thinking about a toxicity LFTs are normal I agree with you in terms of like a little bit of white count it's hard to say the significance of it. Thinking about like people who have malignancy and on different type of therapies are at higher risk of infection. Again, we're not really getting a flavor of an infectious ideology here. So I would, yeah, I would agree with like getting some imaging to help us out here. All right. You asked and you shall receive. So thet abdomen pelvis is obtained and it reveals diffuse abdominal lymphadenopathy with a retroperitoneal conglomerate measuring 19.3 by 7.2 centimeters let's like think through this like a diffuse abdominal lymphadenopathy um so this the things that comes out to, just like we know he has this history of CLL, but thinking about like other ideologies, like infectious ideology can cause diffuse abdominal lymphadenopathy to the retrotunile mass, like that big makes me think of malignancy as well. So is this a kind of a progression of his disease versus like another secondary malignancy? I think is a question. I think at this point in reality, honestly, I will be going down to the radiology and being like, hey friends, can you help me out here? And thinking about like the significance of it being retroperitoneal, thinking like the organs that they're in, thinking pathology of those organs, like kidneys being one of them? Or is it just a big, big, really big lymph node? Yeah, I agree with you, Charmaine. I would definitely be hitting up our radiology friends to help kind of describe it in a little bit more detail. And Robbie, is it clear if this conglomerate is a conglomerate of lymph nodes or if it's lymphadenopathy and a retroperitoneal conglomerate? That's such a terrific clarification because as you're implying, it makes a huge difference. And here, I think that they're saying that there's diffuse lymphadenopathy that all kind of bundles up and is enormously huge, but each of them is actually individually lymph nodes. Oh, wow. So there's no mass. It's just a bunch of lymph nodes in the retroperitoneum that are pretty large. Oh, wow. Okay. So this is helpful. I mean, I think what this does for us is it gives us a good sense of why he has early satiety and his abdominal firmness. So we're localizing our lesion to diffuse lymphadenopathy. Now, I think, you know, our job is to come up with explanations of why he has diffuse lymphadenopathy in a patient whose background is CLL with this foreground. Yes, thank you for putting that in. I'm so happy right now. Arcee, now you just need a needle and you'll be golden. Hey, Arcee, is this your pivot point? This is my pivot point. We're hitting all the beautiful diagnostic reasoning terminology. So, Sharmini, let's discuss this. What can cause such all lymph node. And I think if it was like a that diffuse of an infection, we would see evidence of it otherwise, like in his exam or labs. So I think the question is like whether it is like a transformation of his malignancy that has happened. It can happen with lymphomas. I think that's where my mind is going to. That's like what I have the highest suspicion for is either progression or that the likelihood a bit. But I think we can still consider indolent infections like endemic fungi, maybe viruses and TB. So those are something. But I do agree in someone with CLL, this still feels more like a malignancy and possibly progression of that. Oh, Arcee, you're so, so good. Just as a side note, the one and only Dr. Robby Jiha was doing a CPS for one of our teaching sessions today, and he told us that you're never wrong to mention these type of indolent infections, and just nailed it my friend boom learning from the grades here i know i was just gonna say like you not only is this a masterful discussion of like a case just in general but also like you guys are picking up the like cpsers like side pearls which just never ever ever go through a through a case without mentioning TB. So well done. All right. Well, unfortunately, you will not get tissue to help you out with committing to a DX, but you do have one final clue. So a PET scan was obtained and it showed increased hypermetabolic activity in the abdominal lymph nodes and small scattered axillary lymph nodes. Is this saying that the cells are really proliferating quickly? If so, then I think I would be more concerned for like a Richter transformation, CLL turning into something a little bit more aggressive, like a large B cell lymphoma. That's kind of where my thoughts are going. Again, it can still be infectious. I think it's just saying that there's a lot of activity and proliferation in the lymph nodes, whether it's reactive to an infection or if it's a primary process. I don't think this PET scan helps answer.
And like Charmaine said, I think the tissue biopsy would be the definitive way to answer that. So, Charmise, what are your thoughts with this new finding? Again, I'm right there with you, my friend. And I wonder, I'm just like trying to look back at the case and see if there's like any pieces of data or something that can help us decide what this is. And no, honestly, like nothing is like jumping out to me. I'm really, really curious to hear Reza and Robbie um reflections afterwards to see if there's there should have been a pivot point that we didn't see but i agree with you that i would be most concerned for like an erector transformation um at this point but then again like could this be all tb sure um really the 12 pound weight loss like something um hypermetabolic um i'm leaning more towards like erector transformation um but again i think in reality would definitely it would definitely a biopsy and get a biopsy to uh yeah help direct the next steps and before robbie reveals the diagnosis, I'm going to make an interjection here. I just want to say how impressed I am in hearing you guys tag team a case together. And really at this juncture, I love the fact that you said you'd go down and speak with the radiologist and that you need tissue. But this doesn't take away from the journey of this case where you guys talked about abdominal fullness, weight loss, lymphadenopathy, and then you sort of put your money down on a specific diagnosis. But that's not what this exercise is about. It's about all the thoughts you shared along the way. Rez, I'm giving you a virtual hug right now. Aww. Absolutely. Is it because I didn't interject at all, Charmaine? No, it's because you interjected so beautifully. You can interject anytime. I love it. Yeah, I agree with Charmaine 100%. I think a, you know, a malignant transformation from a CLL. Final answer. Let's hear it. We're putting down our nickel. Yeah. Hey, guys, can we do a drumroll? Or is that just like bad podcasting form to like put a drum in people's ears? I don't know. But yeah, there we go. That's a good. So, the final diagnosis is Richter's transformation. Wait, wait, wait, wait. RC, did you finally get a case right? No, I think so. Charmaine, this is the first time for everything. Like, literally, this is the first time for everything. This is just... Yeah, yeah, yeah. I have never gotten a case right. Oh, stop it. You guys are too humble. And Robbie, before you share the teaching points, I think we're out of a job, man. This was way more entertaining than any case you and I have discussed together. We've led to our own demise. I want more of this. We've led to our own demise. What have we done here? What have we unleashed? This is incredible. We've got to kick them out, the sleepy solvers. Give me the mic back. Before you came on, they said to have it in writing that we wouldn't kick them off. They got it wrong. I think it's the other way around. Let me tell you what happened in the case. So there was actually, as you guys alluded to, there was a high degree of concern that this might be Richter's transformation. And so as both Charmaine and Arcee elucidated would be a next step, the patient underwent an excisional biopsy of a hypermetabolic axillary node, and that confirmed the diagnosis. A quick plug for just a little bit of an illness script, Richter's transformation happens in up to 10% of lymphoma, and it usually happens in the first five years. And so the symptoms are very compatible with what happened in this case. And one big tip off that Dr. Patel's incredible teaching here has is the PET CT is actually very helpful in distinguishing progressing CLL from a Richter transformation with a marked increase in the metabolic activity being much more suggestive of an aggressive Richter's transformation versus progression of CLL. Ah, that's very helpful. Yeah, thank you. That's good. That's really good teaching. I was really curious for the audience, because I know that this is maybe one of the first few times that you guys are doing this. And I'm curious to hear just how it felt and how really putting your diagnostic thought process out there for the first time to be cross-examined by all our amazing listeners. How did that feel? And what part of it was great? What part of it was tough? Can you just, we have a few minutes, so please just share that, your feelings along the journey. It's kind of you in a very public, vulnerable way, kind of figuring out what you know and what you don't know. And it's not a bad thing. It's actually a very nice thing. Honestly thing honestly like i if you would have asked me five months ago would i ever be discussing an unknown on a podcast the answer would be a hell no and i think the fact that i was actually uh very nervous but very excited to do it is kind of of a testament to both uh Robbie and Russ to you guys and about the learning environment that you've created that that Ivan from somebody who's like super nervous about this to actually getting excited about just giving it a try and like recognizing as um as Arcee mentioned is like what what are my gaps in my knowledge? Like I should definitely go read more a little bit about rectus transformation after this. And using that as an opportunity to learn and to grow. Because I feel like there is definitely, it's hard to say like, I don't know, it's hard to get things wrong. But like changing your mentality as to um recognizing that it's just an opportunity to grow especially when it's kind of a virtual case right this is all for good old-fashioned education right you don't have an actual patient in front of you and and it's a great opportunity to learn honestly honestly, and to grow and become better. And just like being less afraid of being like, oh, actually, I don't know that. It's not a reflection of your competency. It's just like reflection of your growth, basically. So I really enjoyed it. I was very nervous, but I was among friends. That's a wrap, folks. I love you guys.
Welcome to the Lancet Respiratory Medicine Podcast. I'm Aaron Van Dorn. Today on the podcast, I spoke with Dr. Barbara McNicholas, Consultant Interventionist at Galway University Hospital in Galway, Ireland, and Dr. Jay Lee, Associate Professor in the Respiratory Care Program at Rush University in Chicago, Illinois. Dr. McNicholas and Dr. Lee are co-authors on an open-label superior order meta-trial looking at the efficacy of awake prone positioning for patients with COVID-19 acute hypoxemic respiratory failure. Dr. McNicholas, prone positioning was recommended fairly early on in the pandemic for severe COVID patients. Could you briefly explain how awake prone positioning helps with these patients and whether there are any potentially harmful effects of this technique? Prone positioning is something we do very commonly as part of our management for confirmed moderate to severe ARDS and people who are mechanically ventilated. Prone positioning is where you're on your tummy. It changes the shape of your lung and results in improved gas exchange and respiratory mechanics. So we can reduce the intensity with which we need to ventilate the patient. It's part of our evidence-based guidelines for this disease and it's known to save lives. The same is not so well understood for awake prone positioning and certainly at the start of the pandemic it wasn't really well studied outside of case reports which generally reported an unsustained improvement in oxygenation with the intervention. Despite this, it was included quite early in guidelines across the board as a simple and low risk intervention. We know in critical care that there's lots of interventions that might improve oxygenation but don't really result in a meaningful clinical outcome such as a reduction in need for mechanical ventilation or a reduction in death rate. So as a result a lot of studies were registered at the start of the pandemic on awake prone positioning for COVID-19 patients and there's certainly good physiological reasons for why prone positioning would make your oxygenation better. First of all, your lungs are physically bigger in the prone position. Another thing is that the weight of your heart on the lung tissue is reduced. And as well as that, the weight from your tummy content, so the abdomen, is removed from the base of the lungs and allows this part of the lung to expand. As a result, your oxygenation will improve. We also find that people's breathing in a prone position might be less injurious to the lung, and this can result in a reduction of self-induced lung injury. Although it sounds like a straightforward maneuver, just turning somebody onto their tummy, when you're doing this to patients who already have low oxygen levels from COVID-19, you can put a strain on the physiological system of that person. At the start, when we were designing this study, we were concerned that there was a risk that putting patients in the prone position could precipitate worsening respiratory distress that could require intubation. We also were concerned that this is something that might precipitate more cardiac arrests. And there also was a final concern, which is kind of an important one, was that you might improve oxygen temporarily, but if a patient then goes on to require mechanical ventilation that, you know, you've left them breathing on very inflamed lungs without having controlled tidal volume, that the outcomes for them could be worse as a result once they did get mechanically ventilated, if that was what they required. So at the start of designing the study, we certainly had clinical risks that we wanted to account for in this technique to make sure it was a safe thing to do for patients. Your study aimed to determine whether awake prone positioning reduces the combined incidence of intubation or death in patients with severe COVID-19. Could you talk us through the unusual meta-trial design of the study and why you chose this? Yeah, sure. So the meta-trial approach combines the benefit of a prospective trial design, as well as the high power of a large multinational trial, with that of the faster setup of an individual investigator-led national trial. It combines mainly features of an international prospective randomized control trial and less of that of a retrospective meta-analysis. So how it started was that early on in the pandemic, the lead investigators of five national open-label superiority trials of awake-prone positioning agreed to participate in a meta-trial where we were planning to compare awake prone positioning with standard of care in patients who had hypoxemia from COVID-19 and who were also undergoing high flow nasal cannula support. So we took advantage of the explosion of video conferencing activity to meet online and design the meta-trial. And this involved setting up a collaborative meta-analysis of individual patient data from each of the trials. We had to harmonize the data that could be extracted from each of the trials. We had to agree on a common primary and secondary outcomes for each of our individual studies. We went on to plan a collaborative interim and final statistical analysis at the level of the meta trial and then we also agreed to report our findings jointly as a unified group of investigators. We published our study protocol but we also sent out an invitation for other investigators to join this effort and very soon after we started a sixth group with a very similar research design joined our consortium. So the meta trial is definitely an original way to combine efforts from several investigators to speed up research in the setting of pandemic. It has advantages over the single center sponsored large multinational randomized control trials, which you can often have a long setup time, you know, where implements for agreements of the study need to get set up, but it doesn't lose any of the rigor that offer randomized control trial and that all of these features of a randomized control trials are preserved within a meta trial. There are some disadvantages in that because there were slight differences in protocols along the site, there are slight differences between the studies. And we also weren't able to track as slickly the study entry across the globe as a single center trial would be able to. But it's certainly an improvement on individual led studies where one has to wait for each study to reach completion before you can actually publish your study. Therefore, you can't really include any study into a meta-analysis until a study has reached completion. So there's a high risk that studies may never reach completion or studies may never, ever get published. So the number of patients that need to be randomized is often a lot higher than is necessary for smaller studies. And finally, compared to a meta-analysis, which, you know, this borrows some features off, there's no real opportunity to control for heterogeneity once a study is done. Whereas with the metatron, we had an opportunity to really pull out any heterogeneity between our studies so that we had a very common study and that any findings we have are a lot stronger than studies that are being looked at retrospectively. Dr. Li, could you tell us what were the main findings of the study and how did these results translate into the intensive care unit? In this prospectively designed multi-center international randomized open-label meta-trial with a larger sample size of over 1,100 patients. We found awake prone positioning reduced the incidence of treatment failure with 28 days of enrollment, while the treatment failure was defined as reintubation or death. Different from previously randomized control trial with small sample size and most of their patients treated by conventional oxygen therapy, our patient population had acute severe hypoxemic respiratory failure due to COVID-19 and supported with hyponasal cannula therapy. And our patient population had the mean SpO2 to FiO2 ratio of 150. We also found adverse event was mild. Specifically, we did not find any patient had cardiac arrest associated with awake prone positioning. And those adverse event was infrequent and occurred at similar rate with patient assigned to awake prone positioning group and a standard care group. In addition, we found the patient who experienced treatment success had a longer mean daily duration of awake prone positioning. Specifically, the patient who remained in awake prone positioning for more than eight hours daily on average while on hyphal nasal cannula treatment had higher treatment success rate as compared to those who stayed in prone position for less than eight hours per day. For the clinical implication of our study, we recommend that awake prone position is a safe intervention that reduces the risk of treatment failure in acute severe hypoxemic respiratory failure due to COVID-19 and who require advanced respiratory support with hyphal nasal cannula oxygen therapy. And our funding supports the routine implementation of awake prone positioning in those patients. And more importantly, we should make effort to improve patient comfort under prone positioning in order to help those patients stay at least eight hours per day in prone position. Are there any limitations of the study that we should be aware of? And how might these affect the interpretation of the results? Yes, there are three major limitations in our study. The first one is the duration of awake prone positioning. Different from intubated patients under prone positioning, the duration of awake prone positioning is completely controlled by patients. As clinicians or researchers, we did encourage our patients to stay in prone position and tried to help them improve their comfort under prone position, but the duration of awake prone positioning still varied among different patients.
But definitely this topic needs more investigation, especially more efforts are needed to improve patient adherence to prone positioning. Secondly, due to the very nature of our intervention, which is awake prone positioning, preclude the blending. We cannot exclude that at least part of the effect of awake prone positioning was mediated by influencing the treating physician decision-making. Despite the provision of clear criteria for intubation, clinicians could have refrained from intubation based on transient improvement of respiratory parameters during awake prone positioning. Or conversely, they may have lower intubation threshold for the patient in the standard care group. However, we did not find that awake prone positioning was associated with either longer duration of mechanical ventilation or with higher maternity in intubated patient. This would suggest that the physician was not influenced by correctly identifying patient who required intubation. Similarly, this makes a bias towards excessive intubation in the in-control group unlikely. Overall, those considerations should not distract from the problematic finding that awake prone positionally reduced intubation regardless of the underlying mechanism of this effect. Lastly, in the standard care group, one patient out of 10 underwent awake prone positioning. With those protocol violations, which could have led to an underestimation of the efficacy of awake prone positioning, we still see lower incidence of treatment failure in the awake prone positioning group. The results of the study conclude that awake prone positioning is safe and had a favorable effect on intubation or death within 28 days of enrollment in patients with severe COVID-19 and hypoxemic respiratory failure. When do you recommend this technique be implemented in the patient journey to ensure the best outcomes? Based on this study for patients with COVID-19 acute hypoxemic respiratory failure who are requiring high flow nasal cannula and have a PF ratio less than 200, awake prone positioning should be implemented as standard of care and patients should be encouraged to maintain that position for up to eight hours a day. So that would be the outcome from this study. What we don't know at the moment though is, you know to make patients stay in this position when to recognize that patients aren't benefiting from away prone positioning and to optimize the time for patients who you know are not benefiting from it and then to see what other alternative treatments we should be aiming to get these patients started on. Dr. McNicholas, Dr. Lee thank you for agreeing to speak with us today. Thank you Aaron.
You're listening to The Lancet News Podcast. Find us on iTunes or on the multimedia tab of thelancet.com. It's Friday, May 9th, and you're listening to The Lancet News, your global health news portal. I'm Olaya Studillo. And I'm Tim Dayland. In today's show, we're going to talk about Sri Lanka and the obligations of the government five years after the civil war. We're also talking EU migration. In part two we've got an interview about Canada's Muskoka initiative and the billion dollar initiative to support maternal and child health. And in part three we're talking about hepatitis B in prisons in the UK and a new drug law in Tennessee which is going to criminalise mothers who take drugs. But first up we're going to talk about Sri Lanka. In recent on this podcast, we've heard how fighting in South Sudan and Syria leads to mental and physical health effects, crises of refugee populations, and just how traumatic ongoing civil wars can be. But what about when the dust settles and one side has won? Sri Lanka ended a bloody civil war in 2009 when the ruling government finally defeated the LTTE, sometimes known as the Tamil Tigers, who were based in the northern, and largely Tamil, regions of the country. Both sides were accused of human rights abuses during the war, and some 80,000 to 100,000 people were killed, according to the UN, in the 26-year-long civil war. At the end, the LTTE was pushed back with civilians in tow to an enclave in northern Jaffna province. We're looking back now because it's five years since the end of the war, and it's the a world report written by Talhah Khan Berkey and our short leader this week in The Lancet. During the war, both sides were accused of human rights abuses and in March, the UN Human Rights Council voted in favour of an inquiry into war crimes, which has been rejected by the Sri Lankan government. So the issue comes down to this. The LTTE murdered, raped and tortured civilians trying to flee the war zone, and they used civilians as human shields. However, the government forces are equally accused of having continued to shoot at them, knowing full well that there were civilians in the area, and they really didn't hold back in the final bloodiest days of the conflict. So what happened after the war is important. The military presence in the Tamil north is still oppressive. Talha points out that Sri Lanka has one of the highest suicide rates in the world. Rehabilitation camps set up for ex-LTT fighters are accused of being fronts for torture and the government is accused of employing 18-month detention orders without trial for people accused of terrorism. Yes, there is such a thing as a good winner and the Sri Lankan government needs to prove that it can be a successful winner, not just the victor of a devastating conflict. We can look at Timor-Leste as an example where poverty, ongoing community tensions and persistent feelings of injustice led to mental health problems long after Indonesia left, was forced out. The problem of ethnic tension in Sri Lanka is a key one. The divide between the Sinhalese majority and the Tamil minority will only be widened without some closure on the war that such an investigation could provide. Sri Lankan President Mahinda Rajapaksa is consolidating power and he ended the term limit on presidential offices in 2010. I was in Sri Lanka last year and saw the gulf in development between the southeast and Hambantota and the northern reaches which are more heavily populated by the Tamil minority. As Tala adroitly puts it in his world report, Rajapaska might have won the war, but is he losing the peace? Moving on, the European Commission wants to standardise the health screening of migrants and refugees entering all countries of the European Union. Tonio Borg, the EU Health Commissioner, announced last Tuesday in Athens that this was in order to protect the health of our citizens. The EU wants therefore to create common guidelines on what diseases to screen for, when and how. He said that a new 3 billion euros European fund has been created to help member states to manage migration and the state responsibilities towards asylum seekers' well-being. And Borg said that this fund could be used not only for infrastructure but also to finance health needs. EU member states will need to decide whether they want to join the screening guideline initiative before June 20. Improving migrant health and access to healthcare has a lot of challenges. And if you want to know more about migration and healthcare in Europe, it's very well described in an interesting article by Bernd Reschel and colleagues in our Health in Europe series we published last year. Welcome to part two. The Canadian Prime Minister Stephen Harper launched the Billion Dollar Muskoka Initiative for Maternal, Newborn and Child Health in 2010 with an increased focus on accountability. The following year he co-chaired the UN's Commission on Information and Accountability for Women and Children's Health, which included 10 key reforms covering reporting, transparency and accountability in countries that receive aid. However, critics claim that the Harper government in Canada and his Muskoka initiative is failing to meet the standards its leader has urged on the rest of the world. I'm delighted to be joined by Paul Webster, journalist and regular contributor to The Lancet, who's going to tell us a little bit more about the aims of the Muskoka initiative. The aim of the Muskoka initiative was to bring together the G8 and the broader G20 community around the issue of maternal, infant and child health and to galvanize action to try and meet the Millennium Development Goals that address child mortality and maternal mortality. So the Canadian Prime Minister, Stephen Harper, used the opportunity of a G8-G20 summit here in the Toronto area, actually speaking in a place called Muskoka, north of Toronto, to announce that Canada would substantially step up its funding for maternal, newborn, and child health and had actually pleased substantial pledges out of the other G8 and G20 nations, amounting to something more than $4 billion. So in total, at the Muskoka summit, Mr. Harper announced that his leadership had propelled about $7 or more billion in new investment in maternal newborn and child health programs globally. Yeah, and we see $2.85 billion committed by the Canadian government itself. Correct. That's where the problems start to creep in though, isn't it? There seems to be some problems with accountability and whether this money is actually being channeled into maternal and child health. Yeah, I think traditionally in aid, and particularly in global health projects, pledges have been hard to follow up on. They often have not been met. The G8 has a track record for a lot of talk and less action on humanitarian initiatives. So the Canadian Prime Minister was very explicit in saying that in launching the Muskoka initiative, he would personally push for transparency and accountability and a much greater flow of information regarding whether or not pledges would be honoured and how the money would be spent and what results would be gained. And in following up on that, he joined with the President of Tanzania in co-chairing a United Nations stewarded commission on information and accountability, which in 2011 released a report calling on both donor nations and recipient nations for far greater transparency in the money flows and results for investments in maternal, newborn, and child health. And the commission's report was utterly explicit that Canada and other nations, not just the recipient nations, but donor nations, would be called upon to provide much more transparent accounting, both to demonstrate that pledges were honoured or are being honoured, and secondly, that the money is being spent effectively and that results are being achieved. Yeah I thought that was a really interesting point we're not actually just looking at the recipient countries here are we? No it's the whole you know global health community all the so-called stakeholders both givers and receivers and I think where the your question earlier asked, you know, so do have problems emerge? It seems they have. I think what has transpired is that an independent expert advisory group that has tracked progress on maternal health has found that the commission's recommendations have been met with a fair degree of reluctance, that the record is checkered in implementation, and that recipient nations have struggled to actually meet the recommendations because it's expensive, in fact, to achieve transparency and accountability. It takes highly trained people to track money flows, and many resource-strained countries simply can't do that. But also, I think what's proven to be problematic is that rich donor countries like Canada have not actually met the recommendations either. And I think that's particularly important to point out here in Canada, given that our prime minister has been a global leader on pushing for this accountability. And it seems particularly notable that Canada has not actually achieved the recommendations of our prime minister's international commission on information and accountability. Yeah, it's all very well and good, pledging $2.85 billion.
And they worry, however, that they can't independently verify it and that the government actually is not transparent enough in its accounting. Nobody's suggesting that the government is not acting in good faith, but I think people are saying that given that the Prime Minister's Commission called for much greater transparency and accountability, it's unfortunate that they can't independently verify that the pledges are being met. And the other complaint here in Canada is that although the government actually has stepped up its efforts to provide information about where the Canadian money for maternal, newborn, and child health is going, it's a far-from-complete picture that's being presented, and it's a rather scattered and impressionistic accounting that the government has given. And when I interviewed the government senior official on this issue for this article in The Lancet, she told me that the accounts would be fully rendered about three years from now. And certainly that is not in keeping with the Prime Minister's Commission on Information and Accountability's recommendations. So too slow, you think? Yeah, I mean, there's always been in Canada a very opaque accounting for international aid. It's a potential source of embarrassment to the government, as it is to all donor governments. It's always been difficult to get full accounting for where the aid money is going. And the hope had been that following Prime Minister Harper's commitment to the world that this money within the Muskoka Initiative would be accounted for with much greater precision and accuracy. The hope had been that we would see a dramatic change in Canada. What we've seen really is a very modest change. There we have it, the state of play in Canada. Just leaves me to say thank you very much to Paul for joining us on the podcast. Welcome to part three. According to new data compiled by the Public Health England, hepatitis B is on the rise in prisons in the UK having unprotected sex. But what about vaccination? Was there any data on that? Yes, it seems that over that same period, so from 2010 to 2013, the number of hepatitis B vaccinations in prisons have also gone down. And that is despite the prison population increasing to a record 85,000. So in three years, the number of doses of vaccine administered fell roughly from 110,000 doses to only 74,000 last year. So then maybe we can see why there's this increase. but what about if these people were infected before they got into prison? Is that a potential source as well? Well, yeah, that's the thing. So it's difficult to tell whether people had actually got the infection before being incarcerated or in prison itself. So some people argue that it could be also the change in the prison population, or that it's just a matter of an improved screening within prisons, rather than actually arising the true prevalence of infection. Moving across the pond, as it were, to the USA, where women in Tennessee who take drugs while pregnant will be charged with misdemeanor assault if the baby comes to harm as a result. The law has been brought in in Tennessee despite widespread opposition from doctors and women's rights groups. Yeah, the law is intended to allow police to address illicit drug use and get pregnant women into drug treatment services. So it is more a rod than a carrot approach, punishing addicts for their behavior. Yeah, and it flies in the face of the White House's Office of National Drug Control Policy, which is to reframe drug policy not as a crime but as a public health issue. I can't help but think it will be reviewed in two years and hopefully dropped. So here we are, almost at the end of the show. Just a quick round-up by Aliyah of what else is in the Lancet family this week. Yes, so in the Lancet, the weekly one, the long leader is really interesting. It's about food poverty in the UK. So it follows an open letter to David Cameron from the UK Faculty of Public Health in which the increase in use of food banks is mentioned Thank you. problems about food policy, it makes a very interesting leader about food policy, social inequity and poor population nutrition. Have a read. And then in The Lancet Oncology, there's two interesting pieces in the Cancer and Society section. One of them is written by Catherine Lucas and it's about cancer and couture. So it's quite unusual to see dresses inspired by cancer. Yeah, it's quite nice to see in Cancer and Society some fashion photography. It's women wearing dresses, but they're dresses inspired by cancer, so they've sort of got cells and imaging. Yeah, staining and yeah, so it's great. Very interesting. Yes, and then also in the same section in the Lancet Oncology, there's a nice piece about the breast fest. Yeah, which is a Canadian attempt to get breast cancer more on the map, and that's interesting as well. And that's it. That leaves us to thank our producer, Nikolaj Humphries. As ever, you the listener and say goodbye. Goodbye. Bye.
This is exactly right. or a thrill seeker. You'll find what you came for here and more. So ask yourself, what is it you want? Discover Williamsburg and plan your trip at visitwilliamsburg.com. Welcome to the Flashbinds podcast, the world's fastest podcast where we explore how Facebook can help you with the stuff you're into. I'm your host, Emma Rogue, and today I'm with creator and home decor guru, Julie Souza. Julie, what's your number one tip? So if you're into home decor, I would suggest looking into Buy Nothing Facebook groups. It's a great way to explore your style all for free. Ooh, we love free stuff. Thanks, Julie. See you next time on the Flash Finds podcast, all about discovering the stuff on Facebook you care about. Bye! to be our 100th regular season episode. But when things with Monkeypox started to ramp up, we decided that we wanted to make sure that we got a Monkeypox episode out to you as quickly as possible. And that meant pushing back this immortality episode, which we had actually recorded before Monkeypox. So throughout this episode, you may hear references to this being our 100th episode, even though it's actually episode 101, and we just wanted to explain why in advance. Okay, I they dispensed to mankind, life they kept for themselves. But you, Gilgamesh, let your belly be full. Enjoy yourself always by day and by night. Make merry each day. Dance and play, day and night. Let your clothes be clean. Let your head be washed. May you bathe in water. Gaze on the child who holds your hand. Let your wife enjoy your repeated embrace. Thank you. I still don't actually know the story of Gilgamesh. I still only know a little part of the story of Gilgamesh. So yes, that was from the Epic of Gilgamesh, which is one of the oldest, I think actually considered the oldest surviving document or text. Wow. That's amazing. Yeah. Yeah. It's from a long time ago, like 2000 BCE, something like that. Wow. Yeah. Hi, I'm Erin Welsh. And I'm Erin Allman Updike. And this is This Podcast Will Kill You. And today, we're not just like reading you the story of Gilgamesh. No, that's most of what you'll hear about Gilgamesh. Today we're doing something very different in honor of our 100th episode. 100th. I mean, it is, I can't believe it. I never would have thought we could make 100 episodes of a podcast, Erin. Me either. And okay, here's the thing is that like, technically, we surpassed 100 a long time ago. That's true. I forgot about that. With like all the COVID episodes and the bonus episodes. Still, this is this is our, like our title episode 100. Yeah. And I think in honor of that, as we slowly get around to talking about what we're going to be talking about today, we thought it would be fun to take the name of our podcast and change it up a bit, right? This podcast will kill you. Today, this podcast won't kill you. Yeah. It might make you live forever. Probably not. Give you the secrets to eternal life. Today, we're going to be talking about immortality and aging, and it's definitely not going to be a comprehensive journey through the history of aging and how immortality could be achieved. But I think it's going to be a nice little taste. Yeah. And our structure is going to be a little different than usual because it's such an amorphous topic. Yeah. So I'm going to be starting out talking about the history of immortality and what that means in terms of evolution and then what that means in terms of like human culture. And again, it's just sort of like a brief little jump through this topic. And then I'm going to talk about, I don't really know what, Erin. Maybe like where we stand in terms of like aging today or anti-aging research or the quest for immortality, what we know about the biology of it. I don't know. It's going to be a little bit of a conversation. I think it's going to be really exciting and fun. I'm just looking forward to it. Same, same. Well, speaking of tastes of things, what time is it? Oh, quarantini time. Still is quarantini time. Still is. Always quarantini time. What are we drinking this week? Well, of course, we're drinking none other than the Elixir of Life. We are. And in the Elixir of Life, it's a fun little drink because we've got gin, we've got lemon juice, we've got blackberries, we've got simple syrup. And then to kind of like create the fun little magical, I don't know, aura around it, we've got butterfly pea flower extract, which was sent to us by a very generous listener. So thank you so much. It is such a cool looking drink. It's amazing. I'm really excited, but I want to come visit you so that I can actually taste it. Okay. Let's make that happen. Yeah. We will post the full recipe for the Elixir of Life, as well as the non-alcoholic placebo Rita on our website, thispodcastwillkill kill you.com as well as on all of our social media channels. Our website, this podcast will kill you.com. If you haven't been there yet, you should go and check it out after a hundred episodes. Try it. We have the merch. We have transcripts. We have links to our bookshop.org affiliate account. We have links to our music bloodmobile. We have a Goodreads list. We have all of our sources for all of our episodes. We have our Patreon. We have more than I could say in that single breath. Well, I think you did a great job. Thanks. Love it. All right. Any other business? No, Erin, please tell me, like, I don't know, from Gilgamesh to now, how has humanity fared on our quest for immortality? Great questions there. I will do my very best right after this break. Like we said, this is definitely not our typical format. But then again, this is not our typical episode topic. So the focus of our episode today is immortality. But what does that mean? Not just like, what are we going to cover, but the word or the concept itself. Yeah. Is immortality simply living forever? Not aging? Being invulnerable to any illness or injury? Does it mean that your name and life will be remembered hundreds of years from now? Or that your genes will be carried on in your offspring and their offspring and so on and so on down the line. There are many different ways that we can think of and have thought of immortality. And if your goal is to achieve immortality, which definition you choose has tremendous bearing on how you go about that. And that can also be said for this episode. So how will we consider immortality today? Really, we'll at least touch on the most common concepts in a general sense. But since we're a health and science podcast, most of what we'll talk about is immortality from a biological perspective. First, by talking about not what immortality is and how we can achieve it, but what stops us from being immortal in the first place. Why do we die? Why do we decline as we get older? Are there any organisms that don't? What do we know or think about senescence, decline or deterioration we experience as we age from an evolutionary perspective? And then I'll turn from that to talking about the age-long quest for immortality, which has roots much, much older than these startups in Silicon Valley that have been looking for modern elixirs of life that I know you're going to be talking a bit more about, Erin. Yeah. What patterns do we see in the different ways that people have approached immortality through history? And how has this past century and our ever-growing understanding of biology changed the targets for immortality research? And then that's sort of where I'll hand it off to you, Erin, to tell us how close we are, or probably aren't, to achieving immortality and the nitty gritty of what people are working on. Okay. Okay. All right. So let's get into it.
They also change as time passes. First growing and developing, and then at a certain point, that growth ceases and a new kind of change occurs. One where maybe things don't heal quite as fast as they used to, or those aches and pains get more frequent and eventually recovery is no longer a possibility, with death being the ultimate end. And this is generally how it happens for every living thing. And sure, the amount of time that you spend in each life stage may be different, or how long you can expect to live will vary, but death and aging are essential parts of life. Even for those supposedly immortal animals that you see like clickbait headlines about, like lobsters or certain jellyfish or bristlecone pines. But while senescence, the biological decline part of aging, may not be as marked as in other creatures, those organisms are not truly immortal. They will die eventually because nothing living is immune to death. Why does this have to happen? Like, why can't we go on living forever? Well, let's think about it in the context of natural selection and evolutionary fitness. Let's, Erin. Evolutionary fitness, for those who haven't heard the term before, is essentially an individual's reproductive success, how many offspring they have. If an individual has no offspring, zero fitness. If they don't survive long enough to reproduce, fitness is also zero. But the individuals who do live long enough to reproduce and have a lot of offspring, those are the ones who are going to contribute the most to the next generation's gene pool. Traits that limit your ability to reproduce or survive through reproductive age, those traits lower your fitness and make it less likely for those genes to be passed on to the next generation. And over time, those traits, those genes, will become less and less common, maybe eventually disappearing. But traits that make you more likely to reproduce or survive through the end of reproductive age, those are the traits that are going to be selected for, becoming more common. So we can think of tons of examples of this, right? Like the size of a bird's beak, or the rate of development of a tadpole into a frog, or fur pattern, or susceptibility to disease. But what's so crucial about this for this discussion is not the traits themselves, not these examples, but rather the time window when these traits matter most. And that is the critical period from basically prenatal development all the way through the end of when you are able to reproduce. That is when selection can act. With this in mind, what does it matter, really, in terms of natural selection, if you live past reproductive age? It doesn't. It doesn't at all. It doesn't, yeah. If there are genes that affect, at least in part, your longevity, how will natural selection act on them if they don't have any bearing on your reproductive fitness? It won't. It won't. I mean, and there are genes in humans that are associated with longevity, but it's likely that those play a role in maintenance or development, and they don't just switch on later in life. Exactly. Yeah. So essentially, in terms of natural selection, it doesn't really matter how long we live past the point when we're no longer reproductively viable. And this is, of course, like a big oversimplification. And for humans and other animals, there are some very interesting hypotheses about why we humans live long past the age we reproduce, mostly centering around grandparents. And I'd love to get into that one day with an episode on menopause. Oh, I will definitely do it on menopause because I love all of the evolutionary theories behind menopause and just like aging and like the grandparent. Oh, I love all of that. Yes, the grandparent hypothesis. Oh, it's so interesting. Yes. I love it. But anyway, we humans are not unique in that we live past the age we reproduce, nor are we unique in the fact that our bodies and minds start to deteriorate as we get older. And even if life past reproduction is not part of natural selection, what makes us and other organisms age? Why do we age? And we have been asking ourselves this question probably since we were able to form thought. But it wasn't until Charles Darwin introduced the theory of evolution by natural selection in the mid-19th century that people had a scientific framework that they could use to try to answer this question. Since that time, many different hypotheses have been proposed, none of which seem to adequately explain senescence for every living thing. And I'm going to briefly go through a few of the classical hypotheses of senescence so that we can try to think about possible mechanisms that could explain why aging is universal. The first of these hypotheses was proposed in the 1890s by the German evolutionary biologist August Weissman, the so-called germ-soma theory. And so Weissman suggested that there were two types of cell lines in an organism, a germ line and a soma or body line. And the germ line is made up of the cells that are involved in reproduction. And the soma line consists of the cells that make up the rest of the body. It's the sole duty of the soma cells to do whatever it takes to keep the germ line alive and reproducing. Beyond that, soma cells are basically disposable, and the soma cell lineage will invariably die while the germ cell lineage can be viewed as potentially immortal. Aging happens as the soma line gets beat up by the environment while protecting the germline. And that's the hypothesis. Obviously, it has many shortcomings, first of them being that it doesn't really explain why senescence evolved, like why the soma is disposable. And it doesn't explain senescence in single-celled organisms. But it did introduce the idea that reproduction is first and foremost the priority. And many later researchers built upon this idea, such as the famous mathematician and eugenicist Ronald Fisher, who in the 1930s proposed a mathematical model in which he laid out his thoughts that senescence was the accumulation of harmful age-specific traits. A couple of decades later, in the 1950s, Peter Medawar, whose name you might remember from our organ transplantation episode, he wrote a now-famous essay describing how the force of selection weakens as we get older and past our reproductive age. He wasn't entirely right either. For instance, his belief that animals in the wild don't get old, they don't senesce because they just get picked off by predators or succumb to starvation. They actually do senesce, they actually do get older. But his essay did suggest a sort of mechanism for senescence. If there are certain genes that do exist that shorten our lifespan, they won't really be selected against if they only show their effects later in life. And so they will continue to appear and accumulate over generations. The quote, mutation accumulation theory. That's, I love, sorry, I just really do love these hypotheses. I do too. I find it really it really fun it was it was so interesting because i have never even though i said humans have probably asked themselves this question forever and i've probably asked myself this question too but not in like a okay but why what is the actual evolutionary mechanism behind it i feel like i only ever thought about a about another hypothesis I think you're probably going to talk about next in the context of the evolution of human health class that I TA'd for. So that was like a very specific subset of time that I was thinking about it. Yeah, it is. It's so fun to think about. Okay, so there are a few more. or have negative effects later in life. Like, for instance, let's think about cell growth. If your cells grow super fast, that's potentially great when you're developing, right? You get larger faster and can be independent faster. But later on, that could mean uncontrolled cell growth, aka cancer. Yep. And this is something that's called antagonistic pleiotropy. It's one of my favorite concepts, and I love it. It's so, it's, I mean, and it, like, the thing, they all make sense. And the thing that I like, too, about them is that none of them are really mutually exclusive. Exactly. Like, you have, you can easily have mutations that accumulate, well as have genes that are beneficial early in life and maybe have a detriment later in life. So, like, these mutation accumulation, antagonistic pleiotropy, these hypotheses really do work together to explain aging in a way that I think is just fascinating. Yeah, exactly.
And it also showed that the strength of selection on traits that keep you alive, it becomes weaker over time in anything that ages and doesn't reproduce via fission. Yeah. Really also what it did was create a math model for people to be able to test ideas about aging. The last of the classical hypotheses of senescence I'm going to talk about is the, quote, disposable soma theory proposed by Thomas Kirkwood in 1977, which says that over time, an organism's cells accumulate harmful genetic mutations. Mutations in your DNA happen randomly all the time because of environmental factors or mistakes in DNA replication, and it gets increasingly costly to repair the damage from these mutations. And at a certain point, the benefit of repairing the damage is outweighedescence evolved. But there are certainly others, and no single hypothesis at this point seems to be able to explain aging for all organisms. There's no unifying hypothesis, probably because there's tremendous diversity in life. No, is there really, Erin? Are you telling me that a bristlecone pine is not the same thing as a planarian? It might not be. And even some of the fundamental assumptions about aging have been challenged. It's an extraordinarily complicated thing to study. You have to capture both how different environments and different genes impact aging. You have to consider ecological factors, determine whether aging in the lab is different or the same as aging in the wild, evaluate whether closely related species age more similarly than distantly related ones. And the biggest thing in my eyes is that we've really only begun looking at this within the past 130 years or so, which is shorter than the average lifespan of some organisms that could give us really valuable insight into longevity. Good point. So like, how do you create a data set for giant tortoise? Well, even studying human aging, like we live a really long time. Right. And there have been really cool like census records, and especially in certain countries or certain regions that keep really good track of like people through time. But we still don't have all the bits of information there. Right. Yeah. So it's in a way we've been thinking about it for a long time, but it seems like we're definitely in the infancy of having data to be able to test these hypotheses. Erin, you just summed up my whole section. It was really interesting to read through this also because I don't think I realized just how huge of a field of study this is. And I guess I should have because there are like, you know, entire journals and entire textbooks and entire companies and everything. But like it is, it is really hard to do it justice. Yeah, yeah. So yeah, so I just kind of wanted to like wander through some of these ideas and kind of feel and build a baseline for thinking about aging in an evolutionary context, especially when it comes to like natural selection. Yeah. And wouldn't it be great if we lived forever, but we don't really need to. Yeah. In terms of our DNA getting passed on. Yeah, exactly. Yeah. And I also thought it was important to think about these things, like why we age, before we start exploring some of the ways that we've tried and continue to try to stop or slow that process. Uh-huh. So if there is anything that humans are good at, it's searching for the key to immortality. We're really good at searching for it, but we are terrible at finding it. Yeah. Because we've not found it. Yeah. Spoilers. We don't have it. Spoilers. We don't have it. We may not, he does not. And I'm sure between the two of us, we can think of dozens and dozens more books or movies or poems or songs about the search for eternal life. But it's not just like one of my favorite books growing up was Talk Everlasting. And for a long time, have you read Talk Everlasting? No, I didn't even know it was a book. I thought it was a movie, but I've never seen it. Okay. Or read it. Basically, it's about this family that is trying to find like a home. They're like homesteading and they stumble across this water. They all drink from it, including the horse, I think. And it happens to be like an immortality spring. And then there's like a girl who stumbles across this family. And then she's like, do I drink it? Do I not drink it? Blah, blah, blah. And as a kid, I was like, drink it, obviously. Don't drink it. Don't drink it. And yeah. Anyway, but it's a really interesting contemplation about immortality and life. Yeah. I loved it. And that's just one of like hundreds, dozens, thousands. I mean, an unbelievable number. But it's not just in these fictional stories that people have been on the hunt for a way to live forever. The quest for immortality is a very real thing that takes many different forms. And I want to talk a bit about these forms before focusing on a couple that are more in line with this episode. While researching for this episode, I came across a book titled Immortality, the quest to live forever and how it drives civilization. And in this book, the author, philosopher Stephen Cave, groups the search for immortality into four different themes. The first two deal with the physical side of things. First, there's living forever. You as an individual stopping aging or aging but not dying, living indefinitely. And then there's resurrection, being brought back to life after death. Think Jesus. Third is the soul, the idea that a part of you, but not the physical you, lives on after you die. And finally, there's legacy, which can mean living on through memories or fame, as in you're only truly dead when your name is no longer said. Coco. Or also offspring, the idea that your genes achieve immortality by being passed on. And I wanted to explore some of the ways we've sought to achieve immortality throughout human history, focusing on those that fall into the first two of these themes, staying alive and resurrection. Because in terms of targets for biological research into immortality, all of those projects can be lumped into those themes. And after going through some of these adventures in immortality, I want to end by reflecting on what these stories tell us about human nature. We humans may be unique in our ability to recognize our own mortality, that one day each and every one of us will die. And the knowledge of our own inevitable death, yet the simultaneous inability to actually imagine what it will be like, has driven us to find any way around it, either by delaying it, undoing it, or preventing it entirely. In ancient Egypt, there was an entire industry devoted to preserving the body after death so it could be magically revived. And of course, pyramids and other monuments were built as a testament to the person's life, immortality through legacy. Ancient papyri describe not just preparation for the afterlife or resurrection, but also ointments and elixirs that were meant to extend life and slow aging. The search for an elixir of life or a fountain of youth is similarly old. There are countless stories of emperors and kings searching in vain for a way to escape death. Like the first emperor of China who lived around the 200s BCE. He became obsessed with the idea of living forever and searched high and low for someone who could reveal the secret to him. He did find someone, probably one of the oldest known swindlers, who promised it all but delivered nothing and just ran away with his reward. Of course. Ultimately, the emperor about him. We are. Through legacy. The Terracotta Army. Have you heard of the Terracotta Army? Oh ingest. At various points, it was thought to be a plant or a series of exercises or a special object like the philosopher's stone, which was one of the mythical substances famous in alchemy. Alchemy was a kind of pre-science practiced by philosophers and early chemists, the goal of which was to transform one metal into another, typically gold, and to find the elixir of immortality or a cure-all for any disease. It was practiced all over the world, from ancient times all the way up through the 18th century, when it declined after the rise of more rigorous scientific thinking. Although it might be more accurate to say that alchemy didn't decline, but rather it was repackaged, primarily into the field of chemistry. Nor did people grow tired of looking for the elixir of immortality. Instead, the development of each new field or new scientific discovery was applied to that quest. For instance, electricity.
Oh, yeah. Uh-huh. So his nephew took a page out of his book and held public demonstrations where he reanimated corpses of freshly hanged murderers. Oh, my. Okay. Yeah. And his demonstrations may have been the inspiration for Mary Shelley's Frankenstein. Frankenstein? Oh my goodness. I know. Connections. And this pattern continues to be repeated. In the mid-20th century, advancements in cellular technology allowed researchers to use previously frozen sperm for insemination, resulting in three pregnancies, which was revolutionary. And that soon turned into whole body freezing plans. Mm-hmm. And the amazing thing, in my eyes, is that despite humanity's continuous and innumerable attempts to achieve immortality over thousands and thousands of years, we have not been remotely successful. And we probably never will be. Maybe you'll change my mind. Yeah, we'll see, Erin. But this has not been an extension of our inherent lifespan. Humans have been able to live to 80 years old, 90 years old, for thousands of years, but were prevented from commonly achieving old age because of extrinsic factors, like insert any vaccine-preventable disease here. Or also taking like mercury and arsenic as a vitamin. Just like that too. But from what I've read, there's not a single anti-aging serum, pill, potion, whatever, that has been shown to actually slow aging or reverse or stop it. There is some evidence that diet and exercise may play a role. Longevity and aging are both such incredibly multifaceted processes that are nearly impossible to predict. And I'm not saying at all that I don't think this research should be done. Some of these projects have uncovered knowledge that has had huge implications for improving quality of life and treating diseases that primarily manifest later in life. I guess I'm just expressing my skepticism that a meaningful extension of both lifespan and quality of life alongside that will be achieved in the near or even kind of near future. This section definitely came out differently than I had planned. When I started it, I thought I'd take us through the history of the search for the elixir of life or the beginnings of cryonics. And those stories are fascinating and worth telling. But I think that overwhelmingly, while doing the research for this part, and while going through it just now, I think that what sticks out to me most is how so many things have not changed. We will continue to keep looking for ways to live forever, to upload our brains or slow our aging, to reanimate frozen bodies or download our memories into a cloned body. And if any of those technologies are successful, you can also be sure that the select few, the richest and most powerful, will be the only ones to benefit from them. Which is also how it has been throughout history. But would it truly be a benefit to live forever? Would it be something you want? I've talked about a few stories about people who have searched for a way to live forever. Now let's think of some where they achieved immortality. How did those stories end? Never well. Never well. Almost universally, they end in profound loneliness, sadness, and regret. Not at first, maybe, but over time, as their mortal friends and family grow older and die, as days pass and time becomes meaningless. Granted, all of those stories have been imagined by mortal humans, so perhaps these endings are just consolation for not being able to live forever. But, I don't know, personally, I don't think so. I think too often we decide we want to live forever without considering what that could truly look like. I want to end this section with a quote by Stephen Cave that I think puts it nicely. Quote, The deep problem is this. The value of a thing is related to its scarcity. People conscious of their mortality value their time and aim to spend it wisely because they know their days are numbered. But if our days were not numbered, this incentive would disappear. Given infinity, time would lose its worth. And once time is worthless, it, gosh. I'll turn it over to you to tell me how close we are to such consequences. Oh, my goodness, Erin. This episode turned out so different than we expected. I'm going to need a break. Okay. Yeah. And then I'll dive in to research for this episode, I had a really hard time because I wasn't sure how to really approach this question. And I actually wasn't sure what my question was. I normally do the biology section of whatever disease or thing we're talking about. And then I talk about the current status. Where do we stand today? So what was my question for immortality? Is it how close are we to immortality? Is it are we still pursuing this quest? Which, spoilers, you already told us. And the answer is yes, we still are. Oh, yeah. And I read a lot about the various Silicon Valley startups that exist, the number of companies, the number of billionaires and millionaires, and the amount of dollars that are going in to try to solve this, quote, problem of aging or the problem of death. It kills me, the problem of aging or death. It's really, really interesting. And I think I got a little bit overwhelmed and also maybe a little cynical by the end of it. Oh, for sure. I got cynical by the end of it. Yeah. But it's not to say like what you said, Erin, it's not that what any of these researchers are doing is unimpressive or unimportant. It's just that we remain in the very early stages of this research. So let's kind of go through the way that I at least try to frame thinking about this. If we're talking about immortality, like you said, Erin, at the top, then we're kind of talking about the idea of anti-aging, or we're talking about increasing our lifespan. And if we're talking about halting aging to the point of halting death, then for me, the way to get there logically is to answer a series of four different questions. The first question, you kind of answered, Erin, and that is, why do we age? I think that you provided a lot of evolutionary perspective on the idea of why we as humans and we as living organisms on the planet Earth age evolutionarily. But we still don't fully necessarily know. We at least have a lot of hypotheses. But a very closely related question to why do we age is how do we age? Like fundamentally, what governs the process of how our cells senesce and how is this process related to those evolutionary reasons of why we age. Because if we could answer those two questions really well, then we could ask the next question, must we age? Are those processes, like we said, from an evolutionary perspective, necessary for life? And are they immutable? And if the answer to that question is no, they're not immutable, and if we can figure that out by virtue of figuring out the answers to the first two questions, then we can ask the final question. If we don't have to age, do we have to die? So at least to me, those seem like the four fundamental questions that have to be answered if we have any hope of answering this riddle of immortality. And suffice to say, those four questions are massive. And I think the biggest issue for me in talking specifically about immortality is the leap between those last two questions. Must we age and must we die? Right. They're not invincible. And so that's, I think, one of the biggest issues I see with even just entertaining this idea of true immortality. Oh, yeah. Right? Immortality is not invincibility. Exactly. Yeah. Okay. But so is that what people are working on? Are people working on immortality? Or are people really working on the first few questions, but selling it, packaging it as the idea of immortality? Maybe that's more accurate. So what do we actually know about these first couple of questions, especially how we age and must we age? There has been, like you said, Erin, without a doubt, huge increases in the estimated life expectancy for humans globally. And there is a lot of variation in estimated life expectancy between countries, between genders, et cetera. And most of that increase is, like you mentioned, credited to early life advancements, things like antibiotics, vaccines. Basically, we know for sure that we've had huge reductions in early life mortality because of scientific and biomedical achievements over the last 50 to 100 years. However, there has also been a decline in late-life mortality. So the fraction of each birth cohort that reaches old age has been increasing year after year, or at least it had been until about the 1980s.
But the maximum reported age at death has plateaued. You may have heard of Jeanne Calmet, who was a French woman who died in 1997 at the ripe age of 122 years and five months. She still holds the verified longevity record by a lot, by a couple of years. And while there are over 500,000 centenarians alive worldwide, at least that's what the UN estimated in 2020, 500,000 people over 100, that number is 20 times higher than 50 years prior. But the average age at death for these centenarians has not increased since 1968. So there is a lot of research and mathematical modeling, like you mentioned, Erin, as far back as the 1800s, that really suggests that there may be a true upper limit to the human lifespan. And while this idea is still a little bit controversial, there are people who don't like to agree with the idea that there is a limit to human life expectancy. A lot of studies that have used various methods and are to varying degrees controversial have converged around this idea that perhaps between 120 and 150 years might be the maximum human lifespan that one could expect. So could we even live forever? It seems highly unlikely. Yeah. But there is another piece to this puzzle. Besides actual lifespan is like you mentioned, Erin, quality of life. This is often called healthspan. So if lifespan is the length of your life, healthspan is often defined as the period of your life that is free from disease. I personally will take slight issue with this definition because health is, of course, a lot more than merely the absence of disease. But this is generally how healthspan is defined. So we'll go with it for the purposes of this episode. Okay. And if we look worldwide, despite how much lifespan has increased, chronic diseases are the leading cause of morbidity and mortality worldwide. And many of these, cardiovascular disease, cancer, dementia, these are often considered diseases of aging. And an estimated 58% of chronic disease-related mortality happens in people over age 70. So if we look at the discrepancy between health span and lifespan, there's an estimated gap right now in the world of nine years. So there's a nine-year gap where you are still alive, but you are no longer, quote, free from disease. And a lot of the field of what is called gerontology research isn't truly focused on the idea of immortality, at least not overtly. Or in a lot of cases, they're not even focused on the idea of increasing our lifespan, but rather they're focused on increasing healthspan. So they talk instead about the idea of compressing our morbidity to the end of life, such that we live healthier lives for longer and can either avoid or prolong the onset of these various age-related diseases. And this, I think, sits as both a more palatable goal, for sure. I would agree with that. But I also think that it's closer to what seems maybe feasible. Yes. Although I do stress that we're not there yet. It's so interesting because I think that like, given the past 150 years of scientific research, we tend to view things as science will always progress at an increasing rate. Yeah. Right? Like we make bigger leaps and bounds in our understanding and in our technology and so on. And it doesn't, that's not necessarily the case, I think, with every field. Yeah. It is really, really interesting to read a lot of this research and then also read the media reports about this research or about the companies that are funding this research. I bet. Because it's very different, right? Yeah. This is where reading between the lines of popular news articles is tricky. It's tricky and important. Where there's like, have a heavy dose of skepticism and go to the original text. Yeah, definitely. But there are, I will say, a lot of researchers out there that are trying to really get into the nitty gritty of answering those first couple of questions that I posed. How and why do we age? And can we alter this process? flavors or nine different targets that are related to aging and potentially modifiable, at least in cell culture and or in animal models, or maybe just theoretically modifiable. So I'll mention all of these, but spoiler alert, reading some of the papers that go into detail on this, I had a very difficult time following through. But let's at least look at what we know about aging. Because it turns out we know a lot more than you might think. So when we look at the mechanisms of aging, one of them, Erin, you mentioned already, and that is damage to our DNA, be that nuclear DNA or mitochondrial DNA. Basically, over time, insults to our bodies result in the inability of our bodies to properly repair damage to our DNA the way that it is supposed to. And there are a lot of different potential genes involved in this and specific mechanisms that researchers have altered in flies or in worms or just in cells. But essentially, this genomic instability does play a really big part in the process of aging. So if there was a way to make our DNA more easily able to repair itself, that could then delay that process of aging. And we know delay a lot of the age-related diseases that are related to this, like cancers, like maybe heart disease. There's also telomere damage. Telomeres, I think we talked about in our HPV episode. Was that right? You talked about it in some episode, but can you do a refresher? Of course, I'd love to. So telomeres got a lot of press in aging a while back, but basically they're the end caps of our DNA. They're these strings of repeat DNA that sit at the ends of our chromosomes. And in a lot of cases, they don't get completely copied over when our cells divide. So over time, telomeres can become shortened. And this process of telomere shortening or telomere exhaustion then leads to a decline in the regenerative capacity of tissues and therefore accelerated aging. So in mice models and in other animal studies, telomere length has been shown to be associated with lifespan. In humans, it's not quite that simple, but this is at least another potential target. What do you mean it's not quite that simple? It's not like the length of your telomeres determines how long you're going to live. It's not a one-to-one association. So just adding on to our telomeres doesn't necessarily mean that we're going to increase our lifespan or our health span because this is one of nine processes related to the aging process. Nine that we know of so far. talked a bit about it in our folate episode. It was kind of fun. I was thinking that. Yeah, yeah. Basically, epigenetics are changes to DNA patterns that are not within the DNA itself, so not within a gene. But it's changes to things like methyl groups that are attached to our DNA. It's changes to things like histones, which are like the proteins that our DNA wraps itself around. It can be changes to how our DNA is stored. Any of these changes are considered part of epigenetics. And changes in a number of different things, from methylation to histone proteins, have been shown to be associated with aging. There is a family of enzymes called sirtuins, I think that's how you pronounce it, that are involved in DNA methylation and got a lot of press because in yeast and in worms, when these enzymes are manipulated, then you can increase lifespan by significant amounts in a worm. Again, in humans, we don't have any data to show that as of yet. But that's at least the idea that epigenetics likely plays a big role in the process of aging. So if this is something that we could target, we could maybe affect it. Yet another target would be proteostasis. So basically, our cells are both DNA and proteins, right? So as we age, our cells become less able to maintain proteins in the correct stable configurations and correct functionality. If you think of something like Alzheimer's disease, this is largely a disease of protein misfolding. So there are a lot of studies in cells, in yeast, and I think at least some in worms and flies, that if you mess with some of the genes related to protein stability, then you can precipitate aging, make them age faster. So that suggests that these systems are directly involved in the process of aging, and thus, if they could be manipulated in the opposite way, could perhaps promote longevity or reverse aging. Reverse aging. Interesting. Yeah. Yeah. There's more. I'm only on number four of nine. I don't have as much detail on all of them, let me tell you.

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