Split (1)

train · 37.8k rows

text stringlengths 1.05k 5.31k
But we have many more tools now than we did a year ago or two years ago. And I'm certain we will see data emerging that will help inform these different approaches and combination of approaches. To pick up on your last point, Lindsay, I think it's really important to think about the fact that we're using already very different tools than we did only a few years ago. We've learned a lot over the decades that we've been making vaccines. However, I'm not sure all the same rules will apply as we look at different vaccines and different ways of delivering them. So although I know that there is a feeling among some in the community that we're doing about as well as we can, I'm not sure that that's fair. I think that we might be able to do better and we'll learn about that as we try these new approaches. Nonetheless, from everything you say, it's clear that making vaccines that have lasting effects is going to be challenging. So, is there any good news we can take into the new year? I think there are several good stories. Remember that we're doing a lot better. Hospitalizations have fallen dramatically. Death rates have dropped dramatically. There are still populations that we need to reach in order to further improve. And there might be technologies that we can improve on that will also bring these numbers down. And I don't think that addressing the issue of infection is out of reach. It's something that I think is still on the radar. But clearly, we know a lot more about the pathogenesis of this disease, and we're learning more about what immunity means. Lindsay already alluded to the fact that there are lots of different kinds of immunity, and we've been measuring antibodies largely. We have measured other sorts of immunity, but we don't really understand what those numbers mean right now. And I think we're going to learn more about that. And as we do learn more, I think there will be dividends to come. And I keep in mind that while we're discussing vaccines, treatments have improved markedly. There are now good outpatient treatments. There are more on the way. And I think that we're going to continue to be able to decrease the morbidity of disease and the mortality induced by disease in the coming year. Steve, I actually view this whole discussion as good news. I would look at it the other way around. In the three years since this virus emerged, and it was three years ago, it was December of 19 when it was first emerging, and January when the world really appreciated it. In this three years, we have been able to define the pathogen, define the pathogenesis of illness, understand immune dysregulation, understand viral parameters, and develop multiple countermeasures. Vaccines, treatments like monoclonal, small molecules, as Eric mentioned. We've also been able to not only deploy these interventions to communities that need them, we've also been able to respond to viral evolution. It's not a static problem. And the ability to identify escape mutants and other aspects of viral pathogenesis that's emerging under selective pressure in real time, I think is terrific and allows us to then adapt our therapies to be appropriate to changes in the pathogen. I think it's remarkable that all this has occurred in the last three years or two years in particular in relation to treatments. However, it's still incredibly frustrating, the burden of infection that is going on globally as well as domestically, and that we have to continue to respond in a way that's proportionate and appropriate to the diseases that SARS-CoV is causing. But I actually am full of hope that scientific progress enables us to be responsive and to go to scale as quickly as we have done. It doesn't mean there aren't plenty of challenges. But as we go into the new year, I think we should be inspired with what science can do for us if we allow it. Over the three years that the epidemic has been around, the world has changed. And mostly it hasn't changed for the better. Now we are much more restricted in the kinds of things we can do. We've had these large economic shocks to the world associated with lockdowns and the social costs and consequences of those lockdowns.
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 interview. This is Howard Bauchner and this is Conversations with Dr. Bauchner. And I'm here with Jeff Linder, who is the Michael Gertz Professor of Medicine and the Chief of the Division of General Internal Medicine and Geriatrics at Northwestern University School of Medicine. Jeff, thanks for joining me today. Thank you so much for having me. Jeff's a general internist and a primary care clinician investigator, and he's written on one of my favorite topics, Delayed Antibiotic Prescriptions in Ambulatory Care, Reconsidering a Problematic Practice. So, Jeff, before we begin, could you just tell us a little bit about your co-author? Absolutely, and we're talking about delayed antibiotic prescribing, and so Dr. Teresa Rowe is a trained infectious diseases doctor and a geriatrician. And so she is all about using medicines appropriately for infectious diseases, for antibiotics, and then avoiding polypharmacy for our older adults. So I think our listeners who've heard me before probably remember when I've said much of my early research was in this area. One of my mentors was Jerry Klein, who I always think of, finally, I just emailed him yesterday. Jerry is one of the founders, modern founders, of pediatric infectious disease, and an extraordinary gentleman, an extraordinary scholar, and had been a wonderful mentor. And we were close friends. I remember we were out to dinner, our families, our wives, and the two of us were out to dinner together. And this was almost 20 years ago. And my wife said, you know, Jerry, I think children may be getting too many antibiotics. This was almost 20 years ago. And I started doing some research in the area, and I ended up doing quite a few trials in the area. Because I think maybe two decades ago, it finally emerged that perhaps children were getting too many antibiotics. And certainly, the drug regimens were too long. You know, antibiotics for otitis for 14 days or UTIs for 14 days. I always said, thankfully, parents never gave it for that long. So they shortened the course, although that wasn't the best approach. And then maybe a decade or more ago, people in the attempts to reduce antibiotic prescribing began to go to this kind of delayed or backup antibiotics. It could have been more than a decade ago, but about a decade ago. So do you mind, Jeff, just defining what that is? Yeah. So we start with a common ground, then we'll walk through the viewpoint. Sure. So a delayed antibiotic prescription is a prescription where the physician, for a variety of reasons we'll get into later, I'm sure, gives the patient a prescription and says, I don't think you need an antibiotic right now, but here's a prescription. Fill it in a few days if you're not getting better, to put it simply. So delaying the filling of the prescription. And some people have studied delayed prescriptions given to the patient right away. Some people have retained the prescription at the practice and asked the patient to come and collect the prescription. But that's some of the underlying ideas behind delayed antibiotic prescriptions. And what conditions do people generally use it for? These are overwhelmingly used for acute respiratory infections. So things like sinus infections, otitis, bronchitis, common cold. And we'll get into the appropriateness of all of that momentarily, I'm sure. Your viewpoint is more demonstrative than many that we have and you know it's softer after it went through our editing process. Thank you for being encouraging us to be a little bit more diplomatic and a little less strident. Right, that's right. Sometimes I think viewpoints do really evoke emotional responses but we think it's better to argue with evidence than just words. It's our general view about viewpoints. But why don't you summarize for our listeners why you think this is not the right approach? I've been concerned about delayed antibiotic prescribing for a long time, but I'm more concerned recently because it's actually made its way into a few guidelines.
And then NICE, the National Institute for Health and Care Excellence in England and Wales, has this in their guideline too as a way of decreasing antibiotic prescribing. And I'm kind of concerned because it just doesn't make sense for a number of reasons. So people who come in with viral illnesses, so people who have the common cold, they have a virus and it doesn't make sense to give them an antibiotic now or a few days later. Guidelines are pretty clear about which patients need antibiotics. So for example, among acute respiratory infections, the only four common diagnoses that really should be treated with antibiotics are otitis media in some cases, strep throat, the minority of sinus infections, and pneumonia. And anything else really shouldn't be treated with antibiotics. Another concern we had is that it really ignores the natural history of many of these infections. So sore throats last for five days, colds last for two weeks. The one that frustrates most people and most doctors is if you have a cough with acute bronchitis, it's perfectly normal for it to last three weeks. And I totally get why that drives people insane. But giving an antibiotic, there's 40 years of randomized controlled trials showing that giving an antibiotic doesn't change that three weeks at all. Other problems are people pick up erroneously on the false effectiveness of antibiotics. So you're just petering along and your sore throat is going to get better in five days whether or not you take an antibiotic. And if you took an antibiotic, it's perfectly reasonable to ascribe your improvement to having received that antibiotic. I think delayed antibiotic prescriptions give a profoundly mixed message to patients. We're being very careful about who should get antibiotics. And yet here's a situation where the doctor is saying, in effect, you don't need an antibiotic, but here's an antibiotic. And so no wonder people are confused. And one other reason is that I feel like this is one case where we're really abdicating our professional training and responsibility to the patient for some reason. There are gray areas in medicine, of course, but this is one where there's good evidence who should and shouldn't get antibiotics. And leaving the decision up to the patient just seems like we're giving up our professional responsibility. The background, of course, is increasing concern about the development of antimicrobial resistance, the lack of new antibiotics. We had made some progress. Oral antibiotic use had declined in the U.S. up to about five or six years ago, and it's increasing again. Once again, there's this concern, both in the United States and also other places around the world, that far too many patients are getting oral antibiotics. And I feel like the irony of delayed antibiotic prescriptions is the reason why they appear to be an effective intervention is because the background rate of inappropriate antibiotic prescribing is so high. I'm sensitive to the accusation that we're taking perfection being the worst enemy of the good and being a little too strident, as I was accusing myself of being before. But I think the reason why delayed antibiotic prescriptions look good is because the background rate of inappropriate antibiotic prescribing for colds, the flu, acute bronchitis is so high that anything you do, delayed antibiotic prescriptions, random number generator, unnecessary tests that are linked with decreasing antibiotic prescribing look good, but most of those patients shouldn't have even been considered to have been given an antibiotic in the first place. Right. So it's being compared to a control group that was way too high. So of course it looks better, but it shouldn't have been that high in the first place. Absolutely. antibiotics. So here's an antibiotic right away versus take this prescription and fill it. And the rates of antibiotic use is 930 prescriptions for the immediate group versus 348 per 1,000 patients in the delayed group. And so you look at that and say, well, a lot fewer people are using antibiotics in the delayed groups. But then when you compare delayed antibiotic prescribing to no antibiotic prescribing, again, none of these patients should be receiving antibiotics. The rates are 287 in the delayed antibiotic group versus 137 versus the no antibiotic group.
Yeah. So again, it depends on what you want to use as your reference. in patient symptoms or outcomes when you compare an immediate versus a delayed versus a no antibiotic prescribing strategy. So if that's the case, why are we exposing people to a chemical that has the potential to hurt them and doesn't help them? Now, I know you currently see patients. I used to see patients, and I would work in the primary care clinic in the walk-in section. And, you know, I could sometimes see 20 patients in a three-and-a-half-hour session, and I was busy. I saw patients pretty efficiently. We had a very efficient EHR that had been homegrown by us and then eventually replaced by Epic, our homegrown version, which was better. Bill Adams had developed it for us, and people loved it. And, you know, if I saw someone with what I thought was acute otitis media, it was pretty fast to write a prescription. Absolutely. And it was a little slower to try to explain to families why I didn't think that patient needed an antibiotic. I could never understand why if someone gave an antibiotic, why they didn't at least then code the appropriate diagnosis to justify the antibiotic. But could you talk a little bit about the psychology of what's going on when you see a patient and you want to make them happy and you're busy and you have to see a lot of patients? So a perfectly reasonable question. I'm completely sympathetic to the factors that drive doctors and other clinicians to prescribe delayed antibiotic prescriptions. There's a lot of data showing that the number one predictor of an antibiotic prescription in kind of these gray cases is not whether or not the patient wants an antibiotic. It's whether the doctor thinks the patient wants an antibiotic. And there's a presumption on our part that patients frequently want antibiotics. Some do, to be clear. Most don't. Most want reassurance, make sure nothing worse is going on. There's uncertainty. I laid out these four very clear diagnostic categories about who should get an antibiotic. Real life may not be quite so clear. Does the person have acute bronchitis versus pneumonia? Patients are uncertain. They're a little bit afraid. They want to make sure nothing worse is going to happen, even though there's tons of evidence showing that it's on the order of maybe one in 4,000 patients who have a viral upper respiratory infection will have some kind of bacterial complication. You alluded to the convenience factor. It's just faster to write an antibiotic prescription than take the time to explain why somebody might not need it. And we actually looked at this years ago, and it was indeed about a half a minute faster to prescribe an antibiotic than to not prescribe an antibiotic. And we all fear the inconvincible patient. And so we actually referenced this in the perspective and with some other co-authors did a qualitative study where we all remember that one really awful interaction we've had. That's incredibly memorable. You don't remember the other 99 you had where the person said, thank you very much, doctor. I appreciate your time. Have a good day. You remember the person who got into a heated argument with you about why you were a terrible doctor for not giving them an antibiotic and wouldn't leave. And we all fear running into that inconvincible patient. And then a final thing is a little concerning in the American healthcare system anyway. You can theoretically bill for a higher level of service if you've given somebody a prescription medicine. There's all these factors going on that are organizational, economic, and social kind of pushing us to maybe prescribe an antibiotic. And the factors discouraging us to prescribe antibiotics are not quite as salient when you're right there in the room with the patient. It's interesting because my research was in the early 2000s. And then around 2005, 2006, and 2007, there was a fair amount of press saying why you didn't want your child to get an antibiotic. And I did a lot of interviews. Rich Besser, who's now at the Robert Wood Johnson Foundation, did quite a few interviews. He led the judicious use of antibiotic campaign for the CDC.
Absolutely. So it had changed for a few years. And somehow I feel like that progress has ended in the last four or five or six years. And that's really concerning that we had been making progress and it seems to have been stymied. Right. And I think even looking at data going up to about 2016, it did look like the antibiotic prescribing rate in the U.S. had decreased slightly. And to give credit where credit is due, that was all attributable to care of kids. And so probably pediatricians kind of leading the way in antibiotic stewardship. And then for those of us who take care of adults, we have not had the same success. The antibiotic prescribing rates have remained very high, sort of stubbornly right around 800 prescriptions per thousand Americans per year, whereas Sweden is 325 prescriptions per thousand Swedes per year. So we're nearly three times the rate in some other countries, and they're trying to get theirs down to 250. And if I'm not mistaken, I think the French are even higher than the US. Yeah. We are 17th of, I think it was something on the order of 70 countries in terms of rate of antibiotic prescribing. Now, one of the paragraphs is entitled, what should clinicians use instead of delayed antibiotic prescriptions? So you've described the problem, the conflicts when you're seeing patients and you're busy and what patients want, what you think patients want. Your next patient is around the corner. You had patients added on. So what can an individual clinician do and what can a practice do? Yeah. So I'll give some credit to Dr. Rita Mangione-Smith, who's now at University of Washington. She's the chief of general peds there. She has a four-step process for how to communicate with patients and parents effectively and efficiently to avoid inappropriate antibiotic prescribing. And that is describe your physical exam, give a clear diagnosis. So that is don't say something wishy-washy like, you know, you seem kind of sick. Say, you know, you have a cold virus, a clear diagnosis. Give a paired negative positive treatment recommendation. So, for example, on the one hand, you don't need an antibiotic. But on the other hand, there's things we can do to help you feel better. And that paired negative positive statement reminds us we still need to take care of the patient. This idea about not giving an antibiotic is not the same as not treating the patient. You don't get to stop treating the patient if you feel like an antibiotic is inappropriate. And then the fourth thing is a contingency plan. Like what does the patient need to call back for? The vast majority of patients don't call back, but things like high fever, chest pain that's not associated with a pulled muscle from coughing, coughing up blood, profound fatigue, and then some time course over which you'd expect the patient to get better. So being clear, doing this with a patient is way faster than me having just described it to you. It's very efficient. And like I said before, the vast majority of patients are reassured to know that they don't have anything more serious. Yeah, judicious use of antibiotics or overprescribing, we've been at it for 20 years. It's been a difficult problem in the U.S. And we have some interventions that I and other collaborators have tried out that seem very effective. And it's no surprise that many of those effective interventions turn on the social aspects of appropriate antibiotic prescribing to combat the social aspects of promoting inappropriate antibiotic prescribing. You know, we sort of have to meet those social concerns with other socio-professional concerns too. I like when the viewpoint came in because I lived under the misconception that this prescribed antibiotics or this delayed antibiotics could actually save prescriptions. But then when you read through the viewpoint, you realize, well, it depends on what you're going to compare it to. Absolutely. And it still ends up doubling or tripling what would have been a reasonable base rate of 125 or 200 per thousand. Right. And so if you want to compare it to overprescribing, yeah, it does. But perhaps we shouldn't have compared it to overprescribing.
I'm Jan Engmeyer with JAMA. I'm speaking with Dr. Peter Pronovost from the School of Medicine at the Johns Hopkins University in Baltimore. Welcome, Dr. Pronovost. Please tell us about yourself and what you do at Johns Hopkins. Sure, thank you. I'm a professor of anesthesia and critical care medicine. I work clinically primarily in the intensive care units, and I'm the director of the Quality and Safety Research Group that does research on designing, implementing, and evaluating programs to improve safety and the quality of care. You've co-authored a commentary in JAMA that's entitled A Physician Management Infrastructure, in which you write about the physician's role in quality improvement. What is the current role of physicians in hospital quality improvement? Yeah, Jan, currently I think there's insufficient physician leadership in improving quality. In too many efforts, they're a bystander, that quality efforts are being run by hospital administrators, by nurses, and they certainly need to be part of the team. But because of the way our physicians are paid, many of them don't have time to be on this role. And I believe deeply that it's essential that they're on these teams. What are the benefits and some of the problems that are associated with the current structure of the physicians' roles in quality improvement programs? Well, you know, in virtually every hospital, the physicians cover their income by treating patients and typically managing individual patients. What we know for quality of care is that we need infrastructure to manage populations of patients. So how is the care for patients in a certain area or with a certain disease or treated by a particular group or hospital? And that requires physician input for a number of reasons, simply to help judge this quality of care, to make sure that the interventions are evidence-based and wise and, importantly, sufficiently nuanced to account for the variations among patients where care should deviate from one particular standard or another. We also need physicians to help make sure the measures are wise and valid. You know, so many of the measures we have in health care, physicians appropriately push back on because they just don't make clinical sense and sometimes physicians may even perceive that they're negative on patients. And lastly, I think what we really need physician leadership in is to help galvanize and engage the rest of the physicians so that if we're going to standardize practice or require that we ask doctors to do a certain thing, that communication, that networking with other physicians really has to be done by a physician who could explain the whys and the hows of what's going to happen. So what are some of the roles you think physicians should play, and why do you think that it's important that physicians help lead these quality improvement efforts? Well, what we'd love to see, I'd love to see, is physicians having some of their time supported to help lead quality improvement efforts, and that is at an individual unit level. So might it be a cath lab or a medical surge floor or an ICU to help look at quality, help develop protocols, help implement interventions to improve quality. I also think we need then to aggregate those units into a departmental or a hospital role of, okay, how are we looking at all of our hospital care? And then also along product lines. So if we're going to improve care for, say, knee replacement patients or heart failure patients, who's managing that population of developing those protocols, making sure we have good measures? And then also I think all of our outpatient practices need this kind of infrastructure. If you look at what's on the horizon with accountable care organizations and all these different efforts that are needed and long overdue to manage populations of patients, no doubt they need to happen. But I think they're not going to happen if we don't have some physician oversight or physician management infrastructure to help guide these, and that's going to require investments. What the challenge is, we're at this conundrum right now where the promise of health reform is that we move away from paying for volume and pay for value. That is, we pay for higher quality at lower cost. But the market signals, the payment methods, aren't yet mature enough to fully reward better quality. And they're largely just paying provider physicians and provider organizations less.
Hi, and welcome back to Sharp Scratch. You're listening to episode 70. There's no pill for homelessness. This is a podcast brought to you by the BMJ and sponsored by Medical Protection, where we bring together medical students, junior doctors and expert guests who discuss all the things you need to know to be a good doctor, but that you might not get taught so much at medical school. I'm Pat, I'm the editorial scholar here at the BM the BMJ and I'm also a medical student at Anglia Ruskin University. Today I'm very pleased to be joined by our friends Lily and Kaode. Lily, would you like to introduce yourself? Yeah, hi, I'm Lily. I'm a final year medical student in East London and I'm just revising for my final exams, which are in two weeks. And then I'm basically done. I have elective, which is insane. So that's very exciting. Yeah, time flies so quickly. I know, it's insane. Have you received your allocations as well? Oh yeah, we get them in two weeks. In two weeks, okay. Yeah, on the 10th of March, I have my final ever written exam of medical school. I get told where I'm going to be for the next two years. I have my UCL intercalation graduation. Anything else? Maybe that's it. And there are some personal things as well. Lots of anniversaries on that day. It's so weird. Oh my God, that's so much. But very exciting at the same time. It's exciting. Yeah. Yeah, nice to have you back with us. And Kayode, would you like to introduce yourself? Hello, I'm Kayode. I am a final year medical student at the University of Dundee. It's not so sunny today, but it's snowing, which I wasn't expecting. I'm not happy about this because it just delayed everything this morning. I couldn't walk as quickly as I wanted to. For some reason, the snow trucks seem to like, oh, I don't know if you can tell, the sun is shining on my face now. They seem to just neglect my streets, but every other street around me gets like gritted and everything. Just my streets, my specific street gets left icy and I live on top of a hill and I'm always scared I'm going to just slide down which has happened before in the past so yeah I wasn't expecting this to know otherwise I'd have put the grit myself because I bought some last year because I was like I'm not having this anymore but yeah other than that I'm I'm a-okay I've already done my finals. Same position as Lily, waiting to hear back from allocations, which I'm surprisingly nervous for. I usually don't care about stuff like this until the day of it. I was like, oh my God, this is happening today. But I've been, yeah, all over the place this week. It's kind of refreshing. Fingers crossed that you guys get your first rotation. And yeah, thanks for joining us. I'm also delighted to introduce our expert guest today, Dr. Andrew Moskrop. Andrew, would you like to introduce yourself? Hiya. So, yeah, my name's Andrew. Gosh, I've done my finals and my first rotations, and I'm just sort of having palpitations at the sort of the flashbacks to that. So I currently work as a GP here in Oxford at a practice that works with people who are homeless in the city and yeah I've been doing that for the past few years. Yeah thank you for joining us today. There is often a debate whether medicine is an art or a science. Our curriculum tends to favour the science bit. We bury our heads in the pathophysiology of diseases and management algorithms and guidelines a lot but are we treating the symptoms or the cause? We are taught a holistic approach to medical history and examination you know with the social history of the patient embedded in the algorithm when we're taking history.
What can doctors do to better address the true cause of people's ill health? So I thought in this episode, we could talk a little bit about whether our medical education is teaching enough about social determinants of health and whether there's a disconnect between our undergrad training and actual clinical practice. So, Kaode and Lily, well, you know, we're taught to elicit social history when we're taking a full medical history. How much do you learn about social determinants of health at med school? Oh, I'm not sure how much we get explicitly taught. I'm sure we've had at least one lecture with a nice slide that has social determinants of health on it. But I don't know whether I think the people that tend to be more aware of that stuff are people who just naturally have an interest and kind of passion for that sort of thing and also there's a difference between naming social determinants of health like tokenistically like a list and actually be able to have a conversation where you fully understand the scope and the depth of how people's lives can affect their health and I don't think that all medical students could do that but I would challenge most medical students to be able to list three things that would affect health that aren't necessarily just organic problems if that makes sense yeah yeah I think I saw you nodding there when you when Lily was mentioning you know people when people are interested in it then you know they kind of can link between the social determinants of health and um about one day taking a history yeah definitely i think it's one of those annoying things where attempts can be made to teach these things but it's one of those things that you find not that many people engage in i know for um my job so in my unit we do two general practice um placements in one in fourth year one in fifth year and for each of those placements we have to do like a poster about like um one pages that we've seen and sort of like describe their life story and look at the data surrounding their postcode and everything and i think some people really engage with it some people not so much and And I don't know, I think attempts are made to teach these things, but I don't know if they're taken very seriously because like you said in your introduction, people focus a lot on the science because that's what you're ultimately going to be mostly examined on and they sort of forget about all the social stuff. I think it probably can't be taught in a lecture format which is tricky because I don't think medical students would respond very well to being given like a seminar or like being split into tutorial groups like you do for like social science degrees but again I think medical students approach most of medical school as what is examinable material and what can I tokenistically learn to pass, which I don't blame them for because you have to pass these exams and they're really hard. But if we teach everything in that way and we kind of put that onus on exams, things like this, which aren't necessarily to try and get one more mark on the exam, they're just to yourself a better and more rounded doctor they will always fall to the wayside won't they yeah I agree um I mean personally I'm interested in kind of surgery determines health side of things and that's how I kind of learn more about it rather than learning it from lectures I suppose um I think we can talk a little bit more about this later. But Andrew, I know you've written about this gap between the undergraduate education and actual clinical practice. Yeah, so in your opinion, do you think that this connect between the undergraduate precepts and actual clinical practice? Well, it's kind of interesting, because, you know, sort of hearing you guys, I mean, it totally resonates to my experience 20 years ago, like, you know, when I was sort of finishing up at medical school and, you know, like what you're saying about sort of how it's really not that examinable or at least not quite as readily as, say, naming the bones of the fingers or, you know, whatever else might be sort of at stake and sort of more, you know, easily accessible in an exam format, you know, like which drug to use for which problem, all that kind of stuff. These things definitely are sort of rather more complex. That's, you know, that's, there's no question.
And I'm sure that actually at the time I didn't particularly. So in a way it's kind of nice to know that my experiences and recollections still hold currency and remain valid. At the same time it's kind of a bit of a shame that things haven't quite sort of moved on as they might because I think that our understanding of the importance of these things probably has sort of progressed and it's sort of a shame that by the sounds of it medical schools haven't quite found a means of making that apparent in the curriculum and in the teaching because you know these things aren't really just a sort of or they shouldn't be merely a peripheral interest of those that sort of happen to find it moderately interesting, because all of our patients will be impacted to some greater degree or other by what we sort of term the social determinants of health. They're tremendously important. tremendously important. I mean, like, you know, even to the extent that some authors would sort of claim that, you know, deprivation, for example, can have as big an impact on your health as smoking or obesity. You know, the things that we would sort of consider to be, you know, that's what we work with in terms of health care. And this is, you know, what's important to us in terms of sort of understanding patients' risks and their likely outcomes and so on and so forth. Actually our social circumstances should be really right up there. So it's kind of unfortunate to hear that that hasn't quite gathered the pace that it might have done. Like when Andrew was talking it made me think a bit more about the teaching that we get in my medical school. And I would say, actually, in hindsight, we probably don't get that much teaching on it, but we get a lot of assessment on it, at least within my medical school anyway. The importance of these topics is there, but I think the delivery and ensuring that people understand and learn more about it isn't quite there. I think universities or at least my university does the central teaching on social determinants of health well in that like we're all aware of them and we're taught them and I actually do think that at least my university people are able to research and kind of find the right articles and evidence to back up claims but what I think is missing is which I think maybe relates a bit too much to our empathy episode is the kind of emotional education for me the biggest moments of really absorbing the impact of people's lives on their health has been on our GP placements so we do them every single year at my university and it's always the home visits and it's visiting people's houses where all the mum and the dad and their six children all live in one room and they have maybe have one living room but it's kind of we had there was one family where their daughter was autistic so their entire flat was covered in crayon on all the walls um which they couldn't move out because they were renting and they wouldn't be allowed to get their deposit back. And they all slept in one bedroom. And for me, those moments are the real, like, I remember all of them so distinctly in my mind. And they're the things that I really hang on to. Whereas I think that isn't centralised. You can't, like, mandate that every medical student goes and visits a poor family that like just is ridiculous um and that's kind of just happened by chance I don't know if every medical student gets that eventually but kind of ties into what you're saying is that eventually once you're a doctor you cannot avoid those patients in those situations so you do you will just willingly or unwillingly have an emotional education in how patients' lives can be so different to the lives that we think people just live. I wonder how we can introduce that emotional education into university. I don't know how we'd do that. Yeah, I think in addition to that, as you mentioned, the kind of social circumstances of patients or the people around them can have such an influence on the health of the patient. Andrew, with your background in general practice as well as working with a vulnerable group of people, do you see kind of these healthcare managers kind of play out in the community? I think that's important and it certainly is a big part of my work.
You know, there's all sorts of, and certainly if they're sort of homeless on the street, there's all sorts of ways in which that might impact how I choose to treat them. So, you know, I don't give them 56 tablets of whatever medication it is because they've got nowhere to put it. And I certainly don't give them a pile of medications that might have a street value because it makes them more vulnerable. So, you know, it certainly sort of impacts what I do. But at the same time, you know, those sorts of things in which we accommodate someone's social circumstances into our management plan, whilst really helpful for the individual, it is, I think, to some extent, it is kind of slightly accepting of the status quo. And are we okay with that? You know, like, so am I, you know, am I okay with the fact that, you know, these patients are homeless? Well, I'm not really. So, and if I'm not, then, you know, I've got to gotta kind of I don't think it's enough for me just to sort of you know practice in a way that sort of recognizes it but also to sort of do something to sort of advocate uh for for some kind of change and I guess that and I suppose maybe that's maybe that's the significant difference between uh you know people's attitudes towards this because as you say people very often do sort of incorporate this into management plans but then you know is that where it ends um and perhaps for some people it is um for others it might not be um but you know like i guess you know you can't sort of resolve these issues in the course of your clinical practice but you can sort of, you know, advocate and support, you know, perhaps policy changes that might sort of alter things. And you're quite right, not everyone sort of wants to get political about this. But at the end of the day, you know, it is politics that shape people's context and, as a consequence, shape the presentations that we're met with be that six kids in a single room or whatever. I think you said really beautifully there about kind of standing in the patient's shoes and thinking about say it was a homeless person kind of adapting the management plan to their circumstances and I'm just thinking if it would help to have kind of representation of doctors from that kind of background to truly understand what circumstances people are going through. And it just happens that one of my friends at med school, they kind of come from that background. And I interviewed her about what was she going through when she was in that circumstance. My name is Maz Sadler and I am a fourth year medical student at Anglia Ruskin. I was homeless sporadically for six years between the ages of 14 and 19. It's quite difficult to condense because it's quite, with every person who has an experience of homelessness, it's really multifaceted. There's so many layers to it. it you know you don't just wake up in the morning and then your landlord kicks you out and I mean obviously that's how it happens for some people but with so many others there's like such an array of socioeconomic factors from a healthcare perspective I think we sometimes as medics get frustrated when we see any patient repeating health behaviors that we know like have a negative impact on them you know say if you have an alcoholic who who has dreadful liver disease and they keep coming in over and over again and they don't stop drinking or if you have a diabetic who continues to not manage their diabetes well you know there's all sorts of frustrations that I think we allow ourselves to fall into but with homelessness specifically there's this kind of societal stigma that they are people who just will not help themselves who won't do what it takes and what's necessary to get out of that situation um but when you are homeless your priorities just completely shift like it took me a good five years to be able to shift away from seeing each day as an individual unit that had no relationship to the rest of time because when you're homeless all you see is like the day in front of you you see yeah you just see where am I going to get food today am I going to be able to have a shower today like if you're female you know am I going to be able to get tampons am I going to be able to have a shower today?
Am I going to be able to, you know, wash? Can I afford clothes? All these things like it's it's a very much a survival mindset. And I suppose, you know, with your experience, especially now you're kind of close to the end of medical school. And so I suppose how what kind of things would you want your fellow medics to understand when it comes to proposing a management plan? You know, as you mentioned, the priorities that a patient with no fixer mode have will be very different from the priorities that doctors have. I think that understanding the contributing factors and going out of your way to understand the contributing factors as a doctor can be just as important as treating the disease in front of you, especially, you know, if, especially if you're in a kind of like more community facing role, like maybe GP or something like that. If you have somebody who, you know, is returning with the same issues or you suspect there might be something else going on, like, I think it's really important to not only involve yourself kind of more in what's contributing to this, but also seek help from others in the community, you know, the social workers and the mental health support workers and all these MDTs that can really provide more holistic, well-rounded support to that person. I also think that there's a real fear of judgment. Okay, so say a man is homeless and he's had a sore on his leg for six months and if he'd got it seen six months ago it would have been fine but now it's you know it's septic and it's terrible and the longer you leave it the worse it gets well saying to a patient well why didn't you come in six months ago I mean first and foremost it doesn't help the situation in front of you now and it's not really our place to judge anybody's situation but that will make that person and anybody that they tell about it less likely to seek help in future so I think it's really important to just bear in mind kind of however busy and stressed you are and however frustrating the case in front of you may seem like nobody nobody wants to be in that situation and nobody would choose it for themselves you know like this this misconception that homeless people are lazy and they choose to be that way because they can't be bothered to get a job is just so outrageous to me because, you know, I would do anything in my power to avoid ever returning to that situation. And I'm very lucky in that I was only in it for a relatively short time compared to some other people. And I had the benefit of my education and my friends to help me get out of it where a lot of people aren't that fortunate so I think I'd really like to see medics have a level of compassion for everybody generally of course but for people who find themselves in living in circumstances that that you just think to yourself okay would I choose this for myself if not then they probably haven't either this is probably they're probably a victim of circumstance and so my job here is to treat the person that I see in front of me without judgment first and foremost and secondly establish is there anything that I can do more holistically to help this person's situation and if not I might see them again in two weeks and that's okay because they need my help again in two weeks and I might see them again a week after that and that's okay because they need my help again a week after that our job is to just kind of be there and do what we need to do non-judgmentally without, because lecturing people never got the point across, right? If you're not willing to help in a meaningful way, it's just, you know, it's just words, it's just noise. Yeah, Andrew, I know that you work with people, a lot of people like homeless people as well. I don't know if anything that was said in the clip is kind of similar to the things that you see in practice. That was really interesting. And I was kind of amazed that this person is now a colleague of yours. You know, that's kind of great because I think in lots of ways, not least obviously, because her life clearly significantly altered and she sounds as though she's very much happier about that now, understandably.
I don't think that predictably we've been very good on that in the past. There tends, there tends to be sort of a fairly, we're pretty homogenous actually as a sort of profession in terms of social class, ethnicity. You know, we tend to sort of, you know, like, you know, patterns sort of get repeated. It's kind of like very often medical students, their parents were doctors, this kind of stuff. And it's nice to sort of hear that actually maybe some barriers to entry into medical school are being at least challenged. So that was kind of encouraging. It was fascinating too to sort of hear her talk about how in her situation she had wholly different priorities from those that might have been those of her caregivers. And I think she's quite right to sort of point out how, you know, people in that situation, they can be really frustrating to deal with. You know, it can look like as though they're sort of thoughtlessly just participating in sort of self-inflicted harm, whether that's through alcohol and, you know, the consequence of liver disease that she sort of mentioned too, whether it's sort of drug use or whatever. And, you know, and so it's important to sort of, I think, acknowledge there are frustrations about that and try and sort of put them to one side and sort of recognise where the patient's at. And you don't even need to be sort of homeless to sort of find yourself caught in that trap of self-defeating behaviours you know like and if we allow ourselves to sort of get annoyed with people because they're continuing to smoke and drink too much then we're going to be engaging in an awful lot of victim blaming which as was pointed out in that clip is sort of unhelpful really it doesn't sort of actually bring about behaviour change and it's really the wholly sort of wrong approach. Yeah, I think there was loads to take away from that clip. I found it very moving. Yeah, and not least, definitely my biggest thing was actually kind of, which is, this is obvious, but there isn't this dichotomy between medical students or doctors and patients in terms of, it's not always us as the kind of like traditional like white saviors kind of like trying to solve people's problems and actually as Andrew has said medical students and doctors are becoming more diverse and kind of the more that we challenge the traditions and stereotypes of medicine we're going to have a more diverse workforce which will be able to engage and empathize with our patients better which will only create better health outcomes and then also I think the other thing is that yes other than kind of political activism and advocacy as you said Andrew in terms of what doctors can actually do in their day-to-day jobs to make some sort of difference. I think as the clip says if we come into situations compassionately and we take a moment before we see our patients to remind ourselves that whatever they come in with we need to be safe and non-judgmental and welcoming and not focus on a behaviour and actually focus on the person in front of you and what their life is like, I think we can have more constructive conversations and appointments with patients that actually produce real benefit for their health, which at the end of the day is our job. Because I think if you kind of go about your day, focus on how stressed you are and how busy you are and how many patients you have. You don't go into situations with that mindset. And understandably, you don't have time or you think you don't have time to kind of access that compassionate part of you. You think all you have time to do is treat their broken hand in A&E. And actually, if you just give yourself 10 seconds, you might have a more honest conversation with the patient and actually make a bigger difference in the long run if they feel they can come to doctors and talk to them and share earlier rather than later, which I think is the entire goal of medicine eventually is to be improving patients' outcomes in the long term rather than in the short term. And I think that's important.
So that's great. If you're playing a part in that, that's wonderful. But it's important to recognise that even within the NHS, people who are poorer, people who have poorer education, they tend to do worse. They have worse outcomes from care. They've got less satisfaction. They wait longer for appointments at their GP practice. They wait longer in A&E and they wait longer for routine surgery appointments. And so I sort of suspect that there's something going on there. And, you know, and that doesn't, that shouldn't be a consequence of being poor or having sort of like fewer educational opportunities, opportunities. So I think there's something that's going on there about the way in which the interaction occurs between these people and the health service and probably between the patients and doctors. And so I think that if we can acknowledge their context and actually not allow that to prejudice against people unthinkingly because we're sort of stressed and we're having a difficult day, et cetera, et cetera, if we can actually sort of overcome that, even though they might be frustrating to deal with because some of this might seem like as though they've brought it on themselves through alcohol or whatever, you know, if we can get over that, then I think we sort of go further towards actually reducing some of the disparities, some of the inequalities in outcomes from health experiences and healthcare experiences. We'll discuss more about the wider implications of health inequality in the system, but that'll be right after this message from our sponsor. be with medical protection. There's our free membership during your medical school years, our wealth of training resources to help you become the best doctor you can be, and our international experience that protects you during your elective, no matter how far from home you end up. In fact, there are many reasons why our members worldwide trust us to support and protect them throughout their careers. And if you're looking for one more, every week one lucky new joiner wins £183. That's the average student weekly spend. Just join for free and you're automatically entered into the draw. That's why UK medical students choose to be part of medical protection. You can't blame them, so why not join them? Visit medicalprotection.org to find out more. Okay, back to this show. navigating the healthcare structure. Just to give a really extreme example, so I volunteer at a prison and then you can see people, kind of the same people going through the revolving doors of prison. And sometimes, you know, when you offer to help them, they could just feel very, well, even the patients or the people themselves just feel frustrated and helpless because of this kind of labyrinth that they have to navigate. It's tricky isn't it because I guess that you know I guess what we've got to acknowledge too is you know there's going to be a bunch of people for whom we are the system you know that's what we sort of represent and unfortunately those that it might well be the very people that we're trying to understand and engage with. You know, if you sort of think about, you know, the sort of breadth of patients that we might encounter, there'll be those whom we find it very easy to work with. They may well be graduates and they may well have a similar sort of education and social background to ourselves. But then there's going to be an awful lot of other people who may have an awful lot of health needs and maybe even greater health needs who are you know for whom that's not going to be true they won't have gone to university they won't have had the educational privileges that we've had and we might represent something that's intimidating to them you know going to see their GP might feel a little bit like going to the job centre where they're going to get berated about their behaviour or something like this. It might feel like just yet another engagement that they've got with an authority figure. So they might actually be on their guard and somewhat wary about having conversations with us. So I think we to be kind of in tune with that if we can as well. And it's true not just in general practice but in hospitals too. You know, by the time we've been shoved out the end of medical school, you know, like hospitals are our home.
And yet for an awful lot of people, it's going to be absolutely intimidating. You know, it's full of like really well-educated people who are doing really, you know, sophisticated technical tasks. And it might be, you know, if you're homeless, that's a world away from your day-to-day experience. And it's pretty wacky to find yourself in there. And I think that, so recognising that is kind of important. So yeah, just sort of, you know, being aware of what we might represent to the patients that we're dealing with can be kind of important. Yeah, I was going to say the same thing, which is that part of this challenge is recognising that we also make the system that we're in. And the harsh reality, which is not acceptable, is that there are patients that you leave longer in A&E and you see them later and there are patients that you give appointments later to in GP and that is awful and completely speaks to our prejudices and kind of what we think is an acceptable patient and who deserves care and the quiet nice grateful patient often doesn't align with the patient who needs our care the most. I think that's a again that is just is just a challenge that is so in the scope of this podcast, we're not able to solve that problem, but we just choosing people to go into medical school and then cultivating a culture of doctors who are not prejudiced and who are aware of this sort of thing and do treat everyone equally, inverted commas, is going to be the like challenge of medicine I think for a very long time and one other small point is that the NHS is not free for everyone and we have to accept that we actually have a really unequal system in that people who come to this country who aren't citizens they do not get free health care and that is I think something we can actually challenge as doctors in our workplaces get rid of the posters in A&E I think we can actually do quite a lot to challenge that specific problem which I think would make such a difference to so many patients who do not get the health care that they deserve. I was literally literally in my mind because I was literally like I literally made notes about like yeah, immigration checks like when you're registering for a GP and stuff and I've always found that weird and odd. Like, what? Yeah, sorry, Pat. No, sorry. I was going to say, since there was a charity called Doctors of the World, they were doing a campaign about doctors are not border guards, right? Like, you know, they're coming in to take a box to say that, yeah, they're, I don't know, from the EU or have permanent residency here before treating them. Yeah, that was a great campaign. I tried to do my elective with them, but because of COVID, it was too difficult. But yeah, they're an amazing organisation to follow if you're interested in that sort of thing. I think we have to just cultivate a more compassionate environment, which actually also involves funding and staffing and making the work environment better for staff so that we can actually do our jobs, which is treating patients properly rather than 70% of our job, which is treating the initial problem but ignoring everything else because you don't have time or money. And if we the NHS properly and we fund the welfare state everyone's health will get better but I mean I'm probably not going to be the one to actively change that but what we can do is kind of yeah do some sort of advocacy and activism but if anyone is listening and wants to become the next prime minister then that would be really useful. Lily there's nothing stopping you from becoming the next prime. I think you can do it. I would vote for you. I wouldn't vote for me. I'd vote for you as well. Actually, I'd make you my health secretary. Yeah. But I think also, you don't have to just sort of have a position of power. I mean, as you say, sort of calling out some of the BS, like, you know, if it's sort of posters in A and E departments that are sort of distinguishing some patients that can and can't access care, you know, that's clearly nonsense. And it's clearly within your power to sort of react to that.
I guess the important thing is that we sort of actually get the balance right so that we don't sort of, you know, sort of deliver more care to those people who have less need and that we do sort of try and deliver more care to those people who who have greater need. So but yeah, I think I think, you know, there's there's stuff that you can uh that you guys can uh can do going forward um and you know i think in in you know as long as we're sort of conscious of this we can sort of avoid at least worsening things like sort of health inequalities uh and we can actually sort of go some way towards uh mitigating them or sort of reducing them as far as we can um so i've got a question um i think within between four of us, I think we're quite a self-selected group of people who are just quite interested in social determinants of health generally. So what would you recommend to the listeners who may not know very much or don't know how to become more aware of things what would you recommend that they do like right now in this instance like after listening to this podcast what would you say they should do so i guess um i mean it depends because i guess everyone's sort of you know probably pretty busy preparing for various other things you know we heard lily at the outset sort of describe how uh much she had sort of going on uh in the near future and i'm sure that's true for a lot of medical students but i think sort of uh being aware of these issues and sort of gaining an understanding of how people's social context impacts their health and their health presentations i guess that's something that you can sort of do through reading but also just sort of thinking about it like when you're next sat in front of patients when you're next sort of sat in a clinic and you know my recollection of like sometimes sort of sitting in clinics you know be that in sort of GP surgeries or hospital outpatient appointments sometimes it could be a little bit dull but if you sort of take that that frame and sort of try and sort of think about sort of people's backstories and what might brought them here and like what some of the tensions might be in their sort of their context that, you know, and like whether actually the advice of the consultant or GP is going to be sort of manageable for them. You know, if you sort of think about those sorts of things and maybe sort of keep it on your mind, maybe it becomes a little bit more interesting and maybe you start to sort of engage in it a little bit more. Yeah, I think, I know earlier I joked that you can't have every medical student go into a really deprived environment intentionally. But actually, I wonder if making home visits a compulsory part of medical school would make such a difference, especially in East London. There's such a huge deprived community in East London that actually it amazes me that some medical students have managed to avoid that. And I think with, obviously, boundaries and appropriateness and professionalism, I wonder if having every medical student on every GP placement at some point encouraged to go on a home visit, I think that would probably go quite far to the emotional education part of it yeah I think that's a good idea instead of just seeing patients in you know kind of the sanitized area of hospital or in a clean hall without putting a background exactly and also people who are who get home visits at least in my experience there are they're a specific group and other than kind of people who are immobile or in nursing homes actually they often are more deprived and more isolated.
About $10 billion are spent on 600,000 patients a year who are hospitalized for pneumonia every year. Pneumonia is still a killer. About 5% of all comers who get admitted for pneumonia die. For the sickest of patients, that mortality increases to about a third of all patients. The key to saving these patients' lives is the prompt recognition of pneumonia and starting the right antibiotics at the right time. Sounds easy, but it's not. In really sick elderly patients, the diagnosis is not always clear. So, okay, you can shotgun it, but you have to get it right. You have to give potent antibiotics, and they have complications. Aside from the usual drug reactions that can be caused by these antibiotics, the really broad-spectrum antibiotics needed for this situation frequently cause C. diff colitis, not a small matter since C. diff is increasing in epidemic proportions and can be a very nasty disease that in itself is really hard to treat. Pneumonia is also a really common problem. If everybody coming in with it just got, a big blast of potent antibiotics, eventually resistance to those antibiotics would develop and future generations of patients would be much harder to treat and have a higher mortality. Hello, I'm Ed Livingston, Deputy Editor of Clinical Reviews and Education for JAMA. Today, we discuss community-acquired pneumonia. The basis for this discussion is a review article published in JAMA in the February 19th, 2019, and it's called, The I'm speaking to one of the authors of this review, Dr. Jonathan S. Lee, who's currently in the Division of Internal Medicine at UCSF. Dr. Lee and his colleagues did a systematic review of the literature to answer a couple of questions. The first was the necessity to cover atypical pathogens with antibiotics such as fluoroquinolones or the combination of beta-lactam antibiotics with macrolides. The other question they asked was what clinical criteria can be used to determine when it's safe to transmit the virus to the patient. to transition patients from intravenous to oral antibiotics. Let's start at the beginning. The basic disease entity we're discussing is community-acquired pneumonia. This may not be so easy to diagnose. Dr. Lee, how do you go about making the diagnosis of community-acquired pneumonia? So the classic medical standard is, you know, you get a chest x-ray or, you know, in some cases you may end up getting a CT scan of the chest. But the diagnosis of pneumonia generally requires that you have clinical signs and symptoms. So just like I said, they're having fevers, they're having correct coughs, you know, they have some crackles on exam. I forgot to mention crackles earlier, but certainly have crackles on exam. You get a chest x-ray. I think they have pneumonia. And the chest x-ray shows that they've got, you know, an infiltrate in the right lower lobe or the left lower lobe. They may have, you know, leukocytosis as well. So the radiographic evidence, you know, plus clinical signs and symptoms, you can never forget the clinical signs and symptoms together is what you need for the diagnosis of pneumonia. Now, I will say for the medical students that what, what is often seen is that people who get this illness tend to be sicker, tend to have other conditions. And so sometimes that, that x-ray in the emergency department is not the most clear. You know, it's not a crystal clear infiltrate in the right lower lobe and the rest of the lungs looks fine. They may have some heart failure on top of that. You know, they may have some chronic lung issues. And in those cases, the x-ray is not as clear. It's not as diagnostic. And this is a situation that is often faced, certainly in the emergency room and by clinicians everywhere. Then it becomes a little more, you know, of a clinical diagnosis. Certainly. You could get further imaging. You could get a CAT scan to really get a better look. Before we can answer these questions, it's important to define what population was studied. Dr. Lina's colleagues looked at patients who were really sick.
But if you get it right, the benefits are big also. Fortunately, there's a couple of risk stratification tools you can use that work pretty well at putting sick patients in the right category so you can figure out who needs antibiotics and admission to the hospital. The first one is the, the pneumonia severity index. And this was actually developed by one of my mentors and my co-author, Michael Fine, at the University of Pittsburgh. And it was developed based off of a large cohort of patients with pneumonia. And it is calculated actually using 20 variables, which include age, comorbidities, as well as lab values. And so, you know, these days you can actually, there are a lot of apps on your phone that you can actually use to calculate these things. And you actually plug the scores in. But essentially, if you don't have all 20, you can plug in as many as you have. And at the end, it'll actually give you a score. And that score places patients into a risk class. The pneumonia severity index gives you five risk categories. If your score is three, you may need to be admitted to the hospital. But if it's four or five, you definitely need to come in. The studies Dr. Lina's colleagues looked at were all for class four and five patients. The curb score is a slightly simpler score that's just based on six variables. But it does. It's a similar stratification. The curb score is somewhat simpler to use and only involves five clinical features. There are confusion, a BUN more than 19 milligrams per deciliter, a respiratory rate greater or equal to 30, a systolic pressure of less than 90 millimeters of mercury, or a diastolic blood pressure of less than 60 millimeters of mercury, or an age greater than or equal to 65. Each of these factors equals one point. Patients with a score of zero to one may be treated as an outpatient, and a score of two generally requires admission to a monitored inpatient setting, where scores of three to five require inpatient or intensive care unit admission. The mortality associated with a score of zero is only about 0.6%. But for patients with scores of four or five, the mortality may be as high as 28%. So we have a good way to know who's sick enough to require antibiotics and inpatient care. That's going to be people with curb scores of two and above. So a patient who's older than 65, and confused, has a score of two, and they should probably be admitted and be given antibiotics. The same older patient who's confused and has some renal insufficiency or hypotension has a score of three or more, which is associated with a more than 14% mortality, and they should definitely be admitted to the hospital and be given antibiotics. Same for the older patient who's confused and tachypneic. They also have a score of three and should be admitted and be given antibiotics. If you're going to give somebody antibiotics, you need to pick the antibiotic that covers the most, likely organism that causes the patient's pneumonia. So the organisms we worry about most are streptococcus pneumonia, which is the classic kind of typical cause, as well as Marexella and Haemophilus. So those being kind of the more typical causes of pneumonia. And then there are what are called atypical organisms that can cause pneumonia that are Legionella, Chlamydia, and Mycoplasma. One limitation here is that, in over one half of pneumonia cases, the organisms causing pneumonia are never identified. So there's an array of organisms, both typical and atypical. One of the big questions asked in the review Dr. Lee published in the February 9, 2016 issue of JAMA is if patients who get empirically treated for atypical bacteria that cause their pneumonia do better than those who are only treated for typical bacteria. The antibiotics they looked at were the beta-lactams that covered the typical bacteria compared with the beta-lactam antibiotics combined with macrolides. Which provided the added coverage for atypical organisms. They also looked at outcomes for fluoroquinolones, which cover both the typical and atypical organisms.
The classic beta-lactams that are used for pneumonia are ceftriaxone, which is a third-generation cephalosporin. So ceftriaxone is the classic one. Cefuroxine is used at various times. Generally a second or third generation. Cephalosporin is used. And then the most common macrolide is azithromycin. Clorithromycin and erythromycin are also used interchangeably as well. But azithro tends to be the most common these days. The respiratory fluoroquinolones are a relatively newer class of antibiotic. And we discussed this a little bit in the article. That a lot of the newer, what are called respiratory fluoroquinolones, which are levofloxacin, moxifloxacin, and then gemifloxacin, weren't developed. So relatively recently. And so these actually will cover the typicals and the atypicals at once. So they have a much broader spectrum of coverage compared to the beta-lactams alone or compared to the macrolides alone. And so you can actually use them as monotherapy. The literature base that Dr. Lee and his colleagues looked at when trying to answer the question regarding the need for additional antibiotic coverage for atypical organisms was not particularly solid. The studies were mostly observational studies, and there were only two. There were two randomized clinical trials, which had somewhat conflicting results. I asked Dr. Lee to summarize what he learned as a clinician from looking at all this literature. My conclusion as a clinician is that we should cover atypical organisms empirically when people come in the hospital, whether it be with beta-lactam and macrolide or with fluoroquinolone. The justification based on the studies, the two high-quality studies certainly, you know, one is that one did not show that beta-lactam, and the second one, that one did not show that beta-lactam monotherapy was non-inferior. So, you know, that one essentially supports using combination therapy. In the second randomized trial, you know, there were certain aspects of it that diminished my confidence slightly, you know, in their findings that were contradictory. So a lot of patients in that study actually received atypical coverage when they came in or, you know, at some point during hospitalization. So there's some contamination of the groups in this pragmatic trial. The second thing is, you know, their non-inferiority margin was, you know, relatively low. There's no clear way to choose these margins, but 3%, an absolute 3% for mortality is a pretty big difference, something we would comment on in the paper as well. So as a clinician, to me, the two high-quality trials disagree. And so as a clinician, you know, part of the bottom line is when someone's coming into the hospital, they have to be admitted, generally means they're pretty sick. And if they're pretty sick, then I think, you know, as a clinician, we need to go with doing, you know, at least a little more initially until we know for sure. Which organism is causing the problem, and then we can narrow the coverage. But as a clinician, since the evidence is not clear that, you know, less is more in this case, I would go with covering a little more in someone who's sick enough to be admitted to the hospital. So we need to provide coverage for both typical and atypical organisms. The major choices are using a beta-lactam with a macrolide or a fluoroquinolone. Which is the best strategy to pursue? First, I think that you always have to take into account patient allergies. And so sometimes that makes a decision for you. You know, in some cases, if a patient has a penicillin allergy or a cephalosporin allergy or a beta-lactam allergy that you're not exactly sure what it is, that may spur you to go more towards the fluoroquinolone. And likewise, if they've had issues with fluoroquinolones before, that may make you go the opposite way.
The macrolides, there have been many studies recently concerning macrolides and cardiovascular morbidity. There was some concern about, you know, QT prolongation and about inciting heart attacks and things like that. And there have been a lot of studies. So that's certainly a concern. There have also been good studies. And there's a thought that, you know, macrolides have anti-inflammatory properties that actually help beyond treating the bacteria. And so there's that side as well. So there are pros and cons from that aspect. The fluoroquinolones, you know, again, are broader. And they're also... Like any drug, they also have a lot of side effects. You know, they can cause delirium in elderly people. And there are concerns about C. diff infection and diarrhea. And so, you know, those are concerns as well. For me, in general, I would tend to go towards the beta-lactam and the macrolide, assuming that, you know, there were no allergy issues. And for me, that's because I would try to avoid some of the adverse effects that can come from the fluoroquinolones and from, you know, what is kind of much broader coverage with the fluoroquinolones. But that's my opinion. You know, in the guidelines and certainly in the article, you know, they would recommend either as appropriate first-line therapy. Okay. So we have our sick pneumonia patient. They got IV antibiotics to cover the typical and atypical bacteria. Now, how long do they stay on the antibiotics? When do you stop them and convert to oral antibiotics? What I generally do when I'm deciding, you know, if someone's ready to go from, you know, interveneness to oral antibiotics, it's exactly what you said. It's looking at their vital signs. You know, if they had a fever, you know, have they deferred that? Has the fever come down? You know, if they were tachycardic, has the tachycardia improved? I want to see a normal blood pressure for that patient. You know, if they need oxygen, that can often lag behind a little bit and take longer. I certainly wouldn't want to see that getting worse in terms of how much oxygen they need. And certain laboratory markers as well, you know, in terms of that, they had some renal dysfunction initially. It's not getting worse or, you know, or something that's getting better and that their white count is coming down as well. So, you know, general clinical factors, that would indicate that they are getting better. And along with that, and we do comment, as you mentioned earlier, the importance of confusion and altered mental status. And so one of the things that I would also want to see is that if somebody had come in confused, that that has gotten better and actually resolved. And of course, they have to be able to take the antibiotics orally for you to transition them. And certainly the confusion, you know, can play into that as well. If you're unsure about getting someone who's confused medications to actually take. And what oral antibiotics, you know, can be used to treat the patient? What kind of antibiotics should you use? The oral forms of what you give IV? Yeah, so you could use cefuroxime orally, which is, you know, or a different cephalosporin orally. Amoxicillin, clavulanic acid, or Augmentin is used very commonly as the beta-lactam component. And then azithromycin, you know, can come PO or IV as well. And so that can be just converted to an oral form for them. So the respiratory fluoroquinolones actually come in both IV and oral forms. So you can directly switch to levofloxacin orally or moxifloxacin orally when they go home. How long should the antibiotics be given? There isn't a clear consensus about that. Either five to seven days is generally what I would use. The azithromycin has a long half-life. It's given for five days as well.
Welcome. This is the New England Journal of Medicine. I'm Dr. Lisa Johnson. This week, April 28, 2016, we feature articles on transcatheter versus surgical aortic valve replacement, exazomib in myeloma, Ebola vaccine trials, and an experimental approach to treating Duchenne's muscular dystrophy, a review article on violence against health care workers, a case report of a woman with hemiplegia and aphasia during a transatlantic flight, and prospective articles on Tobacco 21 laws, on a moonshot to Malawi, and on colorectal cancer on the decline. Transcatheter or Surgical Aortic Valve Replacement in Intermediate-Risk Patients by Martin Leon from Columbia University Medical Center, New York Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic valve replacement, TAVR, and surgical aortic valve replacement. In this trial, 2,032 intermediate-risk patients with severe aortic stenosis at 57 centers were randomly assigned to undergo either TAVR or surgical replacement. The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group. At two years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group. In the transfemoral access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery, whereas in the transthoracic access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation. Surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. In intermediate-risk patients, TAVR was similar to surgical aortic valve replacement with respect to the primary endpoint of death or disabling stroke. Neil Mote from Royal Brompton Hospital, London, writes in an editorial that there is a consistent message emerging from the three large trials published to date involving patients at high, intermediate, and very high risk. Transcatheter aortic valve replacement is non-inferior to surgery in terms of early and midterm mortality and is likely to be superior if the patient has vascular anatomy and vessels that are healthy enough to be treated with the use of a transfemoral approach. As with many trials involving new technologies, the findings have to be interpreted with the understanding that the technology in both groups has advanced since the design of the trial. The results of further trials are awaited with interest. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma by Philippe Moreau from the University Hospital Hôtel-Dieu, Nantes, France. In this Phase III trial, 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma were randomly assigned to receive exazomib, an oral proteasome inhibitor, plus lenalidomide dexamethasone, exazomib group, or placebo plus lenalidomide dexamethasone, placebo group. Progression-free survival was significantly longer in the exazomib group than in the placebo group at a median follow-up of 14.7 months. Median progression-free survival, 20.6 months versus 14.7 months. A benefit with respect to progression-free survival was observed with the exazomib regimen as compared with the placebo regimen in all pre-specified patient subgroups. The overall rates of response were 78% in the exazomib group and 72% in the placebo group, and the corresponding rates of complete response plus very good partial response were 48% and 39%. The median overall survival has not been reached in either study group, and follow-up is ongoing. The rates of serious adverse events were similar in the two study groups. Thrombocytopenia of grade 3 and grade 4 severity occurred more frequently in the exazomib group. The addition of exazomib to a regimen control of a future outbreak.
No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the CHAD3 vaccine, Zaire Ebola virus, Zeebov-specific antibody responses were similar to those induced by RVSV Zeebov vaccination, which was assessed in another Phase 1 trial. Zeebov neutralization activity was also similar with the two vaccines. Boosting with the modified vaccinia oncara MVA vector increased virus-specific antibodies by a factor of 12 and increased glycoprotein-specific CD8 T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants. Virus-specific antibody responses in participants primed with CHAD3 remained positive six months after vaccination, but were significantly higher in those who had received the MVA booster. The CHA3 vaccine, boosted with MVA, elicited B-cell and T-cell immune responses to ZBOV that were superior to those induced by the CHA3 vaccine alone. Phase I trials of RVSV Ebola vaccine in Africa and Europe by Seleji Agnangi from the Centre de Recherche Médicale de l'Ambaréné, Gabon. Four Phase I studies assessed the safety, side effect profile, and immunogenicity of a recombinant vesicular stomatitis virus-based Ebola vaccine, RVSV-ZBOV, at various doses in 158 healthy adults in Europe and Africa. No serious vaccine-related adverse events were reported. Mild to moderate early-onset reactogenicity was frequent but transient. Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within three days in 95% of the participants receiving 3 million plaque-forming units or more. RVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting 1 to 4 joints developed in 22 percent of participants in Geneva, with pain lasting a median of 8 days. Two self-limited cases occurred in 3% of participants in Hamburg, Germany and Califi, Kenya. The virus was identified in one synovial fluid aspirate and in two skin vesicles of two other vaccinees, showing peripheral viral replication in the second week after immunization. Zeebov glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. In these studies, RVSV-Zibov was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. Workplace Violence Against Healthcare Workers in the United States, a review article by James Phillips from Beth Israel Deaconess Medical Center, Boston. In January 2015, a surgeon at Brigham and Women's Hospital in Boston was shot and killed at work by the son of a deceased patient. Even though the event received substantial media coverage, reporters did not highlight the fact that although the murder of a health care worker is rare, episodes of workplace violence against medical providers happen daily across the country. Although the majority of these incidents of workplace violence are verbal, many others constitute assault, battery, domestic violence, stalking, or sexual harassment. This review focuses on our current knowledge about workplace violence in various health care settings, including the prevalence across professions, potential risk factors, and the use of metal detectors in preventing violence. Between 2011 and 2013, the number of workplace assaults averaged approximately 24,000 annually, with nearly 75% occurring in health care settings. Researchers have yet to discover statistically significant, universally applicable methods of risk reduction. To date, most research has been directed at quantifying the problem and attempting to profile perpetrators and their victims. The few studies that have focused on interventions to reduce violence have highlighted the unlikelihood of finding a simple, one-size-fits-all solution to prevent this violence. A 49-year-old woman with sudden hemiplegia and aphasia during a transatlantic flight. A case record of the Massachusetts General Hospital by Lee Schwamm and colleagues. A 49-year-old woman was brought to the emergency department two hours after the onset of hemiplegia and aphasia during a transatlantic flight.
The patient's husband alerted a flight attendant, and a passenger who was a physician informed the crew that they must transport her to a hospital within three hours to enable proper treatment. The pilot accelerated the aircraft to arrive in Boston within two hours after symptom onset. The patient was evaluated by emergency medical technicians on her arrival at the airport. She had a right facial droop and was unable to lift her right arm. The patient was brought to the emergency department. On the initial examination, the patient was alert and followed simple commands, but answered, yuck, to all questions. A diagnosis of acute ischemic stroke due to occlusion of the left middle cerebral artery was made. A bolus of tissue plasminogen activator was administrated 13 minutes after the patient's arrival at the hospital. Imaging studies were consistent with infarction involving the territory of the left middle cerebral artery. One hour after the patient's arrival, she was transported to an operating room for endovascular thrombectomy. The left internal carotid artery, anterior cerebral artery, and middle cerebral artery were successfully recanalized. Hints to the cause of this patient's stroke became available by the second hospital day. The CRISPR Way to Think About Duchenne's, a Clinical Implications of Basic Research article by Michelle Kalos from Stanford University, California. Today's hottest genome engineering method, CRISPR-Cas9, has recently been used to treat mouse models of the most common form of muscular dystrophy, Duchenne's muscular dystrophy. Three groups of investigators have recently described the use of CRISPR-Cas9 to remove a mutation in the gene encoding the dystrophin protein and thereby to affect the expression of the protein. The researchers used the CRISPR-Cas9 genetic engineering system to cut out the mutated part of DMD in the MDX mouse model of the disease, thereby allowing the synthesis of a shorter version of the dystrophin protein in muscle fibers and restoring partial muscle function. This type of approach could potentially remove disease mutations in about 80% of patients with Duchenne's, although it would require sequence-level knowledge of each patient's specific mutation and a customized strategy for its removal. Have Tobacco 21 Laws Come of Age? A Perspective Article by Stephanie Moraine from Baylor College of Medicine, Houston. On January 20, New Jersey Governor Chris Christie vetoed a bill passed with strong bipartisan support by his state legislature that would have raised New Jersey's minimum age of sale for tobacco products to 21. The veto is a setback in an otherwise accelerating movement toward dissemination of Tobacco 21 laws as a new tool for reducing young people's access to cigarettes and e-cigarettes. By March of this year, at least 125 localities and the state of Hawaii had adopted Tobacco 21 laws, and California was on the cusp of following suit. In September 2015, the first federal Tobacco 21 legislation was introduced. Are Tobacco 21 laws ready to go to scale, as these legislative developments suggest? These authors believe they are. Recent research has shown that laws raising the minimum age for purchase of tobacco products to 21 are effective, enjoy very high levels of public support, and have minimal economic impact in the short term. Over the longer term, the revenue loss from decreased smoking prevalence will be substantial. But allowing future generations to become addicted to nicotine in order to preserve tobacco revenue fails the red-face test as an argument against Tobacco 21. Moonshot to Malawi, a perspective article by Satish Gopal from the Malawi Cancer Consortium, Lilongwe. In his 2016 State of the Union address, President Barack Obama called for a moonshot to cure cancer. The announcement energized the cancer community to continue building on the remarkable collective progress made in recent years. The pace of that progress has been dizzying. But Dr. Satish Gopal now lives in Malawi, a small, resource-limited country in southern Africa with a population of 17 million. From there, it can be difficult to appreciate the tangible fruits of a decades-long international war on cancer. Despite small daily victories and immense Thank you. The neglect spans the continuum from awareness to prevention, diagnosis, treatment, and palliation.
Okay, welcome. My name is Devine. I'm a resident. This is episode 206 of the Devine Intervention Podcast. And in this podcast, I'm going to begin a family medicine shelf exam rapid review series. I'll just be doing a bunch of cases that highlight topics and concepts that are commonly tested on the family medicine exam. It will be completely random. But hopefully as you listen to this series and as I build up this series, you'll find it to be very helpful for the exam. So let's just jump right into it. So the first thing I think I want to start with is talking through like an algorithm that's frequently tested on the family medicine shelf. And that is the algorithm that relates to a thyroid nodule, right? So if a person has has a thyroid nodule what is always your first step in diagnosis if you're pressing you know a physical exam you'll palpate a thyroid nodule what is always your first step in diagnosis well i would really hope that you're thinking that uh you'd want to go ahead and measure the tsh right because the thing is when you measure the tsh that will help you delineate between the person potentially having a hot nodule or a cold nodule okay a hot nodule or a cold nodule so you measure the tsh and basically the way i teach people this concept is essentially if the tsh is low you know you're dealing with a hot nod right? Because the algorithm can get complicated real fast if you try to overcomplicate things, right? So the best thing to just ask yourself is, is the TSH low? If the TSH is low, it's a hot nodule. If the TSH is not low, so any other results, be it normal, high, whatever, it doesn't matter, then it goes into the TSH, not low pile. So let's talk about the TSH low pile, right? So if the TSH is low kind of pile, right? Then we know we're dealing with a hot nodule, right? And once a person has a hot nodule, right? The thing is the chance of like thyroid cancer, because when you see a thyroid nodule, right? The thing that freaks you out is thyroid cancer, right the tsh is low you know it's a hot nodule super low risk of cancer so your next step in diagnosis on an mbm exam will be to order a ryu scan okay you want to be able to reinterpret those ryu scan results right so if for example a person you get a ryu scan and you find like a single hot spot on the ryu scan, that's going to be a toxic adenoma, right? That's pretty easy. But what if they told you that, oh, you see multiple hot spots? What are you thinking about under those circumstances? Well, I hope you're telling me that it's a toxic multi-nodular goiter, right? Okay. And then what if they tell you that there's diffuse, there's a diffusely increased uptake on the Ryus scan? What are you thinking about? Well, that'll be Graves' disease, right? That'll be Graves' disease, right? That'll be Graves' disease, right? So whenever you see those kinds of things, think about, again, those are kind of like the big things you want to keep at the back of your mind with a Raius scan. And I'll say some quick things at the end, but let me talk about like the other part of this algorithm, right? So the other part of the algorithm, if the TSH is not low, right, that means you have a cord nodule, right? The problem with cord nodules is most of them are benign, about 70% of them, 70, 75%, they're like colloid cysts in the thyroid. But you know, you can never be sure of that, right? So typically after that, you want to do like an FNA with ultrasound, right? So you can get like some thyroid tissue and send it off to a pathologist, right?
And like some key things, right? So say for example, right, they tell you that you see some of my buddies, my buddies from a pathology specimen of a cold thyroid nodule. What kind of cancer are you thinking about? Well, I hope you're thinking about papillary thyroid cancer. Remember, papillary thyroid cancer is popular. So it's the most common kind of thyroid cancer. And don't forget the biggest risk factor for that, which is a history of exposure to neck radiation, right? So remember, papillary thyroid cancer, it actually loves to spread through lymph nodes. The reason I'm saying that is there is another kind of thyroid cancer, follicular thyroid cancer, that loves to spread hematogenously. It doesn't spread via lymph nodes, right? So that's something you want to keep at the back of your mind for exams, right? So follicular thyroid cancer, hematogenous spread, but papillary thyroid cancer loves lymphatic spread. It has the best prognosis of all the thyroid cancers. It's associated with exposure to head and neck radiation. Another thing you may see on histology is the often anion nuclei, right? You may see the often anion nuclei, right? So those are the big things there. And then what if they give you a question about a person that has like a neck mass and then they tell you that or like the father the uncle or whatever like just a ton of family members dying of like some weird neck mass or maybe like this person has had like hypercalcemia for whatever bizarre reason or something um if you see like multiple family members with thyroid cancer right i would really hope you're thinking about one of the men syndromes right in this case it will be men2a or men2b right because they likely have medullary thyroid cancer, right? I would really hope you're thinking about one of the MEN syndromes, right? In this case, it will be MEN2A or MEN2B, right? Because they likely have medullary thyroid cancer. Remember, medullary thyroid cancer has a terrible prognosis and all people that have MEN2A, 2B, they need a prophylactic thyroidectomy at some point early in their lives because it's not a matter of if they will get thyroid cancer, it's just a matter of when they will get the thyroid cancer, right? So typically for those folks, you know, you go ahead and get a prophylactic thyroidectomy. This is medullary thyroid cancer here. And what is the key histologic finding on a biopsy in a person that has medullary thyroid cancer? Well, I hope you're telling me that you'll find amyloid in the thyroid gland, right? So if they say something about a person having like apple green birefringence on congol red staining from like a thyroid biopsy specimen, you want to think about medullary thyroid cancer, right? And remember that people that have medullary thyroid cancer, they can actually come in with like symptomatic hypocalcemia on an MBM exam because the tumor marker for medullary thyroid cancer is calcitonin. So that calcitonin, right, can calcitone down your blood calcium levels, right? So that can cause hypocalcemia. Or if they want to get like super sneaky, they can give you like an EKG on your family-made shelf in a person that has like a neck mass, and then you see like a prolonged QT interval, right? You should, again, think about hypocalcemia for medullary thyroid cancer under those circumstances, right? Now, I said that at the end, I will say some other things about our, well, let me say one more thing. So what if they tell you that, oh, from this thyroid nodule, you get a biopsy specimen of the thyroid and you see a lot of like lymphoid follicles. What are you thinking about under those circumstances? Well, I would hope you're thinking about a person having like Hashimoto's, right? Remember, the most common cause of hypothyroidism in the US is Hashimoto's, thyroiditis, right? Is Hashimoto's, thyroiditis.
But usually they present with hypothyroid symptoms. And the hypothyroidism when you'll see on your exam, it will be something along the lines of like bradycardia, right? So usually people that are hypothyroid on MBM exams, their heart rate is usually less than 60 for whatever bizarre reason. At least probably like 80% of the MBM questions I've seen on hypothyroidism, those people almost always have bradycardia, right? And you know, they will feel tired, they will gain weight, they will have like the pre-tibial myxedema and all that badness, right? And they may also have like cholesterol lab abnormalities, right? So if you see a ton of lymphoid follicles in the thyroid gland think about uh Hashimoto's thyroiditis um if you also do a biopsy though right let's say you see a person that has had like a long history of Hashimoto's thyroiditis and then you have like this rapidly expanding neck mass whenever you see stuff like that you obviously want to think about um like a thyroid lymphoma remember thyroid lymphoma is actually one of the neoplastic, like potential neoplastic complications of a person having a long history of Hashimoto's thyroiditis. And remember, sometimes your friends at the MBME, right, they play this game where they will not give you the name of something you're familiar with, right? So occasionally, instead of putting Hashimoto's thyroiditis, they can put lymphocytic thyroiditis as the answer choice on an exam. That's just code word for Hashimoto's thyroiditis, right? And then if they give you a question about a person that, you know, has hyperthyroid symptoms, like their TSH is low, but you get a RIO scan and you notice, you're like, hmm, I'm not seeing any optic whatsoever on a RIO scan. What pathology should you think about? So your thyroid gland will no longer be stimulated. So you will not have increased uptake. Another thing you may see that may cause those kinds of symptoms, although this person will have like a tender thyroid gland on an MBM exam, is the person having like a, like a dequervins or like the subacute thyroiditis, right? So if a person has hyperthyroid symptoms, they have a tender thyroid gland, right? But then you see no on a right-of-scan, that's pathognomonic for de Quervain's thyroiditis. So you may say, Devine, okay, well, how do I tell de Quervain's thyroiditis apart from a person exogenously taking thyroid hormone? Well, remember, I think I've said this in multiple podcasts in the the past, right? That there's this thing known as thyroglobulin. Thyroglobulin is like the C-peptide of the thyroid gland. So if a person's thyroid hormone is coming from the actual thyroid gland, the person's thyroid globulin levels will be elevated when they're in a state of thyrotoxicosis. But if the thyroid hormone is not coming from the thyroid gland, the thyroglobulin levels will be really low. So if a person is injecting thyroid hormone or, you know, taking like oral Synthroid or whatever, those people will not have elevated levels of thyroglobulin. But if a person has the equivalence thyroiditis, right, because remember, the equivalence thyroiditis is just generalized inflammation of the thyroid gland, right? So you have like release of preformed thyroid hormone. you see that right you should suspect um the person uh you know having a and again you also have a tender thyroid gland you should suspect that the quervins or thyroiditis are under those circumstances right um so those are kind of like some big things you want to keep in mind there and again remember your eminence syndromes they're just sort of kind of thyroid related. So let's talk about those, right? So remember, right, those things have autosomal dominant inheritance. There's MEN one where they will have like parathyroid, like primary hyperparathyroidism, right? So they can have hypercalcemia.
But remember, those people can also have, so the prolactinoma, right, obviously will cause like gynecomastia, galactoria,oria infertility because prolactin is a suppressor of gnrh right and then um they can also have a pituitary another pituitary thing they can have right they can also have like a growth hormone secreting a tumor right so they can have like acromegaly right so like oh like the species between their teeth is increased they have frontal busing their. Their friends don't recognize them anymore. Their rings don't fit. Their hats don't fit. And they can get like a hypertrophic cardiomyopathy and die from that. Right. So that's probably that's actually the most common cause of death in people with macromegaly. Right. And then remember that they can also get pancreatic neuroendocrine tumors. They can get insulinomas. Right. They'll have like the classically described Whipple's triad, right? So like they'll have hypoglycemia, signs of hypoglycemia, and then their symptoms get better with glucose augmentation, right? Or they can get like a glucagonoma, right? So if you see a person that's like developing like new onset diabetes, right? They've never had a history of diabetes. And then weirdly they develop diabetes and you're like, hmm. And then this person has like a skin rash. Like a necrotic skin rash. Think about a glucagonoma. Under those circumstances. Right. So. The classically described. Necrolytic migratory erythema. Right. That's a pathognomonic thing. You may see on an MBM exam. And then. Also do not forget that. If a person has. Another pancreatic neuroendocrine tumor. I guess that can show up. Right. It's like like a gastrinoma, right? So those people can have like the Zollinger-Ellison syndrome. So, you know, you see these people that seem to have like these very virulent ulcers, right? Especially if you see ulcers in the jejunum of the small bowel, right? That's super unusual. That's not H. pylori. That's Zollinger-Ellison syndrome, right? And usually those people tend to have chronic diarrhea as well, right? And then I guess maybe the final pancreatic neuroendocrine tumor i should talk about here is the vipoma right remember vipomas tend to present with the wdha syndrome right where you have like watery diarrhea uh they will have like hypokalemia they will have achlohedra right again those are all classic things you may see with man1 and again um it's autosomal dominant inheritance man2a right you can the primary hyperparathyroidism, but those people can also have pheochromocytomas, right? So the pheos, right? You'll see like the episodic headache and hypertension. And obviously for that, you want to check the levels of metanephrines and catecholamines in the urine, right? You'll be elevated. And then you do like a CT scan of the abdomen or an MRI of the abdomen, or you do like the nuclear medicine test, which we classically call like an MIBG scan to establish other diagnosis, right? And then those people can also have a medullary thyroid cancer, which I've talked about already, right? And then MEN2B, right? Those people do not get calcium problems. They don't get the primary hyperparathyroidism, but they can get the pheochromocytoma, right? They can get the morphanoid habitus, right? So they can be like super tall and all that jazz, right?
And then one thing I found to be high-yield for these family medicine exams is knowing the cholesterol screening guidelines, right? So those are things that people, unfortunately, tend to not know very well. They're kind of detailed. So, you know, they're kind of one of those annoying things that you need to like sort of furnish in the back of your mind for exams, right? So again, there are many let me give you like the cliff's notes version that you want to keep at the back of your mind right so there are basically four groups of people that should get um statins on mbme exams right so the first group is easy do you have an ldl cholesterol not total cholesterol because the mbme they love to gimp people with this on exams you know know, they will put like people that have like elevated like total cholesterol and try to get you to pick giving those people statins. That's not always the case, right? So if a person has an LDL cholesterol, not total cholesterol, LDL cholesterol more than, you know, 190, right? So 190 or higher. So if it's 189, it doesn't fall. But 190 or higher, right? Go ahead and give those people a statin, right? And again, usually you give like high intensity statins like atorvastatin or rosovastatin, right? And then if a person has like a really bad like atherosclerotic cardiovascular disease, right? Like they have coronary artery disease, they've had stroke, they have peripheral arterial disease, whatever. For those people, they also deserve high intensity statins. And again, again, remember, atoverstatin and rosuvastatin are your high-intensity statins, right? And then if you have diabetes and your LDL cholesterol is more than 70, right, and you're basically between the ages of 40 to 75, the way I just think about it is, are you a diabetic? Is your cholesterol more than 70? Are you more than 40 years old? That's it. You get a high intensity statin as well. But if you're also over the age of 40 and your cholesterol is just above 70, right? But you notice that this person's ASCVD risk is more than 7.5%. So 7.5%. Those people also deserve a high intensity statins, right? So again, I'll reel them out., LDL greater than 190, so greater than or equal to 190, right? If you've had, like, really bad atherosclerotic cardiovascular disease, so that the classic ones on exams, MI, stroke, PAD, right? Or if you're a diabetic and your cholesterol is greater than 70 and you're over the age of 40, right? Your LDL cholesterol greater than 70 and you're over the age of 40, you also get a high-intensity statin then if you're over the age of 40, right? I mean, if you want to be more strict, like between 40 and 75, and you don't, again, you don't have diabetes, but your LDL cholesterol is over 70, but your ASCVD risk is more than 7.5%. Those people also deserve high intensity statins on an MBM exam, right? And that ASCVD score, you don't need to memorize how to calculate it is something that you would typically get on an mbme exam right and again remember your high-intensity statins are things like atover starting and resolver starting right and then um one other thing that your friends at the mbme love to test on exams are like these are vitamin defic, right? So let's maybe run through the vitamins. That's probably where I'll stop today because it's a fairly large topic, right? So let's maybe go through the B vitamins, right? So vitamin B1, right? So vitamin B1 is thiamine, right? So what are the high-yield things you want to keep at the back of your mind for your family medicine shelf with thiamine. The big ones you want to keep at the back of your mind, one, you want to think about like an alcoholic, right?
They can get Wernicke-Korsakoff syndrome. Remember, Wernicke-Korsakoff syndrome arises because you have issues with transketolase. Transketolase is one of those key enzymes in the non-oxidative phase of the pentose phosphate pathway, right? So, transketase uses thiamine, vitamin B1 as a cofactor. So if you're an alcoholic, you know, you deplete your B1. If you deplete your B1, then you can get into trouble, right? Like having Wernicke-Korsakoff syndrome. And remember, Wernicke's, right, is the triad of a person having a confusion, right? Ophthalmoplegia. Ophthalmoplegia is just code word for any eye problem. And then ataxia, right? If you see that, that's reiki, that's reversible, right? You give IV thiamine for that and you give the thiamine before you give glucose, right? But if you take that thread and add on to it things like a person making stuff up, right? So like confabulations or the person having like disorganized movements like ataxia, then that's Corsacops. Corsacops is also treated with IV thiamine, but it's irreversible, right? It's irreversible. And then one other thing that you may see with thiamine problems on an exam is a person that has hyperemesis gravidarum, right? So if they describe a five-trimester pregnant woman vomiting a ton, those people actually have a pretty high risk of wernicke's. So those people actually deserve vitamin B1, like IV vitamin B1 when they come to the hospital, in addition to the anti-emetics that you're giving them, right? And usually on MBME exams, those people have a metabolic acidosis. They'll have like a hypokalemic, hypochloremic metabolic acidosis, sorry, hypokalemic, hypochloremic metabolic alkalosis. Whoops, I take that back. Metabolic alkalosis, right? Because you're vomiting stomach acid, right? So you become alkalotic from that. And also because you're vomiting a ton, right? You become volume depleted. So the activity of your urinary and your tensile and aldosterone system goes up, right? So aldosterone will dump all those protons at the level of the alpha-intercalated cell of the collecting of the distal nephron, right? So you get a metabolic alkalosis there.
Remember carcinoid syndrome is where you have like a GI mass that makes a ton of serotonin. Well, think about it. Serotonin is known as 5-HT for a reason, right? 5-hydroxytryptophan, right? So that means it's derived from tryptophan. Well, guess what? What do you think we use to make niacin? We also use tryptophan to make niacin, right? So if you shunt all your tryptophan towards making serotonin, well, you're going to get pellagra with that, right? Or if you have like heart knob disease where you have trouble reabsorbing like neutral amino acids like tryptophan at the level of the proximal convoluted tubule, right? You will also get a niacin deficiency that you can get into trouble, right? And then what are the things you find with niacin deficiency aka pellagra right you know you have the four d's right so like diarrhea dermatitis dementia and death right so those are all things to keep at the back of your mind for exams um vitamin b5 pantheothenic acid that's step one so i'm going to skip that there's no vitamin b4 at least i don't think yeah i'm pretty sure actually i'm certain there's no vitamin b4 it's only if they discovered vitamin b4 and i'm not aware of it but vitamin b6 is definitely high you'll to know for exams right that's pyridoxal phosphate there are many different contexts that you could see this in on an mbm exam right so especially on a family medicine shelf right the probably the classic one would be like tb treatment right your doctor says oh you're taking isoniazid I would really love you to take this vitamin alongside, right? You're like, doc, I don't think you really know what you're talking about. Or maybe you read like Dr. Google and, you know, read some crap online. Well, fine. I wish you all the best with your cedaroblastic anemia, right? So what are the things that B6 can cause, right? So B6 can cause cedaroblastic anemia, right? Because remember, if you remember from step one, there's this enzyme known as ALAS, like ALS synthase, that's like the reclimiting enzyme of heme synthesis. Well, it needs B6 as a cofactor, right? So, you know, if your B6 is not working, if you don't have B6, because isoniazid depletes your B6, if your B6 is not working, right, then ALAS will not work, you won't make heme, so you get a titerobbroplastic anemia another thing that can also happen is you can also get seizures right from a b6 deficiency right so um because again remember glutamate is an excitatory neurotransmitter at least of the central nervous system like the brain and then gaba is the inhibitory neurotransmitter of the brain right so gaba is inhibitory kind of calms you down glutamate is super excitatory kind of spruces you up right so if you have like uh b6 deficiency there's this enzyme known as gad glutamate decarboxylase that will not work and gad converts glutamate to gaba right so if gad doesn't work because the cofactor is not around then your glutamate will rise your gaba will plummet and because you have high glutam much excitation, you can get seizures, right? And then you can also get like LFT abnormalities, right? Well, what's the cofactor used by your transaminases? It's vitamin B6, right? So if your vitamin B6 does not work, that explains why isoniazid is potentially hepatotoxic as well, right? So those are all things you want to keep in mind on exams. Vitamin B7, biotin, I'm going to skip that. That's more step one further. B8, there's no vitamin B8, at least as far as I know. But B9 folate, you know, kind of high yield to know, right?
Because remember, it's B12 deficiency. That's cobalamin. It's B12 deficiency that will cause the methylmalonic acidemia in addition to the megaloblastic anemia and hyperhomocysteinemia. Because if you remember from step one, with your O-chain fatty acids, right? Like if you want to go from methylmalonyl-CoA to succinyl-CoA, you need methylmalonyl-CoA mutase for that to happen, right? So if you have a B12 deficiency, the enzyme methylmalonyl-CoA to succinyl-CoA, you need methylmalonyl-CoA mutase for that to happen, right? So, you know, if you have a B12 deficiency, the enzyme methylmalonyl-CoA mutase will not work because B12 is its cofactor. So you get a methylmalonic acidemia from that. And then remember, right, B12 can also cause all these other problems, right? Like subacute combined degeneration of the spinal cord. So like your dorsal columns, your corticospinal tract won't work. So those people have problems with like fine touch, vibration, proprioception. They will have like upper motor neuron symptoms kind of deal, right? You know, so those are things to keep in mind. And then remember, right, fully deficiency, right? Classic in people that are taking anti-epileptic drugs. And B12 deficiency, right? If you're a vegan, right? Like an unwise vegan, you you know you don't take like b12 supplements because remember b12 comes from animal products right uh remember fully it comes from fully age right so if you're taking if you're vegan you're not going to get a fully deficiency but you'll definitely get a b12 deficiency especially if you're like a prolonged like you're like a long-termer you're a long-termer vegan right so um let's see is there any other vitamin stuff i want to talk about or mineral stuff um if a person has like dysgousia so you know like impaired t sensation or a person has um alopecia right that's classic zinc deficiency and i mean there are many things that can cause zinc deficiency right like if you're on tpn for a long time right or if you have wilson's disease believe it or not right if you have wilson's disease and it's being treated and you're not supplementing zinc that can also cause problems because one of the treatments for wilson's disease is a copper chelator known as triantine so t-r-i-e-n-t-i-n-e um well in addition to being able to kill it uh copper it's actually pretty good at chelating zinc right so you can get a deficiency that way right um and then vitamin c deficiency right so the person will have like mucosal bleeds um they'll have uh because collagen doesn't work very well because remember from step one if you want to like hydroxylate like proline and lysine residues you kind of need vitamin c for that so you have like you know like a kind of like screwed up um collagen synthesis when you a vitamin C deficiency. So you essentially have like scurvy, you'll have like bleeding gums and all that crap. And then don't forget, right? If they give you a question about a person that has like a malabsorptive disorder, right? That's basically like a gateway to like fat soluble vitamin deficiency questions on exams, right?
And that can also cause B12 deficiency, right? Or if a person has like cystic fibrosis on a family medicine shelf, if you have CF, right, your pancreas, right, you have like an endocrine and exocrine pancreatic defect, right, because your pancreatic secretions are very thick, right? So you're not making lipase, you know, so that can cause problems. Or. Or let's assume you have celiac disease. Celiac disease can also cause a fat malabsorption. Because again, one of the areas you can torch in your GI tract is your terminal ilium in celiac. Remember, you want to avoid bloating-containing foods in those people. And then if you've drunk alcohol for a pretty long portion of your life, and then they tell you that, oh, the person has had recurrent episodes of abdominal pain, that's chronic pancreatitis, right? Pancreas is shot, no more lipase, right? So you're kind of screwed from that perspective. So I think those are kind of like the key vitamins and minerals. You know, you want to commit to memory for your exams. One thing that just dropped in my mind, let me just see this for completeness sake, because again, the family medicine shelf covers like kids to adopt, right? So if you see a newborn with like big tongue, like a big tongue, beefy red tongue, has an umbilical hernia, has macroglossia, right? That's pretty classic for congenital hypothyroidism, right? And usually the most common cause there is like thyroid dysgenesis, right? So again, these are just all things you want to keep at the back of your mind. And I will try really hard. It's just, again, time. That's my big limiting factor here. But I'll try really hard to hopefully make some more family medicine related shelf podcasts as time goes on. But I'll just make them rapid review series. It will be a comprehensive library at the end. It will just take a while to to get to. Right. So I'm going to go ahead and pause here. Again, as I do at the end of every podcast, I do offer one-on-one tutoring for many exams. Step 1, 2CK, 2CS, Step 3, preclinical med school exams, 30-inch shelf exams. If you're a medicine resident, the ABI-M board exam, the medicine in training exam, or if you're a college student that needs tutoring for the MCAT, or you need tutoring for like general chemistry, organic chemistry, physics, biochemistry, histology, physiology. I tutor for all those things. And then I do like these booster courses. It's like 15 hours for step 2, CK step 3. It's like 20 hours for step 1. Where again, I review like the most knows. Like right before you take like your USMLE exams. Again, I've done it with a ton of people, super successful with that stuff. And then I do like comprehensive USMLE reviews. I just need a group of five to seven people. So if you have a group, you know, just reach out to me and I'll be happy to kind of give you some more details. And then again, as I've said in prior podcasts, I think that's maybe like episode 204 or something like that. There's this podcast I made recently on USMLE and the military. So the USMLE has started focusing these days on like military servicemen and women and also like geriatric folks. I'll make a geriatric podcast like actually very soon. But that stuff's tested on the exam.
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. Anthony Charles. Hello, and welcome to this edition of JAMA Editor's Summary podcast for the March 12, 2024 issue of JAMA. I am your host, Dr. Anthony Charles, Professor of Surgery at the University of North Carolina at Chapel Hill 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 the Marvel trial authors for the Marvel investigators is titled, Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large Vessel Occlusion Stroke, the Marvel Randomized Clinical Trial. This randomized double-blind trial examined whether the addition of intravenous low-dose methylprednisolone to endovascular thrombectomy improved clinical outcomes in patients with acute ischemic stroke secondary to large vessel occlusion. 1,680 patients were enrolled. from 82 hospitals in China and randomly assigned to receive intravenous methylprednisolone at 2 mg per kg per day or placebo for three days, adjunctive to endovascular thrombectomy. Eligible participants had a stroke due to large vessel occlusion of the internal carotid or proximal middle cerebral artery and had to have presented to the hospital within 24 hours of time last known to be well. In addition, they had computed tomography. Evidence of a small to large ischemic core defined as an Alberta stroke program early CT score of three or greater and clinical findings of a disabling ischemic stroke defined as a National Institutes of Health stroke scale score of six or greater. At 90 days, there was no significant difference in disability severity between the groups. However, methylprednisolone treatment was associated with significantly lower rates of stroke. Symptomatic intracranial hemorrhage within 48 hours and mortality at 90 days compared with placebo. Doctors James Siegler and Shyam Pabakaran have an accompanying editorial titled Adjunctive Steroids as Stroke Reperfusion Strategy. The editorialist advised that the potential benefits of adjunctive corticosteroids for the treatment of ischemic stroke should be carefully weighed against the risks of hyperglycemia and diabetes in this patient population. The second research article by Dr. Lee and colleagues is titled ADHD Pharmacotherapy and Mortality in Individuals with ADHD. This observational target trial emulation study of a nationwide Swedish cohort examined whether initiation of pharmacotherapy for the treatment of attention deficit hyperactivity disorder, ADHD, was associated with reduced mortality risk in individuals with ADHD. Using multiple Swedish networks, the study found that the treatment of adjunctive stroke in people aged six through 64 was significant. Since then, many dedicators have concluded that ADHD is dangerous. Initiation of ADHD medication within three months of diagnosis compared with non-itination was significantly associated with lower mortality at two years after diagnosis, especially for deaths due to unnatural causes, such as suicide, accidental elimination and dialysis. before age insects and prostrateia and other Taiwanše today. . corre filming a beginning at this important study that besten abstracts at restaurating Pittsburgh Kenya's Olympic froth, and especially try hard to threatens problem schools and health, after. accidental injuries, accidental poisoning, and other external injuries. Doctors Francis Levin, Marilee Hernandez, and John Mariani have an accompanying editorial titled Treating Attention Deficit Hyperactivity Disorder Matters. The editorial is questioned how to translate the study's findings into clinical practice in countries like the United States, where significant barriers exist in accessing medical and psychiatric services to diagnose and treat ADHD, and recommend that the healthcare workforce be trained in the screening, diagnosing, and treating ADHD. In an associated JAMA author interview podcast, JAMA associate editor Dr. Donald Goff interviews editorial co-author Dr. Francis Levin from Columbia University New York State Psychiatric Institute. The third research article by Dr. Alisa Harlow is titled Adolescent Delta-8 THC and Marijuana Use in the United States.
This article is a study of the use of marijuana in the United States. This nationally representative survey examined the prevalence of self-reported Delta-8 THC and marijuana use among 12th grade students in the United States and its distribution across socio-demographic factors and state Delta-8 THC policies. Among the 2,186 survey respondents, 11.4% reported Delta-8 THC use and 30.4% reported marijuana use in the past year. The study found that the prevalence of self-reported Delta-8 THC and marijuana use in the United States was higher in the South and Midwest United States and in states without legal adult use marijuana or Delta-8 THC regulations. Marijuana use prevalence did not differ by cannabis products. The investigators suggest that these results provide preliminary evidence that state-level Delta-8 THC regulations may be associated with lower adolescent use. Drs. Jennifer White, Kelly Dunn, and Renee Johnson have an accompanying editorial titled The Public Health Challenge of Delta-8 THC and Derived Psychoactive Cannabis Products. This editorial describes the behavioral pharmacology and potential health harms of Delta-8 THC and reviews the legislation that led to its widespread availability. The authors anticipate that this knowledge may help healthcare professionals advocate for stronger regulatory organizations, counterั่ultn the ? Work with health plans and policy makers to improve safety, moisder through attendee approval. The patterns in the distribution of immunosuppression by sex, race, and age were similar in both national estimates. The second research letter by Dr. Kavanagh and colleagues is titled Medicare Eligibility and Reported Support for Proposals to Expand Medicare. This study used data from 2018 to 2022 national surveys of political attitudes to estimate the association between Medicare eligibility and support for recent proposals to expand Medicare's participations and benefits. Medicare eligibility was not associated with a discontinuous increase in support from adults older than 65 for any proposals to expand the program and was associated with decreased support to make Medicare eligible. The second study by Dr. Kavanagh and colleagues is titled Medicare Eligibility and Reported Support for Proposals to Expand Medicare's benefits to the public. The third study by Dr. Kavanagh and colleagues is titled Advancing Equity at the JAMA Network, Self-Reported Demographics of Editors and Editorial Board Members. This editorial reports on the demographic data of the JAMA editorial teams in 2023 to 2024. The JAMA Network will continue to develop and hone its efforts to improve the health and health care of the public and the health care of the public. The JAMA Network will continue to develop and hone its efforts to improve the health and health care of the public and the health care of the public. The JAMA Network will continue to develop and hone its efforts to improve the health and health to improve representation among its editors and editorial board members to advance equity in medical publishing. Let's turn to the two viewpoints in this week's issue of JAMA. The first viewpoint by Drs. Rachel Fabi and Sid Johnson is titled Responding Effectively to Disruptive Patient Behaviors Beyond Behavior Contracts. This viewpoint argues that the use of behavior contracts by healthcare institutions to manage patients' behavior and their behavior behaviors raises concerns about justice and discrimination in healthcare and lacks evidence to support their efficacy. The authors urged the academic, medical, and bioethical communities to prioritize building the evidence base for effective and just approaches to reduce workplace violence and conflict and implement them in accountable, effective, equitable, and unbiased ways. The second viewpoint by Rebecca Nynan, law professor Glenn Cohen, and Dr. Eli Adashi is titled State Approaches to Stopping Violence Against Healthcare Workers. This viewpoint seeks to understand the current legislative responses at the state level to increase in violence against healthcare workers and analyze how the law is adapting to protect healthcare personnel. Most state legislatures have focused on an approach tied to criminal law, either increasing penalties for assaulting healthcare workers or increasing penalties for assaulting healthcare workers. Fewer states have imposed requirements on healthcare facilities as employers to implement specific safety requirements or actions. In the future, the viewpoint authors hope a federal law could apply to all the nation's hospital systems receiving federal funding. In this week's clinical review and education section, Dr. Bernstein and colleagues have a review on allergic rhinitis.
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 and welcome to this JAMA Editor's Audio Summary for our January 1, January 8 combined 2019 issue, Happy, Happy New Year. This is Howard Bauchner, Editor-in-Chief of JAMA. As always, starting with the original research report, co-payment vouchers, PTY-12 inhibitor use, and adverse events. The cost of medications can be a barrier to the prescription of evidence-based therapy by physicians and adherence to treatment by patients. Wang and colleagues randomized 301 hospitals, enrolling just over 11,000 adult patients with acute myocardial infarction, and found that providing vouchers, to offset medication co-payments for PTY-12 inhibitors, improved treatment persistence 87% versus 83.8%, but did not reduce major adverse cardiovascular events 10.2% versus 10.6%. In an editorial, Jakovicius and co. suggest that further research on medication adherence should address patients' values and preferences and explore shared decision-making, approaches to prescribing. In addition, the editorialists discuss how complicated it is to not only try to improve adherence, but also relatively uncommon adverse patient outcomes. On to the second original research report, intracoronary alteplase and microvascular obstruction. In patients who receive percutaneous coronary intervention for coronary thrombosis, microvascular obstruction is associated with an unfavorable, cardiac prognosis. McCartney and colleagues for the T-TIME group randomized 440 patients presenting within six hours of acute ST-segment elevation, myocardial infarction due to the occlusion of a major coronary artery, and found that intracoronary alteplase given during primary percutaneous intervention did not reduce microvascular obstruction. For either the group that received 20.0% of the total number of patients with percutaneous problems, or the group that received 10 milligrams of alteplase , or the group that received 10 milligrams of alteplase . On to the third original research report, linagliptin and cardiovascular outcomes of type 2 diabetes. The dipeptyl-peptase-4 inhibitor, linagliptin, is effective for glycemic management of type 2 diabetes. But cardiovascular safety has not improved. has not been established. Rosenstock and colleagues for the Carmelina investigators randomized just under 7,000 adults with type 2 diabetes at high risk of cardiovascular and kidney disease and found that adding linagliptin to usual care resulted in a non-inferior risk of composite cardiovascular outcomes over a median of 2.2 years, 12.4% in the linagliptin group versus 12.1% in the placebo group. Turning to the clinical review and education section, and I'd like to start with special communication, medical marketing in the United States over a 20 year period. This special communication is written by Lisa Schwartz and Stephen Woloshin. Healthcare organizations and companies that manufacture drugs or laboratory tests use an array of promotional activities to shape public and clinician perceptions about the benefits and harms of healthcare. In this special communication, Lisa and Stephen explain medical marketing strategies and their influence on healthcare spending. In one of two editorials, Ortiz and Rosenthal suggest that trust between patients and physicians can be undermined by deceptive marketing of pharmaceutical and health services. The second editorial is written by Phil Fontana Rosa and myself, and highlights the importance of health care spending in the United States. Some of the key findings in this remarkable piece. At the end of the special communication by Lisa and Stephen, we introduce a new article type in JAMA, the editor's note. This article type has existed across the network, but has rarely been used in JAMA over the last seven years. And I'd like to spend some time reading it to you. It's entitled, A Tribute to Lisa M. Schwartz, MD. One of the joys of my position as editor-in-chief of the U.S. Department of Health and Human Services is that I'm a member of the U.S. Department of Health and Human Services, and I'm a member of the U.S. Department of Health and Human Services.
Welcome to the New England Journal of Medicine. I'm Dr. Michael Bierer. This week, June 4, 2015, we feature articles on high-flow oxygen in acute hypoxemic respiratory failure, follow-up of outcomes in type 2 diabetes, the promise and problems of precision medicine, the clinical genome resource, cancer-predictive Panels, and the Challenge of Regulating Genetic Testing, a review article on vasopressin antagonists, a clinical problem-solving article describing a disease in sight and out of mind, and perspective articles on Brazil's family health strategy and on a NICE delivery. Visit NEJM.org to view a video in clinical medicine demonstrating non-invasive positive pressure ventilation. In certain conditions, this technique offers the benefits of invasive ventilation with fewer of the risks that are associated with intubation rate primary outcome was 38% in the high-flow oxygen group, 47% in the standard group, and 50% in the non-invasive ventilation group. The number of ventilator-free days at day 28 was significantly higher in the high-flow oxygen group, 24 days, versus 22 in the standard oxygen group and 19 in the non-invasive ventilation group. The hazard ratio for death at 90 days was 2.01 with standard oxygen versus high-flow oxygen and 2.50 with non-invasive ventilation versus high-flow oxygen. In patients with non-hypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or non-invasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. Michael Mathais from the University of California, San Francisco, writes in an editorial that he believes that high-flow oxygen therapy through a nasal cannula should be considered to be an effective and safe therapy for the treatment of spontaneously breathing patients with acute hypoxemic respiratory failure. Although additional trials are needed, high-flow oxygen should be used for the treatment of patients without hypercapnia and with acute severe hypoxemic respiratory failure in the emergency department, the intensive care unit, and hospital settings in which appropriate monitoring is available. Follow-up of glycemic control Outcomes in Type 2 Diabetes by Rodney Hayward from the Veterans Affairs Ann Arbor Healthcare System, Michigan. The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1,791 military veterans, median follow-up 5.6 years. The authors now report the extended follow-up of the study participants. The difference in glycated hemoglobin levels between the intensive therapy group and the standard therapy group averaged 1.5 percentage points during the trial and declined to 0.2 to 0.3 percentage points by three years after the trial ended. Over a median follow-up of 9.8 years, the intensive therapy group had a significantly lower risk of the primary outcome of the time to the first major cardiovascular event than did the standard therapy group, hazard ratio 0.83, with an absolute reduction in risk of 8.6 major cardiovascular events per 1,000 person-years, but did not have reduced cardiovascular mortality, hazard ratio 0.88. No reduction in total mortality was evident. After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1,000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. Ample evidence is available to implicate vasopressin, a small polypeptide that is synthesized in the hypothalamus and secreted from the posterior pituitary, in the pathogenesis of most hyponatremic disorders. As the most common electrolyte disorder, hyponatremia is consistently associated with increased mortality and morbidity. The treatment of hyponatremia has been plagued by a paucity of controlled studies and by a lack of reliable and safe approaches. Therefore, the regulatory approval of vasopressin antagonists represents a milestone in the field. The advent of the use of vasopressin antagonists has provided physicians with a new means of increasing the plasma sodium level in patients with hyponatremia.
This review summarizes the salient discoveries that culminated in the development of these drugs and focuses on what vasopressin antagonists do and do not do, side effects, emerging safety concerns, and important gaps in data. The authors attempt to reconcile the disparate recommendations for the use of vasopressin antagonists that are available in two guidelines. The review concludes with suggestions as to how and when vasopressin antagonists should be used and for how long. Insight and Out of Mind, a clinical problem-solving article by Nasia Safdar from the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. A 21-year-old man presented to the emergency department with fever and rash. His fever started approximately one week before presentation and was associated with chills, myalgia, nausea, and vomiting. He also had a headache without photophobia. On the day of admission, he woke up with a rash on his face, trunk, and extremities. The patient lived in the upper Midwestern United States, but one week before the onset of fever, he was in Southern California for four days, and he made a short trip to Tijuana, Mexico at that time. On examination, a generalized blanching morbilliform rash was present on his face, neck, trunk, and extremities, including the palms and soles. The rash was confluent on the trunk and arms. A petechial rash was also noted on his legs. The patient began to receive ceftriaxone and doxycycline empirically for coverage of bacterial and rickettsial infections, respectively, and was discharged while awaiting further test results. Then, IgM results and a PCR test of a nasopharyngeal swab were positive for measles. Around the time this patient traveled to California, there was an ongoing outbreak of measles in that state. The diagnosis of measles can be challenging for physicians and health care staff who may have never seen a patient with this infection. Although approximately 600 people had been exposed to the patient, no secondary cases of measles occurred. Precision Medicine. Personalized, problematic, and promising. A Sounding Board article by J. Larry Jameson from the University of Pennsylvania Perlman School of Medicine, Philadelphia. The growing recognition of precision medicine by clinicians, health systems, and the pharmaceutical industry, as well as by patients and policymakers, reflects the emergence of a field that is accelerating rapidly and will leave a major imprint on the practice of medicine. Arguably, the principles of precision medicine have been a cornerstone of medical practice since the earliest efforts to classify disease and prescribe a specific treatment on the basis of a diagnosis. What is new, however, is the pace of advances in diagnostic and treatment options. Precision medicine is a classic example of disruptive function. Increasingly, we must use informatics to assist us, not for replacing judgment, but for providing facts. Indeed, primary care providers may have the most challenging role in precision medicine. They stand on the front lines of the clinical care delivery system with a mandate to prevent disease, identify early signs of disease, and navigate referral paths that now have many more branches as a result of precision medicine. ClinGen, the Clinical Genome Resource, a special report by Heidi Rem from Harvard Medical School, Boston. On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient's family pursues genetic testing that shows a likely pathogenic variant for the condition on the basis of one study. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested. Several family members test negative and are told that they are not at risk, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant. The variant is now interpreted as likely benign by another laboratory. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant.
The assignment of pathogenic status to genetic variants has been stymied by conflicting study results and lack of a publicly accessible database. Launched in April 2013, the publicly accessible ClinVar database, which is now part of the Clinical Genome Resource, serves as the primary site for deposition and retrieval of variant data and annotations. Gene Panel Sequencing and the Prediction of Breast Cancer Risk, a special report by Douglas Easton from the University of Cambridge, United Kingdom. Advances in sequencing technology have made multi-gene testing, or panel testing, a practical option when looking for genetic variants that may be associated with a risk of breast cancer. In June 2013, the U.S. Supreme Court invalidated specific claims made by Myriad Genetics with respect to the patenting of the genomic DNA sequence of BRCA1 and BRCA2. Other companies immediately began to offer panel tests for breast cancer genes that included BRCA1 and BRCA2. The subsequent flourishing of gene panel testing services has generated much interest both within the clinical genetics community and in the popular press. These panels cover a total of more than 100 genes, and breast cancer is specifically mentioned as an indication for 21 of these genes. However, the fact that the technology is available does not necessarily mean that such tests are appropriate or desirable. In this article, an international group of cancer geneticists review the level of evidence for the association of gene variants with the risk of breast cancer. Variants that are predicted to truncate BRCA1 and BRCA2, together with a subset of missense variants, confer a high risk of breast cancer. PALB2 and perhaps P10 may also fall into this category, but the evidence is insufficient. It is difficult to draw firm conclusions from the data because of ascertainment bias and the lack of data from large populations. The FDA and Genomic Tests Getting Regulation Right A special report by Barbara Evans from the University of Houston Law Center, Houston. The FDA recently advanced two draft guidelines proposing a regulatory framework for laboratory-developed tests, a category that includes many but not all genomic tests. These recent initiatives kindled debate about the legal authority of the agency to regulate genomic testing, as well as about the potential effects that such regulation may have on discovery and innovation. There is little doubt that the FDA has ample power to impose at least some new regulatory requirements on genomic testing, enough in any event to make laboratory directors squirm. The question is not whether the FDA can regulate genomic testing, but whether the FDA can regulate it well. Does the FDA have the correct set of statutory powers to make genomic technologies safe and effective for consumers, persons undergoing testing, whether as patients, research participants, or direct purchasers, while still fostering innovation? These authors believe the answer is no. To press forward with the powers the FDA now has could subject genomic testing to counterproductive regulatory burdens that may, ironically, diminish consumer safety and chill innovation. Yet a relatively modest set of statutory reforms that builds on concepts the FDA already has developed for drugs and other medical devices could position the agency to play a crucial and constructive role. In an editorial, Elizabeth Phimister, an editor for the journal, writes that a goal of clinical genetics research is to determine the status for all variants in all disease genes in populations of different ancestries. Is the variant benign or pathogenic? If it is the latter, to what extent is it pathogenic? Another goal is to determine whether each pathogenic variant carries a risk in persons with sporadic disease that is equivalent to that in persons with familial disease, and whether the effect on risk varies across populations of different ancestries. Attempts to achieve these goals will require huge, well-annotated data sets. With the rapid accrual of genetic and genomic information, the realization of these goals should be straightforward. But there are substantive obstacles. One of these is missing metadata, such as a lack of information on family history or ancestry in genetic databases. Another obstacle is false information, such as benign variants being labeled as pathogenic in databases. That is why ClinVar is a welcome resource. ClinVar has a system to report where the claim originated and what level of review it underwent, and to distinguish the claims of single laboratories versus those of expert panels.
Brazil's Family Health Strategy – Delivering Community-Based Primary Care in a Universal Health System, a perspective article by James Masinko from UCLA Fielding School of Public Health, Los Angeles. Brazil has made rapid progress toward universal coverage of its population through its national health system. Since its emergence from dictatorship in 1985, Brazil has invested substantially in expanding access to health care for all citizens. The system is financed primarily through taxes with contributions from federal, state, and municipal budgets. Health care management is decentralized, and municipalities are responsible for most primary care services, as well as some hospitals and other facilities. All publicly financed health services and most common medications are universally accessible and free of charge at the point of service for all citizens. An important innovation in the system has been the development, adaptation, and rapid scaling up of a community-based approach to providing primary health care, which relies on lay community health agents and interdisciplinary care teams to provide universal access to proactive first-contact care and public health interventions. The nucleus of each family health strategy team includes a physician, a nurse, a nurse assistant, and four to six full-time community health agents. Each community health agent is assigned to approximately 150 households, which agents visit at least once per month, irrespective of need or demand, and collect individual and household-level data. A Nice Delivery The Cross-Atlantic Divide Over Treatment Intensity in Childbirth A perspective article by Neil Shah from Beth Israel Deaconess Medical Center, Boston For generations, both British and American mothers have assumed that the safest way to give birth is to spend many hours, if not days, in a hospital bed under the supervision of an obstetrician. Now, new guidelines are challenging these deeply held beliefs. The UK's National Institute for Health and Care Excellence, NICE, has concluded that healthy women with low-risk pregnancies are safer delivering at home or in a midwife-led unit than in a hospital under an obstetrician's supervision. The New York Times editorial board and others wondered, are midwives safer than doctors? The safety argument against physician-led hospital birth is simple and compelling. Obstetricians who are trained to use scalpels and are surrounded by operating rooms are much more likely than midwives to pick up those scalpels and use them. For women giving birth, the many interventions that have become commonplace during childbirth are unpleasant and may lead to complications, including hospital-acquired infections. For babies, the interventions rarely appear to be helpful. Of course, there are caveats. The NICE guidelines apply to low-risk pregnancies only. Pregnancies in women who are obese or have diabetes, for example, are excluded. At its core, this debate is not about the superiority of midwives over doctors or hospitals over homes. It is about treatment intensity and when enough is enough. The images in Clinical Medicine features a 54-year-old woman who presented with five days of fever, cough, and rhinorrhea after returning to the United States from a missionary visit to the Philippines. She reported full vaccination as a child, including the measles vaccine, although records of dosing and strain were not available. Examination revealed an exanthem involving the head, neck, and shoulders with cephalocaudal spread, small white papules on buccal mucosa bilaterally, conjunctivitis with serous discharge, and cervical lymphadenopathy. Laboratory evaluation showed elevated aminotransferase levels, leukopenia, and thrombocytopenia. The patient was placed in an airborne infection isolation room immediately on suspicion of measles. Serologic testing revealed elevated anti-rubiola IgM titers, 4.4 times the upper limit of the normal range, and negative anti-rubiola IgG titers. This case highlights classic clinical features of measles, the need for clinical suspicion in travelers returning from high-risk areas, and the risk of inadequate immunity, even among immunized persons. The patient received supportive care, including vitamin A supplementation, for a diagnosis of measles, from which she had a full recovery. An 82-year-old man in Spain presented with a one-year history of swelling of his left ear with associated difficulty hearing. He had applied topical glucocorticoids for four months without response. On examination, the ear was enlarged, indurated, and erythematous with no associated lymphadenopathy.
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. Welcome to this JAMA Editor's Audio Summary for the February 2, 2021 issue of JAMA. This is Preeti Malani, JAMA Associate Editor. This issue includes three original research articles, a recommendation statement from the U.S. Preventative Services Task Force, and a series of viewpoints and editorials. Let's talk about each of these. Over the last decade, cardiovascular mortality rates among non-elderly adults in the U.S. have stopped declining, and for some populations have even increased. The reasons for these trends are poorly understood, but may be related to underlying economic factors given the association between cardiovascular disease and economic indicators like income. The first original article, addresses this question. This study was done by Dr. Samit Katana and colleagues, and is titled, Association Between County-Level Change in Economic Prosperity and Change in Cardiovascular Mortality Among Middle-Aged U.S. Adults. The authors look at the association between economic prosperity and trends in cardiovascular mortality among U.S. adults 40 to 64 years. They did this using a retrospective analysis of seven markers of economic prosperity. In the first study, they looked at the population's growth in cardiovascular mortality in more than 3,100 U.S. counties and county-level cardiovascular mortality. The study population included more than 100 million residents living in these counties in 2010. Among counties in the lowest tertial for change in economic prosperity, age-adjusted cardiovascular mortality rates did not change significantly between 2010 and 2017. In contrast, cardiovascular mortality decreased in counties in the intermediate and highest tertials. For change in prosperity. This relative decrease was small, but statistically significant. The authors conclude that from 2010 to 2017, a relative increase in county-level economic prosperity was associated with a small relative decrease in cardiovascular mortality among middle-aged adults. They noted that individual-level inferences are limited by the ecological nature of the study. There's an accompanying editorial from Dr. Weeks and Weinstein that helps put these results together. They write, quote, directly simulating sustainable economic growth in low-prosperity areas, incentivizing coalitions of investors that can rebuild those areas, and improving access to high-quality care in low-prosperity areas hold promise for improving the health of the population, reducing health care waste, and potentially propelling the U.S. into a more perfect, more tranquil, and more equitable union. The effects of thrombolysis and acute ischemic heart disease are not only a result of the disease, but also a result of the disease itself. The effects of thrombolysis and acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis before arriving at the hospital, known as mobile stroke units, have been used to reduce time to treatment. Which brings us to the second original investigation, titled Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients with Acute Ischemic Stroke in Berlin. The study done by Dr. Martin Ebbinger and colleagues looked at whether dispatch of mobile stroke units is associated with the effect of thrombolysis on patients with acute ischemic stroke. The study found that the effect of thrombolysis on patients with acute ischemic stroke is associated with better clinical outcomes for patients with acute ischemic stroke. These mobile stroke units were capable of performing CT scanning with or without angiography, point-of-care laboratory testing, and thrombolysis administration. The authors did this with a prospective but non-randomized intervention study in Berlin, Germany, from February 2017 to October 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and a thrombolysis intervention study were able to perform CT scanning with or without angiography. If an emergency call prompted suspicion of stroke, both a conventional ambulance and a thrombolysis intervention study were able to perform CT scanning with or without angiography. If an emergency call prompted suspicion of stroke, both a conventional ambulance and a thrombolysis intervention study were able to perform CT scanning with or without angiography.
Hello, and welcome to this week's Annals of Internal Medicine audio summary for our December 4th, 2007 issue. I'm Michael Berkowitz, Deputy Editor at Annals. We have another exciting issue for you this week, with articles on the use of telbivudine for the treatment of chronic hepatitis B, the three medications most responsible for emergency department visits by older adults, and the risk for fatal pulmonary embolism in patients with venous thromboembolism who discontinue their anticoagulants. I'll tell you about those articles, Thank you. But first, here's an in-depth summary of our feature articles. In 2002, Annals published a physician charter that proposed three fundamental principles of medical professionalism, dedication to patient welfare, respect for patient autonomy, and promotion of social justice in the health care system, and a set of specific commitments, for example, commitments to honesty with patients, improving quality of care, maintaining professional competence, and managing conflicts of interest, Thank you. Boston, report the results of a national survey assessing physicians' commitment to those standards first proposed in the Charter on Professionalism. The authors sent a survey to about 3,500 providers in three primary care and three non-primary care specialties, asking if they agreed that the charter commitments were important, and asking, with the use of patient scenarios and direct questions about past actions, if provider behaviors tracked their commitments commitments. A weighted 58% of providers who were sent the survey responded, and the study had three main findings. First, most respondents agreed that the commitments were important, with the exception that about 25% did not agree that respondents admitted to inappropriately revealing confidential information about a patient, and only 25% said that they had actively looked for racial or sex disparities in their practices, clinics, or hospitals. Finally, there seemed to be differences in behaviors by specialty, and no one came out looking lily white. If anything, anesthesiologists and pediatricians came out on top, being more likely to report an impaired colleague, accept new uninsured patients, and participate in quality improvement programs in the case of anesthesiologists, and being more likely to undergo competency assessments, report serious medical errors, and see patients who were unable to pay for services in the case of pediatricians. Internists tended to provide responses in the top half of the response distributions, but they were less likely than other providers in other specialties to provide care without reimbursement in settings serving poor and underserved patients. There were also differences by practice setting and reimbursement mechanisms, but to be clear, all of these differences were differences in proportions of providers who said that 4 and seeing which overlap and which do not. Based on these findings, the authors conclude that the professional aspirations embodied in the Charter on Professionalism are relevant and meaningful to physicians, even though professional behaviors don't always match attitudes and appear to vary by norm. They acknowledge that their measures are far from perfect and that the association between self-reported and actual attitudes and behaviors may be limited. They don't acknowledge that there are health system and other forces that keep even the best intention providers from acting on these professional ideals. Thank you. You imply in the paper's introduction that promoting professionalism among physicians is one way to improve the quality and efficiency of health care. In what ways would you say professionalism improves health care quality, and in what ways would you say it improves efficiency? I think that if you look back at the recent history of the U.S. healthcare system, you'll see that we've tried very hard to improve the functioning of the healthcare system through using regulatory means and through promoting competition in markets. We've done neither of them perfectly, and neither strategy has significantly improved the cost of care or the quality of care. That leads us to look for alternative ways of making the system function better. One of the reasons why markets don't function well is that there are asymmetries of knowledge between patients and providers of care, a fundamental flaw. And one of the reasons regulation doesn't function well is that there are just too many decisions made by doctors and patients and healthcare institutions every day for regulation to effectively control them. It would work much better if those who are most informed about decisions made decisions that were consistent with their patients' interests and with the interests of the larger society.
And ultimately, I think professionalism is about, in a major way, self-regulation in the patient's and society's interest. One of the primary findings of the paper is that professional behaviors don't match attitudes. So how confident are you about that finding, given that all your behaviors were self-reported and that there are selection and desirability and maybe other biases that could have inflated responses to both parts of the survey? You raise a very important point, which you mentioned in our studies, the fact that there is this thing called social desirability bias, and that not just physicians, but most people answering surveys don't like to admit to behaving or holding attitudes that may be considered against what are the prevalent norms in one's field or social reference group. So clearly, we might say, for example, that the level that we found that physicians support attitudinal norms about professionalism are probably likely to be overestimates. We've found that behaviors probably run along the same lines as that people may overestimate engaging in behaviors that are seen as positive, but at the same time they're likely to underestimate engaging in behaviors that are seen as counter to the norms. Now with that said, we've used a number of survey techniques to control for these things in that we allowed people to respond anonymously, which research in the survey field has shown that reduces this bias to some extent. Now we can't totally eliminate it, but we certainly believe that it's reduced given the way in which our study was conducted. And let me ask you another methodologic question, which is that your response rate was something like 58%. What implication does that have for the generalizability of the findings to physicians? Well, 58% in terms of surveyed physicians is a very good response rate. And it's getting harder and harder all the time to achieve those response rates. With that said, there's also no magic number. The issue is not the response rate. The issue is the extent to which the people who respond differ in any systematic way from the folks who don't. And as long as your responding group is big enough, in theory, you don't have a problem. We're very confident in what we've achieved, partly because of the high response rate and because of the fact that we didn't see differences in response by specialty, for example, which suggests at least along one variable, our respondents were similar to the population from which they were drawn. We found that physicians differ significantly on many of the attitudes and behaviors regarding professionalism by their specialty, and clearly that's something that I think we need to explore in the future, that there are really kind of systematic and predictable ways in which, for example, primary care doctors differ from other specialists such as anesthesiologists and or cardiologists. And I think the next step in the survey has to kind of begin to address those specialty-specific differences and what impact that might have on really the concept of professionalism within a specialty and between specialties as well. Cardiologists don't see the owning of an imaging facility and referring patients to that imaging facility as problematic nearly as often as other physicians do. So that the principle of putting patients' interests ahead of your financial interests, they're not as sensitive to that norm as some other specialties might be. Another thing that is interesting, though, is that cardiologists are more likely to report that they see uninsured patients, for example, than general internists are. And that may be because they see fewer of them in general, or it may be because they, in general, earn more money and feel less pressured and have more time. These are all speculative conclusions. But I think it highlights the fact that physicians are not all alike, that their circumstances, their training, and maybe their self-selection into professional areas affect their conformance to professional norms. And specialists were significantly more likely to report that they feel prepared to evaluate new clinical information. They were more likely to report impaired and incompetent colleagues than were primary care docs. Especially anesthesiologists. And I think those reflect the culture of these specialties. And also perhaps the risk for impairment, right, in some specialties. Absolutely. The ABIM charter and the questions in the survey reflect our modern preoccupations, for example, with improving health care quality and reducing disparities and managing conflicts of interest and errors.
So that's embodied by classic images of a doctor sitting at a patient's bedside through the night waiting to make sure that they get better, or stories of physicians canceling important personal commitments to attend to emergencies. And I wonder if you thought you could speak to that, and if there's a role for that kind of behavior, and if that idea would be enough to address all English painting of a physician sitting at the side of a sick child. But I think that within the ABIM norms, there are questions about putting the interests of patients ahead of personal interests of physicians. On the behavioral side, they're not explicitly stated or as fully developed as one might like, but they definitely are there with respect to, for example, financial conflicts of interest and a willingness to see patients who are not insured and therefore can't pay, as well as a willingness to get involved in relationships with industries that might lead to biases in medical decision-making. But I would agree that we haven't explored that traditional notion of altruism and of putting patient interest ahead of professional interest as fully as we might. And we are, by the way, repeating this survey sometime next year, the end of next year. So we have an opportunity to expand on some of these dimensions. And I think this would be one that would be worth exploring. There's a parallel set of questions that have arisen very explicitly in some countries other than ours. Actually, a very interesting national experiment with that set of questions about professionalism that occurred as part of the SARS epidemic. Institute on Medicine as a profession is exploring the opportunity to do a similar survey in China. And in the pilot study that the Chinese developed based in part on our survey, they had a whole battery of questions about the willingness to care for SARS patients and what their respondents actually did during the SARS epidemic. So I think that is in some ways a paradigmatic instance of what you're talking about. The ultimate willingness to next step? What is the Institute on Medicine as a Profession or the American Board of Internal Medicine or we as individual providers do with this information? I think that one locus of activity should be the specialty society. I'd like to see other specialty societies besides the American College of Physicians and the American Board of Internal Medicine engage systematically in whatever assessment they think is appropriate for measuring the conformance of their members with professional norms and then to develop interventions that might improve that rate of conformance. So I think that's one locus of action. And I think our survey suggests that different specialty societies may emphasize different norms because their members will conform differently with different norms. The other thing where I think we collectively need to apply some effort is in public policies that can affect professionalism and organizational settings that can affect professionalism. Once you focus on professionalism as a kind of third force, aside from competition and regulation, in managing the healthcare system, it becomes reasonable to ask what mechanisms can be used to reinforce professionalism and almost to do an impact analysis when you're making policy or organizing your physician workforce, asking how will this affect professionalism. So it seems to us that large groups and prepaid group practice have certain advantages in terms of stimulating professionalism. Universities have certain advantages. And similarly, some other solo practice seems to have a lot of disadvantages. And we think that that's another reason to look at organizational setting and how you pay doctors may also have some impact. So I think that's especially society's public policy physician organization are all potential points of influence. Is the idea there that pay for performance wouldn't just be process measures such as HBA1C and clinical outcomes, but that physicians might be reimbursed for adherence to professional norms? I think we would need to do much better than we have in terms of measuring adherence to those norms. But yes, I could see that as one type of outcome if you can get consensus about which norms payers, employers, and physicians agree are core to appropriate functioning of the health system. This was really our first try, and we are going to be doing this survey again in about a year. We're going to be doing some additional work on the survey instruments, trying to refine it, make it a little more comprehensive, fix a few of the questions that didn't work so well.
And we should be in the field, I would guess, within the next year or so. But in addition, we also plan to do this study comparing doctors in the UK versus doctors in Scotland so that we'll be able to get both a U.S., non-U.S. comparison as well as a comparison looking at the differences in professionalism while taking into account the differences in the changes that have happened in England compared to Scotland and their health care reforms as well. And as I mentioned, we're talking about other international collaborations. We're having discussions with some collaborators in the Netherlands and in the EU and in China. I guess one of the questions that one could ask is whether professional norms and behaviors are attributes of Western culture uniformly, or whether they vary across nations and cultures within the West, and even across cultures West and East. So we're asking, I think, some more generic questions about the universality of professionalism as a concept. Dr. Campbell and Dr. Blumenthal, thanks so much for talking to me. You're very welcome. Listeners interested in thinking more about medical professionalism should consult the charter itself, an editorial accompanying this week's report entitled Medical Professionalism and the Parable of the Craft Guilds by Hal Sox, Annals Editor-in-Chief, and check out the website of the Institute for Medicine as a Profession, a nonprofit foundation and research institute affiliated with Columbia University that's focused on promoting professionalism in medicine. They're at www.imapny.org. Our other featured article this week is a college position paper on pay for performance that's being called an ethics manifesto by the college's Ethics, Professionalism, and Human Rights Committee. The paper raises the concern that pay-for-performance systems could create unacceptable conflicts of interest because rewards from favorable quality ratings could create provider incentives that conflict with what's important to and for our patients. Measuring hemoglobin A1c is a good example. Systems that reward good performance on such a highly specific measure could lead providers to give up on or refuse to accept new patients whose hemoglobin A1c is difficult to control. Such systems could lead providers to neglect other aspects of their patient's care, even if they don't deselect the patient from their practice, and to order tests or even give treatments that patients don't need to ensure that the measure meets the system's definition of quality so that the provider can maintain their income. The principles that emerge from these concerns are that pay for performance incentives should reward providers who care for more complicated and more vulnerable patients at least as much as they reward the care of less complicated patients. The paper makes the additional claim that measures of quality on which rewards are based need to incorporate domains of care quality that are important to patients and key to improving their health, such as provision of good counseling and good communication, continuity of care, maintaining patient confidentiality, and ensuring access. The authors make the case that ethical pay-for-performance systems need to develop broad and reproducible measures of these care elements and to recognize not just isolated care measures, but comprehensive care of the patient. Such systems need mechanisms to notify patients that incentives are in place, and they need to introduce administrative oversight of physicians, admittedly a potential burden to providers, the sole purpose of which would be to ensure that patients aren't fired from provider practices because the patients literally don't measure up, and to prevent providers from not accepting new patients who might make their quality measures worse. So these are great principles, and I'd vote for all of them in a minute if I were handed a ballot, but they also seem pretty abstract. So I went to the authors and asked for a little more detail about what they were trying to say and do. Lois Snyder is director of the Center for Ethics and Professionalism at the American College of Physicians, and Richard Neubauer is a member of the committee, a regent on the college's board of regents. He's chief of internal medicine at the Alaska Native Medical Center in Anchorage, Alaska, and he's a clinical assistant professor of medicine at the You bet. Thanks for having us. What does pay for performance look like in 2007 and 2008? Are there programs in place now in health systems or large practices or elsewhere that meet the committee's definitions of pay for performance? The committee used a broad definition of pay for performance, performance measurement tied to financial incentives to bring about clinician and systems change.
For example, the Agency for Healthcare Research and Quality found that more than half of HMOs use pay-for-performance programs. And the Commonwealth Fund found that more than half of state Medicaid programs have one or more pay-for-performance programs, with nearly 85% expected to have them within the next five years. And I would add that there's also the so-called pay-for-reporting program that was recently started by CMS and Medicare over the past year, and that may evolve into a pay-for-performance program in the future. And also, England has put in place a pay-for-performance program that involves a very large number of performance measures. So what does the committee see as the potential downsides to those programs? Let's say most internists are giving patients their flu shots and their Pneumovac shots, for example, or checking HbA1c levels in their patients with diabetes. Why is rewarding them for doing those things consistently and consistently well a problem? Okay, so the potential is that pay-for-performance programs that rely on a limited set of measures may have a number of unanticipated consequences. Most people agree that paying for higher quality can be valuable both economically and ethically. Reaching agreement on the details of how the program should work is a bit harder. The committee expressed in this paper their concern that medically appropriate care for individual patients should take precedence over other considerations and that incentives should encourage that. Potential pitfalls of pay-for-performance could include the selection of challenging patients, gaming the system to achieve good scores on a limited set of performance measures rather than focusing on the patient, and finally harm to the patient-physician relationship as another unintended consequence. The committee makes recommendations that sound like they might balance the potential adverse effects of pay-for-performance programs. What are those recommendations? Overall, the college wants to ensure that pay-for-performance programs help improve the quality of care in a manner that aligns with the goals of medical professionalism and also with the views of patients. Measures need to reflect what's important to patients, things like access and continuity of care with trusted physicians, effective communication, adequate time for office visits, coordination of care across settings and providers, the role of the family in care. There also needs to be transparency in these programs so that patients are aware of incentives, and there needs to be monitoring of programs to ensure that so-called challenging patients are not deselected or otherwise discriminated against. So in an ideal world, who do you think should be responsible for those actions, say notifying patients of incentives that might work against their interests or developing procedures to prevent patient deselection? That is not addressed specifically in this paper, but the college has said in the ACP Ethics Manual and other college policy that physicians should disclose potential conflicts of interest to patients and that purchasers and health plans should also disclose to patients any arrangements that may influence care. A particular problem in this specific area of pay for performance is that many physicians may not personally identify being paid for performance as a potential conflict of interest. A valuable outcome of addressing this issue prospectively could be that the public will better understand the incentives that may influence their care. So let's take that a little further. You acknowledge in the paper that notifying patients about incentives that work against their interests could increase the risk that patients won't trust their physician. But you say that secrecy and not being transparent has worse consequences. What consequences are you imagining? Well, of course, every payment system creates incentives and potential conflicts of interest. Patients should know the basis for health care recommendations they receive and whether contractual or other arrangements might influence clinician judgment to promote or limit treatment. We feel that trust is imperiled when potential conflicts of interest are not disclosed, leaving patients in the dark or leaving them to wonder if anything influenced their doctor's recommendations. The paper mentions developing objective measures of the values that you emphasize as a way of ensuring that a full range of values are represented in pay-for-performance programs. Let's take developing objective measures of continuity as a way of presumably preventing deselection of patients. Wouldn't that kind of measure penalize providers for non-adherent patients who disappear for long periods in much the same way that pay-for-performance programs might? Yeah, I think that's a very good observation. That's why these sorts of programs are very complicated.
But at the end of the day, the sorts of measures that are going to reflect the best care, especially for patients with multiple chronic problems or the elderly, are very important. What we don't want, as we say in the paper, is the outcome where the patient died, but the electrolytes were in balance. Who does the committee intend as the audience for the paper? Who do you hope is going to read it and will take notice? We hope that physicians, patients, policymakers, payers, that they all read the paper, since all of them need to recognize and support the importance of the patient-physician relationship and the ethical obligations of physicians to their patients. And why is this a manifesto rather than a position paper or a recommendation statement? Yeah, while this is a position paper of the college, we purposefully chose the word manifesto in the title. The definition of a manifesto is a public declaration of principles, policies, or intentions. And we specifically wanted to focus attention on the fact that pay-for-performance programs need to adhere to basic ethical and professional standards that place the whole patient in the forefront, not just a few aspects of their care. I wonder if part of the problem lies in the language that we use. That is, pay for performance sounds venal as if it puts financial incentives first ahead of caring for the patient. I wonder if we talk more consistently about value-based purchasing, if that idea would more easily accommodate a range of values, including those that you emphasize in this week's paper. Do you think there's a difference between pay-for-performance and value-based purchasing? And do you think this paper might look different if the committee were addressing value-based purchasing of health care instead of pay-for-performance? Well, I think that the problem with pay-for-performance is that if it's grafted onto a dysfunctional payment system that doesn't recognize the care of the whole patient and continuity of care as one aspect of that, that's where the problem lies. You know, if we look at value-based purchasing in a global fashion, I think what that really means is trying to figure out what we want in our health care system, and our current payment system doesn't really address that. Well, and I would just add that I think you're absolutely right about the language, pay for performance, that pay for and performance don't really recognize the importance of what's going on here, the patient-physician relationship and the delivery of health care. And, in fact, patients would be rather surprised probably by the term pay for performance when their expectation is that their physician is doing for them, you know, the right thing in the first place. Why would they be paid extra to do a test that they should be getting anyway? So I think you're absolutely right. The language is perhaps part of the problem. One other additional thought on that, it's always seemed to me that the best way to improve physician performance on any specific set of things would be to give point-of-care feedback. In other words, if you knew that you're only meeting expected goals and how often you're doing hemoglobin A1C measurements 50% of the time, you would correct that as a caring physician. The problem is that we don't have the tools to know that in our practices. I'm not sure that paying for performance on that is the best way of changing that behavior. Are there initiatives that you're aware of that would allow individual providers or practices to monitor their own performance in that way? Well, I think the patient-centered medical home concept that the ACP is promoting is on the right track to getting to that answer. Well, and electronic medical records would go a long way toward collecting that information. And that is part of the patient-centered medical home concept. Ms. Snyder and Dr. Neubauer, thanks so much for talking to me. Thank you. Thank you. That was Lois Snyder, Director of the Center for Ethics and Professionalism at the American College of Physicians, and Richard Neubauer, a committee member and a regent on the college's Board of Regents, talking about the position paper they co-authored this week entitled Pay for Performance Principles that Ensure the Promotion of Patient-Centered Care, an Ethics Manifesto.
From the JAMA Network, this is JAMA Author Interviews, conversations with authors exploring the latest clinical research, reviews, and opinions featured in JAMA. Hello and welcome to this author interview. This is Howard Bauchner, Editor-in-Chief of JAMA, and I'm here with David Cutler, a member of our editorial board. Good morning, David. Good morning. It's a pleasure to be with you. Before we start, I'd just like to mention some of David's credentials. He is currently the Otto Eckstein Professor of Applied Economics in the Department of Economics and was named a Harvard College professor in 2014. So David, before we discuss both your editorial and this fascinating article, why don't you tell our listeners how you've gotten involved in health economics and health policy? For about 25 years or so, I've been teaching and writing about health economics and health policy. My background is actually in the economics of the public sector, and the public sector cares an enormous amount about health care, so I've been involved from that perspective. I spent one year working in the Clinton administration on health care, and a couple of years being an advisor to the Obama presidential campaign in 2007 and 2008. And I'm currently a member of a commissioner on the Massachusetts Health Policy Commission, which is designed to help improve quality and lower costs of medical care in Massachusetts. Well, before we start discussing both your editorial and the paper, I just want to mention to our listeners, you've just been a wonderful colleague for me since I arrived at JAMA and you joined the editorial board. Your depth and knowledge about health policy and health economics is remarkable. And I just really want to thank you for all the advice and time you've given me. Well, thank you. And it's something that anytime we economists can help physicians to understand what's going on or convey our thinking or simply indicate where we're confused as well. I think that's always helpful for us to do. So we're going to discuss your editorial, which is entitled Life and Death in Norway and the United States. But this editorial really grows out of what has now been an area of research that John has published in, which began in 2016 with a colleague of yours, Raj Chetty's paper, which was entitled The Association Between Income and Life Expectancy in the United States, 2001-2014, which is a remarkable piece. Over 1.1 billion de-identified tax records used for that study. It's been viewed over 165,000 times on our website and has 327 citations and clearly attracted a great deal of attention. And then the paper that is a subject of your editorial came in. That's by Jonas King, and it's entitled Association of Household Income with Life Expectancy and Cost-Specific Mortality in Norway, 2005-2015. I think many people thought the U.S. was unique because of the disparities between rich and poor. And so the study from Norway, when it came in, raised eyebrows amongst our reviewers because some of the data are really quite similar, and that's what we'll discuss. But I thought it would be helpful for our listeners for me to just read from the abstract, the results section of that study to help frame the discussion. David, then we'll walk through some of your comments in the editorial, which are fascinating. So the results section of the paper we're going to discuss, just over 3 million persons contributed over 25 million person years, all from Norway, and 441,000 deaths in the study period. Mean age of the patients was 59.3 years. Life expectancy was highest for women with the top 1% income at 86.4 years, 8.4 years longer than women in the lowest 1%. So again, this differential between high and low income. Men with the lowest 1% income had the lowest life expectancy, 70.6 years, 13.8 years less than men with the top 1% income. So again, same thing with men. There's tremendous difference in life expectancy between high-income earners and low-income earners. From 2005 to 2015, the difference in life expectancy by income increased.
Over the same period, women in the top quartile gained 3.2 years, while life expectancy for women in the lowest income quartile was reduced by 0.4 years. For men, the top quartile gained 3.1 years, and the bottom gained only 0.9 years. David, these results are remarkable. I think they were surprising to the peer reviewers. They were surprising to the editors of JAMA, and so we're publishing the paper. What's your thoughts about it? The paper is a really wonderful paper. It tells us so much, obviously, about Norway, but also in comparison to the United States. So I think there are a couple of lessons that I draw. The first one is that even in a country as socially democratic, that is with as much public sector involvement in various aspects of life as Norway, universal health care, greater subsidies for education, all sorts of areas of social programs where the government spends more. Even in that kind of country, we still observe big differences in health between the better off and the less well off. So there's really no point in Norway or in the US where having additional income is not associated with increased longevity. And that's really something to make me stand up and really wonder about what's going on. How can it be that even in a system like Norway, there's still benefits to having more income throughout the distribution of income? And the differences are very big. They're big in the US, they're big in Norway as well. So these are not trivial matters at all. The second conclusion is about the comparison between Norway and the U.S. And I was particularly interested in the question, we know that people in Norway live longer than people in the U.S. How much of that occurs at different points in the distribution? That is, one might guess that lower and middle income people in Norway live longer than in the U.S. Do upper income Americans live longer than upper income Norwegians? That is, is it something where in order to provide more health care to low and middle income people, one has to provide an amount less to higher income people that harms their health? That's a set of questions that are really intriguing. What the paper shows extremely convincingly is that low and middle income Norwegians do indeed fare much, much better than Americans. Their life expectancy is much higher. In fact, to give you an example of that, the typical Norwegian at the 20th percentile of the income distribution, so someone who would be earning $20,000 if they were in the US, has a life expectancy as long as an American who's in the 60th percentile of the US distribution, so someone earning about $60,000 in the US. So enormously higher life expectancy at low and middle incomes in Norway. And then at the top of the income distribution, life expectancy seems to converge in Norway and the US. That is the very wealthiest Norwegians live about the same amount as the various wealthy Americans. They are not harmed. That is, there's nothing about universal health care or any kind of rationing that harms upper income Norwegians, but it requires less money to live in those upper incomes. So for example, Americans don't reach the level of longevity of high income Norwegians until somewhere around $165,000 of income. And then above that, it's roughly about the same as high-income Norwegians. So there's no group for which the U.S. does better. There are many, many groups for which Norway does better, even though within Norway, as within the U.S., there are huge differentials in health by income. Now, David, you were the senior author with Raj on the paper we published in JAMA in 2016 about the United States. And you've seen this paper in detail. You've written the accompanying editorial. So here they use life expectancy, obviously something everyone is concerned about. But people have said generally the provision of health care only contributes a small percent to people's life expectancy. Much more of it is around health habits, smoking, exercise, diet. What do you think these two studies tell us about our health care systems? What do they tell us about our social service systems?
Yeah, it's a great question. We know some things by looking not just at the national data, but by looking within the country. So in the Chetty et al. paper in 2016 that you referred to, we did an analysis of how various aspects of medical care in different areas are related to life expectancy in those areas. Somewhat interestingly, there was not a big relationship between various measures of quality of medical care and life expectancy overall. That may not be so surprising. As you said, within a cross-section, most of the differences across people are not due to medical care differences. What they are due to are adverse behavioral characteristics. So there's a very clear relationship between areas where people smoke more, areas where people are more obese, areas where inappropriate use of prescription medications, particularly opioid medications, is high, and mortality at all ages. And so those are the strongest things that come out of that cross-section work. Some of the medical care components matter little, but nowhere near as strongly as do these behavioral risk factors. What do you think that observation means for the current debate about our healthcare system, the $3.5 trillion increase above gross domestic product or inflation? Ultimately, we'll consume 20% of the gross domestic product. Let's avoid how we pay for it in the U.S. That's a slight aside. But what do you think it means for the delivery of health care? Should the focus change? I think the focus does need to change some. We all know that the U.S. is poor at prevention. Some areas are much better at prevention than other areas are. So for example, if you look even in the lowest 25% of the population, the bottom quartile of the population of income, you see areas where rates of smoking are very high and even nearby areas where rates of smoking are quite low. So it's not just a phenomenon of parts of rich Southern California or Northern California and parts of the poorer Southeast. But even when you look within regions, within incomes, look at people who are earning the same amount of money with very similar lifestyles, what you see are behavioral risk factors that are very different. So there's clearly something that one can do for better and worse that affects people's risk of death and of serious disease. We also see that in the opioid epidemic, which is much more medically related in the sense that a lot of it goes through prescription medications, where in some areas it's gotten much worse than in other areas. And that, again, leads one to ask, what is it that areas can do that would help to reduce some of these adverse impacts? So I think on the prevention side, it gives us some leverage to look at, some leverage to try and ask questions about where can we do better and worse. Of course, that's not where the money in medical care is. The money in medical care is in acute treatments, people with complications, people with very expensive courses of illness. We know that that varies enormously across the country. And some of what these results show is that even at the aggregate population level, they don't look like they're related to improved health. And so it ought to keep us firm in the idea of trying to address those costs and not spend so many resources on them to the exclusion of other parts of medical care. The story gets even more complex, I think, for many people if you said, wow, social services, probably a lot better in Norway than in the U.S. in the sense of postnatal care, family leave, other ways in which somehow people will feel that the social service component of Norway is better than the U.S. And let's assume it is. That's what you had mentioned at the beginning. But they're seeing disparities that are similar to the U.S. even in a system in which there's far more social support. So how does that add to the complexity about trying to reduce differences in life expectancy? That fact adds to the complexity an enormous amount. So if what's happening in Norway is representative of the rest of the rich world, which I'm hopeful we'll have more studies that will let us know that, that really suggests that there is something even beyond the traditional welfare state approach that one would need to do to address some of these disparities.
So it would say that they would need to be doing even more than that. percentile of the income distribution to the hundredth percentile of the income distribution in Norway is not as big a gap in life expectancy as from the 20th percentile of the income distribution in the US to the hundredth percent of the income distribution in the US. Below about the 20th, maybe the 10th percentile, life expectancy really drops off a lot in Norway as it does in the US. And so what's happening at the very, very bottom, I think, is particularly concerning in a country like Norway because the gradients in the rest of the population are a little bit smaller. Is there something magical about income, David, that we just don't understand or is it so related to health habits, education? But is there something else about income that we just struggle in measuring? It's a great issue. Income is a proxy for lots of things. It's obviously directly related to what one can afford. And there are certain things that one can afford, better food, maybe safer housing conditions, maybe less worry, less stress over being able to afford things. So there's a lot that income itself can buy that's likely important. But I think it's also a marker of things. To the extent that income is associated with, on average, more years of education, we know that years of education are associated with knowledge of risk factors, with having the space in life to address health concerns and to engage in preventive behaviors. It's associated with who one lives near, what kinds of things are happening in one's local environment, what kinds of things are happening in schools, where one's children go. So it's a very rich marker for people. And I think we haven't yet figured out all the different ways in which income is associated with improved health. As the population ages and life expectancy for many countries for women is into the high 80s, approaching 90 years. I think in Japan it is close to 90 years for women. The discussion is going to be enriched by quality of life. It's not just going to be life expectancy. So I've mentioned on podcasts before my wonderful, wonderful father-in-law passed away a year ago. He was 94 and he lived and was healthy for virtually his entire life until two weeks before he passed away. And I mentioned to someone, you know, do you think you would ever take that contract? These were people who were in their late 60s, early 70s that I was discussing it with and they just started laughing. And they said, I said, why are you laughing? They go, take the contract, live to 94, be healthy for the next 20 years, and then just die suddenly. I'll sign on the dotted line now, which it was just striking to me. I don't know why I was even thinking about that. So as we add the complexity about quality of life, are you aware of much work? I mean, we publish periodically in the area about where people spend the last few months of their life, dying at home, dying in the hospital, how many people are being cared for. I've never felt that the data about Medicare spending so much money in the last six months of life is that relevant because that's when people get sick. So that's when I'd expect Medicare to spend those dollars. Have you seen comparisons about end of life and quality of life? So these articles, the Chetty piece with you and the Norway piece have focused on life expectancy. But have you seen any information about quality of life? Across countries, I have not. Within the U.S., there's been some look at what's happened to people as we've aged. That is, have the additional years been healthy years, or have they been years of increased impairment? One of the happiest findings from that literature is that the years seem to be additional healthy years and not years of impairment. And I think the way to understand that is, as the paper on Norway shows and as other papers in the US show, the biggest reason why mortality has declined is because cardiovascular disease death rates are falling. And it's not that people are living but are now severely impaired by cardiovascular disease.
This is Derek Paul, and welcome to the Anti-Racism in Medicine series of the Clinical Problem Solvers podcast, where, as always, our goal is to equip our listeners at all levels of training with the consciousness and the tools to practice anti-racism in their health professions careers. Today's episode is titled Dismantling Race-Based Medicine, Part One, Historical and Ethical Perspectives. And I am just beyond excited to be co-hosting this episode with two of my colleagues and anti-racism in medicine team members of people I admire a lot, learn a tremendous amount from every day, LaShira Lash-Nolan and Rohan Kazanchi. So I'll hand it over to Lash and Rohan to introduce themselves and today's guest, who many of you will know already, a critical race theory scholar, Professor Edwin Lindo. Amazing. Derek, it's so great to be here with you. Rohan, always a pleasure. Just to introduce myself, my name is LaShira Nolan. Most folks know me as Lash, and I'm an LA native now at Harvard Medical School, my second year where I'm serving as our student council president. I'm very passionate about this work. That's why I'm so blessed and excited to be a part of this team. I write about these issues a lot, speak on them often on panels and doing different presentations. And I'm just stoked for our conversation. Yeah, totally echo everything Lash said. I'm really excited to be here. Even more excited that Professor Lindo is joining us today. My name is Rohan Kazanchi. I'm currently an MD MPH student, getting my MD down at University of Nebraska Medical Center in Omaha, and doing my MPH this year at the University of Minnesota School of Public Health in Minneapolis. And completely echo what Lash said, I think we're all here because we care about these issues. These are our passions. These are our professional interests and, you know, the ways that we spend our personal lives outside of the classroom too. So I want to introduce the series that we're starting with today's episode. This is episode number one in a three-part series on dismantling race-based medicine. And our goal for this series is to answer fundamental questions. What is and isn't race? How have the ways our medical community defines race changed over time? And most importantly, how should we think about these issues in the context of ongoing discourse about racism in medicine and beyond? So today we're going to take a deep dive into the history of how racial categories have been defined in America. We'll talk about why it's important to distinguish between concepts like race, ethnicity, ancestry, and genetics. And we'll think about how the medical field's dark history of scientific racism plays into the broader struggle for racial and health equity. And I am so excited to introduce our esteemed guest, Professor Lindo. Edwin Lindo, JD, is a critical race theory scholar and educator who is an acting assistant professor in the Department of Family Medicine at the University of Washington School of Medicine, Assistant Dean for Social and Health Justice Office of Healthcare. Edwin teaches, presents, and writes on issues of racism within medicine and society. He's also the creator of the Praxis podcast, which I'm so lucky to have been a guest on. It's a vibe, y'all. Please check it out. And you can reach Edwin on Twitter via at Edwin Lindo. Edwin, thank you for being here with us. I get to, I had the honor of asking you our first question. I'm going to start off with a question that I think seems sort of easy, but it actually is more difficult. And that is, what is race? It's something that we are all, it's part of our lives from the moment we're born. Honestly, before the moment we're born is playing into our lives. But sometimes folks are a little later in life before they start thinking about it critically. So, you know, if you're new to this conversation, someone's having, you know, one of your students and they ask you, what is race? How do you think about it? Yeah.
In many instances, it's like doing quantum physics because at its core, it doesn't actually make sense. And what I mean by that is we have something. So I'll get into the definition. You have folks like Dorothy Roberts and other critical race theory scholars that have guided us towards an enlightening definition of race being a socially, politically constructed taxonomy. And I use this definition a lot. And I go on to say, and it's based on perceived skin color and oftentimes culture with no scientific or biological determinacy of the physiology used for the purposes of allocating and or extracting resources from melanated black people when they were stolen and brought to this continent. If that's the beginning, then we really have to wrestle with that beginning, with the impetus of it. Now, we are in 2020 and folks say, well, and people always respond, well, great, Edwin, we should just get rid of the concept of race and we will be a unified human race and it's like wouldn't that be nice but that's not the world we live in race from the beginning was something that was created and I know we're going to talk more about that and it was created by we'll name very clearly. But we have to sit with the reality that medicine has grafted the social political endeavor of race to what is believed to be a physiological determinant, a biological identity. And the truth is that's just not accurate. And we know it's not accurate, and we'll talk more about that. But it's now our job to start ungrafting, removing that graft and saying, actually, there's a huge difference. One is the social construction. And social meaning is not just the white scientists that created the concept of race, but it's also us engaging with each other, right? That's why I don't think we need to get rid of race because it helps us identify with each other, understand what solidarity looks like, understand different struggles, understand culture, food, ceremonies, traditions, religious beliefs. And that's beautiful. We can embrace those differences and race helps us identify those. What it doesn't help with is identify how we are biologically different, yet people can't disassociate the two. And I think it's our job to say, it's okay that someone identifies as black, someone else identifies as brown, someone identifies as Asian. That's beautiful. It's unhelpful when folks start trying to identify how those different categories are physiologically different from each other. So long answer, but that's what and how I see race. Yeah, thank you for that. And that whole statement was a word. And now I'm just wondering if you could talk a little bit more about the history behind that. And we often hear people say that race is a social construct. And I'm wondering if you can also touch a bit more about what do we mean when we say that? And talking a little bit about how history and where we're at now kind of comes together to create this moment. Yeah. I mean, race is only a social political construct. Now that delves into a deeper question that I don't know as a society we're equipped yet to wrestle with, but there are some people that say, well, if it's a socially politically, a political construct that was created by white folks, then why are we still holding onto it? Why do we still identify with the colors that Johann Blumenbach and Carl Linnaeus created? That's a different conversation. I think it's a needed one. It's a different conversation because I'm going to start from the assumption that race is beneficial in the social endeavor and social project. Again, like I mentioned, to identify and engage with each other. But when we get to the question of what it means, it means that the project, I keep calling it a project because it isn't something that finishes, right? Race is changing, at least the way people view it. Mixed race, multiple races, single race folks. What does the identity mean? I think it depends on the consciousness that we're bringing forth to this conversation. But we are the ones that give value to the concept.
And the reason I say in my definition that it was used for the purpose of allocating resources is that you have Johann Blumenbach, Carl Linnaeus in 1767 writing the book Systeme Naturae, and he literally created a taxonomy. There's an apex of the taxonomy and there's folks who are at the bottom of it. And if you look at that taxonomy, you see how resources throughout history in this country have been allocated. Black and Native folks, not getting many of them. European and Asian folks, Asian folks getting slightly more. White folks perceived as the most intelligent. You have Carl Linnaeus that says that they are intelligent, they are witty, or sorry, they are smart, they are imaginative, and they are governed by laws. That was the categories, the definitions associated with the color to perpetuate this racial taxonomy. And it's not an accident. What I mean by that is there was a vested interest in whiteness as a property right to ensure that certain racial categories were at the apex of this taxonomy and certain groups were at the bottom of it. What we need to sit with is how do we ensure that our social relationships around race are not the conversations that we have in the biological realm because they're not the same. And so you ask about the history. I am a believer that medicine is the reason we see the racism that we witness today. And there's a lot of physicians who are listening, a lot of clinicians that hear me when I give my talks and they say, Edwin, how dare you critique medicine? You're not even an MD. And I say, you don't have to be an MD to understand how racism works. And in observing it, what I've seen is that from the beginning, from Portuguese, the Portuguese coming to West Africa, using the term Negro, stealing and forcibly taking slaves into chattel slavery. You have the British, you have the Dutch, a number of other European countries that further endeavored in this project of slavery and chattel slavery. And I always ask the question, like, why? Why did this happen? And when you land in the United States in the 1619 project, or sorry, not project, but in 1619, when the first slaves were sold in the auction block guess what you had doctors that were at that auction that were hired by slave owners and they were effectively they were the the physical checkup for those slaves because they were they were paid to ask a. Are these people equipped to do the manual labor that we're expecting them to do? And to know that medicine played an integral role there and then pulled it even further and said, not only is our job to ensure that the slaves are fit, it is a conditioning of medicine. And people say, wait a minute, it was political, it was legal, it was economic. And I say, yeah, but all those things couldn't have existed until science and medicine let the world know that we were physiologically different people, right? Segregation doesn't exist unless white people think that black people are physiologically different, that they are inferior. And where do you think they got that idea from? They got it from science. They got it from doctors. And we have the evidence to prove it. Wow, Edwin, I appreciate this conversation so much. And what I'm sort of hearing you say is that human beings, we kind of, we develop race as a way to, as part of an important mechanism to subjugate people. And that medicine plays a role in sort of providing the various rationales for that, that are sort of now proved not to be the case, but about these ideas of biological inferiority, superiority in this way and that way. And that is, you know, a piece of how, an important piece of how you understand what it is that we're talking about here in the first place. I'm going to, if I may, quickly, I want to articulate some specificity. So I wouldn't say humans. So I focus my work in the United States. In the United States, it's white folks.
And I think that's important because there's many white folks say, oh, well, slavery existed across the globe. Yeah, but it was never actually based on the false articulation of physiological difference based on color. It was either you lost the war, it was religious persecution, but it wasn't race. And something about the United States, they said, oh, this is the thing. This is where we can gain and manage and hold the control of marginalization and oppression. Absolutely. And I want to touch on one of the points that you've made here, which is that, you know, folks say to you, you know, if race is not biological and it's not based in physiology, then it doesn't exist. So shouldn't we sort of act like it doesn't exist? Shouldn't we sort of perform colorblindness? And the problem with that, because there are all of these, because the social construct is extremely real and the implications are extremely real. The laws are extremely real. The genocides are extremely real. The enslavement is extremely real. The segregation is extremely real. And colorblindness also erases all of that. So, not just, you know, not just will we lose some of that richness that you were talking about, but it also does harm when we're colorblind to race. Hugely. I mean, absolutely. It's a huge impact on it to the extent that colorblindness, and this is actually at the heart of critical race theory, it is to critique racial liberalism that we see no color, things are fair. If you work hard enough, you'll make it. Stop harping on race as your oppressive variable that you can't control. And I push back and I say, yeah, if we actually treated everyone equal at this moment in time, and it's exactly what you're saying, it's an erasure of all the inequality and inequity that existed before this moment. And it's the same thing we're seeing with the allocation of scarce resources during the pandemic, right? We ask questions, who gets the ventilator? Who doesn't? It's someone who has a survivability that is better than the other person. Well, if you're coming with a pre-existing respiratory disease, your survivability is lower, but no one's considering that you have a pre-existing respiratory disease because you live on the South side of Chicago with the highest rates of asthma and you come into the hospital predisposed to this because of racial segregation, redlining, and systemic racism. So unless we consider that, then we're not actually treating everyone equal. We're just furthering the disproportionate impact that occurred in the past, blinding ourselves and saying, well, my job, and doctors do this all the time. My job is to treat everyone the same, Edwin. Why would you ask me to treat them differently? I said, because you already had. Professor Kimberly Crenshaw tells us when there is a disproportionate impact that harms people, there needs to be a disproportionate impact in the solution, which means we will be treating people differently, not because of the color of their skin, thinking there's a physiological difference, but because of how this country treats people who are of a darker hue. When we hold that, then it's, yeah, some groups do deserve more. And it's not deserve more so that they get extra. It's literally to just bring them to the starting line. Yeah. Edwin, I think this is really, really powerful. And I hope we can dive a little bit more into how to rectify, how to repair, how to reconcile with the harms that we've created, you know, in American society because of how we've stratified folks by these phenotypes, you know, that were rooted in medicine's perception of biology, but are just phenotypes, are our perceptions. So I kind of want to dive into that a little bit because I think you started there. And I think it's important for our learners and listeners who are thinking as, you know, future physicians, as future providers of healthcare, but maybe don't know the history of the role medicine played. How has medicine played a key role in defining this social and political characteristic of race throughout history?
Yeah, and it's, it runs deep. Again, going back to the early 18th century, going even before that, and I won't dig too far into it, but science and religion in the early 18th century and 17th century were like cousins. You couldn't read a scientific journal that didn't mention God. And so, religion was used in the medical sphere, in the scientific sphere to publish, to say, not only is this scientifically true, but the deity God has told us that these people should be subjugated to slavery, subjugated to differential treatment. But it started, you know, you can, if we think of chattel slavery era, you have Samuel Cartwright that created the spirometer who said, I'm going to measure lung capacity and I'm going to measure lung capacity of the slaves that he owned who have worked for weeks and days in the scorching sun and compared their lung capacity to his and said, well, there's something wrong with these folks. Their lung capacity doesn't seem to be equal to mine. Yeah, let me work someone nearly to death and then ask to get their lung capacity measurement and compare it to mine when I'm just watching them. And then it becomes this false idea that there is innate physiological difference. And I mentioned this point because guess what? That data that he published researching his slaves was then used by life insurance companies to not give life insurance to black folks post-slavery and reconstruction saying, well, you are more likely to die because of poor lung strength and capacity. And therefore we're not going to give you life insurance. We then fast forward today and Lindy Baum at Penn has written extensively about this, Professor Lind Wendy Baum, about how even to this day, we have the spirometer machines that use race as a factor in calculating respiratory function. That's wild. Let's back up a little bit more before Samuel Cartwright. You mentioned Samuel Morton. You mentioned Samuel Cartwright or Samuel Morton. And there's even Josiah Knott. But these were folks who were polygenicists, physicians who studied at Penn and Harvard and were professors who believed that people of different races were of a different origin. And that's why they, in their mind, were able to rationalize that one group was inferior versus another. And you had evolution, a concept that existed that they didn't agree with for much of the time. And Darwin was like, no, you got to believe this because the evidence shows it. And their response is, well, I don't know. I don't know if your evolutionary theory is true. But what do we know about species of a different kind? They're unable to do what? They are unable to procreate. You can't make anything if you are of a different species. Well, we see the history. You had white slave owners that were having children by women on the plantation, black women. That completely destroyed this concept. But again, they knew that. They knew it. So they were willfully making up these things to maintain the power that they had. They finally accepted Darwin and evolutionary theory and said, yes, we'll accept it. However, Europeans are still evolutionarily wise, leaps and bounds beyond black folks and native folks. They even say in published pieces that black folks and native folks are just one step above the chimpanzee in the evolutionary chain and that Europeans are at least four evolutionary chains away. And therefore, we should hold the construct and the systems that we currently have. Again, a rationalization. We fast forward into the early 1900s and you had eugenicists, you had social anthropologists that were pathologizing black folks at the ends of Reconstruction, suggesting that black people had a predisposition to crime, to violent crime. In the 1920s and 30s, when this was at the forefront, you had Nazi Germany bringing over researchers to study how we, the United States, were doing such a good job of subjugating black people that they used those tactics to do the same things to Jewish people in Germany. That's how terrible this country has been, has continued to be. And yet we don't feel, we have to still make the argument for it.
And the response, well, Edwin, what about heart disease? Or what about this comorbidity? It has higher rates in black people. Yes, it has higher rates in black people because we've subjugated black people through the arms of racism and strangled a community intentionally. And then you want to talk about gaslighting and then tell them there's something wrong about you that we can't figure out. No, 100 percent. I think that everything you're talking about is the experience that a lot of us have when we're sitting in lectures and we talk about all of these disparities, whether that's hypertension, diabetes, and they give us this graph. And clearly we see Latinx, Black, and Indigenous folks who are dying disproportionately from these diseases that are preventable, but there's no context given. And it kind of makes you feel like this is inherently wrong with this group. And I think a lot of our colleagues who don't get this education, they leave thinking exactly that. So, I mean, you got into this a little bit, but I'm wondering, you know, what are some ways that this is an example of this willful knowledge that these things are happening, but then choosing to ignore it in order to really maintain power? Yeah, that's the interesting thing about the scientific method in science is that it believes that it is apolitical. But the history and the data shows us that there is nothing apolitical about medicine. It has been political since day one for the purposes of holding power, maintaining power, excluding people from the spaces of power. And I do think when you talk about science, it's the same in law. People say, oh, Edwin, I'm not racist. This is just what the law tells us we have to do. The same in science. I went through the scientific method, Edwin, and I can't be racist because I use the subjective truth. I said, but the scientific method is only as good as the variables that you input into it. And if you aren't being critical of what you're imagining, the questions you're asking, what you're researching, who you're researching, how you're doing that research, then the biases, the history, the legacies, they seep in whether you wanted them to or not. And you're speaking of your colleagues or classmates, there's always someone who's like, well, I'll play the devil's advocate here. What about hypertension? They tell us that black people's response to channel blockers versus ACE inhibitors is different. And I'm like, yeah, well, what about the data that tells us if you use a dual therapy and you add a diuretic, that that difference disappears. So clearly it's not race. It's something else that we don't know, but we don't actually want to dig into it. There is something innate in this country that it wants to hold the fundamental physiological difference. And some people say, well, it's because our minds were tribal and we want to hold differences. And that's just, it's just tribalism, Edwin. And I'm like, no, it's not. There's people around the world throughout history that have lived without subjugating other people. That exists. It's a thing. What we're talking about is the property of whiteness. And that's the second time I've used that term. So I want to explain it to folks. There's an amazing critical race theory scholar named Professor Cheryl Harris who wrote the piece called Whiteness as Property. And she outlines and explains that a property right in legal terms is an expectation. That's all it is. It's an expectation to be able to do something. So with your land, if you own land, you have the expectation to put a fence up. You have expectation to own the air rights, the soil rights, to move soil, to sell part of the land, to put a sign up, you have an expectation to do a whole lot. Now, if we place that and transpose it onto whiteness, white folks have an expectation to walk into a bank and get a loan. They have expectation to walk through a store, a corner store and not get followed.
They have an expectation that they can go into any neighborhood they want to. But if they have that property right, that means it's at the exclusion of someone else's right. Because when I walk into a store, I keep my hands in my pocket. When I see blue and red lights, I make sure I slow down or I try to not bring attention to myself. If I am stopped, I've been explained by my dad that you keep your hands on the wheels, you put your hands on the side of the door and roll the window down. Why is this? Because I don't have the property right that white folks expect. How do we deconstruct that white folks shouldn't have a property right? that that property right is the privilege of whiteness. And in that privilege is actually at the exclusion, at the denigration and the dehumanizing of other communities, even when they say they don't want to be doing that. But it has to start from the beginning of, I don't actually think you are physiologically different than me. Because if we can't get over that hump, then we don't actually get to solidarity. Solidarity exists because you think that my liberation is attached to yours. But you can't think that if you believe that we are of a different kind. And so I struggle when people are like, oh, that's the black struggle. That's the Latino struggle. That's the native struggle. I feel that conversation, unfortunately, adheres to the construct that these are different people. Yes, there's different experiences. There's different maneuvering through the world. But solidarity means that their freedom, their justice is attached to mine. And that's why I will fight. I will fight incredibly hard for it. Edwin. Oh, man, we should have had you on the podcast, you know, right away, because I think this is this is a absolutely fundamental conversation that we're having. And the point that you're making about needing to deconstruct these false beliefs about being physiologically and biologically different as sort of being foundational to so much of the rest of what happens. And I think what I'm understanding as we're having this conversation is that actually the racism in medicine isn't just a piece of the conversation. It is in some ways at the base of the conversation and what we're doing is extremely important for that reason. I also just have to appreciate you for talking too about your own personal experience, walking through this world, walking through this society, walking through the US know, the US, because I think, sometimes, even as we get deep into these conversations, whether it's on the data side, or it's more on, you know, we're the philosophical side, sometimes it's like, I know these things to be true, because I've lived them in my own body. And I've, and you're here, you're out. And sometimes you're out here trying to explain this to folks or convince them with data. When I know this to be true through my own lived experience, not just the ways that I may not have those property rights, but also I've seen the way this social construct plays out in different people relate to me in different ways in different spaces. And from being myself, I know that I am, you know, just as much as, just as worth just from being me. So I just appreciate you bringing that in. And I also wanted to make a pitch for a book. I think there are so many, we've already mentioned many great scholars. Isabel Wilkerson has a new book cast and she references and borrows from a lot of other folks who are scholars in the area, but I really like it because it's a very personal book that talks about her walking through the world. And she talks about some of these things that you've mentioned already about how preventing interracial relationships and marriages were so key to keeping racial caste systems. She talks about some of the things you mentioned in terms of the rise of the Third Reich in Nazi Germany, borrowing from some things that are already happening in the U.S. because they were so effective at disenfranchising and subjugating people.
And I, I like edge cases because they sometimes help me understand what it is that, that, that we're saying. And one of the things that she says that I think was really interesting point to me and was about the way that sometimes the success of one person can actually be important to reinforcing the fact that racism doesn't exist, right? Like look at that person, whether it's, you know, Barack Obama is probably the biggest example. There's no racism. And I think that happens too in medicine a lot, both within the conversations on racism in medical education and the conversations that we have around racial disparities. And there's also, she referenced some interesting data about how racism plays out when you switch your social context and maybe you're a person who's now living and working in a predominantly white institution or, you know, sort of environment and how racism works on and weathers the body in that way. So I just want to make it, you know, I think that's a, these are important things for us to think about. And some people have the privilege of not thinking about them. And so if you're there, I would just encourage folks to sit down and do the work and put some time into those sources that we're going to share. We're going to share so much of your work after this and also some of the other scholars that are doing some of this important thinking. Yeah, I want to highlight two points because I have this conversation and oftentimes it's white folks, many non-black folks, many Latino folks like myself who are struggling. I have colleagues that are Latino that they're like, Edwin, I get you, but I don't really get it. And so there's two things. One is to get clarity on how unuseful or useless race is in the biological endeavor of studying the physiology, is that race changes the moment I change any nation-state's boundaries. That is, if I go to South Africa, my race is different than here in the United States. If I go to the Middle East to a country, my race is different. If I go to South America, my race is different. I go from mestizo to colored to Latino to Central American to indigenous. If that is the construct of race, how is it that we're using it in science? Because even us as society don't agree that there's a universal language of race yet we're going to take data points to say that someone's kidney responds differently to a white person's kidney and use race as the holding variable now some people say well then i'll stop using race in my data no that's not what i'm saying what i'm saying is we need to be precise in the way that we use race. That is, if we're going to study race, we should understand how race has affected health by the concept of racism causing that impact. So we should be studying racism as the risk factor that is harming our communities. That's point number one. Number two is, I was hearing you, Derek, and I still remember the conversations of someone's like, well, it improved to me that what you're saying is true. And I say for a couple of years now, I've decided to say, you know what? How about you prove to me that I'm biologically different? I need you to go do the research. I want you to go dig into those papers because you're really just responding to what you heard in class. And that was like two and a half slides. And more often than not, those slides are based on up-to-date. And if you go to up-to-date and you look at those peer-reviewed journals and you dig into it, these folks have no idea what they're talking about when it comes to race. Yet we're taking racial understandings, racial understandings of humanity based on scientists that have never had to study race. And they think they know what it is they're talking about. But I asked them, how many of you have defined race in your publications? 98% of them say, no, I never have.
So we need to be intensely clear in what it is that we're talking about. And so I think if someone were to say, well, what would you encourage folks to do? I say, let's assume the position that science when it comes to race has been wrong. And let's start building from there. Yeah, Edwin, I think that's so excellent. And one other observation I'd make, you're talking about how across space, geographic space, race is defined differently. I think across time, race is defined differently too. And one of the examples that I often talk about is our own U.S. census has changed our racial categories repeatedly throughout history. Every 10 years, it seems like we get a new set of boxes to put people in. And I think that's so important because it shows that race is dynamic, right? Where you are in the world, where you are in U.S. history determines maybe what your race is. And, you know, speaks again to this point that racism, the experiences that people have because of their race are the risk factors, not race itself. And the burden of proof falling on us to prove this in spite of little evidence that proves the contrary. I absolutely think your point here is very strong, that as scientists and as clinicians, we need to be clear about what exactly we're talking about when we're defining these problems. Yeah. podcast team all the time is this starts in med ed. This starts with medical education, how we teach the future physicians of our country. So I want to hit one more teaching point maybe and have you kind of break something down for us. I think a lot of folks can understand this notion that structural racism and structural determinants of health that kind of lie upstream of the way social determinants are distributed, right? These risk factors that we understand for chronic diseases, that's maybe more believable for folks, right? Policy shapes the way resources that are distributed across modern society. As a result, certain groups are disadvantaged, others are advantaged. But another myth that I think is harder to debunk for some folks is, oh, what about sickle cell? What about cystic fibrosis? What about diseases that seem to be linked to race because of ancestry or because of genetics? So the question that I would ask you to maybe answer for our listeners is, is race a good proxy for ancestry? Is race a good proxy for genetics? And can we kind of conclude based on the fact that the prevalence of sickle cell is greater in black populations or the prevalence of cystic fibrosis is greater in white populations that race is linked to these diseases? That's a great question. I'll answer it simply and then I'll answer it in a more complex way. No, they're not linked. The example I always give is if we put white folks in the exact same situation that they put black folks in, they would have all the comorbidities that we're witnessing in the research. Because it's about the conditions that existed and that were created to maintain power. If it was white folks that lived in most of the continent, the African continent, heading into South India and Eastern Europe, yet they would be the ones that have the highest rates of sickle cell trait, but they're not. And the reason there's a high concentration of black folks in the United States is because we stole them. We stole people from their land and brought them here. And we concentrated the populations in this country. But there's white Eastern Europeans that have high rates of sickle cell trait. I know white individuals that I've taught who came to me and said, Edwin, I went to my primary doc when I was a child. My parents were like, there's something wrong. And we think our child has sickle cell. And the doc was like, no, he doesn't. He's white and wouldn't do the test. And so they had to find another provider. This innate belief of physiological difference is killing people, black and white and everyone in between because of the lack of precision. You're asking the question about genetics and ancestry. I think if we're going to be precise in medicine, we have to focus on geography. Where are people from?
It explains the environment. It explains nutrition. It explains the weather. It explains the evolutionary process. Regardless of the race, if we're actually trying to find out what the genetic differences are. But when I start seeing journals that say, oh, black people have a greater concentration of this allele and therefore their kidney is going to respond differently. And I'm like, that doesn't even sound right. Because if it's true, then that means all black people should have that allele. If race is the variable, but if only some black people have the allele, then it's not because of race. It's something else. What is the thing that those people with the same alleles have in common? Our eyes see race. Oh, well, they seem to be black. But there must be something. Maybe they're from a similar geographic region. Maybe it was the food that was eaten. Maybe it was the genetic response like sickle cell trait, which was a genetic evolution to malaria. The malaria belt across that region I just mentioned is the reason those folks in those regions have sickle cell trait. Put the malaria belt in any other part of the world, you would see the same response. So if we detach ourselves, and I always ask the question, and I ask particularly our white colleagues, why are you so attached to try to prove that I have a different bodily function than you do? What does that bring you? Does that add any value to this relationship? Does it add value to science? Because I haven't seen the value. Because more often than not, it's a inclination to get to the point of, well, there seems to be difference in outcomes. And we have many of our colleagues, and I forgot her name. If you know it, please shout it out. But where they call it the racial disparity complex, industrial complex, where, oh, let's study all the racial disparities that exist among comorbidities. Yeah, we know they're there. I want to know the question of how do we prevent them? How do we deconstruct racism causing these disparities? But then asking, going back to asking colleagues, how does this benefit the relationship of you trying to prove that I'm physically or physiologically different than you are? And it's hard for a good response to come. Sometimes it's, well, Edwin, I'm trying to do this to better science so we can provide better healthcare to these communities. I said, if that was true, then you're not listening to the community because the community is saying, we need jobs, housing, healthcare, and the police to stop killing us. Oh, I can't control that, Edwin. That's political. Oh, that's interesting, but you want to control genetics and you want to control other variables that are, you want to control race, which is almost humanly impossible to do because it doesn't it's not something you can so going back to the genetic part you know people will publish these disparity papers oh black people indigenous people latinx folks have higher rates of x and then towards the end of the discussion it's but we't know why, so we're going to assume that it's genetic. And I'm like, is there a class that folks take that they say, if you don't know the answer, let's just assume genetics? Because I'm going to say, I'm going to disabuse us of that class and tell you, if you don't know the answer, we're going to assume racism. Because I think if we start from there, then we can actually get to an interesting place. And I know it works because I had my research colleagues in the Department of Family Medicine when I gave a talk and I said that same thing. And the vice chair came up to me and was like, Edwin, so you're telling me that if it's not genetic and it's not physiological, it's something else. And I'm like, yeah. And he's like, and we don't know what that thing is yet. And I said, I mean, we do, but yeah. He's like, and if we find that thing, we could help solve the issues of these communities. And I said, yeah.
And he's like, okay, I got to do some work for that because I don't know how that one works. But it's the logic steps that I think we've been conditioned with. And we do have to disabuse ourself and start from a place of maybe I don't know what I'm talking about. Maybe it's a shortcut that we use as clinicians, but it affects our decision-making. So, absolutely think these are really important points, and I'll throw it to Lash for the last word. Yeah, well, I can't agree more with everything that's been said today, and I just feel so blessed to be in community with these amazing scholars and folks that we have right now, y'all. The energy is definitely here. And I think like really what it comes down to for me is I've been listening to you is the same rigor that we approach all of medical school with, right? Like we're talking about the lungs, you're going to have a pulmonologist come. If we're talking about the heart, you're going to have a cardiologist come and teach me. So when we have conversations around race, don't send faculty a one pager and then have them give this lackluster discussion or presentation about this topic when there's clearly a rigor to it that is there and folks just aren't doing their research. So we can't continue to copy and paste. We can't continue to just say, all right, we're going to use this proxy. So I really hope that that's what folks get out of this. And it can't stop with just reading how to be an anti-racist. You got to, we can't spark notes this, right? And I think that's really what it comes down to. And all of these resources that you've given us today, Edwin, are definitely things that our learners can take away from this experience in this conversation. So before we end, I just want to know, what can folks who are listening right now start doing today to start doing the work that, you know, we need to start doing to dismantle this idea? Yeah, that's a good question. I'm thinking where, there's so much, but I'm thinking where to start. And I actually think we have to start at home, meaning asking your classmates, our colleagues, what have you been taught at home that is allowing you to believe these things that so many of your other colleagues are telling you are not true? I think that's one, because it starts at home. It starts with the conditioning of stereotypes and the stereotypes coming from the racial definitions created by Carl Linnaeus. Two is, you mentioned research and work. I think that work is absolutely necessary. Reading the book is, as you said, not sufficient. I would actually ask that before you read the book, you start asking questions, that you start digging into concepts of race that is so beyond you. Because it is quantum physics. In many ways, it doesn't make sense. And that was his intention. When you have something that doesn't make sense, I mean, let's think about it. Racism is the real deadly consequence of a concept that is not real. That is race. It was made up. And so I get it when people are like, well, if you just stop talking about it, it will go away. It's like, no. Y'all, if I stop talking about it, the majority of people in this country, which are white, will make sure that we know that they're white. You know, when someone's like, Edwin, can you stop talking about race? And I'm like, what race are you? They're like, I'm white. Clearly, you are beholden to your race. Clearly, you want to hold on to it. We say we want to disassociate, but folks are wholly invested, especially when it comes to power. The third is, it is the institutions. I have colleagues that are specialists, family docs throughout the departments at UW Medicine. And I ask them, especially the family docs, if someone comes to you with a fractured femur, what would you do? Well, I check everything else.
Today on Sharp Scratch, you'll learn whether you ever really stopped being a doctor, how normal it is to want to leave medicine, and what actually is a portfolio career. You're listening to Sharp Scratch, episode 28, Leaving Medicine. This is a podcast brought to you by the BMJ and sponsored by Medical Protection, where we talk about all the things you might want to know to be a good doctor, but that you might not necessarily learn at med school. I'm Anna, and I'm a final year medical student at King's, and I'm also the editorial scholar here at at the BMJ and I'm absolutely delighted to be joined once again by my brand new friends Lily and Oki. Would you like to introduce yourselves? Yeah hi I'm Lily, I am currently intercalating in anthropology and have done three years of medicine prior. Hello I am Oki and I'm a third year medical student from Dundee. Brilliant, lovely to have you guys not with me because obviously social distancing etc. Obviously. But you know in the same virtual space as me and I'm also really really excited that today on Sharp Scratch we'll be joined by Dr Fiona Godley who I'm sure most of our listeners will know is not just the editor-in-chief of the BMJ but the first ever female editor-in-chief of the BMJ. Would you like to introduce yourself? Hi Anna, hi Lily, hi Oki, hi everyone. Yep that's me. I'm Fiona Godley, I'm editor-in-chief of the BMJ, yes, and I have been now for just over 15 years, since 2005. We're so grateful that... You sound impressed, Aki, at that. I'm impressed. 15 years! Too long, I'll say, too long. But yeah, it's so great for us to have you with us today, Fi, and hopefully you'll be able to give us some great insights into what we're going to be talking about. But also, hopefully this will be an opportunity for you to get a little insight into what we do at Sharp Scratch. So in our last episode, we talked about how useful it can be to have experience working outside of medicine before or maybe even during medical school. Today, we're talking about something that kind of has like similar themes, but is a bit different. So we're going to be talking about leaving clinical practice or even leaving the field of healthcare altogether. And I think we all know that increasingly doctors are looking at things like portfolio careers, combining clinical work with other things and some obviously do leave medicine altogether and pursue careers in other areas so I guess a lot of people I know who are no longer in clinical practice like still work in health adjacent fields um but not everyone so Lily okay we're all still at med school have you considered leaving medicine at all like in the time you've been at medical school yeah maybe 3 000 million times yeah okay good I'm glad it's not just me I was I like so sad. But I find that really sad to hear that you feel that way. I love a lot of it.
I would say for me it's more to do with imposter syndrome thinking oh am i actually good enough to be doing this right now rather than it just being oh i see so it's more of a self-doubting than a than a medicine isn't yeah kind of thing oh that's interesting that's really interesting which is completely different i great, Dr. Oki. I can't believe you would have self-doubt. And also, self-doubt is very healthy. Everyone should have some self-doubt. Sophie, I was wondering, maybe you would like to inspire us a little bit and tell us a little bit about your career and when you left clinical medicine. Yeah, so I mean, it's funny that here I am in this job, which is not clinical medicine. And yet I feel absolutely inspired and committed to and fascinated by and embedded in medicine. I don't feel, I mean, people will say I'm deluded, but I don't feel that I left medicine in the way that someone who's gone into something completely other might have done. And certainly to do this job, you couldn't, you have to be a doctor to be this, to be in this role. And we have, you know, on the BMJ, quite a few clinicians who have become editors, some of whom are still practicing. So my route was that I come from a very medical family and I'd always, as far as I can remember, wanted to do medicine and loved it pretty much. Right the way through, I did my training in London and Cambridge and then I did my SHO, as they were, jobs and then I was a medical registrar at the Whittington which is a very busy district general hospital in in North London and got my membership at the Royal College of Physicians and but it is fair to say that I remember wondering where I would go in medicine and I didn't want to specialise I loved general medicine and at the time I was doing this which was in mid to late 80s, general medicine was disappearing as a sort of a route. Everyone was having to decide to specialise. And I think at the time, kind of casualty acute medicine was a place for people who hadn't made it in surgery. And I didn't really feel like the place to be, although I loved working in casualty. It was a fascinating place to be. and I loved the whole sort of social if that's the right word side of hospitals the buzz and the interdisciplinary and the engagement so anyway I wasn't entirely sure of my route and also I was very interested in the kind of art side of things which is you know as I did my history of medicine degree and sorry I've got a dog coming trying to get in the joys of recording from home in addition I'd always had this sense of wanting to do something with the arts and I'd done my history of medicine degree and I wanted to write and I and someone saw the job advertised for the BMJ and the BMJ had decided they wanted to get some clinicians into the team, people who were still active and a bit of a younger kind of breed and so they set up this thing called the editorial registrar scheme and I was the second of those registrars and the idea was you'd come into the BMJ for a year and then go back into medicine but as it happened Trish Groves who was the first and I was the second, Louisa Dilner was the third, Alison Tonks who's also still with us, so the whole sequence of us who came and stayed and so the scheme in that sense was a bit of a, you know, not a failure but it didn't do what it was intended to do but it did recruit a whole load of clinically trained early specialty training clinicians and Cameron Abassi who's the BMJ's executive editor my deputy is also someone who came in through that route so it's been quite an interesting sort of sequence that has happened. And how did you feel about giving up seeing patients? Because, you know, I think a lot of people like myself included, that's a huge part of the reason why I didn't leave medicine, even though I've thought about it so many times is because I love seeing patients. And it's something that actually I've noted this year.
But I have missed seeing patients actually quite a lot more than I thought I was going to. So what was that like? Yeah, I agree. I mean, I think for two things, kind of changing your identity internally was tricky. And for a long time I said to people, you know, I'm a doctor, but I'm currently working as an editor. It took me about five years to stop saying that. Because a doctor is something kind of so substantial and so sort of concrete. And then I began to say I used to be a doctor and now I'm an editor. And then I stopped even bothering to say that. But the patient thing was interesting too because the joy of, it seemed to me, of clinical medicine is the sense of people coming to you at the most vulnerable and you being able to engage and help them. I mean, it sounds very cheesy, but... And also the very wide mix of people you meet through medicine, not necessarily the doctors so much, but the patients. And I really did miss that. And also the sort of physical activity of being a doctor, whereas being an editor, you're tending to sit at a desk. Oh, yeah, definitely. I have missed running around a hospital so much. I did miss all that. So there were a number of things that struck me in that first year. And when BMJ asked me to stay on for a second year and I got my register of rotation to keep the role open for me, which they did, I was sort of still thinking of going back to medicine and feeling rather bereaved of certain aspects of it. But by the time that second year had finished, I was really embedded in the journal and loved the breadth of it, the generalness of it, the academic stimulation. There was a social aspect in terms of all the different researchers and academics and clinicians you were dealing with at a distance, but still through the journal. So lots of travel, the journal allowed. Like, are your siblings still practicing? Like, did they ever make any comments about you not being a quote unquote real doctor anymore? Because I think that's something that people encounter. I was speaking to actually one of the clinical editors at the BMJ and they were saying, you know, I feel like I need to continue doing some locum shifts because otherwise all of my clinical colleagues are going to sort of think I'm not a real doctor anymore and all of this. And I just find it so interesting how much of our identities can be tied up in our professions. Yeah, I think that's true. I mean, one of the things is why does one want to be a doctor? I think, you know, when you say to people, I'm going to do medicine, they go, ooh, that's fantastic. You know, there's a kind of positive reinforcement reinforcement that goes on and so yes when you when you step away there are people who think well why would you do that what a complete you know what a waste of your training or but I think certainly for me I was the youngest of I am the youngest of four my three older siblings are all GPs so I'd already slightly taken a different route and that's one of the joys of medicine I think is that there are these very many different routes to stay within it and to contribute and be you know engaged so I went down the hospital route and did my membership and so that had set me apart a bit my dad had done I was a cancer specialist I think they sort of they kind of didn't really they they I mean they were slightly surprised I think but I think it was always like the sense that I would go back and then by the time I wasn't going to go back I was beginning to publish stuff and write stuff and so that brings you a bit of that feeling that just you know it shows people that it's real and you're actually doing something slightly useful and yeah. Lily and Oki what um if you both kind of considered leaving medicine why why did you stay like what were your pull factors like keeping you in medicine?
And the idea of losing that is like it's not the most significant thing, but it's like a big paranoia at the back of my mind, like telling my mum. But actually, in in reality I have stayed because I can't imagine doing anything else I don't know what my job as a doctor will look like I don't know if it will be look like me on the team in a hospital or as a GP or whether it becomes less than full time or public health or something like that but in reality, I can't imagine doing a job that isn't so directly useful and exciting. Yeah, I definitely get that. Because one of my friends who's a reg at the moment, he always says, if there's anything else in the world that you could do that would make you as happy as medicine, go do that instead instead. Obviously he's a bit negative. But I kind of like you Lily. I've thought about all the different careers. And I genuinely can't think of anything else. That would make me as happy. And also. Part of what I like about medicine. Is the amount of choice you have. So when people hear medicine. They think it's like quite a narrow pigeonhole that you're getting yourself into. But within medicine itself, there's so many different specialties. And then you can also do other things alongside medicine. So I quite like teaching. So as a doctor, I still get to teach. I enjoy doing research as well. As a doctor, I still get to do research. I like the clinical practice of it all. I get to do that as well. So medicine for me is just, it just ticks way too many boxes for me to leave because of not necessarily feeling good enough some days, if that makes any sense. Yeah, I definitely think the prospect of like being able to create your own career, which is like diverse and varied, that keeps me going. I think if I was looking at a trajectory of, yeah, I'm going to become a GP and do that for the rest of my life, perhaps I would struggle to motivate myself. But being like you were saying, like, oh, I could do a bit of teaching. I could do a bit of research. I could do some anthropology. Like that is exciting. And no other job allows you to do that, really. For me, there's also a bit of research I could do some anthropology like that is exciting and no other job allows you to do that really for me there's also a sense of like this maybe isn't a very nice thing to say but you know it people always tell you like how competitive it is to get into medical school and all of this and like I got into medical school like on my first attempt and I know that loads of people don't and it would just feel like I think there was always a sense of like it would be so pointless for you to give that up because someone who actually did want to go to medical school like could have had that place and you've just wasted that like I don't know I don't think that's a huge factor for me but there definitely is that guilt like and I guess when you become a doctor as well you're like oh you know the NHS has poured all this money into training me and now I'm going to give that up and not you know give back my service to to the NHS and to the people who have trained me I don't know if you agree with that Fi? Yeah no I absolutely do think that and um and and I think that's um in some in the same way that is quite it's it's a reasonable feeling isn't it to say, you know, you went to the trouble of all the work you did to get to medical school and people put their faith in you and have given you that training.
But for that reason, they started doing it because their families wanted them to and they had, had you know anxieties about you know having a i don't know all sorts of of sort of reasons other than feeling they want to be a doctor themselves so i think it's important to balance that and the car it can take a lot of courage to move away from it from a from a role that you've taken on for the wrong reasons and i would applaud people who who do that you know what i mean um at the same time it's rather ironic that the thing we've we've set up at the BMJ of encouraging selected people to come um out of medicine to work on the BMJ you know we're sort of pulling we hope talented very like Anna very talented people out of medical um work stream into the BMJ but we do it because we think we are of medicine. We do it that we sort of feel that we're still in there and really making a good contribution. Yeah. And I think that's where, I guess, Fi, you leaving clinical medicine, I suppose, may have had less of an impact on how you conceptualize your own identity in terms of the medical field, because the BMJ is so very kind of embedded into that whole world and it might be a bit different for people who leave and do something different which we're going to talk about in a little bit but what I've also found interesting is obviously at the moment the whole COVID-19 thing that's going on and all of these doctors have come out of retirement and they've fast-tracked final year medical students and i find that really interesting that even after you know you've done your service to the nhs and to your patients and you've retired people are still really really keen to come back and help when they're needed and it just makes me wonder whether you ever like actually stop being a doctor if you've trained and like become a doctor yeah it's interesting because I realize it's something we haven't perhaps looked at enough in this COVID thing period which is you know what is it is it that's led so many retired doctors to come back when we had prior to this had this sense that people were retiring early, they'd lost their mojo, they was feeling exhausted, burnout, you know, paperwork, overwork, all of that. And we talked about people, I mean, amongst my siblings, they retired pretty much bang on, you know, their 60th birthdays. And, you know, they've worked incredibly hard over the years and quite right too. And so I suppose it's really interesting. There's something about this COVID thing that re-inspires people. It's the national emergency, obviously, but it's also really acute clinical need. And also there's an element of sort of service and risk involved. I don't know. I'm really fascinated by it. And someone like Lily as an anthropologist, you could come in as a psychologist and examine this as a phenomenon. And we've also managed on the BMJ, just to give a plug for him, is to get Richard Lehman back out of retirement. Richard Lehman ran a fantastically successful column for us, looking at, you know, summarising and analysing research published in other journals. Very funny at times and critical and wonderful. But he stepped away a year or so ago. And when COVID came back, he's come back. So retirement is not you know i think there's a lot lots of ways in which people can come back into active service definitely i think it's just interesting how it seems like being a doctor like becomes so embedded into who you are and like i i already think that like as a med student maybe not so much in my first and second years but once i started seeing patients when i was in third year you know if someone asked like lily and oki if someone said to you describe who you are a medical student would be like one of the first things exactly exactly it's like one of the first things you would say and that's not to like impress people that's just because... It's just part of your identity. Yeah, it's become so much of what I have hung my identity on. I don't know whether that's healthy or not. Well, to be fair, we do spend most of our lives doing medicine.
For like. Prizes and stuff. And one of the prizes was. The. Do you know. I study medicine. Prize. And I thought. No I didn't. I didn't win it. Thankfully. But. But I thought. No one would ever nominate me for this. But. Three of my friends did. And I was very shocked. And I'm like. Oh. Maybe. I am that person. So now I've decided to embrace it. Interestingly if people ask me oh what do you do I will always say I'm a student and they always say what do you study and I say medicine but it's not because it doesn't being a medical student isn't part of my identity because it absolutely is I haven't somehow escaped that but I think because it is such a strong identity it's such a strong marker people have like a real distinct sense of what a medical student is what a doctor is I really don't want people to think that I'm that person before knowing other things about me I guess um perhaps that's because I see like that image that people have in their brain as like a negative thing. I think that's part, yeah, this is something that I was going to, I wanted us to touch upon. It's like, it's kind of part of the fact that medicine as a profession, like you say, is so visible. Like it's not like doing, oh, but I can't even think, I can't even think of another job now. But you know, most people- There are no other jobs in the world. Most people, when you ask them- Alternative jobs. What they do, unless they're, you know, a doctor or a teacher or you don't have a clear sense of what their day-to-day life might be like unless you're in the same field, right? But I think because medicine as a profession is firstly so old and secondly, so visible in like the media, particularly recently, obviously, and, you know, shows like Scrubs and House and stuff have been massively, massively popular. And I think you're completely right. Like people have an idea of what that means. So you kind of get like your own identity is being sort of seen through the lens of other people who perhaps aren't exactly sure what you do but they feel like they have quite a clear sense of it from the media which is like a really weird position to be in because I completely get what you're saying like there's a reputation there and you're sort of like in so whether you want it or not yeah people have already made a decision about what type of person you are which is stressful yeah it's not it's not accidental i would i would lean away from thinking that this identity has kind of just come unsurprisingly out from medicine i would say that medicine is a field and the media and people themselves have can have deliberately idea of who a doctor is. And actually, for a lot of purposes, it's really useful for patients to think of a doctor as someone who's all-knowing, all-controlling. In a lot of cases, that's really helpful for a lot of patients. There's doctors in every single country in the world doing, you know, essentially at the basics of it, the same thing, right? So you kind of instantly have that connection and it's also a very historic profession. So we can look back on years and years of fascinating medical history and just feel like you're part of something bigger than you and I think that's what draws a lot of people to the profession yeah absolutely and I think you know if you leave it's like potentially like there are I guess there are some other professions where that's similar but I don't know medicine just seems like it it's very much its own thing like for you have more experience you know knowing people from other professions it makes me think also you know when you see politicians who have been doctors like Dr. Lim Fox and Dr. David Ernie they they continue to be um um you know seen as something in I mean a lot of a lot of politicians are lawyers aren't they or businessmen or and we don't sort of feel the need to say that all the time. So there's something additional that this confers on you.
And that's good. That's true. I think at its best, that is absolutely true. Maybe a little bit spurious in some cases, but I agree with you. There is a sense of joining some greater good. And to leave that represents some kind of wrench or some kind of betrayal, even perhaps at its worst. Definitely. I guess the question leave medicine once you've joined the cult you can never leave well certainly the bmj we never let people leave the bmj anna so i'm afraid that's okay i'm okay with that okay cool so we're going to discuss um a slightly different situation where you might leave the health goes wrong, but we're also here to help make sure things go right too. We're the only medical defence organisation that protects doctors all over the world. From London to Brisbane, Cork to Cape Town, 300,000 members benefit from our expert advice and support throughout their career. During your years at medical school, your membership is completely free. You'll get training resources that can help you become an even better doctor, plus a dedicated student team there for you when you need it most. And when it comes to your elective, you can trust in our international experience to protect you wherever you choose to go. It's no wonder that 90% of medical students in the UK choose to be part of medical protection. You can find out more at medicalprotection.org. Okay, back to the show. So Fi, obviously, as we've discussed, you stayed in a field that's, you know, like intimately allied to healthcare. And I think lots of people who leave clinical practice do actually stay in, you know, kind of adjacent fields. So lots of people start sort of medical companies, might work for charities that are sort of allied to health in some way. But there are some people who leave medicine entirely. So I spoke to someone who has done just that. So let's hear from them. Hi, everyone. So my name is Mayank Bhandari. I completed my medical training at UCL. I did a postgraduate qualification at the University of Cambridge and went on to do my foundation training in the East Midlands. I left medical training towards the end of FY2. So right now I work for McKinsey & Company, which is a global management consultancy firm that serves leading businesses, governments and non-governmental organisations across a range of industries and topics. So far, I've spent most of my time working for numerous global pharma companies on topics from AI and ML to marketing and sales strategies, tech and large-scale agile transformations. I've also spent a bit of time working on COVID-19 as well as with some of our private equity and transport and logistics clients. Leaving medicine is a question I get asked a lot and there's three main reasons for leaving clinical practice. So firstly, it was because I realised my excitement for healthcare was really about the potential we can make at a systemic level versus an individual patient. So having the opportunity, as I said, to work with global pharma companies, healthcare payers and providers, and NGOs has really fulfilled my desire to help at such a scale. Secondly, it was, in essence, to feed my intellectual curiosity about other industries outside of healthcare. So I'm a generalist at McKinsey, which means I'm able to work with pharma, medical products, clients within healthcare, but also across other industries like transport and logistics, consumer, banking, private equity, and so on. And that's something that I find very exciting. And thirdly, it was to really develop a robust business orientated approach to solving problems. It's a topic I've always been interested in from my time at university. I had a couple of startups and now I've really been able to throw myself in the deep end. The question around leaving the health sector, I don't really feel like I have. A lot of the work I do and my innate passion is for working on challenging problems or the ultimate aim of improving patient lives and I've had an opportunity to do that at McKinsey. I did not encounter any resistance at all to leaving clinical practice. If anything everyone was very very supportive from the get-go.
I actually have a friend who left medicine completely last year. So this friend was a first year at my uni and she was kind of like my daughter. And then she came to tell me, OK, I've got something to tell you. I was like, oh, what's going on? I thought something really bad was about to happen. And she said, oh, I've decided to sit my first year exams and then leave medicine. And she was really, really worried about telling me that. And I was like, why are you worried? Because I just replied, okay. And she was really confused. She thought I was going to tell her off and give her like a big lecture about it and stuff but i think it's important that she decided to that medicine wasn't for her in first year and i thought that was like a really brave thing for her to do and she's now studying geography which she's enjoying a lot more and it's what she wanted to do in the first place but her parents kind of pushed her into the medicine thing so i think it's good when people know themselves and know what's right for them and no one can tell you that apart from yourself regardless of what the prestige or whatever reason or other things that come with medicine i think that's really interesting okay and it seems to me that there's a broader sense about what education is about and what life is about, because surely there's gain in terms of the training, in terms of the experiences, in terms of the emotional development and personal development that come with being a doctor or training in medicine generally. And those assets, you know, to use that rather business term, will be transferable. You know, you will bring that experience to the next role you take on. So it's not like sort of just saying it never happened. It's saying all of that learning and training and experience is going to go into these other roles. So I think we should see it in a more positive sense than that. And it may be, who knows, that people who move into management management consultancy one of the other things medicine needs is people with good management experience and I was going to make the point earlier that there's in the portfolio that people might take on there is this additional very important role in medicine which is healthcare management and change management and those sort of things strategy that we hope many more doctors will begin to include within their kind of armamentarium of skills. Do we think it's generational? I don't have an answer to this but do you think we're seeing more I guess we're seeing portfolio careers now and as the world of every other job has changed for people to have multiple careers across their life whereas like in the olden days um people would do maybe one or two all their life that medicine is not immune to that mentality so I wonder if we're seeing that more of that now and especially as we're having more like millennial consultants and eventually we'll have Gen Z, loads of Gen Z doctors. I think we will see medicine has to shift dependent on the actual workforce. And if the workforce are a different age, a different generation, then that is what will happen. What is a portfolio career? It's where you like do, I guess, multiple different things. So, for instance, if you did like two days clinical work and two days working at a medical school and then one day doing research or something like that is a portfolio because you do like various different things. Ah, okay. I see. Right. Sorry, I should have explained that at the beginning. I've just been so like, because of all of the like BMJ stuff, people are very interested in like what their career is going to be like. So yeah, I know all of these words. I'm sorry. I should have explained that at the beginning. That's great. Sophie, what we usually like to do at the end of an episode of Sharp Scratch is to sum up our sort of top takeaways from the discussions that we've had. It's been really great to have you here with us today. So are there any sort of final thoughts on anything we've spoken about today that you'd like to leave our listeners with? It's been such a great discussion.
From the JAMA Network, this is JAMA Author Interviews, conversations with authors exploring the latest clinical research, reviews, and opinion featured in JAMA. Hello, and welcome to this JAMA Conversation. I'm Dr. Kirsten Bibbins-Domingo. I'm the Editor-in-Chief of JAMA and the JAMA Network, and I'm joined today by the Assistant Secretary for Health in the Department of Health and Human Services, Admiral Rachel Levine, who is a physician and a pediatrician. Admiral Levine authored a viewpoint in JAMA this week, timed with the release of two reports from HHS on the government-wide response to long COVID. Admiral Levine, thank you for joining me today. Admiral Levine Well, thank you. I'm very pleased to be here. So tell us about these two reports on long COVID. What's the main message in these reports and why were they released now? Admiral Levine Well, thank you for that question. The take-home message is that long COVID is real. Estimates vary, but anywhere between 7.7 to 23 million Americans have developed long COVID, and roughly 1 million people are out of the workforce at any given time due to long COVID. The Biden administration is committed to taking action to help those who need help. In April, President Biden issued a memorandum on addressing the long-term effects of COVID-19. Now, this called for the creation of two reports, and we'll be releasing the reports on August 3rd. The first report is on the services and supports for longer-term impacts of COVID-19. So this is the services report. This outlines federally funded support and services for individuals experiencing the longer-term effects of COVID-19 in the areas of long COVID and associated conditions, but also mental health and substance use, as well as bereavement. The second report is the National Research Action Plan on Long COVID, the research plan. And this proposes a comprehensive and equitable research strategy to inform our national response to Long COVID. Wonderful. I'd love to take the second report first. I think all of us who are physicians who've been following the news, we know that long COVID is a really important way in which the current pandemic will be with us for a while. But it's also been challenging to think about what the definition of long COVID actually is. What kind of definition is used to guide the report for research on long COVID? Well, you know, we have taken our strategy as a reflection of our patients' voices. Long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after a COVID-19 or SARS-CoV-2 infection. The signs, symptoms, and conditions are present for four weeks or more after the initial phase of the infection. They may be multisystemic and may present a relapsing, remitting pattern and progression or worsening over time. With the possibility of severe and life-threatening events even months or years after infection. You know, long COVID is not necessarily one condition. It represents many potentially overlapping entities, likely with different biological causes and different sets of risk factors and outcomes. Yes, it seems that the research plan that's outlined is fairly broad and comprehensive. It appears to move, I know you outlined seven areas that move from really defining a little bit of how do we make this diagnosis of long COVID to things that are very mechanistic to understanding how do we get long COVID to the epidemiology surveillance, a focus on treatments, and then broader implications for the economic consequence and the broader policy consequences. There's a lot of work already being done in this area by different agencies. What's new in the report, though, in highlighting these particular seven focus areas? Well, thank you. You know, I think we are now at an inflection point, and the studies are getting more robust, and they're getting larger. Now, it does take time to set up and analyze studies over time to obtain meaningful data. For example, two recent studies using electronic health records, one from the CDC published in the MMWR and the other from the VA, have sample sizes in the millions. These type of studies are giving us the first reliable glimpse at the scope, the scale, and the diversity of long COVID conditions.
Whether high or low, short or long term, these health consequences represent a substantial impact on our patients, but also a substantial impact on our healthcare system. Third, this report is the first time that we've collected all the research that's happening, and it really is significant, all the research that's happening in one place, looking at the gaps, and we have worked to create a cohesive path to move forward. Can we expect to see more funding of research in this area? Well, we are hopeful that there will be more research for funding by the NIH, by the CDC, by the VA, by the private sector as well. So we are hopeful that there will be more funding for this research. Wonderful. It sounds like that the report is really talking about a strategy for coordinating multiple efforts that are happening, and then with the hope that there's also additional investments in all of these areas. So that is correct. You know, we wanted to emphasize the people impacted by long COVID. We want to do research on all of the different aspects. And so we have the program from the NIH, the RECOVER program, as well as INSPIRE from the CDC. We've also had some great research from the VA and, of course, the private sector. So we're going to try to put it all together. But, you know, the reports are the beginning. The reports are going to come out on August 3rd, and that's the private sector. So we're gonna try to put it all together, but the reports are the beginning. The reports are gonna come out on August 3rd and that's the beginning. And then we need to have an implementation strategy and a path as we move forward. So one of the things that really struck me in the viewpoint that you wrote is that you want to coordinate and put an emphasis on the science and we know the science is emerging. But we also know that people are suffering right now. We have patients, we have healthcare systems, we have clinicians who are really both experiencing the effects of long COVID, or trying to understand how to really provide the best possible services for the many patients and communities who are dealing with the effects of long COVID. So it does strike me that the second report really is focused on the needs on the ground right now, even as the science continues to emerge. And you have a fairly broad scope of the services. You're focused on long COVID, but also you highlight the mental health aspects that we know have worsened during the pandemic, as well as substance use disorder. Why did you choose to take such a broader scope and not just limit it to the long COVID? Well, you're correct. This does have an expanded focus in terms of the second report, which is on supports and services. So on April 5th, the president directed the federal government to coordinate and augment services to three large groups. First group is those with long COVID and associated conditions. The second was those experiencing the behavioral health challenges, mental health challenges, substance use, et cetera. And the third were those experiencing bereavement. The longer-term effects of the COVID-19 pandemic do go beyond long COVID, and it has been impacting patients and communities, as well as the economic and social fabric of all of our communities. Accordingly, the services report inventories over 200 federally supported services to help our patients, to help their families, their communities, and supportive public and private organizations. So we know that the inequities of the pandemic has been the major feature of the pandemic. So we are all affected by COVID, but many communities proportionately more. Those same communities will experience the sequelae of COVID, whether it is the bereavement or the mental health aspects or the effects of the virus directly over time. And oftentimes those same communities don't have all of the resources, both within particular individuals and families, but also the types of infrastructure, healthcare infrastructure that exists in those communities. How does the report speak to the equity issues? Well, you are absolutely correct. Health equity is such a high priority of the Biden-Harris administration, as well as Secretary Becerra of HHS and my office, the Office of the Assistant Secretary for Health.
Research shows that racial and ethnic minority groups, older adults, people with disabilities, those who are poor, they are suffering disproportionately by long COVID as well as the associated conditions. This was highlighted during the COVID-19 Health Equity Task Force, which was organized out of our office and our Office of Minority Health. And I had the honor of having an ex officio seat on the COVID-19 Health Equity Task Force. Equity has really been a guiding principle, a foundational principle in the formation of both reports. Equity considerations are highlighted prominently throughout both reports. For example, health equity considerations are called out in relation to each federal government long COVID research area. And it reinforces the need for equity in every aspect of research, the pathophysiology research, the therapeutics research, the health economic research. In addition, of course, the supports and services reports has a know your rights section. It has a-out for each of the federal government service areas covered in the report to make sure that they are emphasizing health equity. Right. I think about this a lot. I take care of patients within a safety net setting in San Francisco, and I think we have seen both the effects of COVID and the challenges in really getting services. And we see this across many things, how who has the ability to take off of work to deal with some of the issues, who can get access to services that are not directly related to COVID. And so I assume this is part of the reason to think broadly and expansively about what this equality of COVID are beyond those directly related to the virus and its impacts. So that is correct. And that is why the president called for this more expansive report, not only on long COVID and associated conditions themselves, but also on supports and services for those impacted by COVID-19, which we know has had a substantial impact in terms of mental health, in terms of substance use and bereavement. And so we're taking this expansive approach to the report. Great. And in science, we want to have a very strict definition and be very specific about it. But it sounds like the combination of these two reports recognize that the science is emerging, our ability to understand the very strict definitions, but in the meantime, the need to address the needs of patients, communities, the systems that care for them is also going to be important even as the definitions emerge. So that is correct. As again, these are overlapping entities. Now there are two technical terms, post COVID-19 conditions or PCC, and that's largely equivalent to long COVID. It includes both the direct and the indirect effects of the virus. The second term that is commonly used is post-acute sequelae or SARS-CoV-2 infection. That's PASC, P-A-S-C. And that's confined to the direct effects of the virus. And so, you know, we're going to have these overlapping definitions. And we'll try to, you know, as we go forward with the implementation of the reports to try to develop more of a consensus. But there are many different aspects to this complex condition. Yes, this is a virus that we're dealing with right now in its ever-changing forms, and the sequelae of the virus also is complex. This is a report, a set of reports that strike me have implications for patients who might be suffering with this condition, for the health systems, for the clinicians who care for them, as well as all of us who will be continuing to deal with the effects of SARS-CoV-2. Is there anything else that you would like to highlight for our listeners? Sure. A couple of things. You know, this is a very ambitious agenda, and we have a lot of federal activity on both the research aspect as well as supports and services. There were 14 federal agencies involved in drafting the reports. And, you know, this is also, as we address these challenges, it's going to need to be a public-private partnership with a whole government approach, but also working with the states and local governments and public health authorities, and then working with the private sector. But again, the reports are just the beginning. As we look past the reports, we want to offer a holistic approach to addressing all of the work that is necessary across our nation.
Welcome. This is the New England Journal of Medicine. I'm Dr. Michael Bierer. This week, March 19, 2020, we feature articles on discectomy or conservative care for sciatica, no sedation or light sedation in ventilated ICU patients, long-acting therapy to maintain HIV-1 suppression, and a screening program to eliminate hepatitis C in Egypt, a review article on hereditary angioedema, a case report of a man Thank you. forces, on opioid prescribing in the midst of crisis, and on the dishonesty of informed consent rituals. For more information on the ongoing coronavirus epidemic, including audio updates from NEJM Editor-in-Chief Eric Rubin and Deputy Editor Lindsay Baden, visit the COVID-19 Resource Center at nejm.org slash coronavirus. The treatment of chronic sciatica caused by herniation of a lumbar disc has not been well studied in comparison with acute disc herniation. In this single-center trial, 128 patients with sciatica that had lasted for 4 to 12 months and lumbar disc herniation at the L4, L5, or L5S1 level were randomly assigned to undergo microdiscectomy or to receive six months of standardized nonoperative care followed by surgery if needed. Among the patients assigned to undergo surgery, the median time from randomization to surgery was 3.1 weeks. Of the 64 patients in the non-surgical group, 34% crossed over to undergo surgery at a median of 11 months after enrollment. At baseline, the mean score for leg pain intensity was 7.7 in the surgical group and 8.0 in the non-surgical group. The primary outcome of the leg pain intensity score at 6 months was 2.8 in the surgical group and 5.2 in the non-surgical group. Secondary outcomes, including the score on the Owestree Disability Index and pain at 12 months, were in the same direction as the primary outcome. Nine patients had adverse events associated with surgery, and one patient underwent repeat surgery for recurrent disc herniation. In this single-center trial, involving patients with sciatica lasting more than four months and caused by lumbar disc herniation, microdiscectomy was superior to non-surgical care with respect to pain intensity at six months of follow-up. Andrew Schoenfeld from Brigham and Women's Hospital, Boston, writes in an editorial that discectomy was superior to non-operative care for the primary outcome of leg pain intensity at six months after enrollment. These findings may result from the fact that surgical intervention allowed for more rapid decompression of the compressed nerve root. Patients in the current trial who were assigned to undergo surgery received the intervention relatively quickly at a median of three weeks, and it is reasonable to conclude that expeditious removal of the nerve compression minimized the potential for long-term persistence of pain. In patients with disc herniation and persistent sciatica lasting four months or longer, it has been the editorialist's practice to provide information about the association between symptom duration and outcomes and to offer a decision regarding surgical or non-surgical treatment on the basis of the patient's preference. If the patient has no benefit from an appropriate course of non-operative care, they make a stronger recommendation for surgery. Viewed in this light, it is encouraging that the trial reported by Bailey and colleagues shows that surgical intervention still results in clinically meaningful improvement in patients with persistent sciatica. However, the trial does not help clinicians determine which patients are most likely to benefit from immediate surgical intervention or the duration of nonoperative care that is acceptable before surgery is recommended. Non-sedation or light sedation in critically ill mechanically ventilated patients by Henne Olsen from the Odense University Hospital, Svenborg Hospital, Denmark. In critically ill mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the ICU. In this randomized trial, 700 mechanically ventilated ICU patients were assigned to a plan of no sedation or to a plan of light sedation, that is, to a level at which the patient was arousable, defined as a score of minus 2 to minus 3 on the Richmond Agitation and Sedation Scale, RAS, with daily interruption.
Mortality at 90 days was 42.4% in the non-sedation group and 37% in the sedated group, difference 5.4 percentage points. The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the non-sedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 0.3% of patients in the non-sedation group and in 2.8% of patients in the sedation group. Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. In an editorial, Claudeérin from the Hôpital Édouard-Hériault-Lyon, France, writes that in adult patients admitted to the ICU. Sedation and analgesia are provided at the time of intubation and may be maintained for hours or days. The aim of sedation is to minimize oxygen consumption and facilitate a patient's ability to remain comfortably connected to a ventilator. Over the past two decades, it has been recognized that prolonged and deep sedation can increase the duration of mechanical ventilation, delay weaning, impair neuromuscular function, produce delirium, and have side effects specific to certain sedative drugs, such as prolongation of their effect after discontinuation because of pharmacokinetic changes. However, omitting sedation for mechanical ventilation is complicated by the reluctance of caregivers to nurse patients who are agitated or in pain. Intensivists have been attempting to define clinical situations in which the maintenance of deep sedation may be required and those in which a reduction of the level of sedation may be allowed. The results from the trial by Olson and colleagues are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically with the aim of discontinuing it as early as possible or at least interrupting it daily. Such monitoring should be performed continuously, 24 hours per day, every day, on the basis of Nebraska Medical Center, Omaha. Simplified regimens for the treatment of HIV type 1 infection may increase patient satisfaction and facilitate adherence. In the Phase 3 ATLAS trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least six months while taking standard oral antiretroviral therapy, 616 participants were randomly assigned to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand transfer inhibitor, and long-acting rilpivirine, a non-nucleoside reverse transcriptase inhibitor. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 1.6% of participants receiving long-acting therapy and in 1% receiving oral therapy, a result that met the criterion for non-inferiority for the primary endpoint. An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy, a result that met the criterion for non-inferiority for this endpoint. Virologic failure was confirmed in three participants who received long-acting therapy and four participants who received oral therapy. Adverse events were more common in the long-acting therapy group and included injection site pain, which occurred in 75% of recipients of long-acting therapy and was mild or moderate in most cases. 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group. Monthly injections of long-acting cabotegravir and rilpivirine were non-inferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal.
The FLARE trial evaluated whether switching to monthly injections of long-acting cabotegravir plus rilpivirine would be non-inferior to continuing oral therapy in 809 patients with HIV type 1 who had viral suppression in response to oral induction therapy with dolutegravir-abacavir-lamivudine. At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 2.1% of participants who received long-acting therapy and in 2.5% who received oral therapy, a result that met the criterion for non-inferiority for the primary endpoint. An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy, a result that met the criterion for non-inferiority for this endpoint. Of the participants who received long-acting therapy, 86% reported injection site reactions, grade 3 or higher adverse events, and events that met liver-related stopping criteria occurred in 11% and 2% respectively who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy. 91% preferred long-acting therapy at week 48. Therapy with long-acting cabotegravir plus rilpivirine was non-inferior to oral therapy with dolutegravir, abacavir, lamivudine with regard to maintaining HIV-1 suppression. Injection site reactions were common. Judith Currier from the UCLA Medical Center, Los Angeles, writes in an editorial that the monthly injectable treatment was non-inferior to continued daily oral treatment, and participants in both trials clearly preferred monthly injections over daily oral therapy. When approved by regulators, this major advance in treating HIV infection will provide a new option for a select group of patients who currently have viral suppression while taking ART and represents the first step toward making less frequent dosing of ART a reality. For many, freedom from the need for daily oral therapy is a major advance, even at the cost of having to receive monthly injections. That said, the overall effect that this new treatment approach has on the HIV epidemic will depend on our ability to address a few associated questions and challenges. Currently, most people living with HIV who are in care are seen in a clinic for monitoring every six months. Requiring monthly visits for injections will be challenging for busy HIV clinics. Plans to carefully monitor resistance as this treatment is rolled out will be needed. Long-acting injectable treatment has the potential to be a major advance in the treatment of HIV infection during pregnancy and in the postpartum period, as well as for children and adolescents, including those in low-resource settings. However, to date, studies involving these populations are lacking. The ATLAS and FLAIR trials are important milestones in the development of HIV therapeutics and represent major steps into the era of long-acting ART. Version 1.0 of long-acting ART holds promise for the millions of people living with HIV if we make addressing the challenges involved a priority. Hereditary Angioedema, a review article by Paula Busey from Icahn School of Medicine at Mount Sinai, New York. Hereditary angioedema is a rare, potentially life-threatening genetic disease that may include recurrent attacks of cutaneous angioedema, severe abdominal pain, and airway compromise. Over the past 40 years, scientific investigations have identified the fundamental defect of hereditary angioedema as a deficiency of functional C1 inhibitor protein, a protease inhibitor in the serpin superfamily, and have established that bradykinin is the biologic mediator of swelling. In 2000, hereditary angioedema with normal C1 inhibitor levels was described, for which molecular mechanisms are emerging. Despite progress in unraveling the pathophysiology of hereditary angioedema, a delay in proper diagnosis and a paucity of effective therapeutic approaches have hampered effective management of the disease until recently. Advances envisioned in 2008, however, have now been realized, with insights from basic research translated into novel therapies.
This article reviews the progress made during the past decade in elucidating the pathophysiological mechanisms of hereditary angioedema and the subsequent development of targeted treatments for the disorder, with anticipated reductions in morbidity and mortality and an improved quality of life. A clinical vignette illustrates the profound effect of these treatments. A 64-year-old man with shortness of breath, cough, and hypoxemia, a case record of the Massachusetts General Hospital by Kerry Reynolds and colleagues. A 64-year-old man with a history of melanoma presented for evaluation of a mass in the left frontal and left parietal lobes. Four weeks earlier, the patient began to have clumsiness of the right upper arm as well as difficulty writing his name, holding a toothbrush, and coordinating activities with his right hand. MRI of the head showed focal hyperintensity in the left frontal lobe, which corresponded to a ring-enhancing lesion surrounded by edema. CT of the chest, abdomen, and pelvis revealed a solid, non-calcified nodule in the right upper lung that measured 2.2 centimeters in diameter. Metastatic melanoma was diagnosed, and the treatment included combination treatment with the immune checkpoint inhibitors ipilimumab and nivolumab. Fevers, dyspnea, and cough developed, and the patient presented to the emergency department. The oxygen saturation was 48% while the patient was breathing ambient air. CT of the chest showed bilateral airspace opacities. This patient's severe hypoxemia and diffuse inflammation of the lung were consistent with pneumonitis induced by immune checkpoint inhibitor therapy. Methylprednisolone was administered intravenously, and a decision to forego further therapy with a combination of ipilimumab and nivolumab was made. Screening and Treatment Programs to Eliminate Hepatitis C in Egypt A special report by Imam Waqed from the Menufia University, Shabin el-Kom, Egypt. In May 2016, the World Health Assembly set targets for the elimination of viral hepatitis, including reaching 90% diagnosis, 80% treatment coverage, and a 65% reduction in related mortality by 2030. When the targets were set, Egypt had the highest prevalence of HCV infection, a consequence of the prevalence of schistosomiasis and its mass treatment by unsafe intravenous injections in the 1950s to 1980s. With the decreasing cost of direct-acting antivirals in Egypt, from $1,650 for 12 weeks of sofosbuvir plus declatysvir in early 2015 to $85 for local generics in 2018, treatment of more patients and accelerated disease elimination became possible. In early 2018, the Egyptian government decided to embark on a massive effort to identify and treat all HCV-infected persons to achieve disease elimination over the shortest time period possible. These authors present the results of the national screening program. Although participation in screening was voluntary, turnout was very high. By screening 49.6 million persons over a period of seven months, the investigators managed to identify 2.2 million HCV seropositive persons and refer them for evaluation and treatment. The cost of identifying and curing a patient in the current campaign was $131, which clearly shows the magnitude of cost-saving by population screening. Universal Disease Screening and Treatment, the Egyptian Example, a perspective article by William Hazeltine from Access Health International, New York. Thirty years ago, chronic conditions such as diabetes, heart disease, and obesity accounted for less than 45% of the global disease burden. Today, they are the leading causes of death and disability worldwide. Although we are now able to treat many chronic and infectious conditions, few countries, rich or poor, have systematically tested and treated their people for the diseases that threaten them most. Now, however, the Egyptian government has provided an example of how routine testing and treatment for infectious and chronic diseases for an entire country can be achieved. Egypt has the highest rate of hepatitis C infection in the world. Ten years ago, it was estimated that nearly 15% of Egyptians were infected. In 2006, faced with evidence of rampant infection, Egypt's health ministry created the National Committee for the Control of Viral Hepatitis and appointed Dr. Wahid Das to run it.
The goal was to screen all Egyptians 12 years of age or older for active hepatitis C virus replication, hypertension, diabetes, and obesity. Free treatment would be offered in government clinics for people who tested positive for hepatitis C, hypertension, or diabetes, and free counseling would be available for those considered obese. The program has become a permanent part of the Egyptian health system, and Egypt may soon be the first country to eliminate hepatitis C. Misdiagnosis, Mistreatment, and Harm When Medical Care Ignores Social Forces A perspective article by Seth Holmes from the University of California, Berkeley. In a 2019 op-ed in the Wall Street Journal entitled, Take Two Aspirin and Call Me By My Pronouns, former University of Pennsylvania Dean of Medical Education Stanley Goldfarb echoed a dismissal that some physicians have been voicing for decades. Why should medical training focus on social factors, Goldfarb asked, when medicine's purpose is to cure individual patients? His essay assumed that one can effectively cure patients while ignoring the world in which they live. Unfortunately, that is an empirically untenable position. Social, political, and economic structures, those highlighted by Goldfarb, as well as structural racism, settler colonialism, other structures of marginalization, and the inequalities each of these produces, are injuring and killing people. To stop these processes, we need a range of community and team-based interventions, many of which occur beyond clinical practice, such as urban and regional planning to ensure the availability of safe housing and healthy food, and policy and systems changes to guarantee fair access to gainful employment and protection from environmental degradation. As clinicians, we endeavor to treat our patients' diseases and injuries, but when we dismiss social factors as peripheral, we not only miss opportunities to improve outcomes, we may in fact fail at medicine's core responsibilities to diagnose and treat illness and to do no harm. Once simple act of writing an opioid prescription has become fraught, physicians must check prescription monitoring databases to review patients' histories, make sure their prescription complies with state limits on dose or number of days supply, and consider any practice quality measures that might be affected. Beyond regulatory requirements, physicians must contend with growing stigma in the medical community against using opioids for pain management. Not surprisingly, there can be a palpable chill when a discussion about managing pain drifts toward opioids. Should I really start them? What if the patient demands more? What if I end up prescribing them long-term? Years of relaxed attitudes toward opioids have given way to an atmosphere of apprehension. In many ways, this caution is a positive development since 2011. As of 2018, the total volume of opioid prescriptions nationally had fallen by more than 40% from peak opioid around 2011. But like many other public debates, the opioid prescribing debate seems hopelessly polarized. Either opioids are industrially sponsored weapons of mass addiction, or they're a misunderstood last hope for alleviating suffering. The optimal use of these medications lies between these two poles. But where, exactly? There's no definitive answer, but there are persistent myths and misunderstand With his good left hand, he clutched his right to hold that injured arm in elbow flexion a little away from the body, with the forearm internally rotated. Looks like you dislocated the shoulder, Dr. Bivens said. They quickly agreed. Dr. Bivens should put it back. Enter the ritual paperwork. So we have a formal consent process. I consent, he replied. The nurse offered him a form and a pen. He gave her an exasperated look, nodding at his whole situation. Sometime later, a new patient popped up on Dr. Bivens' computer. Even as he clicked on her name, the chief complaint of seeking prescription refill was amended to high blood pressure. She'd just been to an occupational health clinic which had prescribed Hyzar DS, an antihypertensive combining Losartan 100 milligrams with hydrochlorothiazide 25 milligrams. Then the pharmacy told her a month's supply would cost $90. She was not optimistic Dr. Bivens could help, but in despair, she'd paid for one more $150 ED visit to find out.
From the JAMA Network, this is JAMA Cardiology Author Interviews, conversations with authors exploring the latest clinical research, reviews, and opinion featured in JAMA Cardiology. This is Clyde Yancey, Deputy Editor of JAMA Cardiology. I am delighted to be with you today to bring forward a very important podcast. This podcast is yet another effort by the editors of the JAMA Network to really help the field appreciate the nuances, the approaches, the right way to cogitate when we're thinking about how best to address race in medicine. We're privileged to have published the work led by Ambarish Pandey from UT Southwestern Medical Center in Dallas that took a very different approach, which I'll have him explore and explain to you. But we're also accompanied by the Chief of Cardiology at Stanford University, Eldren Lewis, who really has a deep history in appreciating how best to use predictive models for patients with heart failure, particularly in the context of race. Dr. Pandey, Dr. Lewis, welcome to this podcast. Thanks, Dr. Yancy, for publishing our work and the opportunity to participate in this podcast. Thank you. Amber, if I may invite you to begin. First of all, explain to everyone, what was the motivation? Why did you take this on? And then after you tell us why you took on this review of characteristics that might identify risk, what did you do novel with it? How did you try to iterate a new approach so it wasn't like everything else? So let's start at the beginning. Why did you adopt this path? So that's a very important question, and it kind of takes me to the beginning of this project. And this study was basically done to revamp the existing approach to predicting risk of mortality in patients hospitalized with heart failure. And there was an article in New England Journal of Medicine, I think, by Dr. Vyas, I think a year ago, where they talked about reconsidering race in medicine and in risk prediction particularly, and talked about a heart failure score, the guidelines heart risk score, which in its original form assigned black race as a lower risk for calculating risk of in-hospital mortality. And the authors had rightly raised concerns about assigning lower risk to black individuals compared to individuals of other races, as it may lead to potentially raising the threshold for allocating risk-based clinical therapies and add to existing disparities in heart failure care. Let's work with that for just one minute and bring Dr. Lewis in because I think he has a historical perspective on that very set of sentences you just articulated. Dr. Lewis, what can you tell us about the history of using these risk prediction models for hospitalized patients with heart failure who happen to be self-described as African American or Black? Well, I think the risk is if it's an oversimplified model in which race is now conflated with a variety of other factors, it can actually lead to potential more disparities. So historically, we've simply asked the question, what is the race of the patient? And if there is a lower risk of in-hospital mortality, there could then be an assumption in future risk calculators that you can assign a lower risk, which could actually have unintended consequences, including having policy changes, medical decision-making, and even resource allocations that can be different. So that's a terrific historic context. And what I can add to this discussion is that think about how overly simplistic it was in past models and past research to just use race as a global descriptor of a patient cohort. This gets us back to Ambrose because you actually did something very novel and helped us better understand to what extent race was serving as a placeholder for other variables, other circumstances. So why don't you tell us about your really important methods here? Yeah, so just building on that context, so basically we try to address that question that if self-reported race is an oversimplified representation of the potential underlying factors that may be driving risk of mortality in self-reported Black or African-American individuals. How can we best identify risk in these individuals? So we wanted to look at several potential underlying biological factors that drive risk and the social determinants of health that are truly responsible for existing disparities by race.
So for the audience that's listening, what you just said, Dr. Pandey, was novel and triplicate. First of all, you challenged the notion that there is a biological underpinning for race-based differences in our case, cardiovascular medicine. Second, you did a very exhaustive review of covariates, comorbidities, and the usual descriptors like income, et cetera, to use machine learning to better identify, is there a suite? Is there a set of those parameters that aptly defines race? But then you took it to the next level, and that was incorporating the social determinants of health. Give us one or two sentences about how you did that precise task. That was one of the more interesting questions that we wanted to delve into because we and others have shown before that social determinants of health are the key drivers of disparities. And the challenge with studying social determinants of health and health sciences has been the ease of availability of these data at an individual level. So what we did was we linked the zip code of patients' residents from the Get With The Guidelines hospital registry with existing zip code level data on social determinants of health that are available publicly through the different indices like the STI and DCI, which are basically zip code level measures of social determinants of health. And that's the Social Vulnerability Index and the Distressed Communities Index for everyone listening. Go ahead. Yes. And then we link that as a zip code level measure of social determinants for patients who are hospitalized with heart failure and then incorporated it in our ML machine learning models to see whether or not they contributed to predicting risk. And we also looked at the extent to which these social determinants may be contributing towards risk of mortality in self-reported Black individuals and individuals of other races. And it was interesting that once you built the models, you actually did yet another maneuver, which was to take race out of the equation altogether and demonstrate that the model was sufficiently predictive, that the race requirement was not there. But then brilliantly, and I use that word intentionally, you demonstrated that the adjustment for social determinants of health mattered for those that were self-described as Black or African American, less so for the other races. And so I thought that was really quite stunning. So in your voice, Dr. Pena, what's the take-home message here? Yeah, I think that's exactly right. And that was one of the advantages of the machine learning model was that it develops a forest and the trees for the risk prediction in a way that the factors that drive the differences in risk are aligned in a way that even if you take the race out of equation, it still prioritizes the key factors that are driving risk so that the model performance is not limited. I think the most important finding coming to your second question is that the ML models that incorporate social determinants of health are far superior to predicting risk than the existing rather simplified risk prediction models that use traditional statistics and often incorporate race as a covariate. I think as we move forward in medicine, as risk-based approach to care is taking a front seat, we have to think about how to predict risk and allocate resources accordingly to patients who need it the most by looking at the true drivers of the disparities in risk. So, Dr. Lewis, Dr. Panty has done really, I think, important work, and you offered us an editorial on this work, and we'd love to have you summarize your takeaways. Absolutely. Thank you very much. And I also would like to commend Adipandi and the authors. I think this is really important. It allows us to really focus on modifiable social determinants of health. I think we need to better understand how these social determinants of health may influence the decision at the emergency room or the emergency department level to actually admit patients. Maybe there's a bias in terms of who gets admitted for patients who come from distressed communities and who may have difficulty. But I think the big issue is going to be beyond the hospital, because most patients actually get discharged, but we all know that they remain at increased risk for morbidity and mortality, far beyond the discharge.
Okay, welcome. This is the 120th episode of the Divine Intervention Podcast. My name is Divine. I am an R01 Reology resident, I guess PGY2. And today I'll be continuing my rapid review series for the USMLE Step 1. And I will be, so this will be series, I mean, sorry, for the USMLE Step 2CK, and this will be series 4, and I'll focus on a broad range of subjects, but again, I will try to hit internal medicine pretty hard. So let's go ahead and begin, right? So what if you get a question about like an 80-year-old person that, you know, is losing their way, like coming back from a store, excuse me, and they forget to turn off the stove and the MMS is like 20 over 30. What are you thinking about? Right. That is clearly Alzheimer's. Right. So those people have Alzheimer's. And remember, in Alzheimer's. Right. What is the neurotransmitter that is classically low? That would be acetylcholine. And unfortunately, your friends at the MBME, they love to test your ability to integrate neurological disease with neuroanatomical relationships. So the thing is, in Alzheimer's, there's low levels of acetylcholine. thing is if that's all you needed to know everyone will crush step two right but unfortunately that's not the case so they kind of take things a step further right so remember that acetylcholine is made in the basal nucleus of mynert right so when a person has this dysfunction of the basal nucleus of mynert they will have symptoms of alzheimer's disease right and another way they also love to test it on exams is remember that the rate limiting enzyme in the synthesis of acetylcholine is an enzyme known as choline acetyltransferase right so if you have dysfunction of that enzyme right you again that will increase a person's risk of like an acetylcholine deficiency and alzheimer's right and then don't forget right that kids with um um kids with down syndrome right they tend to get early onset alzheimer's because they have trisomy 21 so they have too much of the pre-seniline gene if you may right so if you know right off the bat that a deficiency of acetylcholine is kind of like involved in many of the symptoms in Alzheimer's, or at least in the pathophysiology, you then ask yourself, okay, so how do I treat Alzheimer's, right? So obviously, you want to do something that involves bumping up your levels of acetylcholine, right? So you want to do something like an acetylcholinesterase inhibitor. And those acetylcholinesterase inhibitors that I use for Alzheimer's, you do actually need to know them specifically, right? There's three of them, like a DRG, right? So the one is a donepezil, right? And then the next one is galantamine. And then the next one is a rivastigmine. They are all acetylcholinesterase inhibitors that are used in the treatment of Alzheimer's. Okay. Now, what if you get a question about a kid, you know, let's assume it's a kid that, so this will be a PEDS-focused stem, I guess. What if you get a kid that has, the location of this kid has episodes where he cries and he becomes cyanotic. And let's assume they tell you that, oh, when you listen to his heart, you hear like a harsh, hollow, systolic murmur at the left lower sternal border. What am I going after here? Well, I really hope you're thinking about Tetralogy of Fallot, right? Tetralogy of Fallot, remember, it's a common congenital heart disease, and you should hopefully remember the four findings, right? So those people tend to have, and again, when I give an anatomy lecture in the future on congenital heart disease, I will explain the pathophase with a diagram. It's actually something that's pretty easy to understand. Right.
Because if you understand the pathophase behind Tetralogy of Fallot, it makes perfect sense. Right. But those people, right, they have like the pulmonic stenosis. They have the, in in fact maybe let me try to take a small stab at um explaining it right so the thing is when you want to form the um usually usually the thing that happens is that this is again this is a generalized explanation right again i'll go into more detail in a future podcast. But the thing is, the aortic pulmonary septum usually tries to meet up with the muscular interventricular septum, like sort of align nicely with it. So I sort of think of it as you're trying to form a straight line and you want the aortic pulmonary septum to fall right on top of the muscular interventricular septum. Well, if things don't work out so well and the aortic pulmonary septum comes and descends to the right of the muscular interventricular septum, it's like you're not dividing the two sides of the heart very well. It's like one side has a ton of space, and then another side has very little space. And the side that has very little space, guess what, is the right side of the heart, right? So if you sort of understand that basic pathophys, you see that, again, a lot of what you observe makes sense. Because the uricopulmonary septum and a lot of it is coming off to the right, then that means outflow from the right right side of the heart is very restricted. So those people should have pulmonic stenosis, right? And then because they have pulmonic stenosis, the right ventricle have to work real hard to get blood out. So you have a hypertrophied right ventricle. And then because that overriding a order is not meeting nicely in the middle, you'll notice that those people will have a VSD. You'll have a VSD because again, you're literally creating a space because things are not lining up as they should right and then obviously they have an overriding aorta overriding aorta because it's just taking more space than you should ordinarily take because the aortic pulmonary septum is not dividing things as it should remember the aortic pulmonary septum i mean look at the name aortic pulmonary septum it's a septum between the aorta and the pulmonic trunk right so if you are not dividing things equally and you give too little space to the pulmonic trunk, you have pulmonic stenosis and you give too much space to the aorta, you have a right in aorta, right? Those are the four things that work with Tetralogy of Fallot, right? And remember the pathophys behind those Tet spells, right? So remember those Tet spells because the problem with Tetralogy of Fallot is because you have right ventricular hypertrophy, those kids have a right to left shunt. Remember, any shunt that is right to left is cyanotic, but any shunt that is left to right is asyanotic. So that's why they have those tet spells. With those tet spells, those kids, they cry or they squat. And when you squat, right, guess what you're doing? You're compressing on your blood vessels. So you're increasing systemic vascular resistance. When you up that systemic vascular resistance, right, blood will be harder to eject from the left side of the heart. So you basically turn that right to left shunt to a left to right shunt, okay? And you basically reverse the cyanosis, right? So that increase in systemic vascular resistance or afterload promotes a left to right shunt, right? So that's the pathophase behind those tet spells helping under those, oh, I guess those maneuvers helping under those circumstances. And then just again, some key buzz phrases you want to remember for your order cardiac things, right? Or some other, I guess, high-yield cardiac associations. Again, since this is just a rapid review series, remember, right, they love to test this wide fixed split of the S2 heart sound, right? They love to test that in the context of an ASD, right?
You should be thinking about aortic stenosis under those circumstances. Remember, it's a systolic murmur, right? Heard best at the right upper sternal border, right? And remember that those people, you have to replace the valve. You're not going to be messing around with, let's do a valvuloplastine. You don't do any of that crap. Replace the valve, okay? And remember that once they start having symptoms, their life expectancy is actually pretty minimal, right? So remember, I think I used this mnemonic, ashnemonic ash to remember like oh in order of like decreasing life expectancy right so if they have like so the a stands for angina the s stands for syncope and then the h stands for heart failure if a person with aortic stenosis has heart failure symptoms their mortality within a year is i think like 50 or some? So that's a high-yield thing to know. And then if you see a person in their 50s with aortic stenosis, right, you want to think about a bicuspid aortic valve, right? That's pretty classic for aortic stenosis there. And remember, people that tend to get bicuspid aortic valve early are people that have, like, Turner's syndrome, right? Like, Turner's syndrome. Remember, Turner's syndrome has some other high-yield associations. In addition to the bicuspid iotic valve, they have like congenital lymphedema, right? So those are cystic hygromas. And then remember that they can also have coarctation of the udder, right? So if they give you a Turner syndrome patient that has hypertension in the upper extremities and hypotension in the lower extremities, think about a coarctation of the udder, right? And then remember those people, they also have like a hypergonadotropic hypogonadism, right? Because they don't have, their gonads basically don't work, right? So their FSHLH levels will be high. So that'll be a cause of hypergonadotropic hypogonadism, right? And then remember that they can also have horseshoe kidney, right? So again, if they describe recurring UTIs in a lady that is like four foot and some inches tall, right? Think about horseshoe kidney, right? Because remember those Turner syndrome kids tend to be pretty tiny, right? They tend to be like short, right? So think about like horseshoe kidney where the inferior poles of the kidney fuse, they're stuck on there, the inferior mesenteric artery, right? Again, these are all integrations you need to, that's the thing, like I tell people this, I tell all the people I tutor this, doing well on these MBME exams is not about how much did you memorize. Of course, like you need to have a good memory to do well on this. To be honest, actually, you don't need a great memory. You just need an okay memory. The thing that is important is being able to, one, be a good test taker, and then two, just be able to integrate concepts amongst multiple fields. That's why I do these rapid review series. It's really like literally from requests like, Devine, how do I put this together? That's why I love to do these kinds of podcasts. Okay, so back to the real world, right? So I just talked about aortic stenosis. Now, if you get a question, right, about a person that has, they have like bounden pulses, they have this diastolic murmur that is heard best at the left lower sternal border and then you notice that their blood pressure is like 150 over 50 right so they have like a super wide pulse pressure what murmur are you thinking about I really hope you're thinking about aortic regurgitation right in fact let me tell you this trick for mbmes if you ever see a wide pulse pressure on an MBME exam, your next thinking step is, am I dealing with a kid or an adult?
That's the right answer. If it's a kid, it's very likely going to be patent ductus arteriosus. That is the right answer. The thing is, aortic regurg and patent ductus arteriosus, those things tend to have fairly similar, like, hemodynamic consequences, if you really think about it. Again, that's something for, not something I'm going to be discussing in a rapid review lecture, but it's just one of those things you want to keep at the back of your mind for exams. Again, I promise you, take these MPMEs, take your real exam. You'll see that all these things I'm saying are true, right? And then what is the congenital heart condition that's classically associated with people with Marfan's? Right? So people with Marfan's, they tend to get what? Mitral valve prolapse, right? And I hope you remember the pathophys buzzword for mitral valve prolapse, right? That'll be your myxomatous degeneration, right? Myxomatous degeneration. And then they also can get like aortic dissection, right? And remember, in aortic dissection, the buzz phrase you want to remember is like a cystic medial necrosis, okay? Cystic medial necrosis or cystic medial degeneration. They love to test those for whatever bizarre reason on MBMs, right? So remember Marfan syndrome with those, right? And then also remember like those other connective tissue diseases like Ernest Danlos, right? Those things can be associated with like aortic dissection as well, aortic valve problems. Also, if a person has ankylosing spondylitis, it has an association with aortic problems, right? And then also don't forget, right, if a person has syphilis, remember syphilis loves to torch the vis-a-vis of your aortic arch that can also cause an aortitis, right? And then what if you get a question about a person that has like, you know, they're an immigrant from a developing country and you hear a diastolic murmur with an opening snap at the apex, right? What are you thinking about there? I hope you're thinking about, again, mitral stenosis, right? Mitral stenosis. So why did I mention the term immigrant? Well, I mentioned that term because they likely had an upper respiratory infection that was likely from strep pyogenes, right? So group A strep, and then it was likely not treated, and then they got mitral stenosis from that, right? So remember that their biggest risk factor for mitral stenosis is rheumatic fever, right? That's how you ought to know for exams. And then remember that mitral stenosis itself is the biggest risk factor for AFib. Again, they love to test these risk factors on step 2CK on step 3, right? And then remember that your biggest risk factor, right, for like a myocardial infraction for AAA smoking, right? And then your biggest risk factor for strokes and voyeuric dissection is hypertension, right. These are things you should have on your fingertips as you prepare for these exams. Now, what if you get a question about a patient that has a continuous machine-like murmur? Like they say, oh, you'll hear this murmur throughout the cardiac cycle. What are you thinking about, right? That's pretty easy. That's a patent to Dr. Sartorius. And then remember, people that have a history of like carcinoid syndrome, right? Remember, carcinoid doesn't cause any problems if it's in the bowel, right? Because the liver has the ability to metabolize a carcinoid. But remember, again, carcinoid is a tumor that makes serotonin, right? Pretty much, right? So remember that in carcinoid. But, and remember, again, carcinoid is a tumor that makes serotonin, right, pretty much, right? So, remember that in carcinoid, you need meds to the liver to begin to have, like, systemic problems, right?
And the way I remember the right-sided heart problems is, like, with the pneumonic tips, right? So, like, tricuspid insufficiency and pulmonic stenosis, right? So those people have those kinds of symptoms. The reason you don't get left heart problems with carcinoid is, again, the lungs has the ability to metabolize that serotonin, right? Remember, the lungs, in addition to helping with, like, oxygenated function and all that crap, your lungs are actually pretty solid metabolic organs, right? I mean, like your angiotensin converting enzyme, where do you think it's found? It's found in the lungs, right? It's found in the endothelium of the capillaries of the lungs, right? So your lungs have the ability to work on a serotonin. And you do need to remember the right, and again, I apologize if this podcast seems kind of random. I'm literally like about to go to bed. It's almost 1130. I'm literally about to go to bed. I'm literally just sitting on my bed, just saying out Step 2 CK related things before I sign off and go and sleep but basically um um people with carcinoid right so remember one of the breakdown things from uh serotonin is something called 5-hi-a-a right so remember that if a person has carcinoid you screen first by checking levels of, like you observe elevated levels of 5-HIAA in the serum or in the urine. And the thing is, one nifty way your friends at the NBMA actually love to test that 5-HIAA concept is in the context of depression. So we know that people that right? If you remember like the monoamine theory of depression, those people tend to have low levels of serotonin, norepinephrine, and dopamine, right? So the thing is, if a person is depressed, they probably have low levels of serotonin metabolites in their CSF, for example. Like what? 5-HIAA, okay? So that's a very nice way they can test that factoid on MBME exams. Right? So those are, I guess, kind of like the cardiac things I want to... Actually, let me say one more thing about carcinoid syndrome. So the thing is, carcinoid syndrome, right, you're basically making a ton of serotonin. The problem there is serotonin ultimately comes from tryptophan right i mean another name for serotonin is 5-ht 5-hydroxy tryptophan right so if you're burning up all your tryptophan in making serotonin there is some other high yield amino acid you're not making like niacin right, right? If you're not making niacin, that's a problem, right? Because you can get pellagra with that, right? So you get like the four Ds, the dermatitis, the diarrhea, the dementia, and then the bad D that is death, right? So that's one way they can integrate carcinoid syndrome with pellagra, right? With like a niacin. Remember, niacin, if I'm not mistaken, it's vitamin B3. OK, so again, those are all high yield things to know there. OK, so let me maybe talk about one more topic and then integrate a few more things and then I'll sign off for the day. Let's see. What can I talk about? Okay. So what if you get a question about a patient that... Let's see. So what if you get a question about a patient that over the last three months, he has been feeling really tired, like just feeling super fatigued. He has been losing a ton of weight. He has been having like skin hyperpigmentation. And then you get some labs, right? And then you notice, you're like, man, your CBC looks terrible. You're like, man, this person's eosinophil count is like 15%. And then you look at their BMP, you notice their sodium is like 123, their potassium is like 6.5. What are all those things leading you towards? I really, really hope you're saying Addison's disease, right?
So you're no longer making aldosterone. Your zona fasciculata will not work. So you're no longer making cortisol. And your zona reticularis will also not work. So you're no longer making sex steroids. Although that's maybe not the most important consideration in the world. But you won't be making things like GHEAS anymore. So let's sort of revisit that right so the thing is uh addison's disease right so you see all these things i posed in the q stem right they have hyponatremia because remember when you have an aldosterone deficiency remember aldosterone right so if you go way back to step one you remember like the distal nephron that has like the collecting duct with the principal cells? Remember on the urine side of the principal cells, you have this Enec channel that reabsorbs sodium. That's under the activity of aldosterone, right? And then as sodium is being reabsorbed, you create a negative charge on the urine side that draws out potassium through, I believe, a channel known as the Rhum-Key channel, right? And then you waste potassium in the urine. So aldosterone's job is to reabsorb sodium, waste potassium, right? Easy enough, right? So if a person has an aldosterone deficiency, basically they have Addison's disease, they will have hyponatremia because they are not reabsorbing that sodium, and they will have hyperkalemia because they are not wasting potassium. That's one thing. Next thing is those people tend to get a metabolic acidosis, because if you really think about it, aldosterone, if you scale a little further down in the distal nephrine, right, you have those alpha-intercalated cells. Those alpha-intercalated cells, right, on their urine surface, they have a proton pump that literally just dumps protons into the urine. So the problem is, again, if you have an aldosterone deficiency, you will not be able to dump those protons in the urine. And if you don't dump those protons in the urine, you retain them. And the thing is, if you want to sort of take this thought to a logical conclusion, those people, the metabolic acidosis they have is a non-anion gap metabolic acidosis, right? And taking this even a step further, remember, that non-anion gap metabolic acidosis, right? I mean, it's literally arising from a hypoaldosterone state, right? So that's literally a type 4 renal tubular acidosis that you got there, right? So remember, anything that causes a hypoaldosterone state will cause a type 4 RTA, right? So again, that's a high-yield way to sort of put Addison's disease together with your non-anion gap of metabolic acidosis, right? And then remember, right, people with Addison's disease, they have this eosinophilia, right? So remember, you definitely, like, this is one of those things where you'll be doing yourself a huge disservice if you take Step 2CK without knowing this. You absolutely, positively need to know the differential diagnosis for eosinophilia. It just shows up too often on the internal medicine shelf exams, on the surgery shelf exams, on the MBMs for Step 2CK, on the real exam for many people, right? And that differential is something called DN. I kind of borrowed this from many different sources and then I've progressively expanded it as time has gone on. But probably the more complete one is DN quadruple ACP, right? So what does that stand for? The D stands for drugs, right? The N stands for neoplasms. The first A stands for like Addison's disease. The second A stands for acute interstitial nephritis. Remember that with the threat of a fever rush and eosinophilia. The third A stands for allergies, right? The fourth A stands for asthma, right? And then the, so DEN A, C, P. The C stands for collagen vascular disease. So your autoimmune crap like lupus, scleroderma and all that. And then the P for parasites.
Well, here's the thing. The thing is steroids, glucocorticoids, basically, they cause apoptosis of eosinophils, right? So the thing is, if you have glucocorticoid deficiency, because your zona fasciculata is all knocked out with Addison's disease, well, your eosinophils will persist for a longer time in the serum because they're not just going to die. They're not going to like die before their time pretty much, right? So you have an eosinophilia with that, okay? If you ever see a CBC or eosinophilia, that should be a gimme question on an MBME because they're essentially telling you the answer. Once you know that differential, chances are you'll be able to get to the right answer, right? So how do we diagnose Addison's disease, right? Classically on MBMEs, what you will do is you will do something called an ACTH stimulation test, right? Because if you think about it, if you give ACTH, right, if your adrenal glands don't work, right, your cortisol levels will not rise, right? Your cortisol levels will not rise. So failure of your cortisol to elevate with acth administration is pretty good with regards to diagnosing addison's disease and obviously if you want to treat addison's disease you need to replace the mineralocorticoid they are missing with the fludrocortisone and then you need to replace the glucocorticoid they're missing okay again, remember you have sodium and potassium problems when you have primary adrenal insufficiency. If you had secondary adrenal insufficiency, so let's say for example, you have like some reason why you're, I don't know, like Sheehan syndrome or some weird crap where you're not making ECT, so you're not stimulating the adrenal glands. You're not going to have sodium and potassium problems, right? Because remember, your sodium and potassium balance is maintained primarily by aldosterone, right? And aldosterone is under the control of the renin-angiotensin-aldosterone system. So if your adrenal gland itself is not all screwed up, then that's not a problem at all. That is literally not a problem, right? Because reninnal angiotensin system sort of starts, kicks off in the kidneys. The adrenal gland is right there. It's not a huge issue. So you will get like the eosinophilia and all the other weird crap, but you won't have like the, you won't necessarily have the hyponatremia or the hyperkalemia, right? Because again, your aldosterone is alive and well. The reason you get those problems in primary adrenal insufficiency is like literally angiotensin 2 has no sites to act on because the adrenal gland is essentially gone, right? So on this whole topic of primary adrenal insufficiency, right? So why do they have the skin hyperpigmentation, right? Clearly, they have that because remember, there's this agent known as POMC or pro-opio-melanio melanocortin right that is a precursor to ACTH and MSH right and so an MSH right is melanocyte stimulating hormone so if you're making a ton of ACTH because there's no negative feedback from the adrenal gland because you're not making cortisol you'll be making MSH at the same time you. You stimulate your melanocytes. And you get a skin hyperpigmentation. And some other weird high yield things. You want to know there. So remember the term. Pro-opio-melanocortin. That should kind of tell you. What POMC gives rise to. So if by some weird chance. You're step one or you're taking step three in the future and you're listening to this podcast, because believe it or not, on step three and also on step two, CK, to a very large extent, they test these basic science thingies every now and then. So what does pro-opio-melanocortin stand for? So pro, I mean, let's break down the term pro. So precursor, opio, so some kind of opioid-related thingy.
Welcome back to Run the List, a medical education podcast in partnership with McGraw-Hill Medical. Our hosts are Dr. Naveen Kumar, Dr. Walker Redd, Dr. Emily Gutowski, Dr. Joyce Au, and myself, Blake Smith. As a quick disclaimer the most important areas in the practice of medicine, goals of care conversations. We're really thrilled to have Dr. Andy Lawton as our guest expert to share his wisdom today. He's a palliative care physician at Dana-Farber Cancer Institute, as well as director of communication skills education in their department of psychosocial oncology and palliative care. He's also really involved in medical education within the Brigham and Women's Hospital internal medicine residency. Dr. Lawton, thanks so much for being here with us. Joyce, thanks for having me. I've listened. I've heard so many great things about Run the List. Really glad to be joining you guys today. That's really kind. We're really, really excited to have you. So before we dive into a case, I think it's important in this particular episode that we're all on the same page about some key terms. So when we refer to this idea of goals of care conversations, what do we actually mean? How does it fit into some of these other terms such as advanced care planning, MOLSTs or POLSTs, as well as this idea of determining code statuses? Absolutely. So Joyce, what we mean by a goals of care conversation is really just a conversation that explores patients' values and concerns in order to guide the treatment plan that we're going to make. And so really the intent is to create a plan of care that aligns with those values that we elicit from the patient, what matters most to them. We typically have these conversations with seriously ill patients, and that may occur early in the disease course when the diagnosis is new, when things are stable and we're just thinking about the future together, or later in the disease when things are changing and advancing in some way. We often have goals of care conversations as well when we're facing a treatment decision. And that might be things like whether to pursue more chemotherapy or whether interventions like dialysis make sense for a given patient. And in some cases, though, these conversations can be particularly urgent, especially if the decision we need to make is right in front of us, such as, for example, deciding about intubation for someone who's sick and in the hospital. And I agree with you, Joyce, there's a lot of different terms. Goals of care conversations are really one part of this broader work that we call advanced care planning, which includes actually having the conversations themselves, as well as documenting the patient's wishes on forms like a healthcare proxy form, a MOLST form, as you mentioned, or advanced directives. That's super helpful. Thanks for clarifying. So what it sounds like is that the goals of care conversations are really in its essence about understanding the values of our patients and their wishes and really understanding this idea of what matters most to them, which I love. So with that, let's dive into a case now. So I will tell you about Mr. R, and he is a 44-year-old male with a past medical history that's significant for hypertension and alcohol use disorder. He comes to his primary care physician for a follow-up after a recent hospitalization where he presented with subacute fatigue and abdominal swelling, and he was diagnosed with decompensated alcohol-related cirrhosis. When preparing for this follow-up visit, his primary care physician realizes that he hasn't yet had any conversations with Mr. R about his goals of care, as this was really his first hospitalization in his life. And the primary care physician hopes to get that conversation started today. So Dr. Lawton, let's now step into this primary care physician's shoes. Do you have a general approach to having effective goals of care conversations? And how might it maybe relate to Mr. R's case here? Absolutely. So, you know, first of all, I want to applaud you, Joyce, for suggesting that we have a framework. I think more and more we're trying to think about communication skills and difficult conversations as, in fact, a medical procedure.
We want to have a framework going in, and that's going to allow us to be more successful. The framework I use to navigate goals of care conversations is called WeMAP. And this is a five-step framework, or what we often call a talking map, for navigating goals of care conversations. And this was developed by the communication experts at Vital Talk. And I'll just kind of overview each of the five steps here, and perhaps we can get into them in a bit more detail. The first step is what we call reframing, which is really just getting everyone involved on the same page about the fact that our patient, their health or this illness that they have has changed in some important way, and we need to talk about it. And reframing the situation involves a couple steps. First, I need to ask the patient and family what they understand about the illness. Asking for understanding is really the key first step to almost any goals of care conversation. So asking their understanding, what have they already heard from other doctors, from other clinicians about this illness? If there's a key piece of information that they don't have, but they need in order for us to have an effective conversation, then I need to tell them that information. The second step in our framework is expecting and responding to emotion. And this is really a key important step throughout a goals of care conversation, but especially after we reframe the situation. Because if patients and families heard and took in what we had to say about the seriousness of the situation, about the things that we're worried about as the clinicians, then we would expect that patients and families would become emotional. And the way we respond to emotion is we use empathy. We use empathic statements to respond and help the patient and family feel heard. What's really important here, and in fact, Joyce, I would say, if folks take away nothing else from our episode today, I hope they take away this idea that expecting and responding empathically to emotion that comes up during a goals of care conversation is probably the most important skill of any that you and I could talk about. Really briefly, I would say the reason this is so important is because if you and I think about when we're emotional, it often kind of overwhelms our ability to think concretely about what to do next. We often say, oh, emotion overwhelms cognition. So if we can make space for the emotion, help patients and families feel heard, and drop the emotional temperature in the room, then not only will patients and families feel aligned with, but we'll actually be in a place where we can move forward together in the conversation. So it's often really helps us kind of unlock the conversation and move forward. Once we've made space for the emotion, then we're going to move on to the third step of our REMAP framework, which is called mapping values. And this is really a key step because what we're going to do here is pause. And before we get into the details about specific treatments, you know, doing option A, option B, chemo, no chemo, dialysis, no dialysis, we're not going to get into that right away. We're going to pause and explore what's important to this patient and family. What concerns do they have? And we're going to map out the values using what we call mapping questions. So as you look forward to the future, what feels important? What do you hope to be able to do? As you think about your health, what worries do you have? And we're going to listen for hopefully a variety of things that are important to the patient family. And we're going to end up using those values to guide the plan that we make. The fourth step is going to be aligning with patients' values, summarizing and reflecting back the things that we heard them say when we were asking about what's important, when we were asking about what they're worried about, and make sure we heard them right. The last step then, Joyce, is going to be making a plan, planning treatments that match those values that we heard. And this is really the skill of making recommendations that incorporate both the values that we heard and the medical reality of the situation we're in now. So five steps, reframing the situation.
Great. This is incredible. So I think this REMAP framework can be a really good way to walk into a room or talk to a patient with this approach in mind. So let's go back to this PCP of Mr. R's. So he does exactly this. He follows a framework such as REMAP. And he has this conversation during which he's struck by how strongly motivated Mr. R is to stop drinking and how he wants to reset his life so that he can see his two high school children graduate. Mr. R actually completes a MOLST form that documents that he wants to be full code during this conversation, and he leaves the office on both pharmacologic and psychosocial treatment for alcohol use disorder. He's followed up closely by his gastroenterologist. He's put in touch with transplant hepatology, and he does all the medical things that we won't dive into here. So nine months later, Mr. R presents the ED with hematemesis. He's hypotensive. He requires two units of red blood cells, and he undergoes an emergent endoscopic treatment of a variceal bleed. He requires a brief ICU stay and is ultimately transferred to the floor where he stays there because of a tenuous volume status. His wife comes in to visit him and they ask to check in with the team about next steps. So now I want to step back for a second. Without getting too much into, again, the medical details of this case, Mr. R's liver disease has now taken a turn for the worse. So you decide that you want to use this opportunity in the hospital to revisit his goals of care. How can REMAP apply more specifically here in what might be considered to be a later conversation when a patient has become very sick and there may be a change in urgency? Sure, Joyce. So, you know, as you say, Mr. R is certainly sicker now. And I think most of us would call this a late goals of care conversation, meaning that we're having the conversation in the context of the illness progressing as it is sort of more quickly now versus months back when we were in the clinic, the diagnosis was new, things were stable. We often call that an early goals of care conversation. And back then, we might have done the work of moving through those REMAP, the remap steps, over multiple visits, over multiple conversations. But things are different now. They're more urgent now. And we're going to revisit where we're at with the goals of care. And part of the work that we need to do now is really make sure that we're still on the same page with Mr. R and his wife about how things have changed. We want to talk, you know, compassionately and honestly, openly about the fact that the liver disease has worsened and there's a real possibility he could continue to get sicker. Again, the key part there is all going to be in that reframing, that first step of our framework. And doing this important work of reframing how things are different now is going to allow us to revisit his goals and values, really with a shared understanding of the new place that we're in, so that we can make a good plan together about what kinds of treatments are going to be helpful to Mr. R at this point, and what kinds of treatments may not be as helpful at this point. Great. So for me, as well as for our listeners, I think sample language can sometimes be very helpful. I think that actually saying the words can be very challenging. And when we try to have these conversations, we can sometimes just beat around the bush. So can you give us some words of how you can actually go through all of these steps with Mr. R? Absolutely. So I'd start by reframing. That's, again, our first step. I'd probably ask, what have you heard about what's going on here in the hospital? What have you heard or taken away from your conversations with the other doctors? I'm listening for, do they understand what's different now? Do they understand the seriousness of the situation?
And I'm going to use that information headline again, that key information that they need to know for us to move forward. So that might be something like, Mr. R, I'm worried that you're getting sicker overall as a result of the liver disease. And I hope we'll see things improve. And also there's a real chance that things could continue to get worse. And I really think we're in a different place now with the liver and your overall health than we were nine months ago. And then we're going to pause and see what reaction he and his wife may have. And again, we're expecting and going to be ready to respond to emotion at that point. This must be overwhelming. I can only imagine how hard this is to hear, naming and acknowledging or understanding the emotion at that point. We might say, I really wish things were different. I really wish this wasn't the situation we were in today, that I wish statement can be so partnering. After we've had time to express that empathy, use those empathic statements and sit with the emotion, then at some point I'd ask Mr. R, you know, given what we've talked about in this new place that we're in, I wonder if we could spend some time thinking about where we go from here. And I'd ask him for permission to kind of move the conversation forward. And we would move into that third step of the REMAP framework, mapping values. And I'd ask him, you know, given what we've discussed, what feels important moving forward? If time were shorter than we hope, what worries might you have? And what else are you hoping for? What else feels important? What else worries you? Joyce, one of the things we often find is that patients and families don't necessarily share with us the more deeply held concerns that they have or the values that they have right away. And we often have to ask several of these mapping questions in order to get a strong sense of what really is important to this patient and family. We might hear things about having meaningful time with loved ones naturally, right? Like that's something a lot of us care about. It might be about being at home. It might be about being outside and being as independent as he can be. Whatever it is, we want to make space for what those important values are. The fourth step then is going to be to align with the values that we heard. And again, that's summarizing and reflecting back. You know, Mr. R, what I hear is that staying active, having time with your family, being as independent as you can be are really some of the most important things. And I also hear that you're worried about your wife and how she might handle all this, how she might handle taking care of you if you really needed extra help. Do I have that right? Checking in, making sure he knows I was listening. He can add other things. And then I would end the conversation by making a plan, making recommendations that pull together what I heard as the important values and what I know about the medical reality of the situation that we're in. That might sound something like, Mr. R, given what you've shared with me and given what I know about this condition, I'd recommend a few things that we focus on medications and treatments for the liver disease that ideally will help you feel as well as you can and have that good time with your family that we want. And I'm hopeful that we can do that. At the same time, if you're getting sicker, I think we should avoid things that aren't likely to get you that good quality time that we're all hoping for. And that would include things like a breathing tube or CPR. I'm really worried that if you were that sick, that those things wouldn't help and might only cause you to struggle. And really, Joyce, we're ending the conversation with recommendations there, starting with the things that we do recommend. And then in this example, following up with things that we don't think would be helpful at this point, including a recommendation about code status. Wonderful. This is super, super helpful.
And also there's a very real chance that you may continue to get worse, that you use and instead of but. I think this is something that I've noticed that you can have both of them at the same time. And I think the second thing was when you talked about this plan to start with something that we would do before we dive into the things that we recommend not doing. And I think that oftentimes probably leaves patients feeling a little better than talking about all the things we do not recommend. So I want to talk about this idea of prognosis because I think that figures into how we have some of these conversations. Do you have any tips on how to broach prognoses? Absolutely, Joyce. So I think you and I could probably book a whole separate episode just to talk about prognosis. But let me share a few thoughts about that. I often ask patients how much they want to know and what kind of information they want in terms of prognosis before I start giving information. Because people can mean different things when we start to get into the prognosis space. Some people want to know about time in the way that we typically think about prognosis, but other people may want to know about other things. Maybe it's about how they're likely to feel or how functional they're likely to be, what kinds of things they'll still be able to do over time. And maybe other people want to know about, are they going to make it to a certain life event? So I first try to pause and ask, what kind of information would be helpful? And then when we're actually getting into sharing information that I hope and I worry language again can be really helpful. So maybe for Mr. R, it might sound something like, you know, Mr. R, I really hope that we have a long time, even years. And also I worry that some patients with this liver disease can get sicker quickly. And it's possible that time will be shorter than we hope. ethically, giving a general recommendation such as, I think you should continue treatment, I think you should stay full code based on some of your values, which for some people can be seen as very paternalistic, and balance that with giving patients the ability to choose from a menu of options in all these different scenarios, which may foreground patient autonomy over specific choices. How do you balance those two aspects? Joyce, this is such an important question. And I would say a few things. Many of us are taught, I think, in medicine, or it's modeled for us, that we should, as you say, present patients with a variety of options and then allow them to decide what feels right for them. I think many of us have seen clinicians do that. And while that certainly comes from a well-intended place, I think this idea of presenting a menu of options often ends up being pretty challenging for patients and families. Most patients don't have the medical background to weigh the complexities, the nuances of decisions about being in the ICU or dialysis or chemotherapy. And furthermore, we want to remember that we're often talking with patients and families about these decisions during some of the most stressful emotional moments in their lives, which really makes it even harder for folks to weigh these decisions and weigh options. And really, most often patients and families are looking for our guidance. And I see it as my job to give them that guidance wherever possible, to make recommendations to them. This is so, so important. I, of course, want the patients and families input, and I'm going to ask for that. But I give my recommendations first. Making recommendations, Joyce, is just so important. And frankly, it can be really a gift to patients and families. One story comes to mind from my own training. I'll always remember talking to this mother of a patient I was caring for during my residency. And this young gentleman was declining pretty quickly. And as a team, we were worried that he may die even very soon. And after exploring their goals and values, we made a recommendation to this patient's mother against going back to the ICU, against being re-intubated. And she looked at us and she said, thank you. You have no idea what this means to me. And Joyce, I was so struck by that reaction from her.
And it was clear that what she meant was that she was relieved of the fact that she wouldn't have to carry the weight of having to have made that decision with her forever. She could hold a narrative of, I just followed the doctor's guidance. I just did what the doctors recommended that I do. And that was so powerful. So making recommendations can be so helpful, so valuable to our patients and families. Thanks so much for sharing that story. I think it really strikes a chord with those family members who feel guilt for withdrawing care and having permission from their doctors to do less rather than more can be really liberating sometimes. So I want to turn towards now cases in the ICU, for instance, where patients are really, really sick and their families are seeing them every day and they feel very strongly that the length of time that they live and even hope that the smallest chance is really important. So in cases like these, I think sometimes we consider recommending time-limited trials for intensive or aggressive interventions. Can you define time-limited trials and tell us a little bit more about your thoughts around this? Sure, Joyce. And just to say, I think the example you're giving in the ICU, really sick patient, family that is hoping that what we would consider to be more intensive or aggressive interventions are going to be continued, I think this really gets to the heart of what's challenging about these conversations. Specifically with regard to time-limited trials, I agree. I think this can be a really valuable tool and concept to bring into our practice. So with a time-limited trial, we establish that we're going to try a given intervention for a defined period of time to see if it's helpful. And we set up front how long the trial will be and what improvement would actually look like for us, what parameters we'll use to monitor for improvement. If the patient does improve and is tolerating the treatment, then we would continue it and we'll make that clear to the patient and with the family. And if it's not helping or the patient isn't tolerating the treatment or improving, then we'll discuss stopping it. And so what might recommendation language sound like that incorporates this idea of a time-limited trial? Well, maybe it's something like, you know, it sounds like your dad would do most anything for the sake of more time with his family. I really hear that. Given that, I'd recommend that we try another 48 hours on the breathing machine to see if he might improve. And if he's getting better, that's wonderful. And if he's not improving or if he's getting sicker, we can discuss how we would continue to care for him even if he can't recover. So again, Joyce, that's some of the language I might use. And I really agree with you that that time-limited trial concept can be a really helpful one. I think that's a super helpful final point to be clear about what we're talking about when we talk about timing or timeline, to be very clear that even if things don't go the way that we hope, that we're still going to intervene in ways that are supportive. So the final question that I wanted to ask is about troubleshooting. So I know sometimes conversations can get into a place where we're really kind of feeling stuck. The conversation might be going in circles. We're not moving forward. How do you think about getting stuck? In other words, what's your differential when we're getting stuck during these conversations? Yeah. So I think, Joyce, that high on our differential for why we feel stuck in conversations really has to be the idea of, am I missing emotion? And am I missing an emotional cue in the room from the patient and family? So what's notable here is if we think about places where we feel stuck, many times patients and families may be asking questions or making statements that can sound like their requests for more information when actually they're an expression of emotion. An example might be when a patient or family says, you know, there's got to be another treatment you can try. There's got to be something more you can do. We might think to ourselves, you know, why are they not hearing us?
Well, on that Indian note, welcome to the 13th episode of the Divine Intervention Podcast. My name is Divine. I am a fourth year medical student. Some friends of mine, I have an appreciation for Indian music and I've been trying to learn one song. So I was discussing with some friends of mine yesterday about trying to learn this specific song. That was just a teaser release for my new album. I'm just kidding. But hopefully I can learn that song at some point in the future. Okay, so today we're going to be talking about metabolism. I'm going to break this up in parts. Metabolism is something that's probably a little too big to discuss in one podcast. So I'll discuss it over a series of podcasts. And by the end, hopefully you should have a very good review going into step one. So let's go ahead and jump right in. So the big things I'm going to say I'm going to talk about today, I'll talk about nucleoside synthesis. And I will also talk about some problems with proteins and drawing a lot of like pharmacology and other biochemistry and pathology and all that crap. So let's go ahead and start. So summary of nucleotide synthesis. Remember that nucleotides include DNA and RNA. So to make DNA and RNA, you do in fact need nucleotides. And nucleotides basically contain a sugar, a nitrogen base, and a phosphate group. Okay, a sugar, nitrogen base, and a phosphate group. So that nucleotide, the precursor to a nucleotide is a nucleoside. A nucleoside is just the sugar and the nitrogen base. You haven't added a phosphate group just yet. Okay, but those nucleosides need to come from a nitrogen base. And those nitrogen bases can be one of two kinds. It can be a purine or it can be a pyrimidine. So you start with the nitrogen base. If you add a sugar, you form a nucleoside. If you form a phosphate, you form a nucleotide. And those nitrogen bases, like I said, they can be one of they can be a two ringed nitrogen base they are called the purine nitrogen bases those include adenine and guanine okay and the way you differentiate between adenine and guanine is adenine has an amino group at a like the top most position like the 12 o'clock position guanine has a ketone right so it has like a carbonyl group carbon double bonded to an oxygen the pyrimidine nitrogen basis they're one base they're one ring uh nitrogen basis okay and there's three kinds there is cytosine there's uracil and there's thymine uh there's a classic mnemonic, cut the pie, that can help you remember those three. And one nice thing about them that I think is actually kind of helpful is that order also shows you how those nitrogen bases are made, right? So cytosine, if you deaminate cytosine with cytosine deaminase, you make uracil. You'll see a pharmacology time with that in a bit. And if you methylate uracil, you actually form thymine. So you'll see a pharmacology time with the first step shortly. And this sugar that joins up with a nitrogen base to form a nucleoside, where does this sugar come from? The thing is the sugar actually comes from the hexose monophosphate shunt, which is also known as the pentose phosphate pathway. So that pathway makes ribose 5-phosphate. That ribose 5-phosphate can join up with a pyrophosphate group from ATP, right? So two phosphates to make something called phosphoribosyl pyrophosphate. And the enzyme that makes that happen is PRPP synthetase, okay? So that's a summary of nucleotide synthesis. So now we know how to actually synthesize nucleotides. Let's then go into a little bit more detail. But first, let's talk about pyrimidines. As you can see on the second slide, I say that pyrimidines, to make them, you make the nitrogen base first and then you add the sugar.
So let's talk about pyrimidines. Let's make the nitrogen base first and then we add the sugar. So to make the base first, all of this actually happens in the cytosol or nucleotide synthesis in general happens in the cytosol. So the first thing that happens is that you condense glutamine and carbon dioxide with some other stuff. And you make something called carbamoyl phosphate and the enzyme that makes this happen is cps2 carbamoyl phosphate synthetase 2 okay and again this is a cytosolic enzyme uh there's a cps2 you should probably know that there's a cps1 okay remember the one in cps1 as being like an eye to help you remember that cps1 works in the mitochondria okay works in the mitochondria of the urea cycle we'll talk about that in a later slide okay so you make carbamoyl phosphate and then that carbamoyl phosphate is then made into erotic acid by some magic that we don't are not really interested in for the purposes of board exams and then that erotic acid is the nitrogen base. So we've accomplished our first objective. Okay. Now we want to make a nucleotide. Okay. So we are adding a sugar and we're adding phosphate, right? And that's done by an enzyme known as UMP synthase. UMP synthase takes that phosphoribosyl pyrophosphate I talked about on the previous slide. Okay. and helps us make uridine monophosphate. I'll talk about pathology associated with that in a bit. And then that UMP is made into UDP. Don't care much about that. But that UDP is a ribonucleotide, okay? UDP is a ribonucleotide. The thing is, we have RNA and DNA. If you want to go down the DNA pathway, you need to convert your ribonucleotides to a deoxyribonucleotide the thing is we have rna and dna if you want to go down the dna pathway you need to convert your ribonucleotides to a deoxyribonucleotide ribonucleotides in general have hydroxy groups at the two prime and the three prime uh carbons of the sugar structure okay but a deoxyribonucleotide does not have that two prime hydroxy group it only has that three prime hydroxy group that it uses to form those phosphodiester bonds with a 5' phosphate. So to remove that 2' hydroxy group, we need an enzyme known as ribonucleotide reductase. I'll talk about some pathologies related to that. So that UMP, DUDP, you can clip off a phosphate, make DUNP, and then that DUNP can then be be converted to D-TMP and if you remember I said that the difference between uracil and thymine is a methyl group okay so this reaction clearly needs a methyl donor okay and one high yield methyl donor that exists in the body is the methylated form of tetrahydrofolate the methylated form of tetrahydrofolate can give a methyl group to D-UMP, and then we make deoxythymidine monophosphate from that. And then that cycle needs to keep going, and I'll talk about some pathologies relating to that shortly. So, what are those pathologies? If you go to the very top of the slide, top right, I guess, I talk about how having a UMP synthase deficiency is associated with erotic aciduria. The thing is, if you have a deficiency of the enzyme that metabolizes erotic acid, obviously your levels of erotic acid in the serum will go up. You'll see how this is related to another disorder that I'll talk about in a later slide. Now, ribonucleotide reductase helps you go from RNA land to DNA land. The thing is, you can actually inhibit that enzyme with an anti-cancer drug known as hydroxyurea. Hydroxyurea, yes, it's an anti-cancer drug, and it is in fact used for some hematologic malignancies. But the thing is, hydroxyurea is primarily used in the real world for the treatment of sickle cell disease, okay?
Now, if you then jump down to thymidylate synthase, thymidylate synthase, which helps us go from DUNP to DTNP, that enzyme can be inhibited by a drug known as 5-fluorouracil. Okay, 5-fluorouracil. So 5-fluorouracil is an anti-cancer drug. The thing is, if you look further upstream, there is an arrow going from 5FC to 5FU. The 5FC actually stands for 5-fluorocytosine. If you remember, this is an antifungal that is used to treat cryptococcal, neoformance, meningitis in AIDS patients. The way 5-flu-cytosine actually works is that it is deaminated by cytosine deaminase. Remember that principle I talked about on the preceding slide. Cytosine deaminase converts the 5-flu-cytosine to 5-fluorouracil. That 5-fluorouracil inhibits thymidylate synthase. You make less thymidine monophosphate, and then you basically treat the cryptococcal meningitis. So that's a very nice tie-in there. Now, I also said that for thymidylate synthase to work, you need a methyl group coming from methylene tetrahydrofolate. So when methylene tetrahydrofolate gives that methyl group to thymidylate synthase to make DTMP, dihydrofolate is made as a byproduct of that reaction. If you want to keep thymidylate synthase doing its job, that dihydrofolate has to be reconverted back to tetrahydrofolate by an enzyme known as dihydrofolate reductase. This enzyme is inhibited by methotrexate, trimethoprim, and pyrimethamine. Methotrexate, remember, it causes pulmonary fibrosis as a side effect, and it can also cause a liver dysfunction. And remember that methotrexate can be used to treat hydratidiform moles, right? So like molar pregnancies. Remember the snowstorm appearance on ultrasound of the pelvis. Trimethoprim, it's usually combined with SMX, right? So trimethoprim sulfamethoxazole to treat the pneumocystis gyrvetsi pneumonia. You can also use it to prophylax against the PCP when the CD4 count drops below 200. And remember that trimethoprim TMP-SMX by TrimRite can also be used to treat UTIs. It can also be used to treat the nocardia. Okay, remember as a review from a previous podcast, remember that nocardia is an aerobic organism. It's a gram-positive branching filamentous rod, and it's also weakly acid-fast, right? So stains positive with a zeonilcine stain. And then pyrimethamine combined with sulfur diazine can actually be used to treat the toxoplasmosis, right? So classically, if you think about an AIDS patient that has ring-enhancing lesions on an MR, on a MR magnetic resonance imaging, you think about toxoplasmosis. Okay, so that's what I'm going to say about this slide. So let's jump on to the next one. So an interesting comparison of two cycles, right? So these two cycles, they are not just, I mean, intellectually, it's stimulating to compare these two cycles, but these two cycles actually are USMLE relevant. Okay, so these two cycles include the urea cycle and the synthesis of pyrimidines. I just said that to make pyrimidines, you do that in the cytosol. But the thing is, the urea cycle actually operates in two spots in the body. I mean, in the cell. The first two steps actually work in the mitochondria, and then the final steps work in the cytosol. Okay, you may ask yourself, Devine, this is too low-yield to know. Well, think again.
So, in the urea cycle, stuff, including ammonia, is acted on by carbamoyl phosphate synthetase 1 to make carbamoyl phosphate okay that's the first step of that cycle and then that carbamoyl phosphate can be converted to citrulline by an enzyme known as onythine transcarbamylase okay so onythine transcarbamylase converts carbamoyl phosphate to citrulline okay and that citrulline can then go into the cytosol to complete the remaining steps of the urea cycle right so it condenses with aspartate and all that fun stuff now um so that is the urea cycle okay but the thing is uh if you contrast that with pyrimidine synthesis pyrimidine synthesis i said that instead of using cps1 you actually use cps2 okay cps2 carbamoyl phosphate synthetase 2, works in the cytosol, okay? It converts glutamine and CO2 with some other stuff to carbamoyl phosphate, and then that carbamoyl phosphate, by some magic, becomes erotic acid, and then that erotic acid, okay, is converted to uridine monophosphate by an enzyme known as uridine monophosphate synthase, or UMP synthase, okay? So So if you notice, I put two red star Xs in those two pathways. So first we've contrasted those pathways by location. So like mitochondria for the first two steps of the urea cycle, cytosol for all the steps of pyrimidine synthesis. But the thing is you can have two enzyme deficiencies in both pathways that can create an erotic acidemia, if you may. OK, that erotic acidemia. Right. It's like similar phenotype, but they're different. There are some extra findings that can tell you that, oh, it's this enzyme deficiency that's in operation versus this other enzyme deficiency. Right. So if you have an OTC deficiency and only think trans-cabamylase deficiency, you will have a very big buildup of carbamoyl phosphate, okay? And if you're thinking with regards to Loschuttle's principle from college chemistry, as carbamoyl phosphate builds up, okay, it can spill into the cytosol, okay? It can spill into the cytosol. That's one fate. Another thing that can happen is as carbamoyl phosphate builds up, the upstream contributor to the synthesis of carbamoyl phosphate in the mitochondria also builds up. Okay. So ammonia in this case, so you can get a hyperammonemia with OTC deficiency. But this carbamoyl phosphate that spills in from the mitochondria into the cytosol, it can actually just basically join into the pyrimidine synthesis game. That carbamoyl phosphate can be converted to uric acid and you can get an uric acidemia under those circumstances. Now, if we go to the pyrimidine synthesis side of things, if we have a UMP synthase deficiency, we have a disease known as erotic aciduria. So if you have a deficiency of UMP synthase, erotic acid builds up. But because this is part of the pyrimidine synthesis pathway and not the urea cycle, you don't have any elevations in your ammonia. So that is how you tell the urea cycle deficit, only thing transcarbamolase deficiency apart from the pyrimidine synthesis deficit, UMP synthase deficiency. And then in the middle, I put as an aside, if they wanted to make this a more nifty step one question, they could talk about, oh, a person has hyperhormonemia, sorry, they have like the encephalopathy you get with too much ammonia dancing around in your blood. But these people have no erotic aciduria. OK, you may be like, hmm, how did that happen? Right. So that's one very nice way you can test your knowledge of the urea cycle. OK, if you have a CPS1 deficiency, your ammonia will build up. But because carbamoyl phosphate is downstream of that, you have decreased levels or normal levels of carbamoyl phosphate. So that's how you can compare these three enzyme deficiencies.
If you have a CPS deficiency, it's a urethyl cycle problem. So your ammonia levels are up, but your carbamoyl phosphate and uric acid levels are down. If you have another uric cycle deficiency that's a little more downstream, onythin transcarbamolase deficiency, your ammonia levels go up because again, it's a uric cycle problem. Your carbamole phosphate levels also go up because onythin transcarbamolase converts carbamole phosphate to citrulline. And then your uric acid levels also go up because that carbamoyl phosphate spills into the circulation, I mean, spills into the cytosol, and that joins in pyrimidine synthesis, so you make more uric acid, okay? But contrast that with the pyrimidine synthesis deficit, like UMP synthase deficiency, where your levels of ammonia are normal, okay, because it's not a urea cycle problem, but your carbamole phosphate and your uric acid levels are elevated because again, these two things come upstream of UMP Synthase. And really the way you treat UMP Synthase Deficiency is just to give back what is deficient. You give back uridine in the diet and you can largely relieve the sequelae of UMP Synthase Deficiency. But if you have a CPS CPS1 or OTC deficiency, it's really bad because that ammonia can build up in the brain and cause a lot of problems for the infant. So those kids usually don't live super long, unfortunately. So next slide. So we've talked about pyrimidines. Now let's talk about purines. So let's talk about how you make purines and let's talk about how you break purines. So to make purines, we said that you start with the sugar first and then you add the nitrogenous base. So we make the sugar first. I've talked about how the sugar is made with PRPP synthetase in a previous slide. So you make PRPP and then you make something known as 5-phosphoribosylamine with an enzyme known as PRPP amidotransferase. The reason I'm mentioning PRPP amidotransferase is that it's actually the root-limiting enzyme of purine synthesis. So you definitely want to know that for step one. So you make 5-phosphoribosylamine, and then you have some magic happen, and then you make inosine monophosphate. Now, the inosine monophosphate can either be converted to adenosine monophosphate or guanosine monophosphate. And the enzyme that helps you go from inosine monophosphate to adenosine monophosphate is inosine monophosphate dehydrogenase. Now, why do I mention this enzyme? I mention this enzyme because it's inhibited by certain drugs, okay? So, one drug that inhibits this enzyme is mycophenolate morphotil, okay? It's an immunosuppressant. It's used after transplants, okay? Ribavirin, which is used to treat the RSV and also like hep C under certain circumstances, also works by inhibiting inosine monophosphate dehydrogenase. And the rate-limiting enzyme PRPP amido transferase, if you notice, I put like five red thins by PRPP amido transferase. I put AMP, GMP, IMP to help you remember the regulation of PRPP amido transferase, those products of that enzyme go back and feedback inhibit the enzyme. And then allopurinol and 6-mecaptopurine actually go back and also inhibit PRPP amide transferase. So you may be like, hmm, divine. How is that relevant to our discussion? You'll see why when we're done talking about purine breakdown. I'll talk about some integration with that. So let's break down our purines. Right. So, again, remember, nucleotide, nucleoside, nitrogen base. OK, so the nucleotide, AMPG, AMP, you pull out a phosphate, you make the nucleoside, you pull out the sugar, you make the nitrogenous base.
And then those nitrogenous bases, they can be converted by xanthine oxidase in two sequential steps to uric acid. And then that uric acid is actually poorly soluble. So if you have too much uric acid in your blood, you could get gout or you could get nephrolithiasis from uric acid stones. Remember, uric acid stones are radiolucent, so you don't see them on an x-ray, but you can see them on a CT scan. And then in birds, the uric acid could actually be converted by an enzyme known as uricase to allantoin. Allantoin is water-soluble. It's much more soluble than uric acid. So now that we understand this, we can then begin to bring in some integration. And then I'll go back to that PRPP amidotransfer story that I was fleshing out a few minutes ago. So one thing we could do is if a person has gout, right, or they have tumor lysis syndrome, where they have some kind of hematologic malignancy and the person's white cells or whatever are dying, and they're dumping a lot of purines into the serum and making a lot of uric acid that's clogging up the kidneys and also causing gout. You could try to solubilize that uric acid by giving a pharmacological agent that replicates the activity of uricase. That's where drugs like piglotticase and rasburicase come in. Piglotticase and rasburicase, they are uricase analogs that help you dissolve uric acid nicely by converting it to something that's a little more water soluble. Now, another thing you could do to prevent tumor lysis syndrome, right, is to say, okay, you know what, let me go ahead and inhibit the enzyme that helps us make uric acid in the first place, xanthine oxidase, right? So that's how drugs like allopurinol and feboxostat work, okay? They inhibit xanthine oxidase so you don't make uric acid. Now, the thing is, xanthine oxidase, in addition to helping us make uric acid, it actually has another high-yield USMLE role. One thing it does is that it breaks down 6-mecaptopurine to inactive metabolites. So if you think about it, if you give a xanthine oxidase inhibitor like allopurinone of a boxostat, you decrease the breakdown of 6-mecaptopurine. And that can do one of two things. One is that it could do a bad thing to you. It could increase the toxicity of 6-meca purine alternatively if you're a wise uh pharmacologist or physician you can actually give allopurinol with uh as part of the drug cocktail for a person that's being treated with chemotherapy that includes six make up the purine to decrease the dose of six make up the purine that you have to administer okay so that's a very nice time there now the thing is um if you have to administer. So that's a very nice tie-in there. Now, the thing is, if you want to take this nitrogenous base that you got from breaking down the purine and remaking, if you wanted to say, okay, you know what, why don't I conserve my purines instead of wasting them in the urine? Why don't I conserve them by converting the nitrogen base back to a nucleotide uh you do that in a pathway known as the purine salvage pathway okay and the one big enzyme you need to know for that pathway is hgprt okay uh hgprt stands for hypoxanthine guanine phosphorybosotransferase okay it's the enzyme that takes hypoxanthin and guanine and adds a sugar and a phosphate back. So phosphoribosyltransferase, it transfers a sugar and a phosphate back to hypoxanthin and guanine and remakes the nucleotide. So why is it important to know this enzyme? It's important for certain reasons. One is that you have, one is that it's the enzyme that helps us in the purine salvage pathway.
Okay. Lesch-Nyhan syndrome, it was actually discovered at my, at my med school by a med student, go figure, and some physician. You can look that up in your free time so lesh-nyhan syndrome it's a hgprt deficiency and the thing is if you think about it if hgprt is deficient you basically kill the pathway that helps us deal with a nitrogen basis okay because these nitrogen bases we can deal with them in one of two ways at least on this slide you can deal can deal with them with HGPRT, which is what happens more than 85% of the time, or you can deal with them with xanthine oxidase, okay? So if the 85 percentile plus pathway is gone, then this other pathway then becomes the 100% pathway, okay? So make a ton of uric acid. So gout is a classic finding in Lesch-Nyhan syndrome, although you also tend to get self-mutilation and all that stuff in Lesch-Nyhan syndrome. So one treatment for Lesch-Nyhan syndrome is that you can give a xanthine oxidase inhibitor to sort of prevent the gouty sequelae that you get with the disease. Although the self-mutilation and the neurological problems, those are unfortunately not very treatable. Now, the thing is, if you notice, another rate I put by HGPRT is isothioprine. So the thing is, isothioprine is an anti-cancer drug that is a precursor to another drug known as 6-mecapsulpurine. So the way ezathioprine works is that it's converted to a purine analog by the action of HGPRT. HGPRT helps us activate ezathioprine, helps us convert it to 6-mecaptopurine. 6-mecaptopurine has purine in the name. That should help you remember that it's a purine analog. So 6-mecaptopurine goes and inhibits PRPP amidotransferase. And by inhibiting PRPP amidotransferase, you basically shut down the synthesis of purines. It also so happens that 6-mecaptopurine can also inhibit HGPRT. So overall, you decrease purine synthesis, and that's how isothioprine slash 6-MP work as anti-cancer agents. So that's what I'm going to say on this slide. And let me just talk about one last offshoot of the purine salvage pathway. So again, you start with a nucleotide, you break it it down to a nucleoside and then that nucleoside is broken down to a nitrogenous base okay so amp is a nucleotide it's broken down to adenosine okay that's a nucleoside and then you pull off the sugar with uh actually you don't uh you actually don't pull off a sugar just yet you deaminate the adenosine to make another nucleoside known as inosine. And the enzyme that makes that happen is adenosine deaminase. And then you make inosine. Inosine, you then pull off the sugar. And then you're left with a nitrogenous-based hypoxanthin. So the thing is, if you notice, I put ADA, adenosine deaminase, between adenosine and inosine. The thing is, if you have a deficiency of adenosine deaminase, it's an autosomal recessive disease, you have a buildup of adenosine. And again, if you're walking backwards with the Lushatli principle, as your adenosine levels go up, your AMP levels go up. If your AMP levels go up, your deoxy ATP levels go up. And that your higher levels of ATP, that ATP can combine with methionine to make SAM. We'll talk about SAM in a different podcast. As you'll come to know, SAM is a very good methyl carrier in the body. It works like in the adrenaline dollar, for example, to help you convert norepinephrine to epinephrine. But that's a different story for another podcast.
The thing is S-adenosyl homocysteine is actually toxic to B and T lymphoblasts, okay? So if you kill your B and T lymphoblasts, you do not make B or T cells. So you get something called a severe combined immunodeficiency, okay? So that's the pathophysiology behind adenosine deaminase deficiency being one cause of autosomal recessive SCID. Now, another thing that could also happen is that AMP that's building up, right, because it's not being, because of a buildup of adenosine, that AMP that builds up, okay, remember, if you remember your negative feedback, that inhibits PRPP amido transferase, which, as we said, is the rate-limiting enzyme of purine synthesis, okay? So you also have decreased purine synthesis under those conditions. That's why you can get into a lot of trouble with adenosine deaminase deficiency. So next slide. So protein metabolism. Protein metabolism, basically, for the rest of this podcast, I'm just going to talk about how you deal with proteins. So let's assume you eat some protein-containing dish like meat or chicken or turkey, whatever. So you guzzle it down your throat. And as it goes down your esophagus, it gets to the stomach. The stomach, remember, there's parietal cells that make acid through a hydrogen potassium antipoder. It's an antipod, it's an ATPase. So you make a ton of acid, that acid denatures the protein. And then that protein, pepsin, in the stomach begins to digest the protein. Remember, pepsin is the active form of pepsinogen. Pepsin actually comes from chief cells okay chief cells another cell type you find in the stomach uh to actually go from pepsinogen to pepsin you actually need the acidity of the stomach to make that happen as well so that's a nice gi tie in there okay now that protein then makes its way to the uh to the small intestine okay and the pancreas releases certain like trypsin, chemotrypsin, carboxypeptidase, whatever. They also help with digesting the protein. Although remember that enterokinase is what kickstarts this process, right? So enterokinase converts trypsinogen to trypsin, and then trypsin can then go and break down the zymogen forms of chemotrypsin and carboxypeptidase to the more active forms, okay? So you break down those proteins to amino acids, okay? Amino acids are like the monomers that build up proteins. But another thing that could happen is instead of breaking the protein down completely to an amino acid, you can break it down to like a dipeptide or a tripeptide, okay? And then the dipeptide or tripeptide or monopeptide, which is an amino acid, they can all go, they can be pumped into an enterocyte in the small intestine by sodium glucose linked transporter, okay? Sorry, not sodium glucose, sodium amino acid linked transporter. Okay. So remember, sodium is primarily an extracellular ion because of the activity of the sodium potassium ATPase pump. So as that sodium goes down its gradient into the enterocyte, you have the active transport, I guess not pumping, active transport of amino acids, okay, or dipeptides or tripeptides. And if you notice in the slide, I see that O versus glucose. I just want to remind you that you cannot transport disaccharides or trisaccharides across an enterocyte membrane with sodium-linked transportation, okay? Contrast that with your amino acids where, oh, you could take like a diamino acid, okay,-peptide or a tri-peptide, and bring it into the enterocyte with a sodium-linked transporter, okay? Now, if you have a problem, some kind of mutation in those transporters for amino acids, you can have two high-yield diseases for step one, okay? You can have something known as heart knob disease, or you can have something known as a cystinuria. Okay.
They actually also work in the proximal convoluted tubule. Okay. They actually work in the kidney as well. In fact, I'll just tell you this as a general principle. Most transporters you'll find in the small intestine are also found in the proximal tubule. Why does that make any sense? The thing is, both parts of the body, okay, are involved in reabsorption, right? So if they are both involved in reabsorption, it should make sense that they have similar transporters. If you even wanted a very nice tie-in here, if you remember like the sodium glucose linked transporter, right? So we have SGLT transporters in the kidney, like SGLT2, but in the enterocyte, in the small intestine, we actually have SGLT1, right? So remember your SGLT2 inhibitors like canagliflozin and dapagliflozin that basically help you pee out sugar in your urine. So these are sodium amino acid link transporters. You find them in the GI tract, in the small intestine, and also in the proximal tubule. In fact, if you also think about both parts of the body being involved in reabsorption, you can see why there's microvilli in the small intestine and there's also microvilli in the proximal convoluted tubule. So just some nice tie-ins between those two parts of the body. So Hartnett disease is basically a problem with neutral amino acid transporter. And again, this transporter is found in the small intestine and the kidneys, right? So if you have a mutation in this transporter, you do not reabsorb. You do not reabsorb a neutral amino acids, either in the gut or in the urinary tract. And if you have that, you won't reabsorb tryptophan. Tryptophan is a high yield neutral amino acid. The thing is, tryptophan can be used to make things like serotonin, right? Serotonin is 5-HT, 5-hydroxy tryptophan. But tryptophan can also be converted to niacin, okay? So if you have a tryptophan deficiency, you can also get a niacin deficiency, okay, with heart and heart disease. A niacin deficiency, remember the four Ds so like dermatitis uh dementia diarrhea okay and death death is the fourth d i guess that's not very ideal okay so you can get the pellagra presentation if you have a heart knob disease now cystinuria is a mutation in another amino acid transporter but But this transporter, it's classically known as the cola transporter because it transports cysteine, ornithine, lysine, and arginine, okay? Which are all basic amino acids, okay? So the thing is, again, if you have a mutation in this transporter, and like I said, that this transporter operates in the GI tract and in the urinary tract, cysteine can begin to show up in your urine, okay? And the thing is, the cysteine can pair up with a body, another cysteine body, and you make a cysteine, and that cysteine can form kidney stones, okay? Because it's not very soluble in the urine, okay? So it can form kidney stones. Remember, those cysteine stones are like 16 stones. Right. So they're shaped like hexagons, like benzene rings. So that can cause nephrolithiasis. Okay. So that can be a presentation of cysteine urea. Okay. And the thing is, those cysteine stones, you can actually solubilize them under basic conditions. Okay. So you can actually give acetazolamide as treatment for cy treatment for cystinuria it helps you solubilize the cysteine stones now the thing is we like protein right but the thing is protein actually does some bad things to the body okay i mean it's not necessarily bad if you have a good organ to deal with it in this case the liver and your kidneys to a limited extent okay So the thing is, to deal with our protein problem, we also need to deal with the ammonia that we get from proteins.

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.