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Organized labor is having a moment. Medicine has not been immune. In recent months, 75,000 Kaiser healthcare workers went on strike, and that was just one of 26 healthcare worker strikes in 2023. One of the biggest changes for medicine, though, is a significant uptick in the unionization of trainees. As of December 2023, the Committee of Interns and Residents, or CIR, the largest U.S. union for house staff, represented 31,000 trainees, almost double what it was just four years ago. But trainee unionization has been controversial. Some medical educators fear that it detracts from the nobility of the profession or drives a wedge between trainees and educators. Trainees often feel voiceless and undervalued, but also scared that a pro-union stance will hurt their career prospects. Meanwhile, trainees who don't support unions may fear being ostracized by their peers. I'm Lisa Rosenbaum, and this is Not Otherwise Specified from the New England Journal of Medicine. So why do trainees feel the need to unionize? What can unions do for their members, and what can't they do? And why have these questions become so hard to discuss? To try to answer these questions, I first spoke with two trainees with different views on unionization. Philip Sossenheimer is a palliative care fellow at Stanford where he led trainee unionization efforts. David Bernstein is an orthopedic surgery resident at Harvard's Combined Orthopedic Surgery Program. It's part of Mass General Brigham, or MGB. During MGB's unionization campaign, David wrote an article for Stat News advocating for pausing the campaign. I should add that I am an employee of MGB, and I also did my residency at Massachusetts General Hospital. Trainees at both Stanford and MGB have since voted to unionize. I started by asking Philip why unionization is happening now, and what are the problems driving trainees to unionize? You know, I think everybody that I talk to agrees that there's a problem with medical training. Even people who are opposed to unionization as the solution recognize that burnout is high among medical residents. Medical residents feel overworked. We feel underpaid. We feel that we're not receiving the value for the work that we're putting into the institutions and the huge sacrifices that we make to get to the places that we are. And my worry is that it's keeping people away from medicine and that we're starting to see a shift nationally where our profession is losing ground. And it's starting from the bottom with trainees. So what do you think is driving the burnout among trainees? And can unions help? I think that people feel disengaged. They feel like they don't have control over their work, right? I remember during the pandemic, many of us getting jeopardized to COVID wards. And that trend continues. I think a lot of folks feel like they're basically a warm body with an NPI and that they can be slotted in like any other person can be slotted into this equation to solve the staffing needs of the hospital. We have very little control over our working conditions. And that's an area where a union could potentially help. People are also burnt out because they have low wages and they're in the community trying to pay rent, trying to afford child care, and they're having trouble making ends meet. And that's another area where unions can help. People are burnt out because they look at the landscape of American health care and they see patients who are uninsured, patients who have to go home and not be able to afford the medications that they prescribe. They have to fight with insurance companies. And I'll be honest and say that's not an issue that a resident and fellows union can solve single-handedly, right? Those are bigger issues. What does excite me about the movement that's building, however, is that collective action among physicians could potentially address those solutions. And having a large body of residents and fellows who are organized under the same organization, you know, almost a third of residents and fellows now are unionized with CIR. Now we're talking about the potential for larger scale change and for, you know, conversations to actually happen with the ACGME on a larger scale. My individual house staff union at Stanford Hospital can't address the, you know, the structural issues that exist with the ACGME and the match process, nor can we address the structural issues that exist with American healthcare. So one union alone can't solve this problem, but it doesn't need to, right? If my union can get me better pay, if it can get me better vacation, if it can get me slightly better benefits, that's going to go some amount of way to solving my issues. It's certainly going to make my day-to-day life better. And if we can build a movement that incorporates not just a third of house staff, but imagine if 50% of house staff were And David, what are some of your concerns? Ultimately, the power of a union, whether we want to acknowledge it or not, is the ability to walk away and to strike for something, for something that we believe in, for something that we really want to make a difference. And when we saw that happen in the UK, for example, thousands and thousands of patients had their appointments and surgeries delayed, up to 350,000 patients. A lot of this comes with predicted consequences and not predicted consequences. A lot of what we have to think about, I think, in a more granular way is what are we after at its core? Because that was at the core of a lot of the MGB issues that I had a challenge with. I wanted to know what did residents want? If it was a seat at the table, that was perfectly fine with me. You can't walk in and say, we want better working conditions, because the answer you're going to get is, what does that mean? Yeah, I appreciate that perspective, David. And like I have told everybody who I've ever worked with, you know, unions are not going to be the only solution to the problem of American health care, nor are they going to be the only solution to your burnout. What I can say, and the only thing that I promise people is that I will stand with you to try to advocate on your behalf. That's the only thing that we can do. And that's what unions are, right? A union is just the name that we have for federally protected collective action in the workplace. My question is, you know, what's the alternative, right? We have right here a structure that's been tested, that's been used in other workforces, that's been shown in well-studied economic literature to have a positive impact on working conditions. And we can be very specific about what we mean with working conditions, which we are as we're bargaining, right? It means better parental leave. It means lactation accommodations for women. It means getting the vaccine, you know, the COVID vaccine, which was the first collective action that we took as a union, basically, at Stanford. And so I don't think it's the case, at least in my experience at Stanford, that we're promising pie-in-the-sky dreams, right? And as to the point of how the union is going to accomplish these goals and the threat of strike, right, strikes are a last resort. And just like we have the ability to negotiate without walking out of the workplace, you know, there are many steps that we can take before striking. We have engaged our political allies to pressure the CEO at Stanford Hospital to try to work with us. We write op-eds in the Stanford Daily. We write pieces that have been published in JAMA. We try to pressure people in the public. There are many ways that you can leverage your group solidarity without needing to go on strike. And if what you're saying is the only way that we can affect positive change within the workplace is through a strike, then the union would be the only way to go because the implication would be that there's no other effective means of advocacy, which just isn't true. If you look at the literature on strikes within healthcare, it's not even clear that there is an increase in morbidity or mortality for patients during that time. What we're talking about are theoretical patient harm over the real harms that we know are happening to resident fellows daily and the burnout that we know affects the quality of the patient care that we deliver. Again, I think that we should be doing something to accomplish something exactly as you had mentioned that benefits us and our patients. How that comes about, I think, can come about in a number of ways. |
Because in my opinion, having a seat at the table is important, but really having what I need to be the best physician I can be, to deliver the best care possible to my patients, to learn what I need to learn in order to operate safely and well, that's what I really care about, not necessarily for a limited short period of time having a seat at the table. When David argued in his Stott News op-ed that the MGB unionization effort be paused, he knew he was going to hear opposition, which he warned his physician wife about prior to publication. And it's funny because those comments and those discussions with my wife still ring true because I still continue to get threats on social media or via email or telling me that I must be one of the worst doctors that will ever exist. Things that I think are not inherent to why people want to unionize to begin with. Okay, so Philip, what was your experience like during the Stanford unionization campaign? You know, during our negotiations with Stanford, they were pretty clear at the bargaining table that they could afford to pay us more. They were explicit about it, you know. And the reason that they give for not wanting to pay us more is because we receive tuition-free education. Are we learning in residency? Absolutely. But we've conceived of a model in our graduate medical education that for whatever reason, needing to learn something or being a learner means that you should not be paid a living wage or that you should not be reimbursed for the value that you generate for the hospital. In addition to worrying about strikes, I also heard some people express concern that unions could negatively impact trainee education. So I asked Philip and David what they thought about this concern. David Bernstein. As someone who's going to do surgery on people, I want to operate as much as possible in order to learn the skills to take on the responsibility of being in the operating room and providing care in that manner. And I think that's a real concern that needs a discussion because I don't think that there's going to be a simple answer to that problem. A lot of the benefits or proposed benefits of a union don't tackle the underlying medical education concerns and the pipeline, listen, work hours, don't touch them because we need to get our cases. And so we're not touching them. And in fact, there hasn't been a single CIR negotiated contract at a hospital that has surgeons that reduces the work hour. This topic has been extremely difficult to talk about. And I want to understand from the two of you why you think that is. In my experience talking to other trainees, there are people are afraid for repercussions for their careers. People are worried that if they speak out in favor of unionization, that they're going to be passed over for job opportunities. This is something that I worry about. You know, if you Google my name, you're going to see that I'm a union advocate. And so when I'm applying for jobs, I worry that HR is going to look at that and say, listen, we don't want this guy here. I think it's partly what Philip mentioned and partly the era, unfortunately, we live in. We're in a moment in history where if you disagree with me, it's not viewed as you disagree with me. It's viewed as you're the other, that you're this kind of evil person who may or may not have what I think is the best interest of a patient in this situation or another objective in mind. And because of that, we're opposed and we're opposed more than just on an idea, but on our ethics and on our morals, just because we disagree on a topic. The good versus evil nature of the union debate has been hard for those trainees really trying to understand both the risks and benefits of training unionization. But it's also been hard on educational leaders. In the second half of this episode, we're going to talk to Dr. Jay Vias, an immunologist and infectious disease doctor who also directed Massachusetts General Hospital's internal medicine residency program for the last nine years. Though Jay recently decided to step down, he was still the program director during the resident's recent campaign and vote to unionize. So I started out by asking Jay about what he perceived to be the biggest changes in medical education in the last nine years. There were really a number of changes. The most important, I think, had to do with the compression of time on the clinical services. You know, when I trained, we just weren't as busy. The patients weren't as sick. And now as I watched and worked with my residents as they were training, these are incredibly sick patients that get admitted to the hospital. The turnover is incredible in terms of the length of stay being shortened. Therefore, there's an increased amount of churn. You know, when I trained, discharging a patient was a relatively straightforward and pretty lean process. Now, transitioning care to another facility, transitioning safe care to home, requires about as much work as it does for an admission. And I'm just focused right now on the inpatient setting, but there's equal challenges on the outpatient setting as well. So what I noticed was that we're training individuals in a very complicated medical landscape, oftentimes where the real resources that could really make a difference are oftentimes are in short supply or simply non-existent. And resident panels differ from attending panels significantly. And many of those have those types of needs that our system is oftentimes not optimally set up to do. So are these the factors that drove trainees to unionize? You know, the COVID pandemic put into sharp relief, you know, the role that residents and trainees had in the response to COVID. But I actually think if you look back, you'll see that there were seeds of discontent that were there for a longer period of time. And I think it goes back to thinking about who are our medical students and our trainees and what is the path that they've taken when they get to graduate medical education. And I'll take you back to college where many of them have spent a significant amount of time in college trying to perfect a perfect GPA, a perfect MCAT. Many of them have taken a gap year to get requisite research experience to get into a good medical school. They will work hard in medical school, continue to do scholastic work, engage in what I will say sometimes is this process to ensure that they get into a competitive residency. And that oftentimes may require extra time and effort to be able to do that. All the meantime, paying a significant amount of tuition debt, which puts them deeper and deeper into financial holes at a time when most of their cohorts in college have started to get a job and have started to put money into retirement and have started to think about what work and outside of work balance would look like in terms of their life choices. And so they're continuing to work in those spaces. And then they come to internship. So when they come to me, they're going to now start working 80 hours a week, oftentimes taking call, caring for some of the sickest patients, as we just described. And now they're looking for support and they're looking for some sense that there is opportunities for recognition of the work that they're doing in that area. And I think, you know, historically, the grand bargain that my generation had was that there was delayed gratification. Do the hard work now, you'll get rewarded after you finish the training process. And I think one of the byproducts that evaporated after COVID was this concept of delayed gratification. I think people recognize that time is short. There is a feeling like there's a significant amount of uncertainty in the world. I'll leave that as kind of a meta feeling that's out there. And that they need to be able to spend time that feels right in the right spaces. So if they're in an educational institution or educational environment, they want to feel like that they're getting the best education. If they're working hard to take care of those patients, they don't want to be doing things that have low yield in terms of those. And so they're insisting on a number of things that I think are actually aligned with, you know, I think the way many people think now, you know, post-pandemic in terms of the things that they would like to be able to see. But those oftentimes from a program director point of view, we didn't have the levers of power to fix those. And I think that there was a growing realization amongst residents that program directors, even though they served as the direct supervisor of trainees in the graduate medical education space, lack the agency to make the types of meaningful changes that they were looking for, whether that be in compensation, whether that be in benefits, whether that be in restructuring the workplace to prioritize education and enhance patient safety and enhance patient experience. So I think the lever that they felt was most important to pull there was to be able to have the opportunity to have a voice at the proverbial table. |
And so we want to be able to do that through unionization. And so I don't think unionization was the first lever, but rather the ultimate lever that was pulled to try to affect these types of changes. And so how did you respond to them when they came to you saying that we are organizing to vote to unionize? I think to be an effective program director, you have to journey with your residents through both those good times and bad times. And that requires a bit of vulnerability on the residents and real support, I think, by the program director as well as the faculty. When I say the program director, you should always include the incredible dedicated educational faculty that support the residency program. You know, I had wanted to make sure that that relationship, which is built on trust and that has vulnerability shown by the trainees in those situations, that wasn't, there wasn't an opportunity for there to be kind of, at least between the program directors and the trainees and us versus them philosophy. I think that becomes incredibly corrosive. And while I recognize and fully acknowledge that I am part of the leadership of the institution as serving as that program director, you know, I personally felt very sad that we had reached this point because I felt like if we could not, it felt like a personal failing to me that I wasn't able to advocate strongly enough for the trainees that they had to use unionization as the mechanism by which they felt that that change was effective. And it wasn't a lack of effort on my part. It was a lack of being effective in that voice to be able to affect the type of change that was necessary. And, you know, so I had my own personal feelings about that. But, you know, when it came to being pro-union or anti-union, I was neither pro-union. I was not anti-union. I've always been pro-resident, and I've always been pro-residency program. I love my residents, and I love my residency program. Those things will never change. I tried as many times as I could to remind the health system as we moved forward through these processes that this isn't an us versus them because, quite frankly, they are our future colleagues, and we need to treat them as our future colleagues. And sometimes I worried that that got lost in the translation in what became a relatively bitter fight for whether the trainees would choose to unionize or not. I come from a science background, and so I spend a lot of time thinking and weighing evidence and trying to determine whether we have enough evidence to formulate whether a hypothesis is true or not. And I love that exercise, but that process, which is so familiar to me, was not really available in this discussion of unionization simply because we just didn't have the forum by which we could have that type of open conversation. I think it would be helpful to hear a little bit more about what happened when you attempted to have an open and honest forum to talk about the unionization process and some potential pros and cons, benefits and risks, weighing the evidence, however you want to think about it, with your house staff. I've always had and strive to have an open and honest relationship with my residents. I felt that that was the only way to lead in that way. And so early in this process, I had intended to have a noon conference to really speak about the union efforts. And again, in that meeting, I had made efforts to do it the way I, frame it the way I saw it to be important. What were the pros? What were the cons? What are the things that I worried about and the like? It was a well-attended meeting, probably the best-attended noon conference we've had all year. I think that, unfortunately, what was a nuanced conversation got eventually framed up in ways that didn't really reflect the reality of a nuanced conversation when comments were made in social media platforms, including Reddit and Twitter, which painted a strongly different picture, you know, for those things. Just to be clear, Jay was accused on social media, and specifically Reddit, where a lot of students go to seek information about training programs, of being a union buster. Obviously, the result of the social media posts, you know, kind of prevented further open conversations like that, which, you know, I have to say I lamented. This is sort of the one of the root ills of our society, I think, is that I don't know if it's because of social media. I don't know if it's because we're so polarized in other ways. But the opportunities to have nuanced dialogue about complex topics are few and far between. So people did yearn, individuals did yearn to have those types of conversations at that level. Many times I would have those individual conversations with individuals. But, you know, I worry that, you know, sometimes when we fear having those larger conversations in larger rooms, that sometimes that might be a reflection of a lack of trust and whether someone is operating off a specific agenda. I think that there were some people who worried that, you know, being a program director and serving, you know, in a leadership role, by definition, put me on the anti-union platform. And if people got that impression, they didn't really spend any time talking to me about it or hearing what I was saying. But I think they felt that that was largely where program directors were landing. And a lot of it had to do with, you know, I think a lot of program directors, you know, who kind of grew up in education really felt that it was very important and that they do what the health system wanted simply because they've reached the pinnacle of their career being a program director. And there's some element of, you know, I worry about my job security if I'm not really kind of pleasing the people who I report to. When I came on to do, serve as the Red Sea program director, I was already a full-time, I already had a full-time job being a basic science investigator in the Division of Infectious Disease. And so I always operated under having essentially two jobs. And so for me, it was very easy because I only acted how I thought what I felt was right to do and always welcomed the opportunity to go back to my lab full time should anybody be worried that I was doing the job in the wrong way. And so that gave me a level of freedom that I think most other program directors didn't have. I knew from having spoken with Jay previously that one of the issues that became contentious at this forum were snacks for trainees. Every week, Jay filled his office with snacks so that food would be available to residents at all hours. But before we get into the fraught snack discussion, I asked Jay to explain what the snacks represented to him in the first place. The snacks were always a means to an end, right? The opportunity to be able to spend a little bit of time with the residents. And I left my door open at night, and so people could come in and get a snack at 7 p.m. or 3 a.m. or whatever time of the night. It wasn't uncommon that I would come back to my office in the morning and I would have a sticky note on my desk and said, you know, I've had a really bad night with some really terrible complications of some patients and I just needed five minutes and just a break. And I came to your office and I grabbed a snack. And, you know, thank you so much. You know, for me, those were really meaningful notes. I still have them. And, you know, for me, they always represented what I thought was being able to see our residents, right, for what they do. I'm Indian. I grew up in a very kind of a somewhat traditional Indian household. Food was a currency of love, as it is in many cultures. And so for me, the idea that you would withhold food was the equivalent of withholding love, and it just didn't make a whole lot of sense to me. Ultimately, I do think that, you know, there was, even after the union vote did occur, there was, you know, a decision that was made by leadership to remove the food. Even though the snacks for Jay were a gesture of love, my sense is that the forum he held, he ran into a shoot the messenger problem. One thing that often happens when trainees unionize at any institution is that benefits become equalized between programs. In some ways, that's good. For instance, all the trainees may get a higher salary or better benefits. But for programs that had traditionally gotten extra perks, and I can say from having been an MGH medicine resident that we got a lot of perks, there's also a risk of losing things like nice lunches or 24-7 snack availability. And in the end, the snacks did get cut. But I wanted to understand from Jay why pointing out this risk before the vote to unionize wasn't well received. |
And one of those things I did mention was that there would be limitations on those things. And so if we were to simply divide the world of programs into the haves and the have-nots, the Department of Medicine and MGH was clearly one of the ones that had. And I worried that in this effort to kind of make everything the same, what would end up having to happen would be that, you know, things would have to be taken away. And I worried out loud that that was going to happen. And a specific example that I used were these snacks. I've already measured, and you can do the calculations, but, you know, we're in excess of $50,000 a year in M&Ms and popcorn, right? And you can imagine that that's something that's going to be ripe to be removed. And so I use that as an example, you know, in that area. And so, yes, I think people did respond to that. If people saw, you know, again, I want to say there was a small minority of individuals who may have seen the snacks, you a transactional thing, that I just brought in snacks. But I think the point I was trying to make really was that I, as the program director, enjoyed a significant amount of autonomy. And if I thought there were important things that we needed to do to add to the residency program to enhance the resident experience. I recognize that that would likely come to a halt, and I wanted to express my concern to the residents in that meeting. It's ironic to me that, as you said at the outset, part of what was going on before the decision to unionize was that the residents had recognized that you, JVS, don't necessarily have the agency to move every lever at the level of the institution to get them what they want, and that part of the consequence of the unionization is actually taking away even more of your autonomy to advocate for them. And I think that that's an important thing for us to recognize, again, because it's very hard to talk about whether unions have any unintended consequences because the discourse is so fraught that they might. Yeah, and I think that that's one of the things when you're having a conversation where you want to have a nuanced conversation, there's going to be pros and cons of everything. And I believe that medical trainees are very well versed in that concept based on how they practice medicine every day. And so, again, I think the ability to be able to kind of see what are those trade-offs and what are those unintended consequences that come up would have benefited from a broader discussion, but it didn't take place with the faculty or it didn't take place with faculty and residents. I do want to ask you one more question because it's something you said to me when we talked, which is that some of the most gifted educators don't want to get in this game anymore. And I, you know, I've heard that from a lot of educators, honestly, that for some reason, lots of reasons, complex reasons, it's become a lot harder to be an educator in addition to like all of the hard things that come along with trying to train people. And I'm wondering what you think that's all about. It's more than one reason. But, you know, I think the, you know, training, first of all, being an excellent teacher for medical students, for residents, for fellows, that's hard work. But, you know, there's the increased challenges that are faced in a complicated inpatient setting, the fast pace that is required for ambulatory medicine, the increased demands to do more with less, the lack of recognition by academic medical centers on how to promote excellent educators, and then lack of how you value education in an RVU or compensation-based mechanisms pose real challenges to how we're going to educate the next generation. And there are really important challenges here that we need to be working on. Unionization adds to some of that. And I hope that for many people who are thinking and contemplating a career in medical education, that they recognize that that is an incredible and important role. We all play an important role. I'm very interested for a significant amount of self-interest. I anticipate that in the future years, I'm going to grow older and I'm going to need medical care. And I want to be cared for by really great physicians. And that's what I think we all, as humans, want to be able to do. We recognize that, you know, as much as AI sounds wonderful, at the end of the day, if someone needs to be told that they have cancer, it's not going to come from a computer. It's going to come from a human being who's going to walk and journey with that patient through the journey that is known as cancer. And we need to be able to make sure that that human experience is accompanied by people who are incredible. And to take people, you know, we still have incredible numbers of people who want to go into medicine. Look at how many people apply for medical seats in the United States. We have a number of people who want to come into this noble profession. And so we need great teachers. We have great talent in our pipeline. We need great teachers to be able to do that. And I worry that a lot of the things that I just mentioned will continue to dissuade people from a career in medical education because I think that it is both noble, it's necessary, and it's become increasingly complicated. And so I don't have a great solution to it, but I know that there is that need, and we need to be able to make sure that we still retain the very best there. I agree, which is why the rise of training unions has always seemed to me like a tip of the iceberg phenomenon. What bubbles up to the surface are tangible problems unions might be able to solve, like inadequate salaries and benefits. But underneath, we have so many layers of existential problems. Some, like medicine's corporatization, are coming from within the profession. But others, like evolving cultural norms around work and generational change, are coming from outside. Up next on Not Otherwise Specified, we're going to examine some of those generational shifts and the role they're playing in our training environments. The tensions run the gamut. Some will be that new employees are not just willing to fall in line and do what a boss tells them to do. When older generations were entering the workplace, the norm was suck it up. You know, you got to do what they tell you to do. You got to pay your dues. This generation does not necessarily see that that is the case. So sometimes they will feel like they know better. And the reality is sometimes they do know a better way to get something done because they are more adept often at using the tools of today. That can create a frustration where they do have something to contribute, but an older person is going to say, but that's not how we do it here. I'm Lisa Rosenbaum, and this is not otherwise specified from the New England Journal of Medicine. I'd like to thank our editor, Deborah Molina, our senior producer, Mary Rose Madden, and Blue Dot Sessions for the music. Thanks for listening. We're taking a brief pause next week, but we'll be back on March 6th. Until then. you |
I'm very pleased to be joined by Vikram Patel, one of the lead authors on the China-India Mental Health Alliance series. Hello, Vikram. Hi, Niall. So, the first question I have is, why this series and why now? Well, India and China together represent more than a third of the world's population, and I think both countries are at a remarkable stage of their epidemiological and demographic transition. They're also seeing a remarkable amount of social change. They're seeing a remarkable amount of new energy in investing in public health. And it just seemed to me for all these reasons that this was a great opportunity to see how these two giants, neighbors in Asia, were addressing the burden of mental health problems and what lessons could be learned, not only for these two countries, but indeed for other low and middle income countries as well. And also countries which are undergoing massive economic change. Absolutely. Indeed, most of the low and middle income world is seeing the sorts of social change. In some respects, India and China, being middle income countries, are somewhat more advanced in the stage of social change, but certainly where these two countries are today is where many of the less-resourced countries will be in a few years from now. And that brings with it opportunities. It also brings with it challenges. So let's start off by talking about some of the challenges that these changes are bringing. Well, I think the social change is accompanied by, obviously in the way families organize themselves. For example, because of urbanization, there are a range of new social determinants or an increased prevalence of certain social determinants that might affect a person's mental health. So these are some of the challenges that might explain, for example, the increasing rates of suicides that we see in young people in India and that we did see in China. But as the series will show, there have been changes in China in terms of these rates falling in recent years, whereas in India, of course, they've continued to rise. In this business of suicide rates in India, I know that it is an area of concern. And yet the pattern, the demographics are very different to what, say, European or North American suicide researchers. That's correct. Certainly the suicide paper will shed a lot more light on that. I personally think that the bigger area of difference between India and China is the investment that China has made in the last decade or a bit in its public health care system. In many ways, it has rolled out what I consider the largest publicly financed mental health care program in the developing world and possibly the world, with several million people registered now in what's called the 686 program. By contrast, India has a fairly abysmal performance in terms of not just the public financing, but more importantly, the implementation of the public mental health care system. So I think there's certainly a very significant difference between these two countries in the success they've had in achieving publicly funded coverage of mental health care. And I think India could learn quite a lot from China in that regard. Could you give me any idea of the sort of scale of treatment gap that we're talking about in India? In the paper that I lead, we've actually done a systematic review of the treatment gap. And I think the key pictures, the key findings that emerge from that is that the treatment gaps are very large for the common mental disorders, such as depressive and anxiety disorders, and also for substance use use disorders such as alcohol use disorders. They tend to be smaller, not surprising, for the serious mental disorders because those are obviously more frequently noticed. The other important finding is very large inequities in coverage comparing rural and urban areas. Again, it's not terribly surprising, but now we can show this by the systematic review. Also, we can see very little evidence of the measurement of treatment gap for certain groups of people, for example, children, in whom we have almost no literature, no research evidence on the size of the treatment gap. My guess is it's pretty large. So what are the... OK, number one priority is more money, clearly, but what would the other priorities be in enabling India to meet this challenge? I think we need very strong technical leadership. We need leadership by public mental health professionals working within government. These are the kinds of people who have the necessary skill set to design, to organize, to build capacity and to monitor public mental health programmes. At the moment, the problem in India is that most public mental health care programmes are being implemented through departments of psychiatry in medical schools. And whereas these are perfectly reasonable places for providing specialised care, these are not necessarily the right platforms for organising a public mental health care system. I know that in the UK and in the USA, in other countries in recent years, mental health has become far more part of the public discourse with anti-stigma campaigns, with films and dramas and documentaries coming out, it seems, every week on the topic, which is, of course, welcome. In India, is there a similar level of public discourse about mental health issues? Certainly. You know, in the last 20 years that I've been working in India, I've seen a dramatic shift in the discourse on mental health. Just in terms of volume, it has increased dramatically. Almost every magazine or many television programs will have themes related to mental health and mental illness. And it has to be said, it's dealt with in a very compassionate, in a very sensitive, and in a very non-stigmatizing way. So I think this is all very positive. What has happened, therefore, is a much greater awareness about mental health problems. Although that doesn't necessarily mean people use biomedical concepts, but they do recognize these as health issues. What's missing now is the actual supply of effective interventions in community-oriented platforms. And it sounds, though, as if we're getting some momentum building towards that. How can India and China help each other in harnessing this momentum and promoting change that sounds so badly needed? Well, I think both countries face very similar challenges in terms of the large population and therefore the large numbers of people affected by mental health problems and need of care, the lack of appropriate community care arrangements in both countries and the rapidly changing family systems that are used to traditional care for people with particularly serious and enduring mental health problems. So I think if academics, public health academics, policymakers, and relevant stakeholders in the community in both countries were able to come together, share experiences from various demonstration projects or pilots showing how these challenges could be addressed, I think there's a real prospect for learning on an exponential scale. So let's hope that this series of papers marks the start of a beautiful friendship. Well, you know what? I think this is one of the rare examples of academics on, you know, in these two countries which share such a long land border but could easily be living in different continents. It's one of the rare examples I know of, of academics from these two countries collaborating in this way and leading to this series of papers in The Lancet and The Lancet Psychiatry. And we look forward to much more in future. Thank you very much, Niall. Vikram Patel, thank you very much. For the second half of this podcast, I'm going to hear from one of the other driving forces of the China-India and why now? global mental health because of the sustainable goals. I think that not thinking about China and India, you're missing a huge part of the world. Also, China and India are, in some senses, very different countries in that India is the largest democracy, China is the largest communist country, and yet they're both on a very rapid developmental trajectory. And as they are, the health is improving, and so there's increasing concerns about mental health and mental well-being. So you picked up on something very interesting there, which is that these countries have very different histories and very different political systems. But nevertheless, from what I've seen in the series and from talking to you previously and talking to Vikram, they seem to also have some challenges in common and possibly some solutions in common. Challenges, yes. Solutions, we're still working on them. I think one of the challenges is that they're such large countries, there's huge diversity around the country. Now, China has 33 provinces, you include Hong Kong and Macau. And a recent publication in The Lancet showed that, for example, suicide rates around these 33 provinces varied by tenfold. Previous work in India has shown that suicide rates around the 26 states in India vary by ten to twentyfold. And so, yes, they're huge and they're developing and urbanizing very rapidly, but there's still a huge range of diversity within the countries. And that's true for both of the countries. And how do you get a national plan and how do you implement it at local levels where things are so different at local levels is a common problem that they face. |
Now, clearly, of course, within the countries, there's huge amounts of diversity. But I think the other thing for maybe readers in Britain, other European countries in the US to get their heads around, is that the sort of pattern of suicide, the demographics, they seem to be very different in China and in India. If you look over the last 20 years, the Chinese rates, and this is from the World Suicide Report that came out a year and a half ago, have dropped by 50 to 60 percent, an amazing number, whereas the rates in India have gone up maybe 20 to 30 percent. So even though they're both developing, both urbanizing, the rates are going in the opposite direction. And the question is why, and the simple answer is we don't know, and we're certainly trying to figure it out. And the pattern as well, I mean, that must be related to the shift from rural to urban life. Yeah, for example, China has gone for over the last 20 years from 20% urban to 50% urban. That means there's 300 million people less who have daily access to pesticide, which is the most common method of. But I guess this fits into the overall pattern that urbanization brings benefits, but it also brings maybe disruptions. Yeah, well, you know, there's obviously different views on this. One sense is that, you know, with the breakdown of the strong family bonds, family connections that occur in rural areas where people live together and families often extended families as the young people especially go to the city, that leaves the elderly and sometimes the children or the grandchildren in the rural areas who don't have the kind of support they have. But on the other hand, these people, you know, it also is related to hope and the sense of a future. And so it really is a mix. And there's benefits, as you say, some downsides as well. And certainly in some areas, urban, rural residents who move to cities live in kind of ghettos. And so their living conditions and the conditions, education for the kids is problematic. But it's very much mixed. I think in China, at least, I can speak about China a little bit better. There's a continuing sense of hope. People still think, despite the increased gap between the rich and the poor, their kids have a better chance at life and getting ahead than they do. And so there's a sense that things are progressing in the community at large. And that sense of hope, I think, is the positive sense that not only for suicide reduction, but also mental health reduction. The one side that is clearly negative, that the rates I think really are going up, is in substance abuse. As people have more money, they're more likely to drink. And some young groups in some parts of the country, at least in China, there's also increased rates of drug abuse. And even if any society improves economically and socially for the individuals within it, there will, in my view, still be some people who have often very severe mental illnesses. And then the question arises of treatment provision. I'm particularly interested in the long history, really, of mental health law in China. It's taken us a very, very long time, 27 years of kind of draft after draft, draft before it finally got improved. And it just, I think it's part of the international movement, you know, the WHO and the United Nations have now put a lot of emphasis on mental health. The WHO had its first global mental health plan two years ago, and China kind of is on board with that. And so that's finally moved us ahead in the law. Like everywhere, mental health laws are pieces of paper until people actually enact them. And the law is idealistic in many ways. It talks about reducing stigma, which, of course, we've been trying to do for many, many decades. Probably the most controversial or difficult to implement element is moving from an involuntary hospitalization program to a voluntary hospitalization program. Because typically in China, the family makes all the decisions. And that's part of the family culture and the communal versus individualistic approach to culture. And so moving from that to have individuals make the decision about when they go in and when they come out of hospital is a major step that's in the law, though I think it's going to be a while before it's actually implemented. And let's talk about that issue of stigma. When I spoke to Vikram, he felt that in India there have been really great strides against that. Is there a similar situation in China? It varies. Urban and rural differences. The urban areas have more contact with the West and sort of, you know, Western movies and things that sort of normalize some of the behaviors we think of mental illness. In the rural areas, people think of mental illness as psychosis, depression, alcohol abuse, dementia. Those just aren't on the, they're not considered mental illness. They're considered social problems. And so they say it's a stigmatized, yes, suicide and other things. Serious mental illness is heavily stigmatized still. There's some attempt to decrease it, and I think we've had some success. But one of the issues is that a lot of the things that we as professionals identify as mental illness aren't considered mental illness by many people, at least in rural communities. And one of the issues which Lancet Psychiatry has covered in the past and is indeed covered in this set of papers is the idea of using complementary medicine, what we call alternative forms of care, to really help to scale up mental health services. Yeah, I think, you know, in China we have traditional Chinese medicine, which is about a third of the entire medical system is traditional Chinese medicine. And, of course, in India, you have Ayurvedic medicine, you have yogis, you have others. For China and India, one of the big changes, differences that Vikram and I have talked about a couple of times is in India, there's other people. I mean, we're worried mostly about the rural areas now. There's other people who can be kind of health aides and fill out some of the other roles where you don't really need psychiatrists, but you need social support for people of mental illnesses. In China, you have your village doctor, but he or she, usually he or she, has a huge range of other responsibilities. So they have very limited energy to place on mental illness because they have to do diabetes, have to do hypertension, have to do everything else. And we don't have the kind of health aid sort of people in the rural areas. And bringing the TC, the traditional Chinese medicine people into providing more mental health services, I think is a fine idea, but it's not going to, it's really not, at least in the real rural areas, it's not going to, we don't have enough of those personnel anyway. We got to, and the idea is how can we mobilize other types of personnel because you don't really have in rural areas, we don't have enough of those personnel anyway. And the idea is how can we mobilize other types of personnel, because you don't really have in rural areas social workers and things like this, that in India they have a little better coverage. They have NGOs in rural areas, and China has very few NGOs. And so mobilizing additional manpower in rural China is, I think, our major challenge to upgrade overall mental health services. Any possibility that technology would help with this process? Well, we've looked at, you know, M-medicine and, you know, cell phones, because cell phone penetration is reasonably good. Of course, in the real poor areas, people don't have cell phones or certainly don't have apps on phones and things. But it's a possibility. I want to see it before I can believe it, frankly, because we've done stuff with schizophrenics to try and get them to take their medication and things, and it hasn't been that successful. So it sounds nice, but can it really work? I think we need a lot more work to demonstrate whether or not it can be an effective alternative having people on the ground. One of the main problems in China is that with the great improvement in health, people are living a lot longer, and with the one child per family policy, they have fewer kids to support them, and so we're having a very rapid increase in the rates of dementia. And, you know, cell phones and things like that aren't going to help for the large increasing numbers of people with dementia. You need carers on the ground, especially as people get at the terminal end of dementia when they really need high quality nursing care. And where are we going to get the manpower to provide that? That's the question that I lose sleep over because I don't, I can't see a trajectory that's actually going to get us that kind of manpower. |
But it's scary thinking of how much social resources are going to have to be committed to deal with this tidal wave of dementia that's sort of hitting us already. So without wanting to make you lose any more sleep, I wonder if we could conclude by talking about where you'd like to see mental health care in China in that just came out. I would like to see at least part-time, if not full-time, psychiatrists in county-level hospitals who could actually monitor care provision and rehabilitation services in the more rural areas. We just don't have enough coverage at the county level. You've got the big city hospitals, some areas, and the richer rural areas, you might have a hospital, but there's just the idea of having a three-tier system where you have the county, you have the village, the county, and the township and the county, and maybe the urban area just isn't there yet. And getting manpower in the county level general hospitals to at least provide outpatient services and monitor and diagnose people and sort of follow up on services is very essential. That's one area. The other areas that are underserved now, I think that really need resources, I'm very concerned about dementia. I'm very concerned about the lack of extensive services for children. And substance abuse, particularly alcohol, is a problem that nobody sees as a problem. And it looks to me like it's a big problem that's getting bigger, and it's not seen as a mental health problem by, you know, hardly anybody. And I think that's something that needs to change. So some hard work ahead, but also a bit of hope there. Certainly. I've been here 30 years and things are much, much better. I mean, it's exciting to do the work now because the law has happened and the government's putting resources into it. So there's definitely a lot of hope in terms of our opportunity to improve services to people who need them. Michael Phillips, thank you very much. Thank you. And you can access the China-India Mental Health Alliance papers on thelancet.com. Meanwhile, thank you very much for downloading and listening to this podcast, and I hope that you'll join us again next time. Goodbye. |
Welcome to the New England Journal of Medicine summary for the week of December 5, 2013. I'm Dr. Lisa Johnson. This week, we feature articles on APOL1 risk variants, race, and chronic kidney disease, targeted temperature management for cardiac arrest, bivalorudin during transport for primary PCI, and fertility treatments and multiple births, review articles on global maternal, newborn, and child health, and on mitochondrial dynamics in human diseases, a clinical problem-solving article describing a shocking development, and perspective articles on how early obesity prevention should start, on adding value to relative value units, and on assessing participant-centered research outcomes. APOL1 Risk Variance, Race, and Progression of Chronic Kidney Disease by Afshin Parsa from the University of Maryland School of Medicine, Baltimore. In two studies, the authors examined the effects of variance in the gene-encoding apolipoprotein L1, ApoL1, on the progression of chronic kidney disease. In the first study, involving 693 black patients with chronic kidney disease, the primary outcome, which was a composite of end-stage renal disease or a doubling of the serum creatinine level, occurred in 58.1% of the patients in the APO-L1 high-risk group and in 36.6% of those in the APO-L1 low-risk group. There was no interaction between APO-L1 status and trial interventions or the presence of baseline proteinuria. In the second study, involving 2,955 white and black patients with chronic kidney disease, black patients in the APO-L1 high-risk group had a more rapid decline in the EGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes. Renal risk variants in APO-L1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. Winfred Williams from Massachusetts General Hospital, Boston, writes in an editorial that, certainly, all racial disparities in kidney health are not attributable to APO-L1 variation. Differences in the hypertensive phenotype and in mineral metabolism remain to be explained, and we should not dismiss the role of socioeconomic factors, referral patterns, and access to the best practices for renal replacement therapy. Regardless of the genetic and biologic underpinnings of the initiation and progression of kidney disease, lower rates of kidney transplantation among black patients, for example, remains a large challenge. Still, the first step in alleviating a problem is to understand it. Increasing evidence supports a major role of one gene, APOL1, in disparities in kidney health and disease and represents a large advance in combating renal disease among Black patients. Targeted Temperature Management at 33°C vs. 36°C After Cardiac Arrest by Niklas Nielsen from the Helsingborg Hospital, Sweden Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the target temperature associated with the best outcome is unknown. In this trial, 950 patients who had been resuscitated from out-of-hospital cardiac arrest were randomly assigned to targeted temperature management at either 33 degrees Celsius or 36 degrees Celsius. At the end of the trial, 50% of the patients in the 33 degrees Celsius group had died, as compared with 48% of the patients in the 36 degrees Celsius group. At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the Cerebral Performance Category scale, as compared with 52% of patients in the 36°C group. In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups. In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees Celsius did not confer a benefit as compared with a targeted temperature of 36 degrees Celsius. In an editorial, John Rittenberger from the University of Pittsburgh, Pennsylvania, writes that perhaps the most important message to take from this trial is that modern, aggressive care that includes attention to temperature works, making survival more likely than death when a patient is hospitalized after CPR. In contrast to a decade ago, one-half instead of one-third of patients with return of spontaneous circulation after CPR can expect to survive hospitalization. Few medical situations have enjoyed such absolute improvement over the same time period. Future studies can continue to refine protocols, define subgroups that benefit from individual therapies, and clarify how to best adjust temperature or other interventions to each patient's illness. By Val Arudin, started during emergency transport for primary PCI. By Philippe-Gabriel St Steg from the Hôpital Bichat, Paris, France. In a randomized trial, 2,218 patients with ST-segment elevation myocardial infarction were assigned to pre-hospital treatment with either bivalirudin or heparin with optional glycoprotein 2B3A inhibitors. Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome, which was a composite of death or major bleeding not associated with coronary artery bypass grafting, CABG, 5.1% versus 8.5%, and the principal secondary outcome, which was a composite of death, reinfarction, or non-cabbage major bleeding, 6.6% vs. 9.2%. Bivalirudin also reduced the risk of major bleeding, 2.6% vs. 6%. The risk of acute stent thrombosis was higher with bivalirudin, 1.1% vs. 0.2%. Results were consistent across subgroups of patients. By Valorudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding, but with an increase in acute stent thrombosis. Shamir Mehta from McMaster University, Hamilton, Canada, asks in an editorial whether the trade-off of reduced procedural bleeding is worth the increased risk of acute stent thrombosis. This depends on the relative incidence of major bleeding versus that of stent thrombosis and the association between these events and subsequent mortality and morbidity. Few observers would dispute that stent thrombosis is a serious, albeit infrequent, event that results in either reinfarction or death in most cases. On the other hand, major bleeding occurs more frequently, but varies widely in severity, depending on how the term is defined. Severe bleeding is prognostically more important, but far less frequent than less serious bleeding, which has little or no long-term importance. Thus, it is critical that clinicians weigh the relative importance of these events before selecting an antithrombotic strategy for their patients. Fertility Treatments and Multiple Births in the United States by Aniket Kulkarni from the Centers for Disease Control and Prevention, Atlanta, Georgia. The authors conducted a longitudinal analysis to determine the trends in and magnitude of the contribution of fertility treatments to multiple births. The authors estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during in vitro fertilization, IVF, and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF. Over the past four decades, the increased use of fertility treatments in the United States has been associated with a substantial rise in the rate of multiple births. The rate of triplet and higher-order births has declined over the past decade in the context of a reduction in the transfer of three or more embryos during IVF. Global Maternal, Newborn, and Child Health So Near and Yet So Far A Global Health article by Zulfikar Buta from the SickKids Center for Global Child Health, Toronto, Canada. A little more than 13 years ago, world leaders assembled in New York to sign the Millennium Declaration to address some of the greatest moral dilemmas of our times. Unequal global health, poverty, and inequities in development, and to establish a set of interrelated goals and targets to be met by 2015. Key goals included the Millennium Development Goal, MDG 4, targeting a reduction in mortality among children younger than five years of age by two-thirds, and MDG 5 targeting a reduction in maternal mortality by three-quarters. With less than three years to go, these two MDGs are seriously off-target for many countries. |
As we celebrate the fact that the annual number of deaths among children younger than five years of age has fallen to 6.6 million, which is a 48% reduction from the 12.6 million deaths in 1990, despite an increased number of births in many high-burden countries during the same period, the sobering realization is that even in countries that will reach their MDG4 and 5 targets, many will still have high numbers of deaths with much scope for improvement. Mitochondrial Dynamics, Mitochondrial Fission and Fusion in Human Diseases, a review article by Stephen Archer from Queen's University, Kingston, Canada. Mitochondria are mobile organelles that exist in dynamic networks. They continuously join by the process of fusion and divide by the process of fission. Mitochondria are derived from eubacterial endosymbionts that are capable of aerobic respiration. Disorders of mitochondrial structure are just emerging as mechanisms of disease. Although some disorders of mitochondrial dynamics result from monogenic mutation, most reflect changes in the function or activity of fission and fusion mediators triggered by changes in the cellular milieu. There is an emerging recognition that disordered mitochondrial dynamics contribute to the pathogenesis of complex diseases that are not classically considered to involve mitochondria. These diseases include cancer, cardiovascular disease, and neurodegenerative diseases. Recent identification of the molecular mediators of mitochondrial dynamics and recognition of their post-translational regulation by an extensive network of kinases, phosphatases, and ubiquitination mediators offer a new understanding of cell biology and novel therapeutic targets. Fission and fusion fine-tune fundamental cellular processes such as calcium homeostasis and the generation of ATP and reactive oxygen species and consequently have important roles in cell cycle progression, apoptosis, mitophagy, and oxygen sensing. rhinorrhea, followed by two days of vomiting, diarrhea, and abdominal pain. The patient was brought to an urgent care center for evaluation. At that time, she reported abdominal pain related to emesis, but said she had no dyspnea, chest pain, fever, or chills. On examination, the pulse was 130 beats per minute, and systolic blood pressure ranged from 60 to 70 millimeters mercury. Emergency medical services were called, and two liters of normal saline were administered while the patient was being transported to the emergency department of a local hospital. On arrival, the oral temperature was 34.7 degrees Celsius, pulse 126 beats per minute, blood pressure 99 over 52 millimeters mercury, respiratory rate 18 breaths per minute, and oxygen saturation 100% while she was breathing ambient air. Cardiac examination revealed irregular tachycardia without extra heart sounds. This patient contracted an acute influenza-like illness, along with members of her family. While the others recovered, her condition rapidly deteriorated. In a young person with a febrile illness and severe hypotension, the differential diagnosis is broad and must be addressed quickly, given the potentially catastrophic consequences. Any diagnostic evaluation must proceed in tandem with appropriate life-saving measures that include hemodynamic support. How early should obesity prevention start? A perspective article by Matthew Gilman from Harvard Medical School, Boston. Overweight or obese women are likely to gain excessive weight during pregnancy. This increases their risk of disease and potentially causes higher adiposity in their offspring, who may grow up to perpetuate the intergenerational cycle of obesity and chronic disease. It is time to interrupt this vicious cycle. Once obesity is present, it is challenging to treat because of multiple physiological, behavioral, and cultural feedback loops. The good news is that the prenatal period and the first postnatal year hold critical clues that may lead to interventions to reduce obesity. After birth, rapid weight gain in the first three to six months of life is a potent predictor of later obesity and cardiometabolic risk. Emerging risk factors for obesity include exposure to endocrine disruptors, which appear to do the most damage during times of maximum developmental plasticity, and the gut microbiota. Given obesity's numerous developmental determinants, it is logical that effective prevention would target multiple modifiable factors. In combination, two well-studied prenatal risk factors, excessive gestational weight gain and maternal smoking during pregnancy, and two postnatal factors, fewer months of breastfeeding and a shorter duration of daily sleep during infancy, are associated with wide variation in childhood obesity. Observational data raise the possibility that avoiding some or all of these risk factors could substantially reduce the proportion of childhood obesity. Adding Value to Relative Value Units A perspective article by Eric Stecker from the Oregon Health and Science University, Portland. Many important physician activities are not measurable by means of the current Relative Value Unit, RVU, system. A reconfigured RVU system could evolve into the best method for accounting for physician services in new value-based delivery and payment systems. Ideally, physicians' work would be reimbursed on the basis of metrics that signal whether their clinical services efficiently improve patient outcomes and that use effective clinical risk adjustment. An improved RVU formulation for physicians' work could be developed that reflects clinical value by weighting activities according to whether they demonstrably improve patient outcomes. Physician work RVUs are currently based on the relative levels of perceived time, skill, and intensity associated with clinical activities, but value-based elements could be emphasized to align physicians' work efforts with high-value clinical services. Across the board, RVU levels for cognitive clinical work could be increased and those for procedural work could be decreased to create incentives for primary care services. RVU levels could also be increased substantially for high-value clinical activities undertaken by either specialists or generalists. Activities linked to RVUs could be more broadly defined to include team-based and supervisory clinical activities as well. Assessing Participant-Centered Outcomes to Improve Clinical Research, a perspective article by Rhonda Coast from Rockefeller University, New York. The value of patient-centered outcome measures for improving care is now well established. In contrast, research participants' perspectives on aspects of their research experiences, such as whether the informed consent process prepared them for participation, are rarely examined. These authors developed and validated a standardized research participant perception survey. The survey was deployed to 18,890 research participants at 15 U.S.-based clinical research centers. In aggregate, 73 percent of participants rated their overall research experience very highly, at 9 or 10 on a 10-point scale. Similarly, 66% said they would definitely recommend research participation to friends or family members. Participants were more likely to rate their overall experiences very highly when they trusted the investigators and nurses, felt that investigators and nurses treated them with respect, listened to them, and gave them understandable answers to their questions, and could meet with the principal investigator as much as they wanted. A majority of participants indicated that they did not feel pressure from research staff to join the study, 94%, and believed that the consent form covered the study's risks, 81%. One striking finding was that most participants The images in clinical medicine features an obese 50-year-old man with no known medical history who presented with a necrotizing infection of his right foot that had begun 10 days previously. He attributed the lesions to wearing new shoes. He was found to have diabetes, glycated hemoglobin level 10.5%, with peripheral neuropathy. The patient had photographed the lesion twice daily, thinking it would heal spontaneously. The preoperative photographs show erythema on day 1, blisters day 3, a necrotizing abscess day 6, and wound infection requiring surgery day 10. The patient underwent operative debridement and was treated with antibiotic agents for three weeks. The infection resolved with no recurrence or sequelae during three years of follow-up. Diabetic foot infection may evolve rapidly, especially in patients with neuropathy. A 14-year-old girl presented to the emergency department after a car accident. She had been wearing a lap-shoulder seat belt. She had severe back pain but had normal strength and sensation of touch in her legs. She reported no paresthesias. Palpation of the lumbar spine revealed prominence of the spinous process of the first lumbar vertebra and an increased gap between the first and second lumbar spinous processes, findings that aroused suspicion of a flexion-distraction injury. CT revealed disruption of the ligaments in the posterior column and the middle column, as well as disruption of the L1-L2 intervertebral disc in the anterior column. There were also fractures of the anterosuperior aspects of L1 and L2 and dislocation of the L1-L2 facet joints. These fractures are characterized by violent flexion with all elements posterior to the axis of rotation submitted to distraction forces. The fractures are unstable and require surgical treatment. The patient underwent T12 to L2 fusion and was pain-free four months after surgery. This concludes the summary of the December 5th issue of the New England Journal of Medicine. We're interested in your feedback about our audio summaries. Any comments or suggestions may be sent to audio at NEJM.org. Thank you for listening. |
Hello and welcome to the podcast for the September 2009 issue of The Lancet Oncology. Richard Lane here and I'm joined this month by TLO's editor David Collingridge to discuss some of the issue highlights. David, let's start with a study actually looking at two trials concerning the treatment of prostate cancer. Just before we actually go into the details of the study, can you just give us some background here and remind us how prostate cancer is generally managed these days? Well treatment of prostate cancer depends on the type and extent of disease and the options run the full spectrum of modalities typically associated with cancer management from simple watch and wait strategies for very small localised lesions through to surgery, hormonal treatment, chemotherapy and radiotherapy. The precise combination and constitution of these latter options again really depends on the stage of disease. And David these trials investigate the efficacy of a bisphosphonate, the one in question here being sodium clodronate. What do we know about this agent? Well sodium clodronate was one of the first generation bisphosphonates. We know that bisphosphonates have a role in bone demineralisation and they can prevent fractures and it's thought they also have an anti-tumor property by modifying tumor growth factors, adhesion to tumor cells to the bone matrix and also modifying tumor cell apoptosis. As a result bisphosphimates are already well established in the management of multiple myeloma and breast cancer. So given prostate cancer is characterized by osteoblastic metases, the combined analysis of these two trials we're publishing this month tries to ascertain whether bisphosphonates might have a role in this setting also. And David, go on and briefly just summarise the design of these two trials. In these two British trials, sponsored by the MRC, 311 men with metastatic disease were recruited into the trial designated PR05, and 508 men with non-metastatic disease were recruited into trial PR04. In both trials, men were randomised to receive 2,080 mg of sodium clodronate or placebo for up to three years for metastatic disease and up to five years for non-metastatic disease. This new analysis looks at the long-term follow-up, a median of 11.5 years, within these trials. The results, David, there seems to be a clear distinction here between the results for metastatic disease compared with that of local disease. Yes, that's right. These long-term data highlight an important distinction and help delineate who should be prescribed sodium chlodronate. The results show a significant overall survival benefit for men with metastatic disease at presentation equating to a 30% survival at 5 years and a 17% survival at 10 years compared with just 21% and 9% respectively in the placebo groups. Among patients with non-metastatic disease there is no evidence of benefit as indicated by the hazard ratio of 1.12. The authors also present a number of exploratory interaction analyses for both trials, but the results, while suggesting a few nuances, do not materially affect these top-line take-home messages. What's your and the authors' possible explanation of the difference between these two results? As I've just hinted at, these interaction analyses highlight a few nuances that give us some clues to these differences. So, for example, among men with metastatic disease, there were biochemical differences, such as raised alkaline phosphatase and creatinine, which are thought to affect osteoblastic activity and the pharmacokinetics of bisphosphate excretion. So it seems there are biological factors related to the development and progression of bone metastases that affect treatment response. And David, next steps, the usual question really, do we need more research to confirm these findings in larger studies or are there implications for clinical management straight away do you think? The data here support the use of bisphosphamides within the management strategy for metastatic prostate cancer and equally they suggest these agents probably shouldn't be used for men with localised disease. The next steps now are to ascertain whether the next generation of bisphosphamides, which are far more potent than sodium clodronate, can improve outcomes further, and whether various other combinations of chemotherapy can be added into the mix. A number of trials are ongoing to look at these issues, the MRC-sponsored STAMPEDE trial being one of the most ambitious. Moving on David to a randomised trial called PASSION-P and this concerns women with early stage breast cancer undergoing a sentinel lymph node mapping and biopsy. Give us some background here please. Well lymph node mapping and biopsy simply means identifying where the lymph nodes reside anatomically so that several can be resected for pathology. Biopsies are done to determine the stage of disease and as we all know accurate staging in any cancer is important to deciding on the most appropriate treatment options and often gives us some clues on prognosis too. For identifying nodes in patients with breast cancer radiolabel colloids or blue dye is usually injected to visualize the location of the nodes for subsequent resection. Now site of injection is contentious. Different practices exist ranging from peritumoral to interparenchymal, subdermal, dermal and intertumoral injection. This procedure is associated with pain so just to clarify the clear objectives of the current study. Yes that's right there's been very little research looking into pain associated with lymphatic mapping but given this procedure is an important component in disease, it's very important to consider patient comfort in all aspects of their care, including diagnostic procedures. In this American study, 140 patients were randomized to one of four different groups. The groups include a control of topical 4% lidocaine cream plus technetium sulfa colloid, and three study groups of topical placebo cream plus injection of technetium sulfur colloid contained neither sodium bicarbonate 1% lidocaine or sodium bicarbonate plus 1% lidocaine. The primary endpoint was patient reported pain immediately after colloid injection using two different pain scoring systems. The results seem clear based on as you say these two different pain scores. Can you just discuss those results and also the chemistry behind the way different results were observed here? The mean pain scores on both scales were significantly improved for patients who received the colloid injection with 1% lidocaine, with or without sodium bicarbonate. The reason for adding the bicarbonate to the various study groups was to adjust the pH of the injection fluid because there's some evidence that buffering improves patient comfort. However, this study showed no significant benefit to altering the pH of the injection solution. And actually, it was simply the mode of delivery of the local anaesthetic, either topical or subdermal injection, that clearly had the greater influence on patient pain. And David, the implications of these results, is there enough evidence from this to again to auto-clinically practice at centres who can offer procedures like this? is reasonable in the suggestion that centres should now consider administering sub-areola injections of radioisotope colloid in 4ml quantities containing 1% lidocaine to improve patient comfort. And moving on to a slightly lighter issue, if you like, but still important. Back in 1823, when Thomas Wackley founded The Lancet, the weekly journal, he used a column to debunk some of what he considered the nonsense that was being propagated by parts of the medical profession, often concerning homeopathic remedies. And in a kind of similar way, you're introducing a new column into the last oncology, David. Tell us more. Well, complementary and alternative medicines are used widely these days, and use among cancer patients is alarmingly quite high. And often there is very little evidence to support their use, but mass media coverage, lazy journalism, biased reporting and pseudoscience have all allowed these practices to creep into the public's consciousness as valuable medical practices. Somewhat disturbing is the fact that such thinking isn't just limited to lay people. There are a number of supporters among well-educated people who really should know better. With this in mind, it's remarkable that such debates have been ongoing among the pages of the Lancet back to its earliest issues in 1823, and yet here we are nearly 200 years later and the debate still rages on. In those inaugural issues, Thomas Wackley ran a regular column, as you mentioned, called Quack Medicines, to expose the truth behind popular alternative medicines of the day. We decided it would be a timely homage, if you like, to the Lancet's founder, to re and the first column you have is authored by Ben Goldacre, who people may well know in the United Kingdom for his column in the Guardian newspaper about bad science. Just briefly mention the sort of issues he's dealing with in this first column. Well, we were delighted Ben Goldake had found time to write for us, given the popularity of his pieces in the Guardian. |
The article covers the contrasting reports on red wine and alcohol consumption, consumption of various food types, and lifestyle choices. And finally, the piece champions the use of meta-analyses and systematic reviews, with the inference that these types of reports are perhaps a much better source of reliable information, especially for the popular press, because they're less susceptible to large swings in recommendations and conclusions. I guess I just wonder, as I probably would have done in 1823 if I'd been around, isn't there just a slight danger that we're preaching to the converted here? Maybe differently in 1823, but surely in 2009. Do we need to be telling educated, informed readers of the Lancet Oncology about this sort of thing? Well, to be honest, Richard, I'm not sure we are preaching to the converted. There are a number of complementary medicines, for example, where the evidence base is far from conclusive. It's all rather contentious, and even amongst oncologists, opinion is divided. These columns will allow us an opportunity to re-examine some of the evidence and reopen debate. And to help general public. It's a perennial issue. Thanks for that, David. And let's just quickly finish off with the leader, which I see is calling for sunbeds to be banned. Why is that? Well, last month we published a short summary from the recent IARC monograph meeting in Lyon, France, in which the previous rating for ultraviolet-emitting tanning devices was upgraded to the highest risk category available, namely, on the basis of all relevant evidence to date, these devices are officially carcinogenic to humans. The underlying meta-analysis that led to this conclusion showed a startling 75% increase in the risk of melanoma among people who began tanning regularly before the age of 30. Now, given generally agents in this highest risk category are either banned or heavily regulated to reduce risk, and given there are good alternatives to sunbeds such as various lotions and sprays that can achieve the same or similar body image, can we ethically condone the use of such devices in the name of, well, vanity? I don't think we can. And I'm sure the time must have now come to see tanning saloons and sunbeds removed from our streets and homes. Yeah, it's difficult to disagree with that, David. I just want to check that we're also not saying that any exposure to sunlight, which is obviously different to a sunbed, but obviously it's still potentially carcinogenic, is not something that we're talking about about here there's still a way that you can go away on holiday protect yourself against the sun but still come back with a with a healthy color is that right absolutely a little bit of sun is of course good for you but this is rather different from being fried at close range on a sunbed provided you limit your exposure it's all about everything in moderation don't spend large amounts of time in the sun without a high factor sun cream and especially seek the shade around noon when the sun is at its hottest. The Cancer Council Australia have long promoted a brilliant slogan to bear in mind when anyone's on holiday really, slip, slop, slap, which stands for slip on a shirt, slop on the sun cream and slap on a hat. Great, Well, I'm heading off to the Mediterranean in about 10 days time. So I will slip, slop, slap. And I hope listeners are going to do so as well whenever they go into hot, sunny areas. But anyway, many thanks, David. Those are some of the highlights from the September issue of the Lancet Oncology. Thank you all very much for listening and we'll see you next month. |
Hey folks, just a quick reminder that this episode is not meant to be used for medical advice, just good old-fashioned education. All patient information has been modified to protect their identity and the views expressed in our podcast do not necessarily reflect the opinion of our employers. Welcome back Clinical Problem Solvers. We are here again for a schema episode. How's everyone doing today? Can't complain. Doing great. Well, I'm doing better since I can see Jack Penner's mustache. It is epic, full, very Tom Selleck-y. It's wonderful. I had high hopes that the mustache was not going to be referenced on the recording, and there they go. We had this entire conversation about how this needs to be now a visual platform because of that mustache. Well, moving on to the case. I'm very excited that we have an awesome case for everybody today. Are we ready to get started? Let's do it. For the audience, just as a reminder, these schema episodes are an opportunity for us to review some of the core clinical problem solvers schemas through the lens of a clinical case. So none of us are actually blinded to the case, but we're going to be using the case as a mechanism to discuss some of the schemas, which you can find on our website. The schemas that we're going to discuss today are jaundice and lung nodules. You may remember a former schema episode in which we also examined the schema for jaundice. We are going to look at it through a different lens today, which you will see unfold in the case. And we are revisiting the jaundice schema because not only is it one of the most fun ones to think through, but it is also one of the core problems that we see in internal medicine. So get ready for jaundice round two, as well as an approach to lung nodules. And I will get us started with the first aliquot here. So this case is a 67-year-old man who presented to the emergency department with one week of progressive jaundice. For the last four to six weeks, he has had intermittent episodes of dull, achy abdominal pain, and often, but not always, the pain came following a meal. All right, so let's get started. Let's first talk about jaundice. So whenever I like to think about jaundice, I like to break it into two buckets. The first being indirect, which is unconjugated bilirubin, and the second being direct, which is conjugated. Now, once I break them into these two buckets, I first like to review the life-threatening causes of each first, because there are no misdiagnoses. You don't want to forget about these and you want to rule these out first or at least be thinking of them first, just to make sure you're not dealing with a life-threatening cause of jaundice. And so in the indirect bucket, our life-threatening cause is going to be hemolysis. And so whenever you see an elevated, indirect, unconjugated bilirubin, take a quick look at the CBC and make sure you're not having an anemia, thrombocytopenia. Don't need to go ahead and check a peripheral smear. After that, in the indirect bucket, some less common causes. So you can have some drugs can cause an indirect hyperbilirubinemia, a hematoma, and then some rare genetic causes with Gilbert's being the most common. Next, let's move into our next bucket of direct conjugated elevated bilirubin. And this bucket, I like to break into two separate sections after that. So intrahepatic, so that within the liver, so your biliary tree within the liver. And this mainly involves your infiltrated diseases, a viral hepatitis, some drugs, and then cirrhosis. And then you move into your extra hepatic biliary tree, which can lead to elevated conjugated bilirubin. And for that, I like to think about three different types. So you can either have a problem in the lumen itself causing obstruction. You can have a stricture affecting the biliary tree itself and the wall, or there you can have an external cause of obstruction, something that is pressing on the outside of the biliary tree causing obstruction. Is there anything better than learning about jaundice from the future Boss Lady GI fellow? That was awesome. Thanks, Lindsay. Yeah, so this patient's coming in with jaundice. And let's think a little bit about the other aspect of this case, abdominal pain, mostly what it seems like a postprandial pain that this patient is experiencing. And the fact that this kind of a background of the abdominal pain is going on for like subacutely for a while, it's making me a little bit worried that we're dealing with like maybe more of a subacute nature and that this jaundice is not like acutely coming out of nowhere. So we love our Venn diagrams. So right now I'm thinking about the Venn diagram of postprandial, abdominal pain, and jaundice. But first, let's just talk about postprandial pain because it's kind of cool. And then I'm going to leave the overlap to the one and only Dr. Dan Minter to talk a little bit more about. So let's focus on postprandial pain for a little bit. When I think about postprandial pain, I think basically there's a stress test for the systems that needs to help us digest food in the GI tract. So what that could be, it could be the lumen of the GI tract, it could be the vasculature that requires to bring more blood in to help us digest food. It can be the problem with the biliary tract or the pancreas. So in the lumen itself, if a patient has a peptic ulcer disease, gastroparesis, or any external compression of that lumen, it can cause pain. And sometimes with external compression, you can get early satiety as well. Vascular one is an important one to remember because mesenteric schema falls into that category, is that if you have a lot of atherosclerotic disease in the vessels of the GI tract, then when you're eating and trying to digest food, you can get basically angina of the GI tract. Biliary colic and also chronic pancreatitis are the two other things to think about as well when you're thinking about postprandial pain. So think lumen, vessels, biliary, tree, and pancreas. Okay, Dan, what are your thoughts about the overlap of abdominal pain and jaundice? So when we're examining a patient who has postprandial abdominal pain and jaundice, we can look for areas in which those two symptom complexes overlap. And then by virtue of doing that, gain an added layer of specificity. So we can go crossing out the different causes of those specifics that are perhaps not in that sort of dual shaded area of the Venn diagram. So when we think about jaundice, we're thinking prehepatic, intrapatic, posthepatic, with then posthepatic being the sort of like focus on the biliary tree. And then as Charmaine mentioned, when we think about postprandial abdominal pain, then we're going to be again thinking about luminal structures of the digestive tract, vascular structures, the biliary system, and then the pancreas. So where is the element of overlap that most adequately fits this series of Venn diagrams? I'm really going to hone in on the biliary tract. So causes of postprandial biliary abdominal pain really make me think about cholecystitis with a caveat that cholecystitis in itself doesn't tend to cause jaundice, but perhaps if a gallstone is a little bit further down into the caudal duct, or if you have something called Moritzi syndrome, where a gallstone within the neck of the cystic duct then externally compresses the common bile duct. Also with the pancreas, if you have some sort of chronic pancreatic process that is causing a stricturing of the common bile duct, that could also lead to jaundice. And we oftentimes refer to like painless jaundice in patients who have a pancreatic head mass. So, you know, that's all to say that this overlap could potentially give us, you know, sort of a leg up on advancing our diagnostic thinking in this case. It may not be true that both of these symptoms are caused by the same pathology, but if they are, then we've just advanced our thinking a little bit by at least paying more than passing tribute to diseases of the biliary system in the pancreas. Dan, it is not too late to switch from ID to GI. Come on. He did say Moritzu syndrome. So I feel like that is a valid point. |
I like Dan Minter even more now than I thought I could. Well, there's a lot of biliary pathogens, you know, those flukes and whatnot. Oh, this is bringing me a huge smile. Let me give you the next aliquot of the case. So the patient's past medical history included hypertension, hyperlipidemia, and a recent diagnosis of diabetes three months prior. He took lisinopril, Atorvastatin, and Metformin as his medications. Review of systems included a 12-pound weight loss over the last six months, a chronic cough that had developed over a similar timeframe, as well as progressive exertional dyspnea. He had a 12-pack year smoking history and had quit about 30 years prior. He consumed one to two alcoholic beverages per week and lived in the Central Valley of Northern California. On exam, he was afebrile with stable vital signs. Exam was notable for icteric sclera and jaundiced skin. He had mild epigastric tenderness to palpation, and there were no stigmata of portal hypertension or hyperestrogenism. He also had no bruises. Labs were notable for an anemia to 10.2. This is a drop from a normal hemoglobin one year prior, as well as an AST of 25, an ALT of 33, an ALKFOS of 328, and a T-billy of 5.8, which was fractionated to reveal a D-billy of 3.6. A chest x-ray demonstrated scattered nodular opacities throughout the bilateral lung fields. Well, since Lindsay is going to be our resident GI fellow pretty soon, maybe I'll leave the discussion of jaundice to her and I'll kind of focus on some of the other features of this case that have come out, including the weight loss and the pulmonary symptoms. So, you know, basically at this point, we've taken what was something of a more isolated case of jaundice and now are expanding our thought process based on these other symptoms. Weight loss, you know, the way I think about that is I'm a simple person. So I think, you know, you're not getting enough calories in or you're using too many calories. And if you're not getting enough calories in, maybe it's that you're not eating or you're not absorbing. And then if you have too many calories out, it's either, you know, something inflammatory, like an infection, some other inflammatory disease or potentially malignancy. So, you know, that's all to say that, you know, now that we have this degree of relatively well-documented weight loss over the past six months, that raises my level of concern for some serious systemic process. And then also makes me sort of think about, you know, is it a calories in or calories out problem? I'm sure we'll touch on that a little bit more in the case as it comes up. What to do with the lung findings. So this patient not only is experiencing jaundice, but they're also experiencing some cough and shortness of breath and some sort of symptom complexes that refer us to the lung. So, you know, that there's one sort of major helpful action in this case is to move us away from the biliary system as we were sort of beginning to focus in on a little bit more and wonder if this is some process that is, you know, systemic and is truly having sort of primary focus within the thorax as well as within the abdomen. Or, you know, if we're going to draw sort of causal arrows, is something abdomen, the primary process, causing pulmonary findings or the other way around? The objective data that we have at this point is that the chest x-ray demonstrates, quote unquote, scattered nodular opacities in the bilateral lung fields. So that adds a degree of specificity. This is something that we can't ignore at this point and makes me more and more worried about some intrathoracic process. So what are these opacities? As a general rule, pulmonary opacities could be something that's within the alveolar space. That could be pus, water, blood. It could be something within the interstitium, or it could be a sort of tissue-based mass. So if these are pulmonary metastases or primary pulmonary cancer or something like that. Just because I can't help myself, One thing I'll say is that, you know, for those of you who don't practice in Arizona or California, the Central Valley is a buzzword for us for coccidioidomycosis, which is a dimorphic fungal pathogen that we think a lot about here in California. So I'm not sure if that's going to be related to this case. I would be jumping up and down if it was, but I'm holding my excitement. Awesome. Now, as Dan said, I'm going to try to focus on some of the liver lab just as to refresh. So your AST was 25, ALT is 33, ALT-FOS 328, a T-billy 5.8 with a D-billy of 3.6. So how does that help us make progress in our case? So whenever I'm looking at liver labs, I'm trying to characterize them as cholestatic or hepatocellular. And cholestatic liver picture will show an elevated outfoss and an elevated direct bilirubin, whereas a hepatocellular liver injury will show more of an elevated AST and ALT out of proportion to the other two. And so with this patient's lab specifically, you're seeing that really elevated out cost and debilly, which is out of proportion to the normal AST, ALT. And so that puts us in that bucket of cholestatic liver injury. And so then when I think about cholestatic liver injury, I'm thinking about the biliary tree or something either internally in the biliary tree or something externally pressing on the biliary tree causing obstruction. Now that can be from the gallbladder. It can be from the small intestine. It can be from lymph nodes. It can be from the pancreatic head. So anything around that area that can cause obstruction can cause this picture. And, you know, what diagnostic step is next whenever you are thinking about a cholestatic liver injury? There are so many imaging modalities that you can choose to try to investigate this. And so you have an ultrasound, a CT with contrast, an MRI or MRCP that looks specifically at the biliary tree, or you can go straight to GI and ask them for an ERCP or an EUS. An ERCP is endoscopic retrograde cholangiopancreatography. Say it three times fast. I never try to say that. It's mostly because I don't know what it stands for. And then an EUS is an endoscopic ultrasound. And so basically go in with an endoscope and ultrasound the area that you're concerned about. And so really when you're trying to decide between any of those imaging modalities, you're trying to figure out how urgent you need your image, the availability of the imaging modality. And if there's anything else that the patient may have that you want to investigate that may make you want to pick one imaging study over the other. And so ultrasound is really great for the biliary tree. If you're just wanting to look at the biliary tree to see if there's any biliary dilation. A CT is great if you're wanting to look at maybe something else. So this patient has pulmonary nodules, they have biliary involvement. So if you're wanting to give this patient one study that may capture both, that may be better. An MRCP specifically looks at just the biliary tree. And it's actually better at picking up PSC and stuff that may be not a stone. And then, of course, if you're concerned about cholangitis, you may want to just go ahead and call GI for that ERCP. So since this patient has also has pulmonary triming, you may consider just going ahead and doing one study so you can try to capture both. And if you're not able to find the biliary findings on that CT, an ultrasound or MRCP can be more sensitive. Absolutely awesome discussion team. As requested by Dr. Shipley, CT of the chest, abdomen, and pelvis revealed multiple randomly distributed pulmonary nodules, some of which had central cavitation. The abdominal and pelvic portions of the CT scan showed dilation of the common bile duct up to 1.5 centimeters and no discrete stones, masses, or lymphadenopathy. All right. Who am I to get in the way of pulmonary nodules on ID fellows? So I'll leave that up to Dan and then focus with Lindsay's permission under the common bile duct dilation, which kind of makes me think about the extrahepatic ideologies of the jaundice that Lindsay laid out for us in the beginning of the case. |
And in terms of the lumen, you know, we can think about stone, sludge, biliary cast, and I have to say parasites because of that. What can happen within the walls? And the wall pathology usually leads to strictures, cancers in the form of cholangiocarcinoma, trauma, ischemic injury, and autoimmune diseases such as primary sclerosis and cholangitis. And are we really super solvers if I don't mention IgG4 disease? Yep, IgG4 disease can do it too. There are more rare causes of stricture, such as infectious processes like A-cholangiopathy and influx of processes such as mastocytosis, amyloid, but quite rare. So I would always focus my cognitive energy on the most common causes. Lastly, the external compression. So thinking about the environment that the common bile duct, this floppy tube sits in. So cancers of the pancreas and filaria of water and adenal pathologies and cancers can lead to external compression. And so those really big lymph nodes that can surround that biliary duct. Awesome, Sharmin. Thank you so much for walking us through that. And now that we have this comprehensive understanding of what potential processes can cause an extrahepatic biliary obstruction, to move our own reasoning process forward, we can start to think about how we take this list of potential etiologies and prioritize them in terms of what is more and less likely. And so if we think about rooting ourselves in the epidemiology of the causes of extrahepatic biliary obstruction, far and away the most common underlying etiology is going to be gallstone disease. Often, but not always, we'll be able to see gallstone disease on the CT scan. And so the absence of this finding here, while it certainly doesn't rule out that there is potentially a stone obstructing the common bile duct, it makes us start to expand our differential diagnosis to include some of the other disease mechanisms that Charmaine mentioned. If we go back to the reasoning that Dan and Lindsay and Charmaine shared with us earlier in the case, we can start to see an underlying process such as malignancy rising higher and higher, right? We have multiple foci of disease and multiple organs of the body. We have a subacute syndrome of systemic inflammation in somebody who is a bit elderly. And so we can see malignancy starting to work its way up the case. But, right, if we're going to actually test this hypothesis, what we're going to need in the absence of a definitive understanding of the etiology of the obstruction on CT scan is to get a look inside and around the biliary tree. And this is where the assistance of our GI colleagues or the hepatobiliary team can be quite helpful because they have the skills necessary to perform an ERCP. What an ERCP can help us do in this case is be not only diagnostic, but also therapeutic. The ERCP can give us a look at the biliary tree. Do we see a stone there that the CT scan didn't pick up? Or do we see another explanation for the extrahepatic biliary obstruction? And then the ERCP also gives us an opportunity to deploy a therapeutic intervention to relieve the obstruction in and of itself. So it's an incredibly effective, both diagnostic and therapeutic intervention that we can potentially get in one fell swoop. Other things that we can do during an ERCP procedure would be to take more diagnostic sampling, for example, tissues or acquiring the stone if we wanted to send it off for further analysis. Beautiful, Jack. I kind of think that your discussion of epidemiology was put in there in part to just dissuade me from thinking about liver flukes and all the other wonderful parasites. It was not a fluke. I'm dying on the inside. Okay. Well, yeah. Charmaine wanted me to talk about pulmonary nodules as the other part of this case, which is really interesting based on the CT scan. So if you're near a computer, I'd suggest that you go to the CP solvers website and look at the lung nodule schema. Basically, there are three main buckets of diffuse pulmonary nodules. This is in contrast to like the solitary pulmonary nodule that you might see in another context. So this is if you have multiple sort of small pulmonary nodules throughout the lungs. And these are all in reference to the pulmonary lobule, which is the smallest divisible component of the lung parenchyma. And so what that really is, is it's a sort of unit of lung parenchyma that's surrounded by lymphatics, almost in like a hexagonal sort of structure, into which run a main airway, or into which run an airway and then a blood vessel. These are also covered with sort of capillaries. So there's blood flow throughout the entirety of the pulmonary lobule. So with respect to the pulmonary lobule, there are central lobular, randomly distributed and perilymphatic forms of nodules. Let's start with central lobular nodules. These are nodules that are in the center of the pulmonary lobule. And how do you get to the center of the pulmonary lobule? The most common way is through the airway. So these tend to be airway-centric diseases. As an infectious diseases fellow, this is, you know, kind of what we tend to see most of the time is central lobular nodules more reflective of airway spread of infection. The infections that you can see can be viral, bacterial, mycobacterial, or fungal. There are also non-infectious causes like aspiration or hypersensitivity to pneumonitis or even the spread of an endobronchial tumor. But one tip off for central lobular nodules is if you look at the part of the lung abutting the pleura is there shouldn't be any nodules actually touching the pleural space. If we move on to randomly distributed nodules, these are nodules that have no relationship to the pulmonary lobule. And how do you get random distribution of things? It's wherever blood goes, a nodule might show up. So these are things that tend to be transmitted by the blood, like hematogenous infections, like miliary TB or miliary fungal infection, or potentially the transmission of a hematogenous malignancy. So you get metastatic disease. They just sort of randomly distributed throughout the lung parenchyma. So this would be a relatively good sort of picture for somebody who has hematogenous distribution of solid tumor metastases. The last major category, like I said, is perilymphatic nodules. And these, if you think about like the sort of hexagonal-ish pentagonal structure of the pulmonary lobule, these are around the edges of that where the lymphatics really serve to drain the lymph from the pulmonary system. So these can occur most commonly in inflammatory diseases like sarcoidosis or pneumoconiosis like silicosis. Or you can also see them in malignant diseases like lymphangitic carcinomatosis, where you just really have kind of a buildup of stuff around the outside of the pulmonary lobule. So again, to summarize, central lobular, randomly distributed or perilymphatic, central lobular being airway, randomly distributed being more through just kind of hematogenous system dissemination, and then perilymphatic really sort of focusing in on those lymphatic channels around the outside of the pulmonary lobule. Boom. Boom, indeed. All right. So given what Dan has told us about pulmonary nodules, it seems like this, the distribution of the nodules for this patient are, are random. And so that makes us fall into that bucket of hematogenous spread. And whenever we think about hematogenous spread, exactly what Dan was saying, we're prioritizing malignancy, especially in this patient who is having weight loss and postprandial pain, cholestatic picture, liver injury. And so I think making sure we're not dealing with an infection and making sure we're not dealing with two different things, but also realizing that given that this is a random distribution with hematogenous spread, that this could definitely be a malignancy coming from somewhere in the biliary tree. So to give you all the conclusion of this case, after this excellent discussion, blood cultures, toxidioides, immunodiffusion, and complement fixation were both negative. Patient also underwent sputum testing and an AFB smear culture and MTB-PCR were also all negative. Patient ultimately underwent ERCP and endoscopic ultrasound, which demonstrated a four centimeter pancreatic head mass and a distal bile duct stricture. A biliary stent was placed and biopsies of the mass were taken. Biopsies of both the pancreatic head mass and of one of the lung nodules revealed pancreatic adenocarcinoma. And the patient was discharged home with plans to follow up with oncology for initiation of systemic chemotherapy. |
And the fact that these lesions were cavitating also, I learned, was atypical of a pancreatic adenocarcinoma. And so there was some diagnostic uncertainty over whether if we found what was the underlying etiology of the extrahepatic balearial obstruction, whether or not it would definitively explain the pulmonary nodules in this case. For those of you who are wondering, why did they take two biopsies? So team, we'd love to hear your reflections on this case or any other thoughts overall on the topics that we covered today. I will say the last that I heard that this patient is overall doing well, despite what is a very, very sad and very sobering diagnosis overall. Yeah, thank you so much for sharing, Jack. And, you know, I love talking about like jaundice in abstract. And I think a lot of patients that we take care of, unfortunately, I don't like it in real life as much because it turns into usually often like these really terrible pancreatic cancer diagnoses that comes with it a lot of like suffering and poor prognosis. It's still important to talk about, to learn from and to reflect on. And did the abdominal pain get better, Jack, by the way? Fortunately, it didn't change much after the biliar obstruction was intervened upon. Yeah. And that's another reason to kind of like circle back to our one diagram is that our job is not done yet. I think it's also easy to contribute the abdominal pain to this terrible cancer and also making sure that there's no other ideology that we can help this patient with. Yeah, 100%. Couldn't have said it better. And there are some patients if they have, you know, pancreatic, if we do find that the pancreatic cancer is causing a lot of the pain, they can go back and do a celiac plexus block for these patients, which helps a lot. It's more of a palliative procedure, but it can help tremendously with pain in that area. That's such a great point, Lindsay. And one of the reasons I love being a doctor because our job is never done. There's always there's so many tools that we have, whether it's, you know, a diagnosis, treatment or palliative, you know, at the end of the day, it's all done in the service to make sure patients have a good quality of life and be able to help them, whether it's with pain or getting answers. So, you know, we got a pretty awesome job. One of my reflections is it's so much fun to learn from everybody's sort of specific area of interest and Lindsay and Charmaine, you know, just amazing pearls and stuff. So really, really appreciated learning from both of you on this case. And thanks, Jack, again, for presenting and rocking that mustache. It was my absolute pleasure. Thank you all for joining us today for another installment of our Schema episode series. We hope you have a great rest of the day and thanks again for tuning in. |
Welcome to the New England Journal of Medicine summary for the week of February 28, 2013. I'm Dr. Michael Bierer. This week's issue features articles on high-frequency oscillation for ARDS, on dancitron and risk of adverse fetal outcomes, and an artificial pancreas versus sensor-augmented pump, review articles on idiopathic scoliosis in adolescents, and on clonality and cancer, a case report of a woman with long-standing thoracic pain and incontinence, and perspective articles on open access. With this issue, we feature new clinical decisions on medicinal use of marijuana. Currently, 18 states allow the medicinal use of marijuana, but it remains controversial among physicians. This Clinical Decisions presents both University of Toronto, Canada. In this trial, high-frequency oscillatory ventilation was compared with conventional ventilation with a lung protective protocol in patients with new-onset moderate-to-severe acute respiratory distress syndrome, ARDS. The study was stopped early. In-hospital mortality was 47% in the high-frequency oscillatory ventilation group as compared with 35% in the control group. Patients in the high-frequency oscillation group received higher doses of midazolam than did patients in the control group, and more patients in the high-frequency oscillation group than in the control group received neuromuscular blockers. In addition, more patients in the high-frequency oscillation group received vasoactive drugs and received them for a longer period than did patients in the control group. In adults with moderate to severe ARDS, early application of high-frequency oscillation as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure does not reduce and may increase in-hospital mortality. High-Frequency Oscillation for Acute Respiratory Distress Syndromeemia accompanying the acute respiratory distress syndrome. This trial compared high-frequency oscillatory ventilation with conventional ventilation. There was no significant between-group difference in the primary outcome of all-cause mortality at 30 days, which occurred in 41.7% of patients in the high-frequency oscillation group and in 41.1% of patients in the conventional ventilation group. After adjustment for study center, sex, score on the acute physiology and chronic health evaluation, APACHE-2, and the initial PaO2 to FiO2 ratio, the odds ratio for survival in the conventional ventilation group was 1.03. The use of high-frequency oscillation had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. Atul Malhotra from Brigham and Women's Hospital Boston writes in an editorial that these data might suggest that high-frequency oscillation as applied in these trials is not an advance. However, one could argue that it is not high-frequency oscillation itself, but the oscillation protocols studied in these trials that were ineffective, and perhaps worse than usual care. Second, patient selection may be an important factor. Some patients have recruitable lung, that is, lung tissue in which alveolar air volume is increased with small increases in airway pressure, whereas others have non-recrutable lung. Indexes of recruitability may help to define which patients may benefit from high mean airway pressures and which patients are likely to suffer deleterious effects without major lung protection. Third, currently recommended strategies that use low tidal volumes may have effectively minimized mechanical stress on the lung, and further improvements in outcomes are likely to occur only through improved understanding of the heterogeneous ARDS phenotype and its underlying biologic characteristics. On danetron in Pregnancy and Risk of Adverse Fetal Outcomes by Bjorn Pasternak from Staten Serum Institute, Copenhagen, Denmark. Ondansetron is frequently used to treat nausea and vomiting during pregnancy. This historical cohort study investigated whether receipt of ondansetron during pregnancy was associated with significantly increased risk of spontaneous abortion, which occurred in 1.1% of exposed women and 3.7% of unexposed women during gestational weeks 7 to 12, and in 1% and 2.1% respectively during weeks 13 to 22. Ondansetron also conferred preterm delivery, 6.2% and 5.2%, delivery of a low birth weight infant, 4.1% and 3.7%, or delivery of a small for gestational age infant, 10.4% and 9.2%. Ondansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. Nocturnal Glucose Control with an Artificial Pancreas at a Diabetes Camp by Moshe Philipp from the Schneider Children's Medical Center of Israel, Petah Tikva. This randomized crossover trial compared an artificial pancreas system with a nights when the sensor-augmented insulin pump was used, there were significantly fewer episodes of nighttime glucose levels below 63 mg per deciliter, 7 versus 22, and significantly shorter periods when glucose levels were below 60 mg per deciliter. Median values for the individual mean overnight glucose levels were 126 mg per deciliter with the artificial pancreas and 140 mg per deciliter with the sensor-augmented pump. Patients at a diabetes camp who were treated with an artificial pancreas system had less nocturnal hypoglycemia and tighter glucose control than when they were treated with a sensor-augmented insulin pump. Idiopathic scoliosis in adolescence, a clinical practice article by M. Timothy Horesco from Boston Children's Hospital. Scoliosis is the most common deformity of the spine. The diagnosis of scoliosis is suspected on the basis of physical examination and is confirmed by radiography performed while the patient is in a standing position that reveals spinal curvature of 10 degrees or greater. Idiopathic scoliosis is present in 2% of adolescents. Adolescents with scoliosis should have a thorough physical examination to rule out hereditary connective tissue disorders such as Marfan syndrome, neurofibromatosis, or neurologic conditions. Most adolescents with non-progressive idiopathic scoliosis can be seen by a primary care physician and do not require active treatment. Bracing is commonly recommended in patients with an immature skeleton with curve progression of 25 to 45 degrees, but data to support this approach are observational and inconsistent. A randomized trial comparing bracing with observation for idiopathic scoliosis is currently in progress. Surgical treatment is recommended in patients with an immature skeleton who have progressive scoliosis greater than 45 degrees. Listen to the full text of this article at NEJM.org. The Implications of Clonal Genome Evolution for Cancer Medicine, a review article by Samuel Aparicio from the British Columbia Cancer Research Center, Vancouver, Canada. The concept of clonal structure and evolution in cancers was elegantly synthesized in 1976, and it crystallized many prior observations of chromosomal heterogeneity during tumor evolution. Central to these ideas is the notion of a clone, a group of cells related to each other by descent from a unitary origin. Clonal relationships among cells arise when selection operates on individual dividing cells to confer a survival advantage or disadvantage. Within the next five years, international efforts may characterize the distribution of clonally dominant somatic mutations, those present in the majority of cells within a cancer, in more than 21,000 cancers of diverse types. A reduction in costs and improvements in technology have placed the sequencing of patients' tumors within practical reach. Preliminary results suggest that full characterization Thank you. focused on the implications and opportunities afforded by the realization that cancers are composed of cellular clones. The notion that most cancers are ecosystems of evolving clones has implications for clinical application. The authors review these, with particular focus on epithelial cancers. This review article discusses how methods to detect tumor cell clonality may come to inform clinical practice. A 77-year-old woman with long-standing unilateral thoracic pain and incontinence, a case record of the Massachusetts General Hospital by Ann Louise Oaklander and colleagues. A 77-year-old woman sought neurosurgical and neurologic consultation because of a long history of left thoracic pain. The patient had had constant pain under her left breast for as long as she could remember, probably since adolescence, which worsened over time and spread horizontally to involve a band on the entire left side of the chest. The cause for this patient's chest pain had been investigated over decades, and no cause or effective treatment had been found. She had undergone extensive cardiac and pulmonary testing, but the lack of other cardiac or pulmonary signs or symptoms made these unlikely sources of her chest pain. The current complete neurologic examination was normal. Review of imaging studies revealed multiple perineurial cysts in the thoracic spine. The cysts were the most likely cause of her pain because they were located at the same thoracic level as the pain and because there were no other potential causes. Symptomatic perineurial cysts, such as those described by Tarlov, have been reported for more than 70 years. However, most physicians are either unaware of the existence of Tarlov cysts or believe that they do not cause symptoms. |
For the sake of inquiry and knowledge, the inevitability of open access, a perspective article by Anne Walpert from MIT Libraries, Cambridge, Massachusetts. It's difficult to have a measured conversation about open access, Thank you. will undermine the viability of scholarly journal publishing disagree sharply with those who believe that only open access can expedite research advances and ensure the availability of that same scholarly literature. The system that produces, evaluates, and distributes scholarly research results is complex and interdependent. In a system this interdependent, destabilization at any one point perturbs critically important relationships. The extent to which access to knowledge is constrained and controlled by publishers' business models is at the heart of the discontent researchers have for the current journal publishing system. Yet, producing high-quality, peer-reviewed articles has a cost. However, many stakeholders in the scholarly communication system have cause to seek broader access to information and are experimenting with more open, Internet-based alternatives to traditional publishing. Although the transition to open access won't be easy or inexpensive, it is inevitable. Open, but not free. Publishing in the 21st Century, a perspective article by Martin Frank from the American Physiological Society, Bethesda, Maryland. Online dissemination served as the impetus for the open access movement and the call for free dissemination of the information contained in journals. There is, however, a cost associated with this openness, a cost that may reduce the funds available for research. Open access now comes in two flavors, gold and green. Gold open access provides immediate free access to the literature. Thank you. repository, such as PubMed Central. PubMed Central diverts approximately $4 million from the NIH budget in order to collect, process, and convert NIH-funded manuscripts into PubMed Central's archival format. Funding agencies are encouraging or requiring their grantees to publish in gold open access journals, allowing them to pay their author fees with money from their research grants or funds allocated by the agency. Assuming that all articles had to be published with gold open access, Harvard Medical School would have to pay $13.5 million at $1,350 per article to publish the 10,000 articles authored by its faculty in 2010, considerably more than the $3.75 million that was in its serials acquisition budget that year. Should we be diverting funds from research in order to fund open access publishing? Creative Commons and the Openness of Open Access, a perspective article by Michael Carroll from American University, Washington, D.C. Copyright law supplies the baseline terms of use for almost all information on the Internet. Copyright owners, seeking to grant permission to everyone, have issued public licenses broadening the range of permitted uses subject to certain conditions. Creative Commons licenses are the most widely used of these public licenses for all kinds of copyrighted works except software. As part of the open access movement and with the mission of expanding the terms of use for increasingly accessible information, Creative Commons has produced six copyright licenses that permit a range of uses beyond fair use, subject to certain conditions. The four conditions are combined into six permutations reflecting the types of copyright restrictions that people who otherwise choose to share their works for free might like to retain. The licenses, designed to allow all uses except those prohibited by a specified condition, have been adopted by a variety of institutional and individual copyright owners. The Downside of Open Access Publishing, a perspective article by Charlotte Hoogue from the Journal of the Norwegian Medical Association, Oslo, Norway. The open access model in which authors pay to have their work published offers an alternative way of financing quality control in scholarly publishing. But it also opens up opportunities for unscrupulous online vanity presses to exploit authors for profit. Jeffrey Beal, an academic librarian at the University of Colorado, Denver, who is interested in scholarly open access publishing, calls its more questionable incarnations predatory. Whether it's fair to classify all these journals and publishers as predatory is an open question. Some of the publishers are intentionally misleading, naming non-existent people as their editors and editorial board members and claiming ownership of articles that they have plagiarized from other publications. Other journals and publishers may be real, though it's obvious that the people running them are not very professional, and some of the publications may have been created simply because it seemed like a clever business scheme to collect author fees of several hundred dollars apiece to post papers in a journal-like layout at a fraction of the traditional price. Viewed in some lights, such enterprises may not be unethical. Thousands of researchers worldwide need to publish, and not all of them can do so in the highest-ranked journals. But it is surely problematic for journals and publishers to pretend to be something they aren't, misleading authors, readers, and the scientific community at large. The images in Clinical Medicine features a 56-year-old woman who had undergone bilateral lung transplantation for chronic obstructive pulmonary disease and who was found to have fine crystals in the inner retina in the macula of each eye, although she was asymptomatic. The crystals were consistent with talc retinopathy, and a remote history of long-term intravenous drug use was confirmed. Talc is an inert filler in methylphenidate hydrochloride tablets, which are crushed for intravenous drug use. The talc is then unknowingly injected intravenously. Talc particles are usually fine and are distributed intravascularly and extravascularly in the retina in patients who chronically use intravenous drugs and in whom right-to-left cardiopulmonary shunting occurs through collateral vessels that may develop around sites of pulmonary infarction. However, in a patient with a patent form in ovale, larger particles may cause retinal artery occlusions and severe vision loss. Review of this patient's previous lung biopsy specimens revealed interstitial epithelioid granulomas with foreign bodies, giant cells, and abundant polarizable crystalline material typical of talc. The talc particles, although perhaps not the primary cause of the respiratory failure, most likely contributed to chronic lung inflammation and exacerbated the patient's condition. A 62-year-old woman presented for a routine dental examination. During the examination, she was asked about the increased tissue on the lingual surface of her lower jaw. The patient reported that the mass had been growing slowly for years and that several family members had similar growths. On examination, four hard sessile nodules were noted on the lingual surface with normal overlying mucosa. Exostoses are localized benign bony protrusions. The most common oral exostoses are torus palatinus and torus mandibularis, which do not have cartilage involvement, owing to their anatomical location. There are many reasons for the development of exostoses, including genetic and environmental causes. They are generally asymptomatic. Removal of oral exostoses may be indicated before prosthetic rehabilitation or if complications from chronic trauma develop. This concludes the summary of the February 28th issue of the New England Journal of Medicine. We are interested in your feedback about our audio summaries. Any comments or suggestions may be sent to audio at nejm.org. Thank you for listening. |
Hey folks, just a quick reminder that this episode is not meant to be used for medical advice, just good old-fashioned education. All patient information has been modified to protect their identity and the views expressed in our podcast do not necessarily reflect the opinion of our employers. Welcome back, family. It is great to be back for another episode of Queer Rounds, a podcast series that looks to highlight the reality of gender and sexual diverse communities in healthcare and how transphobia and homophobia are important causes of health disparities. This is the first episode of our first season titled LGBTQI plus health 101. Today we will cover terminology and concepts. Joining me today are my two lovely co-hosts, Gabriel and Brody. Hi! Hi family, excited to be back with you. Hello y'all, excited for today's episode. Being comfortable with terminology about gender and sexuality is key to improving our patient care. Couldn't agree more, Bernie. It is incredible how only respecting someone's identity or sexual orientation can go far to create a safe space within our practice. We would like to begin by saying that by no means a list of terms we will search today is exhaustive. You know, language involves with time and definition that may be of widespread use today, may be obsolete a decade from now. This is also true of geographical location. The same terms are not used in South America compared to Europe or Asia. Even within a country or a region, there are multitudes of terms that are unique to specific communities, and we should acknowledge that. That's totally true. So let's begin with the basics. What does LGBTQI plus stand for? It is an acronym that covers diverse groups with respect to their gender identity and their sexual orientation. The L stands for lesbian, the G for gay, the T for trans, the Q for queer, the I for intersex, and the A for asexual. The plus sign is usually added at the end to include all the terms that exist. We should acknowledge that gender and sexuality is a spectrum. So in reality, it would be impossible to have every individual identity and orientation in an acronym. Before we explore what each term means, let's talk about the difference between gender and sex. Yes, you're very right, Vali. This is a point of confusion for a lot of people. We define gender as a socially constructed set of ways that people understand and express themselves along the continuum of masculinity, femininity, both or neither. Sex is different from gender and refers to the biological distinctions that exist between male, female, and intersex with respect to specific genes, sex chromosomes, and or reproductive anatomy. Based on these biological distinctions, most infants are assigned a sex at birth according to the binary framework of male or female. Over to you, Vali. Thank you, Brody. It is key to point out that even though gender and sex are different concepts, they have in common that neither are binary. This means that the idea that there's only two sexes, male or female, is not scientifically or medically accurate. Intersex people exist and have always existed. There are people whose reproductive or sexual anatomy doesn't fit the typical definitions of male or female. For example, a person may be born appearing to be female on the outside, but having mostly male typical anatomy on the inside. Or a person may be born with genitals that seem to be in between the usual male and female types. For example, a girl may be born with a noticeable large clitoris or lacking a vaginal opening, or a boy may be born with a notably small penis or with a scrotum that is divided so that it has formed more like labia. The bottom line of what I'm trying to say is that neither sex nor gender are binary. They're in a spectrum. So next time you hear someone say they're only two sexes, you can confidently say no, they are not. Right, vale. And most people are designated as sex when they are born based on their external genitalia. However, in most of the societies, what is considered maleness or femaleness are associated with not only physical, but cultural, behavioral, and psychological characteristics, as well as the expectations about their roles as male and female. People often play in a certain community. In the bottom line, let's not pretend that we check all the chromosomes or genitalia and we do a very complex molecular study in every person that we met. We only question someone's sex when they don't fit our cultural expectations of what male and female should be. That's so true. For some people, the cultural expectations associated with their sex assigned at birth align with their gender identity. For example, for someone assigned male at birth may identify as a man and with the cultural and social expectations for men in their society. For others, like myself, the cultural expectations associated with their sex assigned at birth do not align with their gender identity. For example, someone assigned at female at birth may not identify as a woman or with the cultural and social expectations for women in the society. Let's discuss some of these terms that can be used to describe someone's gender, gender identity, and gender expression. Let's start with the term cisgender. It refers or is used to describe someone whose current gender identity aligns with the sex they were assigned at birth. For example, I am cisgender, I'm a cisgender woman, which means they assigned me the female sex when I was born. And growing up, I found out that I identify as a woman as well. So these two moments align for me. And following up, someone who is transgender or trans is an individual whose gender identity does not align with the sex they were assigned at birth. Let's put example of John. He's a transgender man, which means he was assigned a female sex when he was born, but identifies as a man. Now, let's make something very clear. Even though we use transgender and cisgender to differentiate two types of individuals, trans women are women, period, and trans men are men, period. Cisgender women are not more women than trans women because they were assigned female at birth. The same goes for men. If someone identifies as a man or a woman, this is a self-identification independent of what anyone assigned them to be. It is based on what is important to them as an individual, including gender roles, behavior, expression, identity, and or physiology. Period, Vale. And you also may have heard terms such as transsexual or, for example, very much common in Latin communities, the term travesty, to refer to trans people. However, these terms are outdated and they can be hurtful because they were used to differentiate trans people who had undergone gender confirmation surgery. That is incredibly invasive. Like, no one is asking you about your gender laws when you meet them. So please don't use them unless a person refers to themselves like that. Thank you for mentioning that, Gabriel. We should emphasize the fact that we should listen to how the person refers to themselves and respect that. Now let's talk about being non-binary, a term used to describe someone who identifies their gender outside the binary of man and woman, either because they identify as both masculine and feminine, or because they identify as neither masculine or feminine, or because they identify in a way that does not conform with the normative views of sex and gender in their culture and historical period. Related terms are genderqueer, gender nonconforming. In my experience of being nonconforming myself, there are times when I feel to be a man, woman, both or none. To me, it's fluid, amorphous, and there is no single box that I put myself in. Thank you for sharing that, Brody. There are also people who identify as a gender, which means that they don't identify with any particular gender. A term that you will hear most likely, especially if you're a health provider, is the term transition. Transition is the process of shifting towards a gender role different from that typically associated with the one sex assigned at birth, which can include social transitions, such as assuming a new name, pronouns, and clothing, and or medical transition, such as hormone therapy or surgery. The transition process is very specific to each person. We as health providers shouldn't expect all our trans and non-binary patients to want to undergo medical transition necessarily. The fact that someone decides they don't need surgeries or to be in a long-term hormonal replacement therapy doesn't make them less trans or not does mean their transition is incomplete. Transition looks different in everyone. This is so true and gender expression grows from person to person. One way gender is expressed is through the use of pronouns. Thank you for bringing that up. I would like to say also that assuming someone's pronouns, even if correct, can be harmful. And it's something that actually has happened to me. I assumed someone's pronouns and turned out to be incorrect. |
So we would like to suggest to you, our listener, that in the setting of meeting a patient, it's not, or really anyone, it's not really the way to start building trust with them by assuming their gender and their pronouns. You don't want to start by that. And so we suggest you offer your pronouns. That way, the person can know that if they feel comfortable to share with you, they will, they can. Of course, you also need to have in mind that when someone shares their pronouns and they do not fit the binary or the expectations that you have on them because of how they look, well, that's also like out in them. So that takes a lot of bravery. That's a very nice advice, Vale. Thank you for that. Okay, let's take a deep breath. We have now covered the basics on gender, the difference with sex, and tried to describe gender identity. For now, we discussed what is asexual, cisgender, transgender, agender, and gender nonconforming. And one piece of advice is that it is best to practice to ask patients how to refer to themselves and to mirror their language. That's very, very true, Ariel. To mirror the language that people use, it's the best way to not make a mistake. And another advice that I would like to share is that I wouldn't suggest people to ask about sex assigned at birth. At least it is extremely necessary, which I think, I don't know, I couldn't come up with a scenario which was extremely necessary. Because if someone tells you, I am a trans woman, your next question shouldn't be, oh, so you were born a man. Because on a way, that's like implicit in them telling you they are trans women or a trans woman and so saying something like you were born a man can be harmful and you really don't want to put a person in an awkward spot referring to them with a gender they don't identify with right love the love those points Another point that I'm just going to make in passing is that asking somebody about their pronouns, I think the first step is to share your own pronouns. That fosters that confidence and interaction that makes them come up with their pronouns. And I think that's how we can not assume, but just ask by sharing our own pronouns. So now that we have covered gender, let's talk about sexual orientation. This is a critical point, as it's one of the most common mistakes I hear people make. Gender and identity and sexual orientation are not the same. Sexual orientation is how a person describes a gender or genders of people they're attracted to sexually or romantically. Gender refers to someone's identity, how they are identified. Sexual orientation is who they like. Let's explore some terms that are used to describe someone's sexual orientation. Let's start with heterosexual. This is a term used to describe someone who is mostly or exclusively attracted to partners of a different gender than their own. The colloquial term used to refer to heterosexual people is as straight. On the other hand, gay is a term used to describe a person attracted mostly or exclusively to someone of their same gender. For example, I am gay. Some people still use the term homosexual to refer to gay people. But, you know, that's like a mouthful and it sounds very serious. So I don't think it's very used within the community. You may have also found yourself confused when I said that I was gay because it is a term used more often by gay men. And gay women can refer to themselves as gay, but another term used is as lesbians. So basically to refer to women who love other women or identify as part of the lesbian community. Nice. Now let's talk about being bisexual. It's a term used to describe a person who is attracted to partners of their same gender and partners of different genders to their own. You may be like, wait, what? I thought gender is not binary. So how come is it called bisexuality? That's a great point. And that's why in practice bisexual is used more or less synonymously with the term pansexual. Yes. And moving on, we have to queue for queer. And what does queer mean? It is in the title of the series, and that is because it used to refer to people who are neither cisgender nor heterosexual. And it functions as a unifying umbrella term inclusive of everyone in the LGBTQ plus community. We reclaim this term after its historical use as a pejorative slur. Finally, let's talk about being asexual. This is a term used to describe a person who experiences little or no sexual attraction. A related term is aromantic, which refers to someone who experiences little or no romantic attraction. Individuals may identify with both or neither of these terms. Importantly, asexual and aromantic people may still pursue sexual and or aromantic relationships for a variety of reasons, and they should still be screened with a full sexual history like any other patient. Wow, what a ride. We have covered a lot today. We would like to finish with emphasizing this. Gender identity and sexual orientation are not the same. This means that some people can be cisgender and gay, some people can be trans and straight, or some people can be gender non-binary and pansexual. They are two different things. The second point is that most of these terms are adjectives, not nouns, which means that you don't call someone a transgender. You say they are transgender. You don't call someone a gay. You say they are gay. Pretty straightforward, right? That was a very much intended pun. So please congratulate me for making that joke. Yeah, thank much vali that was a very awesome point and it was really great to cover terminology with you today we hope you are more comfortable using these terms and don't worry if you make a mistake we all do but give your best effort to learn respect and practice empathy to To finish this episode, let's share our faves. This space is to highlight someone or something that is inspiring us right now. I would like to recommend my favorite book of all time, which is called Las Malas or Bad Girls by author Camila Cesavillada. It is simply beautiful. I cannot recommend it enough. It is about a group of trans women doing sex work in Argentina. It's very poetic, very raw. I really, really recommend everyone should read it. The mic is all yours, Gabriel. Well, my fave for this episode, continuing with the line of Latin, LGBTQ+, arts, literature, and movies, is one of my, I would say, one of my favorite gay movies, and it's called, in Spanish, Contra Corriente, or in English, Undertow. It's a 2009 Peruvian film and it was the Peruvian entry for the face for a movie in Oscars 2010. And the story it's about a secret romance of a local Peruvian fisherman and a photographer. And what I really like about this movie is that it's very organic, very fresh, and portrays pretty well the vision of the Peruvian community at that time of a gay relationship. I feel like if I keep continuing telling you about the movie, I will make a spoiler at some point, but, oh my God, the ending was quite bittersweet and I couldn't recommend it more. Well, I think it's only fair that I share my favorite now, but it's, okay, so what I'm watching queer right now, so I've been catching up a lot of Queer Eye, obviously every queer person sees that, and I have also been following, I just ordered Jonathan Van Ness's book. So I'm looking forward to reading that. And I recommend that to the people who are listening to this. And obviously you need to go to watch Queer Eye, right? But that's what I recommend at this point. So it was amazing to hang out with all you today. And we'll see you in the next episode of Queer Rounds. Happy Pride! |
Welcome to the New England Journal of Medicine audio summary for the week of February 24, 2011. I'm Dr. Lisa Johnson. This week's issue features articles on environmental microorganisms and childhood asthma, heterogeneity of hemoglobin H disease, BMI and risk of death in Asians, perilipin deficiency and lipodystrophy, and melanoma and resistance to BRAF inhibitor, a review article on point-of-care ultrasonography, a case report of Thank you. and on residents, workers, or students in the law's eyes. This week at NEJM.org, we feature a new video in clinical medicine. This video demonstrates the placement of intraosseous catheters in children and reviews the indications, contraindications, placement techniques, and potential complications. Both manual insertion and insertion with the use of a power-assisted device are shown. Exposure to Environmental Microorganisms and Childhood Asthma by Markus Ege from University Children's Hospital, Munich, Germany Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. These authors assessed the prevalence of asthma and atopy among children living on farms and among other children living in the same areas. The reference group measured the diversity of the microbial exposure in both groups and related the diversity of exposure to asthma and atopy. In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma. Odds ratio for the first study, 0.62. Odds ratio for the second, 0.86. In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma. This included exposure to species in the fungal taxon Urodium and to a variety of bacterial species, including Listeria monocyt Wisconsin School of Medicine and Public more than doubled, and although the treatments used to control asthma have improved greatly, there has been little progress in prevention. Identification of the association between exposure to an environment rich in non-pathogenic microbes and reduced risk of asthma offers hope that this and other new conceptual breakthroughs will lead to novel preventive strategies. These findings also raise additional questions about the possible mechanisms through which the nature and range of microbial exposure may alter the developmental biology of the lung and immune system. Resolving these questions is of critical importance if we are to bring the substantial health benefits of being raised on a farm to those who are not. Early diagnosis during newborn screening or infancy has enabled the observation of the natural history of hemoglobin H disease, a subtype of alpha thalassemia. Hemoglobin H disease can result from deletion of three alpha globin genes or deletion of two such genes with a point mutation in the third, as is seen in patients with hemoglobin H constant spring. Nearly all the clinical manifestations occur in patients with hemoglobin H constant spring. Patients with H constant spring have a significant growth delay, require intermittent blood transfusions, have iron overload in the first decade of life, and have a good response to splenectomy. A similar drop in hemoglobin during infection does not occur in patients with hemoglobin H disease, and blood transfusion appears to be unnecessary in the management of this disorder. H-constant spring should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illnesses. Many patients with these disorders had mixed ethnic backgrounds, which highlights the need for extended newborn screening in populations that are traditionally considered to be at low risk for hemoglobin H disease. Edward Benz, Jr., from the Dana-Farber Cancer Institute, Boston, writes in an editorial that, among the most common single-gene disorders in humans, thalassemias are a cause of substantial morbidity and mortality in Asia and the Mediterranean Basin. Symptomatic thalassemia has historically been an uncommon illness in the United States. However, as these authors report, a moderately severe symptomatic form of alpha-thalassemia, hemoglobin H disease, is being encountered with increasing frequency as Asian migration increases to the west coast of the United States. Moreover, hemoglobin constant spring disease appears to account disproportionately for the burden of symptomatic disease. These results highlight the dynamically changing effect of globalization on public health, as genetic disorders indigenous to specific populations become more common in the countries to which they migrate and make a strong case for newborn screening for alpha-thalassemia, at least in states with a substantial increase in their Asian populations. body mass index, BMI, and risk of death in more than 1.1 million people from 19 cohorts in Asia after a mean follow-up of 9.2 years. In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range, by a factor of up to 1.5 among those with a BMI of more than 35.0, and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seeny from the British Columbia Center for Disease Control, Vancouver. Over a three-year period, a total of 41 cases of tuberculosis were diagnosed in a British Columbia community struggling with the challenges of alcoholism, drug use, and transient housing arrangements. Because of the recognized limitations of contact tracing, field epidemiologists used social network analysis early in the outbreak. Whole genome data revealed two genetically distinct lineages of M. tuberculosis with identical genotypes, suggesting two concomitant outbreaks. Integration of social network and phylogenetic analyses revealed several transmission events, including those involving super-spreaders. Both lineages descended from a common ancestor and had been detected in the community before the outbreak, suggesting a social rather than genetic trigger. Further epidemiologic investigation revealed that the onset of the outbreak coincided with a recorded increase in crack cocaine use in the community. These authors show that a socio-environmental factor most likely increased crack cocaine use triggered the simultaneous expansion of two extant lineages of M. tuberculosis that was sustained by key members of a high-risk social network. Genotyping and contact tracing alone The adipocyte lipid droplet is now recognized as a dynamic cell organelle. Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. These authors identified two heterozygous frame-shift mutations in the perilipin gene, PLIN1, in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in pre-adipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue. Point-of-Care Ultrasonography, a review article by Christopher Moore from Yale University School of Medicine, New Haven, Connecticut. recorded by a sonographer and interpreted later, allowing findings to be directly correlated with the patient's presenting signs and symptoms. Point-of-care ultrasonography is easily repeatable if the patient's condition changes. The concept of a focused, limited, or goal-directed examination is important in point-of-care ultrasonography. Point-of-care ultrasonography may involve the use of a series of focused ultrasonographic exam with examples and discussions of its use. A 77-year-old man with dyspnea, weakness, and diaphoresis. A case record of the Massachusetts General Hospital by Atha Sibris and colleagues. A 77-year-old man was admitted to the hospital in mid-spring because of increasing dyspnea, weakness, and diaphoresis. Three days before admission, weakness, loss of appetite, fatigue, and diarrhea developed, followed by progressive shortness of breath. On the morning of admission, he awoke with dyspnea, which was worse when he was lying flat. He was taken to the emergency room. |
There are many causes of septic shock that are consistent with his presentation, so the physicians needed a way to limit and focus their differential diagnosis. The immune status of the patient is an important consideration. No overt immunosuppression is evident, but his advanced age confers a relatively immunosuppressed state. Immunosenescence, a decline in immune system function with age, is increasingly well characterized and affects both innate and adaptive immunity. Immunosenescence may predispose the elderly to more frequent and more severe infections than the non-elderly. And when we cross a list of infections in the elderly with a list of causes of septic shock, keeping in mind this patient's presentation, the physicians believed they could limit their discussion to five infectious processes, pneumonia, infective endocarditis, infectious diarrhea, bacteremia, and tick-borne illnesses. Resistance to BRAF Inhibition in Melanomas, a Clinical Implications of Basic Research article by David Solett from Memorial Sloan Kettering Cancer Center, New York. Approximately 50% of melanomas contain a mutation in the gene that encodes the RAF family member, BRAF, a protein kinase that phosphorylates the MEK protein and activates the ERK signaling pathway. This mutation, which in most cases is a substitution of glutamic acid for valine at position 600 of the protein, activates and deregulates the kinase activity of BRAF. Selective inhibitors of RAF, such as PLX4032, have remarkable clinical activity in patients with melanomas that contain the V600E mutation in BRAF. However, as has been the pattern for other inhibitors of oncogenic kinases, responses to PLX4032 are often profound but temporary. Two recent studies discussed in this article shed light on some of the mechanisms that may underlie resistance to RAF inhibitors and thus suggest new strategies to treat patients with melanomas carrying the BRAF V600E mutation in whom resistance to PLX4032 develops. Transforming Graduate Medical Education to Improve Healthcare Value A perspective article by Glenn Hackbarth from the Medicare Payment Advisory Commission, Washington, D.C. To ensure that health care will be affordable for future generations and appropriate for our burgeoning geriatric population, its delivery and organization must change. Physicians should be in the vanguard of this change, and transforming medical education will be instrumental in preparing tomorrow's physicians to lead the way. To provide high-value care, physicians will need skills in such domains as quality improvement, cost-aware practice, and care coordination. Medicare invested $9.5 billion in Graduate Medical Education, GME, in 2009. It is the single largest payer for GME, but it establishes minimal accountability for achieving education and training goals. MedPAC has therefore recommended that Congress authorize Medicare to use this financial leverage to catalyze more rapid GME reform by linking some funding to programs' performance on relevant measures. Advancing Medical Education by Teaching Health Policy A perspective article by Mitesh Patel from the Hospital of the University of Pennsylvania, Philadelphia. Standards for health policy curricula in medical education are long overdue. Matters affected by health policy ultimately affect patient care, and physicians need the skills to address them. Training must begin with the building of foundational knowledge and analytic skills during medical school, and perhaps even as early as pre-medical education through courses in public health or public policy. Continue with further instruction, dialogue, and application during residency training, and include reinforcement during clinical practice. These authors propose a focus on four domains, health care systems and principles, health care quality and safety, value and equity, and health politics and law. They represent a foundation of core principles on which we might build as we advance health policy education in the United States. A perspective article by Aaron Kesselheim Foundation for Medical Education and Research et al. v. United States, the Supreme Court added its weighty voice to the question of whether residents are workers or students. Mayo in Minnesota offered both functional and structural reasons why House officers should legally be considered students. In defense of the Treasury regulation declaring residents to be employees, government lawyers pointed to residents' vast patient care responsibilities, which absorb 85 to 90 percent of their time and take precedence over educational conferences. At stake in Mayo v. United States were substantial financial implications for academic medical centers and their house staff. The taxes at issue amount to about $700 million per year for U.S. hospitals and academic medical centers. The Supreme Court ruled in an 8-0 decision that the Treasury regulation making residents categorically ineligible for the student exemption was a perfectly sensible way of distinguishing education from service for the purposes of the tax code. Chief Justice John Roberts wrote that residents could reasonably be construed as the kind of workers that Congress intended to both contribute to and benefit from the Social Security system. The images in clinical medicine features a 40-year-old Korean woman who had been immobilized in bed for several weeks while recovering from tuberculous meningitis and who reported having pain in her right hip. Her right leg was externally rotated and flexed. CT showed a well-defined calcified mass within the gluteus minimus muscle, with bony trabeculation and cortex formation. Myositis ossificans, also known as heterotopic ossification, refers to the deposition of extraskeletal bone within soft tissue. Although the condition sometimes occurs spontaneously, it often is the result of trauma, surgery, burns, or neurologic injury. The calcification typically occurs within two to six weeks after injury. Also featured in the images in clinical medicine is a 55-year-old woman with hypertension who presented with a one-day history of periorbital discomfort, inferior chemosis, and conjunctival injection of the left eye. Examination of the left eye revealed a visual acuity of 2060, a relative afferent pupillary defect, exophthalmos, with 6 mm of protrusion, and an elevated intraocular pressure, 48 mmHg. CT of the orbit showed a dilated left superior ophthalmic vein, suggesting the presence of a carotid cavernous sinus fistula. Angiography confirmed that the internal carotid artery was connected to the cavernous sinus by a large fistula. Dilatation of the superior ophthalmic vein is a key feature of this condition and results from the transmission of arterial pressures to the venous system. This concludes the summary of the February 24th issue of the New England Journal of Medicine. We're interested in your feedback about our audio summaries. Any comments or suggestions may be sent to audio at NEJM.org. Thank you for listening. |
Welcome to Intention to Treat from the New England Journal of Medicine. I'm Rachel Gottbaum. For decades, scientists have tried to find effective ways to treat Alzheimer's disease, with very little success. But that could be changing. New medications may help slow the progression of the disease, and new diagnostic tools could help predict who might need treatment before their symptoms even start. My name is Heidi Levitt, and my husband, Charlie Hess, was diagnosed with what we think is early onset Alzheimer's when he was 57 years old. It was in 2019. So his work is extremely particular in terms of details. And he probably was having trouble with the details for quite a while. Charlie's saying, I'm feeling foggy. And he's watched me navigate with my own mom when I've sent her to a geriatric psychiatrist to get another assessment on what's going on with her cognitively. And he says, maybe I should see that person too. And he goes in for this exam, which is like having an SAT and you're 10 years old and it's college level. Like, it's terrible. It's three hours long. And if you ask him, it was the worst day of his life. What the psychiatrist said to us was the test showed problems across the board on cognitive function, like, you know, from the point of view of being visual spatial to the point of view of vocabulary to comprehension to following story, Like everything across the board was off. I said, tell me what is going to happen. And she says, I think because he's young, it can be a lot more aggressive. And then in three years, cognitive abilities will hugely decline. She said it was bad and it was going to get worse and offered me little to no solace. Then I said, look, we need to get scans and at least like confirm what's coming out on this exam. So we started with a study that was really more diagnostic study where we had to do a series of MRIs and we were able to get the amyloid PET scan to confirm the amyloid. So his symptoms started already where he was always feeling somewhat left out of a conversation, then became the executive function, having trouble making coffee. Now it's gotten to the point where he doesn't make the coffee at all. He can't turn on the TV. He can't get dressed by himself. I mean, everybody will say, oh, he looks great. He's taking great pictures because all he does every day is go out and take pictures and post it on his Instagram because he's an artist. You can't see this disease, right? Easily. Until what you see in the media is end stages of people who don't recognize someone or are drooling. But you're not seeing the years of loss. So it's not like you wake up the next morning and suddenly you can't do this. I think that's very hard to understand the pace of this disease. I was offered a drug that they felt it's showing great improvement to take away the amyloid plaque, which will then lead to possibly preserving him longer. And I get a call saying, your name was on the list. And we really want you to tell us if you want to try this drug, because there's a waiting list of 20 people. And if you can tell me, yes, I can get you in it. And if you don't tell me by tomorrow, the spot is gone. I said to Charlie, do you want to do this? And he said, no, we don't know that it's really going to work. And we said, no. I was skeptical about this new drug because there was not enough data that corroborated that it was going to change the course of his disease or stop it. It's not like they're offering me a cure. It's not like somebody saying, take this and it goes away. Nobody has said that. They're saying that this is going to help delay the disease progression. And if you look at the numbers, it's not high enough to take that risk. I feel like there's so much pressure because there has been absolutely nothing out there to delay, to treat, to cure. Just offering people something on the off chance that it will work, rather than finding something that works, is selling hope. My name is Carol Balmer. My husband, Jim, has been diagnosed with Alzheimer's disease. I started recording symptoms, things that I found unusual back in 2013, but it was not until 2017 that he was officially diagnosed. At that time, his condition was called mild cognitive dysfunction. Jim was doing peculiar things. He would lose his way to the shopping mall where we'd been hundreds of times and take the wrong turn. He would drive sometimes at 95 miles an hour on the interstate instead of the 75 that was allowed and not notice. He would miss the turn to our house, but then would catch it when he'd gone a block or so too far. These things began to be more and more troubling. And he had an event where he failed to recognize himself in a photograph just a couple days after the photograph had been taken. That troubled him, and he told his physician about it, and the physician did a screening test. Jim was eager from the very beginning to be part of this monoclonal antibody trial because it seemed so promising. We discussed the possibility of the side effects, but he didn't really care about the side effects. Even if he died in the study, he said, you know, you got to die of something. It would be great if he got the benefit of this medication. But the main thing was that he could help others. Jim's enrolled in the Trailblazer 2 trial that's testing one of the monoclonal antibodies, Donanumab, against placebo. So Jim's decline seemed very slow for a long time, and I hope it was from the drug, but maybe that was the pace of change that he was destined to have anyway. So because of the blinding, there's no way of knowing. Jim's functioning has declined quite a bit over the last several months. So Jim's short-term memory right now is non-existent. His memories go back in his early childhood, but not even his later childhood. We know that the next stages of this disease are terrible, but we're relieved and grateful and excited that he's hadling. She's director of the Center for Neuros Research Institute at the University of California, Santa Barbara. And also Dr. Risa Sperling. She's director of the Center for Alzheimer's Research and Treatment at Brigham and Women's Hospital in Boston. So Dr. Sperling, I'd like to start with you. We've just heard from two families who have very different perspectives on the new monoclonal antibodies for Alzheimer's. What can you tell us about the status of these treatments? We now have two monoclonal antibodies that are targeting different forms of amyloid in the brain and two phase three trials have been positive. One of those drugs is already approved, lakenamab, and one I think is likely to be approved over the next few months. We've had medications that have rid patients of amyloid without any result. So what's different here, Dr. Sperling? I think previous antibodies actually have not fully decreased amyloid sufficiently in the brain. There seems to be a relationship with how much amyloid do you lower and how quickly you do it and how many people you get down below some point. So I think number one is we've learned we have to be pretty aggressive with amyloid removal. Number two is that we're in earlier populations than we were before. And we've seen multiple times now that there's probably a point at which when there's a lot of tau in the brain that I think it's less clear that amyloid therapeutics, in isolation anyway, are sufficient to really bend the curve. And then third, I'll say we haven't hit the home run yet. We can see very consistently across these trials that we can bend the curve with very aggressive amyloid if we start early enough. But of course, we all want to find a way that we really stop decline, where we ultimately keep people stable or one day make them better. So Dr. Kosick, how do you see these medications? Do you see them as a breakthrough? My feeling about these anti-amyloid drugs is that they have bent the curve. There's no doubt about that. I suppose if I had to sum up my feeling about this is how we want to calibrate our enthusiasm because we really don't want to create false expectations. We have to make sure that our patients understand what's been accomplished here. And there's still a long ways to go. |
So what does moving the curve actually mean for patients? What it means for the patient, if we interpret the data literally, it means that they deviated from the control curve according to some neuropsychological tests. And what is hotly debated, do those changes in the neuropsychological parameters, are they discernible by family members? You know, if they are able to do things like spell world backwards or, you know, do some of the things that we measure neuropsychologically, is that going to translate into improved quality of life, lifestyle, all of that? And we just don't have those answers yet. And what about the significance in the realm of research? On the research side, there's no doubt that these medications have an effect on amyloid accumulation in the brain. And that's what part of the breakthrough was all about. And what about tau, which clearly has a role in this disease? Where does that fit in in this approach? We know that we all harbor some tangles in the brain, some neurofibrillary tangles. And with the deposition of amyloid, that pool of tangles gets released and begins to spread through the brain. And since tau tangles are a major driver of the disease, and we know from the second trial, the DENAMIMAB study, that the drug didn't have very much effect on the tau PET imaging, that we really have to be able to say that the impact of this has to be moderated because it only affected one portion of the disease. And you've found in your genetic work clues that a lot of amyloid in the brain does not always translate into developing Alzheimer's disease. We do know from at least one patient, the woman who had the Christchurch variant with APOE, the mutation that will cause early onset Alzheimer's disease at age 45 or 50. She had a head full of amyloid, very few tangles, and did not have very much dementia. She did not have the disease. And when she had a tau PET scan, she had very minimal findings of the tau PET. So that's one case. It's a decoupling, but I do think we have to take that into our consideration here. So Dr. Sperling, what does this mean for the research if having amyloid in the brain doesn't always lead to Alzheimer's. So we've known for a long time that amyloid is necessary, but not sufficient to cause Alzheimer's dementia. So what we've learned more recently is that in the setting of amyloid, tau begins to spread throughout the brain and that is occurring as people start to develop symptoms. So the amyloid occasionally is there for more than a decade before you get this where the tau suddenly explodes out of the deep parts of the brain and the medial temporal lobe and goes around the rest of the brain. And that's very commonly associated with a rapid cognitive decline. So I very much agree that you need both amyloid and tau to get to Alzheimer's dementia. The majority of people who have a lot of amyloid in their brain do show decline over time, and that is associated with tau spreading. And we don't fully understand that relationship. I'll even go so far as to say I'm not sure it's amyloid causing it or whether there's an association between these. Perhaps it's a process that's upstream of both amyloid and tau. You know, people have cholesterol building up for years and decades before they get a heart attack or a stroke. And many people with high cholesterol never have a stroke or a heart attack. And I think the same is true with amyloid. I think if you lower amyloid early enough, you are likely to affect tau. And I think that will help slow symptoms. So I think amyloid is a crucial player, but it's not the only player. And we're starting the first combination trial of amyloid and tau where we will look at multiple tau therapies alone and in combination with amyloid because just like cancer, heart disease, diabetes, when people have symptoms, you're going to need more than one approach. So that's what I want to talk about is this path. Some people say we've put our eggs in the anti-amyloid basket and we've taken oxygen out of the other research. Dr. Kosick, what other research do we need to do? We have taken the approach of antibodies to the amyloid. That's been like close to 30 years or so. And I really do believe that for a large portion of that time, it was somewhat unfortunate that other directions were not given as much attention. That has changed where the NIH budget, if you look at the breakdown of that budget, there is a fair amount of funds going to projects that are not solely focused on a single hypothesis. Just as Risa said, we're probably going to need more than one drug. So what are those drugs going to be? And that's, I think, where the research direction is now going. So we think of Alzheimer's as a triad of conditions, the amyloid, the tau, and inflammation. The other two limbs of the triad are now getting much more attention, and I think that's where the next breakthroughs are going to come. Dr. Kosick, you work in genetics. Talk about some of the things that you've learned and how it might help us towards finding treatments. People that I've been interested in are those with early onset Alzheimer's that have mutations leading to the disease. So I've always thought of that as a more pure form of Alzheimer's disease because they're getting it at a relatively young age. I really think that when people begin to get Alzheimer's well into their 80s and their 90s, there are many, many comorbidities, not the least of which is some vascular disease too. None of the therapies we're currently thinking about are addressing the comorbidities, copathologies actually. What we are also beginning to appreciate, these copathologies don't just exist in the oldest old, but there are even in the Alzheimer brain of younger people, even in the patients I study from very early onset that I always thought of as pure Alzheimer's, they will often have synuclein depositions in a protein that deposits in the brain that we usually associate with Parkinson's disease, but it shows up in Alzheimer's too for reasons we don't fully understand. They will also have some degree of vascular problems. So since our therapies are really targeted toward amyloid, there's a lot of the co-pathologies that are not being treated. And I think that is one area where we sort of fall short a little bit. And in my view, one of the things that has held us up a little in the Alzheimer's field is that we haven't paid enough attention to the underlying direct problem. The answer in cancer was a cell biological answer. We learned how cells proliferate. The question in Alzheimer's isn't why cells proliferate, but why they die. We don't know that. And that's a cell biological question. We need to learn how cells die. And that's why I think a part of the delay here has been not enough attention to the underlying fundamental cell biology of the problem. I want to switch gears to diagnosis and new tests coming online. How do we diagnose Alzheimer's? So I think we do now diagnose Alzheimer's disease as at a minimum the presence of amyloid and that it's increasing certainty that it is Alzheimer's disease if we also have a marker of tau. The newest blood tests we have, which are actually markers of tau, tell us mostly about how much amyloid buildup there is in the brain, but they also tell us that the amyloid is bothering the tau. And some of these high accuracy measures of what we call phosphorylated tau, particularly p-tau-217, is a great marker of amyloid and a pretty good marker of tau. And I think tell us that the underlying pathology is Alzheimer's disease. I think the biomarkers have been a genuine advance. That is where we've really made some inroads. And the fluid biomarkers that Reese is talking about, potentially just around the corner, blood tests that measure phospho-tau-217 and the microtubule binding region of tau look really, really interesting. What we have to learn is how to use them, because exactly how much earlier are they going to predict? How are they going to show us progression and dynamic range? There are so many interesting questions that are going to open the door for the use of these biomarkers. And that's where I think one of our biggest advances has been. So how do we diagnose early onset? How do we diagnose if people come in and they have amyloid in their brain, but they don't have any issues? How do we handle this? Well, I think that's when we should diagnose and treat Alzheimer's disease, just like we do most other diseases where we find it in the asymptomatic stage. I think we have to risk stratify. |
Because the more amyloid you have, the much more likely that you have some tau. And again, these blood tests can tell us whether the amyloid's bothering the tau. So I envision that eventually we will be at a point where we will offer this as a blood test to everybody who's entering the age of risk in the same way we measure cholesterol. But we shouldn't do that until we know that treating at that stage of disease can really make a difference. And that's what these clinical trials like the AHEAD study are really focused on. People who don't yet have symptoms do have amyloid buildup and early tau and trying to say, can we prevent cognitive impairment and dementia? So there's concerns about these new blood tests. There's now at-home versions of these tests for Alzheimer's disease. How do we know how accurate they really are? There's no doubt that this has to be regulated. You know, having home tests that are just coming out from somebody who's a cowboy trying to make money from this is not the way to do it. They must be regulated. And if they are, we really have a great opportunity here. Because as Risa pointed out, the turning point here, the danger, is when the amyloid has deposited to the extent that the tau explosion occurs. Once the tau explosion occurs, then I think we have some problems on our hands and that the anti-amyloid drugs are not going to be as effective. And some of the people that may look like in these current trials, they're responding less well, may have already had a tau explosion. So I think if we are able to treat very, very early while the tau is still quiescent, then that's worth studying. And that's what the biomarkers promise us. Where are we now and where do we need to go in your view? I think everybody would agree that there's more to Alzheimer's than amyloid and tau as well, you know, the inflammation side. And the search for individuals who have mutations but escape the disease, those pathways are really another way for us to learn about therapeutics. I think we have some very interesting clues that have come to light with the approval of these drugs. But I would say this is one more step in a very long process. Dr. Sperling? I think we have seen that lowering amyloid dramatically can bend the curve of decline. And there's two pathways from here for me. One is that we go earlier if we're going after amyloid because we want to go before there's tau spreading throughout the brain. I think that's very clear. And two, that if we're at a later stage of disease, we do amyloid and tau and trying to save the neurons, neuroprotection, inflammation, multiple avenues that would help the neurons be more resilient to the pathology. But I do think this is a really important moment where we can make a difference. It's not enough of a difference. And we have to be cautious that we're not there yet. But we also have to step back and say, it took us a quarter of a century to get here. How do we accelerate so it doesn't take us a quarter of century to get the next breakthrough and make a bigger difference in people's lives? Thank you both so very much. Thank you. Thank you very much. Dr. Kenneth Kosick is a professor of neuroscience at the University of California, Santa Barbara, and Dr. Risa Sperling is a professor of neurology are a viable substitute. But are we ready for human trials? We've demonstrated that the pig kidneys worked right away, made tons of urine. The serum creatinine dropped to normal and maintained that for seven days. And I can tell you as a transplanter, when a kidney performs that well out of the gate, you're looking good. That's next time on Intention to Treat from the New England Journal of Medicine. I'm Rachel Gottbaum. |
This is the New England Journal of Medicine audio summary. The full text of all articles is available to personal subscribers on our website. We offer discounts on personal subscriptions to residents and students. Go to NEJM.org and click on subscribe. Welcome to the New England Journal of Medicine audio summary for the week of November 23, 2006. I'm Dr. Michael Bierer. This week's issue features articles on avian influenza Thank you. Review articles on educational strategies to promote clinical diagnostic reasoning and on the asthma epidemic. A case report of a pregnant woman with new hypertension and perspective articles on burying the evidence of adverse drug effects and on aprotonin and the absence of transparency in observational studies of drug safety. Avian Influenza A H5N1 Infection in Eastern Turkey in 2006 by Ahmet Faik Onur from the Üzüncü Yıl University in Van, Turkey An outbreak of H5N1 was detected in poultry in eastern Turkey from December 27, 2005 through January 26, 2006, and the outbreak was followed by infection in humans. The human outbreak was concentrated in a small geographic area. H5N1 infection was diagnosed in 12 patients, eight of whom were followed at a hospital in Vann. These investigators report the clinical, epidemiologic, and radiologic features and history of exposure of the eight patients with H5N1 infection cared for at the center in Van. The patients were 5 to 15 years of age, and all eight had a history of close contact with diseased or dead chickens. The mean time between exposure and the onset of illness was five days. All the patients had fever, and seven had clinical and radiologic evidence of pneumonia at presentation. Four patients died. Results of enzyme-linked immunosorbent assay and rapid influenza tests were negative in all patients, and the diagnosis was made by means of a polymerase chain reaction assay. An important observation in this case series is that the results of initial diagnostic testing for H5N1 were negative in many of the patients. Because of the difficulties in detecting H5N1 infection, repeated testing from nasopharyngeal swabs or deep tracheal aspiration samples in patients who are strongly suspected of having H5N1 infection should be performed. The Indonesian cluster of H5N1 Virus Infection in 2005 by Ayn Yoman Kandun from the Ministry of Health in Jakarta, Indonesia. Since 2003, H5N1 outbreaks in poultry have occurred throughout Indonesia. Indonesia's first human H5N1 case was confirmed in July 2005, and three clusters were noted among H5N1 cases through October 2005. This report describes the epidemiologic, clinical, and virologic findings of the three H5N1 case clusters. Severe disease occurred, including deaths in two clusters. Mild illness in children was documented in two clusters. Severe disease occurred, including deaths, in two clusters. Mild illness in children was documented in two clusters. The median age of the eight patients was 8.5 years. Four patients required mechanical ventilation, and the overall proportion of deaths was 50%. In each cluster, patients with H5N1 virus infection were family members, and most lived in the same home. In two clusters, the source of H5N1 virus infection in the index patient was not determined. Virus isolates were available for two clusters, and molecular sequence analyses determined that the isolates were clade 2 H5N1 viruses of avian origin. These findings and other reports from Hong Kong, Vietnam, Thailand, China, Azerbaijan, and Turkey raise questions as to whether genetic or other factors may predispose some persons to H5N1 virus infection or to severe disease. Further research is needed to understand the role of mild cases in the epidemiology of this disease and whether genetic, behavioral, immunologic, and environmental factors may contribute to case clustering of H5N1 virus infection. H5N1 Influenza, Continuing Evolution and Spread, a perspective article by Robert Webster and Elena Gavorkova from St. Jude Children's Research Hospital in Memphis, Tennessee. Thank you. The bad news is that these clades and the subclades probably differ sufficiently in their antigenic structure to warrant the preparation of different vaccines. The continuing evolution of H5N1 viruses and the clusters of human infections in Indonesia and Turkey raise important questions. First, can the source of H5N1 be eliminated? And second, is the increasing number of clusters of human infection an indicator of evolution toward consistent human-to-human transmission? Clearly, we must prepare for the possibility of an influenza pandemic. If H5N1 influenza achieves pandemic status in humans, and we have no way to know whether it will, the results could be catastrophic. Fetal Pulse Oximetry by Stephen Bloom from the University of Texas Southwestern Medical Center in Dallas. Knowledge of fetal oxygen saturation as an adjunct to electronic fetal monitoring may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth. In May 2000, the FDA granted conditional approval of the OxyFirst fetal oxygen saturation monitoring system for use as an adjunct to electronic fetal monitoring. This new technology was designed to improve knowledge of the fetal condition by continuously measuring fetal oxygen saturation in the presence of a non-reassuring fetal heart rate pattern. Thank you. at birth between women whose clinicians were made aware of the oximetry results and women whose clinicians were not. These findings do not support the use of fetal pulse oximetry in women in labor. In an editorial, Michael Green from the Massachusetts General Hospital in Boston writes that more than 30 years ago, the new technology of electronic fetal heart rate monitoring was introduced with the noble aspiration to eliminate cerebral palsy. After 25 years of use, electronic fetal heart rate monitoring was associated with an unchanged rate of cerebral palsy in term infants, but a soaring rate of cesarean deliveries. We now find ourselves in the far less noble position of seeking new technology to mitigate the unintended and undesirable consequences of our last ineffective, but nonetheless persistent, technologic innovation. Vivala Rudin for Patients with Acute Coronary Syndromes, by Greg Stone, from the Columbia University Medical Center in New York. Current guidelines for patients with moderate or high-risk acute coronary syndromes recommend an early invasive approach with Thank you. This study, in over 13,000 patients, evaluated the role of thrombin-specific anticoagulation with bivalirudin. Patients with acute coronary syndromes undergoing an early invasive approach were randomly assigned to treatment with heparin plus a glycoprotein 2b3a inhibitor, bivalirudin plus a glycoprotein 2b3a inhibitor, or bivalirudin alone. Rates of ischemic events at 30 days were similar for all three groups, whereas major bleeding was significantly reduced in the group receiving bivalirudin alone. The trial suggests that bivalirudin monotherapy may be similar in efficacy to standard therapy, although bivalirudin monotherapy is associated with a reduced risk of bleeding. Pretreatment with a thionopyridine seems to be necessary if bivalorudin monotherapy is used. Educational Strategies to Promote Clinical Diagnostic Reasoning, a medical education article by Judith Bowen from the Oregon Health and Science University in Portland. Clinical teachers must diagnose both the patient's clinical problem and the learner's ability and skill. The first step in diagnostic reasoning, which is based on knowledge, experience, and other important contextual factors, is always data acquisition. Another early step is the creation of the mental abstraction or problem representation. Other key elements of clinical diagnostic reasoning include the generation of a hypothesis, the search for and selection of an illness script, and making a diagnosis. As learners listen to patients' stories, learn to transform these stories into case presentations, develop their own illness scripts, and learn to reason about clinical information, teachers can use case-specific instructional strategies to help learners strengthen their skills. This article considers how doctors learn to reason in the clinical environment and recommends practical approaches that clinical teachers can use to promote the development of strong diagnostic reasoning skills in their students. For more information, visit NEJM.org slash features. that the prevalence of asthma is still rising in developed countries. Primary prevention strategies to combat the asthma epidemic are therefore urgently sought, but they must be based on a sound understanding of the various determinants of the onset of asthma. However, the disparity and heterogeneity of findings in the asthma literature are daunting, reflecting the complex nature of the illness. This review surveys the data on the increase in the prevalence of asthma in recent decades and finds evidence of a plateau in many Western countries. The authors examine the evidence of possible causal relations to factors such as air pollution, obesity, diet, and exposure to infections, antibiotics, and allergens, including exposure at very young ages. The most strongly supported preventive measure is the avoidance of passive and active exposure to smoke. |
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