#17 PEM: measuring the threshold and understanding the cause with Dr. Rob Wüst

(gentle music) Welcome to Make Visible, the podcast Shining a Light on Complex Chronic Elness. I am your host, Emily Kate Stevens. (gentle music) Welcome. The delightful Dr. Rob Wurst of Fry University Amsterdam is an exercise physiologist. This week he joins me to explain his studies into the impact of long COVID and ME CFS on our muscles, as well as the threshold for post-exertional malaise in a bid to understand what drives it and how we can prevent it. (gentle music) Such a pleasure to be talking to you today. So what I think is quite interesting with the work that you do is that you seem to have this flow between things that you are discovering within the muscle and trying to establish the chicken or the egg, which way round these things are coming is the abnormalities that you're seeing in the muscles, the cause of something or the effect of something. Your first big paper that you did where you discovered that muscle abnormalities worse than after PEM in on COVID. Can you give me an overview of the trajectory of that work that you've done and what you have found in the muscle abnormalities in long COVID and now you have bought in this cohort of ME CFS. - So let's go back. I think it's already four years ago right now that I got a phone call five minutes before a lecture started in a middle of COVID times. I was working from home preparing my lectures on slides. So doing this online teaching and right before that teaching started a clinician from the local hospital called me. And she had was Michelle of on first. She's an infectionologist and she works particularly with patients with acute COVID back then because there was acute COVID clinic in the Netherlands. She explained to me like, "Oh, we have these patients that keep coming back to us, they recovered from an acute infection but they still are not recovered." And they still suffer from fatigue, they feel muscle problems, muscle pain. What is this? Can we take muscle biopsy? That was the direct question that she asked me. And as I'd look, this is super interesting because I heard in my own environment also people who are suffering a little bit from these longer term problems with acute COVID infection. And I thought, "Hmm, that's maybe interesting. Let's just talk again later." So we discussed later more, more, more length and then we decided that we would start a project with this like a smaller student project. But let's just start small and see how big we can make it. So then fast forward a few months because we have to write a medical ethics application for this research. And we try to get some funding, but we didn't get it back then because I think the focus really on acute COVID and not so much on long COVID yet. So we got the ethics in place and we just started, essentially. We just started with two master students in the lab for doing a project. We take a muscle biopsy and we see what happens. And then she did the plan. But they already noticed back then that maybe there is something happening with exercise that exercise worsened this problem. So I quickly realized that maybe it's more interesting not only just to take muscle biopsies and rest, but also after this induction of post-exertional malaise. And that's something that we have to get interested in right now because I'm an exercise physiologist and I'm a master, I do a lot of muscle research. And what we see in people with any type of chronic disease that exercise is good for you. Exercise helps various diseases, heart failure, diabetes, anything, but not in this disease. And scientifically that's super interesting for me. So that's how I would have essentially how we started. - Is that actually the first, I appreciate that now you have also, starts looking at MECFS. But in terms of your studies, is that the first disease of this type that has that signature where exercise is not helpful? - Yeah, it's of course a little bit tricky because I do know back then about the effects of off-ex size and PEM in a patient with MECFS because it was just understudied not nothing that was known about this. But there aren't many other long-term conditions like that that you would say. And I think even in fibromyalgia exercises can be. - Yeah, so of course, yeah, of course. I mean, now we know that's, that's, I mean, and now I know at least that's these post-viral diseases fibromyalgia, but also MECFS along COVID. Probably also other diseases that are linked to a viral infections, Lyme's disease, that's not a viral infection, but it's a, it's a both infectious disease. It's both post-infectious disease. And maybe also sepsis that we also see that not everything is, you know, when the body is dealing with a large inflammatory response, then having an extra stresser in terms of exercise may not be super helpful. So now I know of course of other disease where exercise may not be perfectly healthy and also is counter-effective, but this was a disease that for me at least was a new door because, you know, in my teaching to students here at the university, I always tell them exercise is good for you. Exercise is medicine. But, and I think that still holds, and now I have to be a little bit correct, so to say, because it's still beneficial for patients with long COVID and MECFS, but to a certain extent, if you exercise below the threshold, it's still positive, because there's a difference between being completely inactive and being a little bit active. So, let's talk about that threshold. Because that, I think, is possibly the holy grail for those of us that suffer from these conditions, is being able to establish what that threshold is and how you can stay within it and whether there is any ability to move that. You've recently done a study looking up heart rate variability using wearable devices. And I'd love to talk to you about that study, but one of the primary things that you did at the beginning of that study was you established that what you call VT1 is it first ventilatory threshold. And that is sort of your marker of where you think, well, it's not even the marker of where people need to stay below. It's about 80% below that, is it? - Well, let's talk a little bit. Because, of course, we don't know the threshold. And that's a real problem in terms of research, but particularly patient care. And the idea is always then, okay, just stay below that imaginary threshold that you determine yourself as being the threshold for them. And in our previous research, we went above it to go to maximum research. So we knew, okay, you go over the threshold, whatever the threshold is, you just go to maximum exercise, we've induced both the thresholds from release. - And I read to you saying that you actually have a bit of an ethical problem with doing that to people because you're constantly making them consider. - That's indeed a problem. If you ask patients to do, to form a part of our research, they have to, we have to understand positive nurse, we have to induce it. And that's also the reason why we're only using mild patients, and not severely ill patients, because we have the feeling that with more severely ill patients, the pushback is bigger, and maybe they don't recover fully. And also, then it becomes an ethical for me to do the research that I want to do. Even though patients really want to participate, they really say, please take my whole leg off for research, as long as I understand what's wrong with me. That's of course also an ethical, but that's obvious. But it is a housebound patient, and we would love to do most of biopsies and homebound patients, as I think one of the goals in the future, but to do that, the fact that we enter the room, we put out all our equipment ready, may already induce both the thresholds from release. So we have to be very critical of what we want to do and what we can do. And there's this constant fight, essentially. What do we gain with information? And what do we let patients undergo? And that's the reason why we now, for instance, do a lot of the work on the studies that we've performed already, because we know that we can do a lot of work on this, and we don't have to ask all the patients to participate. So it's actually good that we just keep the numbers low as possible. But then the funding agencies ask us about the generability of the findings, and does it also apply to patients with severe disease? With severe children, our adolescents with oncophores, etc. So we get all these additional questions that you can only answer by looking into this properly. So this is ethically difficult for us, and we don't take this lightly. Coming back to the start of this question, is of course we want to understand what the threshold is. Our final aim is to increase the threshold as much as possible and shorten the duration of the PEM so that you are able to overcome these PEM episodes quicker and they become less severe. And therefore it's good to have an idea about what the threshold roughly is. So what we did, the Echoes Institute of Project, again, are master students who did an internship with a sports physician in the local clinic here in the center of the Netherlands. And that clinic is very specialized on measuring heart rate variability. And you don't get heart rate variability measurements for no reason. You had to have a certain indication essentially to do this. So Kasper, our sports physician, thought that maybe by using heart rate variability, it tells you something about the recovery of patients or the inability to recover for patients, for instance, during sleep. And that helps patients also with basing strategies. So it is really in the setting of basing, that we use these hardwood verbility monitors to get better in that idea. But when do people go over the threshold essentially and what are triggers for lower hardwood verbility measurements? And we used that data then just as our student, Tvanni, was a mass student here in the clever with data science and he really took on the project and did a lot of data analysis using very specialized programs. We don't talk about it now. And what emerged from that was that this fenthatory threshold that we used to demarc mild from moderate exercise tended to be the situation around which people had more difficulty sleeping, more the harder the hardwood verbility reduced after sleep. The recovery after those type of exercises also took much longer in terms of hardwood variability. So we think hardwood verbility tells you something about the recovery of the autonomous nervous system and particularly the way how the body is able to relax. And the inability to relax tells you something about the fact that you don't relax or don't recover proper. And this fenthatory threshold was then seem to be the tipping point so to say. And we don't know if that actually actually calls PEM in the patients if you go over it, but we see things in the wearable data that hint towards PEM. OK, so it's not necessarily then done on patient reported PEM symptoms. It is actually done on the on the data. You had that alongside didn't you had that that I really long side exactly where they die alongside, but the patient didn't mention that they really suffered from PEM. But we saw things in the wearable data that could that could hint essentially to this PEM. So that future work and that's the plan what we are hoping to do in the near future is to really see how PEM symptoms are linked to these to these heart rate variability monitors. Now you actually once you've established that ventilator threshold in your study, you actually found that 43% of patients went over that threshold just doing their daily activities. So we're not talking about them deciding to go for a run. And I think that that is quite something that's quite pronounced because there is so much conversation about oh well, you've got to ease off on the exercise. But so many of us know that some days you can't even you can't hang the laundry or there are certain things that are considered to be daily activities that shouldn't be pushing you theoretically over a threshold. But that in almost half of the people that you studied, that was the case in Longhavid and was this looking at ME/CFS patients as well? Only long, only long COVID. Okay. So yes, that's indeed striking. Also, semi-surprising for me, but remember this was this was also done as a in the face of pacing. So of course, the therapeutic, the reason they came to the sports physician was to get a checkup of their health and their their frontedatory threshold was the sub-maxum exercise test we do. And also how to do the pacing and essentially patients have difficulty pacing because some activities indeed like hanging up the laundry, walking up the stairs, you know, doing the shopping with two two backs of full of groceries for instance can already make your heart go up to a level that is at that Venturatory Tresholt. And it's all patients at Venturatory Tresholt is super low and it's at the level of this daily life activities and that's the problem. And let's go back then to look at some of the series that you have discussed behind this because one of the big things and there you've had some back and forth on this recently, one of the big things is that is the deconditioning. So what you're saying there is you're not suggesting that people are going out for a run and pushing themselves over that threshold, they are just doing their normal activities. You've previously done a bed rest study, have you previously seen that kind of PEM induced by simple everyday activities rather than what we classify as exercise? Okay, so there are various levels of commas I want to put in here but let's first start with did I expect this? To some extent yes because some patients are severely ill or we call them moderately ill. So if mild we would say mild moderate severely ill patients in the mild patients are the ones that we typically study. But at this goal we also had patients that were moderately ill and we classified them as having a very low, a ventilatory threshold at the level of daily life activities. So if you cannot perform daily life activities in a normal way, in a way that you would then become fatigued, then we would classify you as a moderately ill patient. And yes, I think it was surprising but in your hands, we also know that some patients are bedridden. That is then of course a feel ill and then even standing up, I may already give you orthostatic intolerance or pots and may in the lowest activities then it can already induce some poses or chamalase. So we know that there is a continuum of patients that we are around and we typically see the mild patients because you have to come to hospital, you voluntarily participate in the study so you are able to come to the hospital and actively consent to do an exercise test and a biopsy. So we are really looking only at the mildly severe patients. Now of course that is so coming back down to your question about the conditioning, it's a super interesting and then a very important comment to make is that if you are a patient you want to avoid post-trial chamalase and there are two ways to do that is you can just stay below that level or you can be completely inactive. If you are completely inactive then you would expect that like anyone else of us would see the same effects happening when you are bedridden, at least in a skeletal muscle level or the whole body level. But patients are sometimes still relatively active. So we see we have the mildly affected patients and therefore they are still having some step counts per day. So our code is not bedridden essentially. But still you could say is physical inactivity or deconditioning underlying the changes. We don't completely exclude this but there is a level of things that are different, things are diverging and we know from our better study that people who are undergoing better stress do not develop them. That's just a how it works. If you are in bed for two weeks you can get out of bed, you may feel a little bit quicker fatigue but you would exercise, you would train up again and you would be fed again. That's the massive difference isn't it? Between your bed rest study where people are then able to incrementally re-condition themselves. Exactly. That's the huge difference in these conditions. The deconditioning isn't the PM is not improved by that, you know, greater. That's a completely different aspect. So an astronaut in space does not get PEM. And therefore, so looking at PEM and be conditioning are two completely separate phenomena at the body level. They can one can lead to the other to afford PEM, you become inactive but it doesn't mean that then it's causative. Okay. And in terms of what you're actually seeing in the muscles, in the physiology of it, you proposed in a talk that I saw you give recently four other theories that are some from your data and some from other clinician's data, local hypoxia, electrophysiology, auto-minti and central fatigue. The local hypoxia, you can actually see that in the biopsy testing, the biopsies that you've taken, can you? Yeah, technically you can, but it's super difficult. So let's just go through this theory in more detail here because what are the theories is that somehow the muscle becomes less profused or gets blockages. And in the literature, people have suggested that some of the microclots that people find in the blood can block capillaries. And that amelode clotting you are now thinking might be in play in this. Well, so that's a theory. That's a theory that other people have found. Okay, it's not something that you've started looking at. We start looking at it, but we never find that evidence. So the evidence that those clots are blocking larger vessels and capillary flow, we do not find any evidence for it. But the fact that we cannot find it doesn't mean that it's not there. We just cannot find it. So if someone else finds it, then that theory can be true. But we do know from other people's work, and we start looking at this as well, a little bit more detail, is that there are endothelial problems. So the capillaries, so the smallest blood vessels in your body may become problematic and cannot sustain the flow or are becoming disorganized. There are various theories in the literature. How the flow in the smallest blood vessels can be altered. So even if it's not blocked, it can still cause problems with profusion. And that what happens is that the tissue behind those vessels are not getting enough oxygen and enough energy. And that can cause fatigue. Now the problem is a little bit with this theory is that yes, that would be similar as going up to the mountain. If you go up to a mountain, you also get less oxygen and the body will then adapt. So one adaptation is to make more capillaries. to just get more blood vessels. Because that's a one way for the body to deal with hypoxia, with low oxygen levels. We don't see that so much. It's not that there's certainly more capabilities. It's not that they're less, but they're the same or less, essentially. But it's super difficult to test this in theory. And also we now testing some water and trying to circumfer this theory with trying different if this happens than this would happen. And as a result, do we see this happening as or no? And we don't see a lot of evidence for it. But there is this idea that at least there's a problem with an cathedis. That is around. So there is-- but we simply don't know yet if that's the causative problem. Also, there's a problem with PEM, because PEM means that there is an acute worsening of something upon exercise. And that also makes it difficult. Because the theory of hypoxia or an ethereal dysfunction or is chemorep perfusion injury or blockage of capabilities is true then, then you should also see it worsening with PEM. And we just don't know yet. Does that suggest then that it might be more to do with-- and I don't know if you can see this in your biopsies, but I know that it is a big area of research for you, generally. Is it more to do with the mitochondrial dysfunction or an issue of energy production in the mitochondria? Yeah. So again, that could link with this problem with an oxygen flow and energy flow. If there is a problem there, of course, in the places where these energy is being used or oxygen is being used, you should see difference there. So it can easily be an effect. So there might be some problems that we see in our muscle and in the muscle of patients with the tongue of it can be the effect of the problems occurring in the bloodstream or it can be happening on itself. And it's more the problem is primarily there. And then it's of course, for other things. And so course, exactly. With the current study designed that we have, we cannot distinguish between the two. Because we don't know whether changing-- you would then have to change, for instance, one thing or the other and see how the other effects. That's the one way to do this scientifically. But those studies are very invasive and super difficult to do. So it would, for instance, be that you would want to improve mitochondrial function and see if the end of the blood flow changes. Or if you improve blood flow, if the mitochondria function improves. OK. And those studies are super difficult to do. So then in terms of what you can actually see, have you seen in the muscle some of these other theories of the calcium changes or the collagen changes? What have you seen in that physiology? So when it comes to the electrolyte changes that we describe in a recent overview paper or a review paper, is that they're mainly based on work in Germany. They have been some studies suggesting that there are differences in MEC if it's occurring with sodium loadference in the muscle. And that can change the excitability of muscle. And therefore, you can activate your muscles properly. And that may make you more fatigable or early fatigable or you can produce same amount of force, et cetera, et cetera. You're not a clinician, but theoretically, if you see that kind of deficiency, is it something that could be addressed with supplementation? Or once it's in the muscles, is it not such an easy fix? This is a bit of a personal feeling about this theory is that I have the feeling that-- and I don't know what it is true. So this is pure speculation right now, is that the body is able to maintain its ion concentrations in the blood within super-tight boundaries. Sodium, potassium, constriction, blood, are in super-tight boundaries. Calcium as well. Because there are various regulatory systems in place to get rid of it, find the kidneys or by intake of the foods, uptake and tissue, et cetera, that's super-tightly or regulated. So changes in sodium concentration in muscle-- I find it difficult to describe it to the core aspect. There must be something else that makes these changes happen. Because otherwise, there is a system in place that brings it back to the normal concentrations again. So that is suggested of disruption of autonomic function? For instance, yeah. But then it would be a-- It's an effect. An effect, exactly, of something else that happens. But I don't know that because it can easily be that there is indeed something wrong with an ion channel in the disease. And if the ion channel is then certainly the most important aspect of the disease, then it is a causative problem again. So as scientists, we constantly deal with, is it a cause of the disease? Or do we see it as an effect of something else? And that's annoying for a lot of people, including scientists and including patients themselves too. But I think-- I like that you say that. That you have this, that you're still sort of in this dichotomy of which is it. Because there are a lot of people who have come out and said, this is the problem. I knew you'd say, yeah, but if this is the problem, then theoretically, if I just took that, I would be fine again. And I'm not. If for it, I just give you some examples too. So this mitochondrial dysfunction, I think we can all agree that if you improve mitochondrial function, your body function will be better. That's without saying. The problem is a little bit that long-covid is not a mitochondrial-- it's not the same as a genetic metabolic disease, for instance. There are some similarities. And there are some really clinically. There are some good similarities, even. But it's not the same as patient who lacks a gene in a particular mitochondrial protein. And as a result, is it an cause and effect? How does a virus then change mitochondria all over your body? I don't know. Yeah. What is the infiltration? Exactly. In terms of that, now that you've bought the MECFS cohort in this recent study, can you tell me about the differences that you saw-- To me, about the differences that you've seen in the MECFS and long-covid? So what we quite early on, we realized that long-covid and MEC have a lot of similarities. And as a result, we thought, OK, let's see if we can also include a goal of MECFS patients and that there was also something else going on in the Netherlands of a MECFS cohort. And there was lots of research being built around MECFS. But I was actually perfect timing because it could fit perfectly with our long-covid cohort. So what we wanted to do is to see-- do we see similar things happening in patients with MECFS? So that's pretty early on. Refewer comments are also there. That's completely different diseases. How do you say this? How can you say this? This is unproven, et cetera, such. But we were pretty early on that idea that they could link. And now everyone sort of acknowledged that they are two parts of the whole umbrella term. And they're not exactly the same disease. But they have an umbrella term and with a pillar of uncovid or a post-covid syndrome, other MECFS conditions, but also for instance, Lyme's disease and some other post-fire diseases. So we know that they have some similarities. And we thought, OK, well, let's see what we-- if we can also include it in there. And we got some funding from patient organizations to really push this forward. So that was really nice. And actually, we're about to publish those results. That we work on the last changes of our preprint right now from hoping. So we're hoping that it will be published in the next month or so if everything goes well. And in there, we compare at least the change that we see with the long-cofe people with MECFS, who already had MECFS diagnosed before the pandemic started. They are completely different type of patients as well. Longer, ill for longer are probably better able to deal with that PEM because they are dealing with PEM in terms of-- It's such a long time. --for a lot for a long time, exactly. And maybe there are some similarities or differences. We are studying that right now. And we see some similarities in terms of their exercise capacity at this very low, but also other aspects, and so that we are now trying to finalize. Do you see differences within that skeletal muscle? Or can you not say that at this point? Well, so we see-- I mean, of course, the patients have been ill for longer. And you can see that in the muscle fiber. So there are differences, but we don't know whether that's due to the fact that they've been ill for longer or whether they have a different disease. So that would require us to do another study in five, or six, or 10 years' time with our current long-cofe population to see whether they reach the same values as the MECFS people would have. Yeah. We see some differences here and there, but the question is, is it a duration of the disease, or is it a disease itself? Super difficult. Again, trying to work out cause and effects. Yeah. And what is causing? What is causing the things that you see? And I think as a scientist, it's really important to keep thinking and find arguments for factor A or factor B, because that really helps making it clear what you're looking at. In terms of other scientists out there, who either you have worked with or you have been reading about. Who do you think there is out there who's really doing exciting work in this field? Yeah, that's a good question, but I can name more than 10 people that I really like. I don't want to, I mean, if I don't mention a name, it will be also to be bad. So I think I should not say certain, you know, so the names or Jack Jones or. Or tell me areas that you think have real potential for actually holding a key. Obviously, the research that you're doing, you consider to be absolutely crucial for us moving forwards. But your research in conjunction with what other research do you think might hold the key for us? Yeah, what I really like is really biomedical research, so finding the real cause of the disease in terms of biology. I think that's a crucial thing that has been understood so far. And of course, you can do a lot of questioner studies, and I think that's also important, but it doesn't give us the answer to what is causing the disease. It gives a hint towards direction to look for, of course, but then we need to find the biology of those problems. Is it something in the immune system? Is it the far persistent that is causing the disease itself? Whatever disease is causing, that's where I think the future will be moving towards to. Is there maybe a diagnostic criteria that we can find for patients that we can use to diagnose patients? Biomarker, and actually biomedical diagnostic criteria rather than a symptom reported criteria. Exactly. And I think that's where the fuel is moving towards now. And I think in the past, people have tried to study that mainly based on symptomology or questionnaires or for other simple things, but it's now also time to dive deeper and do the really nitty-gritty molecular changes and biomarker studies and looking at the different disease, high-polysis. But that's a really good point when you say looking at the real nitty-gritty, because it's not, you know, we all had the blood tests that says there's nothing, there's nothing irregular in your normal blood tests. But what you're talking about is actually looking at the looking deeper or looking at the more specific things. Exactly. Exactly. And I think that's where everyone in the field now moves towards. And everyone does it from his own perspective and his own interest. So, and that's also super cool because I'm an exercise physiologist. I'm looking at from an exercise perspective, but someone else looks at the disease from an immune perspective and puts all his his scientific life and his scientific work in understanding the immune changes. And that's super important too. To the cross-leaf is really important as well, because you mentioned that you think that you might be able to see a change in the muscle that suggests there's an autoimmune situation. But for instance, it so that really makes us as work together and that this that I think is also super nice as an exercise physiologist to work together with immunologists to see what they how they look at that body function and and and and explaining post-usurgeumelase because it could well be that that there's a big immune component of them and that's you know, the fact that it's that it takes sometimes a day or two to get induced and and some people have fever like symptoms. That's that's a sign that maybe there is also an immune component to the disease. And that's something interesting because then certainly we have a match. It's it's it's like you know you you hear something at a conference about an immune talk. Then you think oh this is interesting. Let's see how where we can we can find common commonalities and also then try to work together to find that that that where this commonality and this common problem for the disease. And I think that really how it's really helpful in this type of stage of the disease that studies is to get this cross-link between different people. People looking at brain immunology we we talk with people who are super nitty gritty idea about brain function and they can explain brain fog and that then I try to integrate my work with their work and I would not have been able to do that if I would look at a different type of disease. Yeah that's fascinating isn't it so it's basically all of the cross-serve is all of the different body systems because it's interesting I speak to people who are looking independently at all these different things and someone says no it's definitely in the prefrontal cortex and someone says definitely in the muscle so that is possibly one positive that this collaboration. I that's actually maybe important because I see I hear this more often that I that it's in the muscle I don't think actually it's a muscle disease and that makes it also makes me sometimes a bit of an outsider because lung ovaries not a muscle disease it's it's may reflect on the muscle function and symptoms relate to exercise capacity and therefore it's important to look at muscle as well but to to find the cure of the disease I'm not 100% sure we should be looking inside the muscle but with our work we can take muscle biopsies and therefore we can look inside the body it's super difficult to take a brain biopsy not possible in healthy bebe in health and you have to die first before you can take the brain out same for your heart if you want to look at hard function you need to wait for someone dies before you can take the heart I don't look at them or decide the structures but with scutum muscle we can do it we can actually take the muscle out when someone is still alive so that gives us a hint into the tissue alterations that we see with the disease but it doesn't mean that disease is there yeah only so it's also a window into those other areas that you can't necessarily see and trying to work out that traffic flow of cause and effects and and what has come from where or is going towards that I really really appreciate your humility when it comes to that as well because just that idea that we can all work together and actually everyone's work to compete into each other perhaps we do then have a chance of actually working out what is what is going on in these situations and I think that's important because it's a multi-systemic disease so we have to work together to find that common cause because it's not going to be you know maybe in one eventually it will be somewhere so someone will be discovering the the or the cause of the disease but until there everyone looks at it from different perspectives and try to uncover what we what we see and what it means yeah amazing thank you so much for your time today welcome I actually had the pleasure of meeting Dr. Vust in person earlier this year and I really appreciate the humility and spirit of collaboration with which he approaches his work he doesn't believe that these are muscle diseases but does believe that we can learn what these diseases are by looking at this physiology as part of the greater picture and this is my usual plea to please feedback and share your thoughts what you would like to learn about I am still working through all of your requests and endeavor to get to as many of them as I can thank you for continuing on this path with me thank you for listening to Make Visible please do like follow or subscribe to listen to our next episode where we'll be uncovering more insights into complex chronic illness this was brought to you by the team at visible a group of scientists and engineers whose lives have been affected by energy limiting health conditions we're building wearable technology that's helping a hundred thousand people measure and manage their complex chronic illness to find out more about what we're working on and how visible could help you visit our website at makevisible.com you