Podcasts about baricitinib

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Best podcasts about baricitinib

Latest podcast episodes about baricitinib

CCO Infectious Disease Podcast
COVID-19 in EU: Inpatient Treatment Options for Severe COVID-19 in People Who Are Immunocompromised

CCO Infectious Disease Podcast

Play Episode Listen Later Mar 13, 2025 24:53


Listen in as Cristina Mussini, MD; Martin Witzenrath, MD, FERS; and Michele Bartoletti, MD, PhD, discuss treatment strategies for people who are immunocompromised with COVID-19 in the hospital setting, including: Antiviral therapy with remdesivirDexamethasone for patients with hematologic malignanciesConsiderations regarding other immunomodulators such as JAK inhibitors or IL-6 inhibitorsA detailed patient case to illustrate key takeaways Presenters:Michele Bartoletti, MD, PhD​Associate Professor of Infectious DiseasesDepartment of Biomedical SciencesHumanitas UniversityPieve Emanuele (MI), ItalyHead of Infectious Diseases UnitIRCCS Humanitas Research HospitalRozzano (MI), ItalyCristina Mussini, MD​Full Professor of Infectious DiseasesChief of the Department of Infectious DiseasesUniversity of Modena and Reggio EmiliaModena, ItalyMartin Witzenrath, MD, FERS Medical DirectorCharite Centrum 12Internal Medicine & DermatologyProfessor and Chair for Respiratory Medicine and Critical CareDepartment of Infectious Disease, Respiratory Medicine and Critical CareCharite Campus Mitte/Campus Virchow Klinikum/Campus Benamin FranklinCharite – University of BerlinBerlin, GermanyLink to full program:https://bit.ly/4fs7HcbDownloadable slides:https://bit.ly/3XP1fpJGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify.

CCO Infectious Disease Podcast
Best Practices for Inpatient Management of Severe COVID-19

CCO Infectious Disease Podcast

Play Episode Listen Later Mar 10, 2025 15:18


In this episode, Stephen Cantrill, MD, FACEP; Rajesh T. Gandhi, MD; and Payal K. Patel, MD, MPH, FIDSA, discuss: Workup of COVID-19 in the emergency departmentMethods of COVID-19 risk stratification Treatment recommendations for people with severe COVID-19, including how to effectively use antiviral therapy, dexamethasone, and other immunomodulators[CC1] in this population A detailed patient case to illustrate key takeawaysPresenters:Stephen Cantrill, MD, FACEP​Associate Director and Medical Director (Retired) ​ Department of Emergency Medicine​ Denver Health Medical Center​ Associate Professor ​ Department of Emergency Medicine​ University of Colorado Health Sciences Center​ Denver, Colorado Rajesh T. Gandhi, MD​Massachusetts General Hospital​ Professor of Medicine​ Harvard Medical School​ Boston, Massachusetts Payal K. Patel, MD, MPH, FIDSA​Systemwide Director of Antimicrobial Stewardship​ Associate Professor, Division of Infectious Diseases​ Intermountain Health​ Salt Lake City, Utah Link to full program: https://bit.ly/4gu2gcUGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify.

CCO Infectious Disease Podcast
Treatment Options for Severe COVID-19 in Patients Who Are Immunocompromised

CCO Infectious Disease Podcast

Play Episode Listen Later Mar 10, 2025 20:32


In this episode, Stephen Cantrill, MD, FACEP; Rajesh T. Gandhi, MD; and Payal K. Patel, MD, MPH, FIDSA, discuss treatment strategies for people who have severe COVID-19, including: Antiviral therapy with remdesivir Dexamethasone and other systemic corticosteroids Immunomodulators, such as JAK inhibitors or IL-6 inhibitors Overviews of clinical trial data demonstrating how and when to use these therapiesPresenters:Stephen Cantrill, MD, FACEP​Associate Director and Medical Director (Retired) ​ Department of Emergency Medicine​ Denver Health Medical Center​ Associate Professor ​ Department of Emergency Medicine​ University of Colorado Health Sciences Center​ Denver, Colorado Rajesh T. Gandhi, MD​Massachusetts General Hospital​ Professor of Medicine​ Harvard Medical School​ Boston, Massachusetts Payal K. Patel, MD, MPH, FIDSA​Systemwide Director of Antimicrobial Stewardship​ Associate Professor, Division of Infectious Diseases​ Intermountain Health​ Salt Lake City, Utah Link to full program: https://bit.ly/4gu2gcUGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify.    

Cytokine Signalling Forum
Discussing RA: Baricitinib dose reduction and switching to bDMARDs vs JAKis

Cytokine Signalling Forum

Play Episode Listen Later Feb 27, 2025 11:17


Join Professors Iain McInnes, Hans Bijlsma, and Peter Nash for the latest episode on The Immune-Mediated Inflammatory Disease Forum, where they discuss the latest updates in RA. In this episode, they discuss two papers: baricitinib dose reduction in patients with RA achieving sustained disease control and switching to bDMARDs vs cycling among JAKis in patients with RA who are inadequate responders to JAKis.

Evidence Based Hair
Season 7, Episode 9: Baricitinib for Pediatric Alopecia Areata: Promising Results and Future Directions

Evidence Based Hair

Play Episode Listen Later Jun 18, 2024 12:37 Transcription Available


Welcome to another episode of the Evidence-Based Hair Podcast. In this episode, Dr. Donovan delves into an insightful study by Zhao and colleagues, published in the Journal of the European Academy of Dermatology and Venereology, titled "Baricitinib Therapy for Pediatric Patients with Severe Alopecia Areata." This episode continues the June series dedicated to JAK inhibitors. Dr. Donovan highlights the increasing global use of these medications for treating severe alopecia areata, including the recent approvals of baricitinib and ritlicitinib. The featured study examines the effectiveness and safety of baricitinib in treating children with severe alopecia areata, focusing on a small group of 10 patients aged between under two years to 13 years. The results reveal promising regrowth and mild side effects, underscoring the potential of baricitinib for younger patients. Dr. Donovan discusses the broader implications of these findings, including the likelihood of future approvals for younger age groups and the importance of long-term safety data. He emphasizes the need for ongoing research and real-world studies to better understand the prolonged effects of JAK inhibitors. Join Dr. Donovan next week for the final episode of the June series, where he will explore a study on the use of topical tofacitinib for treating lichen planopilaris and frontal fibrosing alopecia.

Ground Truths
Aviv Regev: The Revolution in Digital Biology

Ground Truths

Play Episode Listen Later Apr 28, 2024 36:24


“Where do I think the next amazing revolution is going to come? … There's no question that digital biology is going to be it. For the very first time in our history, in human history, biology has the opportunity to be engineering, not science.” —Jensen Huang, NVIDIA CEOAviv Regev is one of the leading life scientists of our time. In this conversation, we cover the ongoing revolution in digital biology that has been enabled by new deep knowledge on cells, proteins and genes, and the use of generative A.I .Transcript with audio and external linksEric Topol (00:05):Hello, it's Eric Topol with Ground Truths and with me today I've really got the pleasure of welcoming Aviv Regev, who is the Executive Vice President of Research and Early Development at Genentech, having been 14 years a leader at the Broad Institute and who I view as one of the leading life scientists in the world. So Aviv, thanks so much for joining.Aviv Regev (00:33):Thank you for having me and for the very kind introduction.The Human Cell AtlasEric Topol (00:36):Well, it is no question in my view that is the truth and I wanted to have a chance to visit a few of the principal areas that you have been nurturing over many years. First of all, the Human Cell Atlas (HCA), the 37 trillion cells in our body approximately a little affected by size and gender and whatnot, but you founded the human cell atlas and maybe you can give us a little background on what you were thinking forward thinking of course when you and your colleagues initiated that big, big project.Aviv Regev (01:18):Thanks. Co-founded together with my very good friend and colleague, Sarah Teichmann, who was at the Sanger and just moved to Cambridge. I think our community at the time, which was still small at the time, really had the vision that has been playing out in the last several years, which is a huge gratification that if we had a systematic map of the cells of the body, we would be able both to understand biology better as well as to provide insight that would be meaningful in trying to diagnose and to treat disease. The basic idea behind that was that cells are the basic unit of life. They're often the first level at which you understand disease as well as in which you understand health and that in the human body, given the very large number of individual cells, 37.2 trillion give or take, and there are many different characteristics.(02:16):Even though biologists have been spending decades and centuries trying to characterize cells, they still had a haphazard view of them and that the advancing technology at the time – it was mostly single cell genomics, it was the beginnings also of spatial genomics – suggested that now there would be a systematic way, like a shared way of doing it across all cells in the human body rather than in ways that were niche and bespoke and as a result didn't unify together. I will also say, and if you go back to our old white paper, you will see some of it that we had this feeling because many of us were computational scientists by training, including both myself and Sarah Teichmann, that having a map like this, an atlas as we call it, a data set of this magnitude and scale, would really allow us to build a model to understand cells. Today, we call them foundational models or foundation models. We knew that machine learning is hungry for these kinds of data and that once you give it to machine learning, you get amazing things in return. We didn't know exactly what those things would be, and that has been playing out in front of our eyes as well in the last couple of years.Spatial OmicsEric Topol (03:30):Well, that gets us to the topic you touched on the second area I wanted to get into, which is extraordinary, which is the spatial omics, which is related to the ability to the single cell sequencing of cells and nuclei and not just RNA and DNA and methylation and chromatin. I mean, this is incredible that you can track the evolution of cancer, that the old word that we would say is a tumor is heterogeneous, is obsolete because you can map every cell. I mean, this is just changing insights about so much of disease health mechanisms, so this is one of the hottest areas of all of life science. It's an outgrowth of knowing about cells. How do you summarize this whole era of spatial omics?Aviv Regev (04:26):Yeah, so there's a beautiful sentence in the search for lost time from Marcel Proust that I'm going to mess up in paraphrasing, but it is roughly that going on new journeys is not about actually going somewhere physically but looking with new eyes and I butchered the quote completely.[See below for actual quote.] I think that is actually what single cells and then spatial genomics or spatial omics more broadly has given us. It's the ability to look at the same phenomenon that we looked at all along, be it cancer or animal development or homeostasis in the lung or the way our brain works, but having new eyes in looking and because these new eyes are not just seeing more of something we've seen before, but actually seeing things that we couldn't realize were there before. It starts with finding cells we didn't know existed, but it's also the processes that these cells undergo, the mechanisms that actually control that, the causal mechanisms that control that, and especially in the case of spatial genomics, the ways in which cells come together.(05:43):And so we often like to think about the cell because it's the unit of life, but in a multicellular organism we just as much have to think about tissues and after that organs and systems and so on. In a tissue, you have this amazing orchestration of the interactions between different kinds of cells, and this happens in space and in time and as we're able to look at this in biology often structure is tightly associated to function. So the structure of the protein to the function of the protein in the same way, the way in which things are structured in tissue, which cells are next to each other, what molecules are they expressing, how are they physically interacting, really tells us how they conduct the business of the tissue. When the tissue functions well, it is this multicellular circuit that performs this amazing thing known as homeostasis.(06:36):Everything changes and yet the tissue stays the same and functions, and in disease, of course, when these connections break, they're not done in the right way you end up with pathology, which is of course something that even historically we have always looked at in the level of the tissue. So now we can see it in a much better way, and as we see it in a better way, we resolve better things. Yes, we can understand better the mechanisms that underlie the resistance to therapeutics. We can follow a temporal process like cancer as it unfortunately evolves. We can understand how autoimmune disease plays out with many cells that are actually bent out of shape in their interactions. We can also follow magnificent things like how we start from a single cell, the fertilized egg, and we become 37.2 trillion cell marvel. These are all things that this ability to look in a different way allows us to do.Eric Topol (07:34):It's just extraordinary. I wrote at Ground Truths about this. I gave all the examples at that time, and now there's about 50 more in the cardiovascular arena, knowing with single cell of the pineal gland that the explanation of why people with heart failure have sleep disturbances. I mean that's just one of the things of so many now these new insights it's really just so remarkable. Now we get to the current revolution, and I wanted to read to you a quote that I have.Digital BiologyAviv Regev (08:16):I should have prepared mine. I did it off the top of my head.Eric Topol (08:20):It's actually from Jensen Huang at NVIDIA about the digital biology [at top of the transcript] and how it changes the world and how you're changing the world with AI and lab in the loop and all these things going on in three years that you've been at Genentech. So maybe you can tell us about this revolution of AI and how you're embracing it to have AI get into positive feedbacks as to what experiment to do next from all the data that is generated.Aviv Regev (08:55):Yeah, so Jensen and NVIDIA are actually great partners for us in Genentech, so it's fun to contemplate any quote that comes from there. I'll actually say this has been in the making since the early 2010s. 2012 I like to reflect on because I think it was a remarkable year for what we're seeing right now in biology, specifically in biology and medicine. In 2012, we had the beginnings of really robust protocols for single cell genomics, the first generation of those, we had CRISPR happen as a method to actually edit cells, so we had the ability to manipulate systems at a much better way than we had before, and deep learning happened in the same year as well. Wasn't that a nice year? But sometimes people only realize the magnitude of the year that happened years later. I think the deep learning impact people realized  first, then the single cells, and then the CRISPR, then the single cells.(09:49):So in order maybe a little bit, but now we're really living through what that promise can deliver for us. It's still the early days of that, of the delivery, but we are really seeing it. The thing to realize there is that for many, many of the problems that we try to solve in biomedicine, the problem is bigger than we would ever be able to perform experiments or collect data. Even if we had the genomes of all the people in the world, all billions and billions of them, that's just a smidge compared to all of the ways in which their common variants could combine in the next person. Even if we can perturb and perturb and perturb, we cannot do all of the combinations of perturbations even in one cell type, let alone the many different cell types that are out there. So even if we searched for all the small molecules that are out there, there are 10 to the 60 that have drug-like properties, we can't assess all of them, even computationally, we can't assess numbers like that.(10:52):And so we have to somehow find a way around problems that are as big as that and this is where the lab in the loop idea comes in and why AI is so material. AI is great, taking worlds, universes like that, that appear extremely big, nominally, like in basic numbers, but in fact have a lot of structure and constraint in them so you can reduce them and in this reduced latent space, they actually become doable. You can search them, you can compute on them, you can do all sorts of things on them, and you can predict things that you wouldn't actually do in the real world. Biology is exceptionally good, exceptionally good at lab sciences, where you actually have the ability to manipulate, and in biology in particular, you can manipulate at the causes because you have genetics. So when you put these two worlds together, you can actually go after these problems that appear too big that are so important to understanding the causes of disease or devising the next drug.(11:51):You can iterate. So you start, say, with an experimental system or with all the data that you have already, I don't know from an initiative like the human cell atlas, and from this you generate your original model of how you think the world works. This you do with machine learning applied to previous data. Based on this model, you can make predictions, those predictions suggest the next set of experiments and you can ask the model to make the most optimized set of predictions for what you're trying to learn. Instead of just stopping there, that's a critical point. You go back and you actually do an experiment and you set up your experiments to be scaled like that to be big rather than small. Sometimes it means you actually have to compromise on the quality of any individual part of the experiment, but you more than make up for that with quantity.The A.I. Lab-in-the-Loop(12:38):So now you generate the next data from which you can tell both how well did your algorithm actually predict? Maybe the model didn't predict so well, but you know that because you have lab results and you have more data in order to repeat the loop, train the model again, fit it again, make the new next set of predictions and iterate like this until you're satisfied. Not that you've tried all options, because that's not achievable, but that you can predict all the interesting options. That is really the basis of the idea and it applies whether you're solving a general basic question in biology or you're interested in understanding the mechanism of the disease or you're trying to develop a therapeutic like a small molecule or a large molecule or a cell therapy. In all of these contexts, you can apply this virtual loop, but to apply it, you have to change how you do things. You need algorithms that solve problems that are a little different than the ones they solved before and you need lab experiments that are conducted differently than they were conducted before and that's actually what we're trying to do.Eric Topol (13:39):Now I did find the quote, I just want to read it so we have it, “biology has the opportunity to be engineering, not science. When something becomes engineering, not science, it becomes exponentially improving. It can compound on the benefits of previous years.” Which is kind of a nice summary of what you just described. Now as we go forward, you mentioned the deep learning origin back at the same time of CRISPR and so many things happening and this convergence continues transformer models obviously one that's very well known, AlphaFold, AlphaFold2, but you work especially in antibodies and if I remember correctly from one of your presentations, there's 20 to the 32nd power of antibody sequences, something like that, so it's right up there with the 10 to the 60th number of small molecules. How do transformer models enhance your work, your discovery efforts?Aviv Regev (14:46):And not just in antibodies, I'll give you three brief examples. So absolutely in antibodies it's an example where you have a very large space and you can treat it as a language and transformers are one component of it. There's other related and unrelated models that you would use. For example, diffusion based models are very useful. They're the kind that people are used to when you do things, you use DALL-E or Midjourney and so on makes these weird pictures, think about that picture and not as a picture and now you're thinking about a three-dimensional object which is actually an antibody, a molecule. You also mentioned AlphaFold and AlphaFold 2, which are great advances with some components related to transformers and some otherwise, but those were done as general purpose machines for proteins and antibodies are actually not general purpose proteins. They're antibodies and therapeutic antibodies are even further constrained.(15:37):Antibodies also really thrive, especially for therapeutics and also in our body, they need diversity and many of these first models that were done for protein structure really focused on using conservation as an evolutionary signal comparison across species in order to learn the model that predicts the structure, but with antibodies you have these regions of course that don't repeat ever. They're special, they're diverse, and so you need to do a lot of things in the process in order to make the model fit in the best possible way. And then again, this loop really comes in. You have data from many, many historical antibodies. You use that to train the model. You use that model in order to make particular predictions for antibodies that you either want to generate de novo or that you want to optimize for particular properties. You make those actually in the lab and in this way gradually your models become better and better at this task with antibodies.(16:36):I do want to say this is not just about antibodies. So for example, we develop cancer vaccines. These are personalized vaccines and there is a component in making a personalized cancer vaccine, which is choosing which antigens you would actually encode into the vaccine and transformers play a crucial role in actually making this prediction today of what are good neoantigens that will get presented to the immune system. You sometimes want to generate a regulatory sequence because you want to generate a better AAV-like molecule or to engineer something in a cell therapy, so you want to put a cis-regulatory sequence that controls gene expression. Actually personally for me, this was the first project where I used a transformer, which we started years ago. It was published a couple of years ago where we learned a general model that can predict in a particular system. Literally you throw a sequence at that model now and it will predict how much expression it would drive. So these models are very powerful. They are not the be all and end all of all problems that we have, but they are fantastically useful, especially for molecular therapeutics.Good Trouble: HallucinationsEric Topol (17:48):Well, one of the that has been an outgrowth of this is to actually take advantage of the hallucinations or confabulation of molecules. For example, the work of David Baker, who I'm sure you know well at University of Washington, the protein design institute. We are seeing now molecules, antibodies, proteins that don't exist in nature from actually, and all the things that are dubbed bad in GPT-4 and ChatGPT may actually help in the discovery in life science and biomedicine. Can you comment about that?Aviv Regev (18:29):Yeah, I think much more broadly about hallucinations and what you want to think about is something that's like constrained hallucination is how we're creative, right? Often people talk about hallucinations and they shudder at it. It sounds to them insane because if you think about your, say a large language model as a search tool and it starts inventing papers that don't exist. You might be like, I don't like that, but in reality, if it invents something meaningful that doesn't exist, I love that. So that constrained hallucination, I'm just using that colloquially, is a great property if it's constrained and harnessed in the right way. That's creativity, and creativity is very material for what we do. So yes, absolutely in what we call the de novo domain making new things that don't exist. This generative process is the heart of drug discovery. We make molecules that didn't exist before.(19:22):They have to be imagined out of something. They can't just be a thing that was there already and that's true for many different kinds of therapeutic molecules and for other purposes as well, but of course they still have to function in an effective way in the real world. So that's where you want them to be constrained in some way and that's what you want out of the model. I also want to say one of the areas that personally, and I think for the field as a whole, I find the most exciting and still underused is the capacity of these models to hallucinate for us or help us with the creative endeavors of identifying the causes of processes, which is very different than the generative process of making molecules. Thinking about the web of interactions that exist inside a cell and between cells that drives disease processes that is very hard for us to reason through and to collect all the bits of information and to fill in blanks, those fillings of the blanks, that's our creativity, that's what generates the next hypothesis for us. I'm very excited about that process and about that prospect, and I think that's where the hallucination of models might end up proving to be particularly impressive.A.I. Accelerated Drug DiscoveryEric Topol (20:35):Yeah. Now obviously the field of using AI to accelerate drug discovery is extremely hot, just as we were talking about with spatial omics. Do you think that is warranted? I mean you've made a big bet on that you and your folks there at Genentech of course, and so many others, and it's a very crowded space with so many big pharma partnering with AI. What do you see about this acceleration? Is it really going to reap? Is it going to bear fruit? Are we going to see, we've already seen some drugs of course, that are outgrowths, like Baricitinib in the pandemic and others, but what are your expectations? I know you're not one to get into any hyperbole, so I'm really curious as to what you think is the future path.Aviv Regev (21:33):So definitely my hypothesis is that this will be highly, highly impactful. I think it has the potential to be as impactful as molecular biology has been for drug discovery in the 1970s and 1980s. We still live that impact. We now take it for granted. But, of course that's a hypothesis. I also believe that this is a long game and it's a deep investment, meaning decorating what you currently do with some additions from right and left is not going to be enough. This lab in the loop requires deep work working at the heart of how you do science, not as an add-on or in addition to or yet another variant on what has become a pretty established approach to how things are done. That is where I think the main distinction would be and that requires both the length of the investment, the effort to invest in, and also the willingness to really go all out, all in and all out.(22:36):And that takes time. The real risk is the hype. It's actually the enthusiasm now compared to say 2020 is risky for us because people get very enthusiastic and then it doesn't pay off immediately. No, these iterations of a lab in the loop, they take time and they take effort and they take a lot of changes and at first, algorithms often fail before they succeed. You have to iterate them and so that is actually one of the biggest risks that people would be like, but I tried it. It didn't work. This was just some over-hyped thing. I'm walking away and doing it the old way. So that's where we actually have to keep at it, but also keep our expectations not low in magnitude. I think that it would actually deliver, but understanding that it's actually a long investment and that unless you do it deeply, it's not going to deliver the goods.Eric Topol (23:32):I think this point warrants emphasis because the success already we've seen has not been in necessarily discovery and in preliminary validation of new molecules, but rather data mining repurposing, which is a much easier route to go quicker, but also there's so many nodes on past whereby AI can make a difference even in clinical trials, in synthetic efforts to project how a clinical trial will turn out and being able to do toxic screens without preclinical animal work. There's just so many aspects of this that are AI suited to rev it up, but the one that you're working on, of course is the kind of main agenda and I think you framed it so carefully that we have to be patient here, that it has a chance to be so transformative. Now, you touched on the parallels to things like DALL-E and Midjourney and large language models. A lot of our listeners will be thinking only of ChatGPT or GPT-4 or others. This is what you work on, the language of life. This is not text of having a conversation with a chatbot. Do you think that as we go forward, that we have to rename these models because they're known today as language models? Or do you think that, hey, you know what, this is another language. This is a language that life science and biomedicine works with. How do you frame it all?Large Non-Human Language ModelsAviv Regev (25:18):First of all, they absolutely can remain large language models because these are languages, and that's not even a new insight. People have treated biological sequences, for example, in the past too, using language models. The language models were just not as great as the ones that we have right now and the data that were available to train models in the past were not as amazing as what we have right now. So often these are really the shifts. We also actually should pay respect to human language. Human language encodes a tremendous amount of our current scientific knowledge and even language models of human language are tremendously important for this scientific endeavor that I've just described. On top of them come language models of non-human language such as the language of DNA or the language of protein sequences, which are also tremendously important as well as many other generative models, representation learning, and other approaches for machine learning that are material for handling the different kinds of data and questions that we have.(26:25):It is not a single thing. What large language models and especially ChatGPT, this is an enormous favor for which I am very grateful, is that I think it actually convinced people of the power. That conviction is extremely important when you're solving a difficult problem. If you feel that there's a way to get there, you're going to behave differently than if you're like, nothing will ever come out of it. When people experience ChatGPT actually in their daily lives in basic things, doing things that felt to them so human, this feeling overrides all the intellectual part of things. It's better than the thinking and then they're like, in that case, this could actually play out in my other things as well. That, I think, was actually materially important and was a substantial moment and we could really feel it. I could feel it in my interactions with people before and after how their thinking shifted. Even though we were on this journey from before.Aviv Regev (27:30):We were. It felt different.Eric Topol (27:32):Right, the awareness of hundreds of millions of people suddenly in end of November 2022 and then you were of course going to Genentech years before that, a couple few years before that, and you already knew this was on the move and you were redesigning the research at Genentech.Aviv Regev (27:55):Yes, we changed things well before, but it definitely helps in how people embrace and engage feels different because they've seen something like that demonstrated in front of them in a way that felt very personal, that wasn't about work. It's also about work, but it's about everything. That was very material actually and I am very grateful for that as well as for the tool itself and the many other things that this allows us to do but we have, as you said, we have been by then well on our way, and it was actually a fun moment for that reason as well.Eric Topol (28:32):So one of the things I'm curious about is we don't think about the humans enough, and we're talking about the models and the automation, but you have undoubtedly a large team of computer scientists and life scientists. How do you get them to interact? They're of course, in many respects, in different orbits, and the more they interact, the more synergy will come out of that. What is your recipe for fostering their crosstalk?Aviv Regev (29:09):Yeah, this is a fantastic question. I think the future is in figuring out the human question always above all and usually when I draw it, like on the slide, you can draw the loop, but we always put the people in the center of that loop. It's very material to us and I will highlight a few points. One crucial thing that we've done is that we made sure that we have enough critical mass across the board, and it played out in different ways. For example, we built a new computational organization, gRED Computational Sciences, from what was before many different parts rather than one consolidated whole. Of course within that we also built a very strong AI machine learning team, which we didn't have as much before, so some of it was new people that we didn't have before, but some of it was also putting it with its own identity.(29:56):So it is just as much, not more, but also not less just as much of a pillar, just as much of a driver as our biology is, as our chemistry and molecule making is, as our clinical work is. This equal footing is essential and extremely important. The second important point is you really have to think about how you do your project. For example, when we acquired Prescient, at the time they were three people, tiny, tiny company became our machine learning for drug discovery. It's not tiny anymore, but when we acquired them, we also invested in our antibody engineering so that we could do antibody engineering in a lab in the loop, which is not how we did it before, which meant we invested in our experiments in a different way. We built a department for cell and tissue genomics so we can conduct biology experiments also in a different way.(30:46):So we changed our experiments, not just our computation. The third point that I think is really material, I often say that when I'm getting asked, everyone should feel very comfortable talking with an accent. We don't expect our computational scientists to start behaving like they were actually biology trained in a typical way all along, or chemists trained in a typical way all along and by the same token, we don't actually expect our biologists to just embrace wholeheartedly and relinquish completely one way of thinking for another way of thinking, not at all. To the contrary, we actually think all these accents, that's a huge strength because the computer scientist thinks about biology or about chemistry or about medical work differently than a medical doctor or a chemist or a biologist would because a biologist thinks about a model differently and sometimes that is the moment of brilliance that defines the problem and the model in the most impactful way.(31:48):We want all of that and that requires both this equal footing and this willingness to think beyond your domain, not just hand over things, but actually also be there in this other area where you're not the expert but you're weird. Talking with an accent can actually be super beneficial. Plus it's a lot of fun. We're all scientists, we all love learning new things. So that's some of the features of how we try to build that world and you kind of do it in the same way. You iterate, you try it out, you see how it works, and you change things. It's not all fixed and set in stone because no one actually wrote a recipe, or at least I didn't find that cookbook yet. You kind of invent it as you go on.Eric Topol (32:28):That's terrific. Well, there's so much excitement in this convergence of life science and the digital biology we've been talking about, have I missed anything? We covered human cell atlas, the spatial omics, the lab in the loop. Is there anything that I didn't touch on that you find important?Aviv Regev (32:49):There's something we didn't mention and is the reason I come to work every day and everyone I work with here, and I actually think also the people of the human cell atlas, we didn't really talk about the patients.(33:00):There's so much, I think you and I share this perspective, there's so much trepidation around some of these new methods and we understand why and also we all saw that technology sometimes can play out in ways that are really with unintended consequences, but there's also so much hope for patients. This is what drives people to do this work every day, this really difficult work that tends not to work out much more frequently than it works out now that we're trying to move that needle in a substantial way. It's the patients, and that gives this human side to all of it. I think it's really important to remember. It also makes us very responsible. We look at things very responsibly when we do this work, but it also gives us this feeling in our hearts that is really unbeatable, that you're doing it for something good.Eric Topol (33:52):I think that emphasis couldn't be more appropriate. One of the things I think about all the time is that because we're moving into this, if you will, hyper accelerated phase of discovery over the years ahead with this just unparallel convergence of tools to work with, that somebody could be cured of a condition, somebody could have an autoimmune disease that we will be able to promote tolerogenicity and they wouldn't have the autoimmune disease and if they could just sit tight and wait a few years before this comes, as opposed to just missing out because it takes time to get this all to gel. So I'm glad you brought that up, Aviv, because I do think that's what it's all about and that's why we're cheering for your work and so many others to get it done, get across the goal line because there's these 10,000 diseases out there and there's so many unmet needs across them where we don't have treatments that are very effective or have all sorts of horrible side effects. We don't have cures, and we've got all the things now, as we've mentioned here in this conversation, whether it's genome editing and ability to process massive scale data in a way that never could be conceived some years ago. Let's hope that we help the patients, and go ahead.Aviv Regev (35:25):I found the Proust quote, if you want it recorded correctly.Eric Topol (35:29):Yeah, good.Aviv Regev (35:30):It's much longer than what I did. It says, “the only true voyage, the only bath in the Fountain of Youth would be not to visit strange lands but to possess other eyes, to see the universe through the eyes of another, of a hundred others, to see the hundred universes that each of them sees, that each of them is; and this we do, with great artists; with artists like these we do fly from star to star.”—Marcel ProustEric Topol (35:57):I love that and what a wonderful way to close our conversation today. Aviv, I look forward to more conversations with you. You are an unbelievable gem. Thanks so much for joining today.Aviv Regev (36:10):Thank you so much.*************************************Thanks for listening or reading to this Ground Truths Podcast.Please share if you found it of interestThe Ground Truths newsletters and podcasts are all free, open-access, without ads.Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in.Comments are welcome from all subscribers. Get full access to Ground Truths at erictopol.substack.com/subscribe

Ground Truths
Jennifer Doudna: The Exciting Future of Genome Editing

Ground Truths

Play Episode Listen Later Apr 14, 2024 31:10


Professor Doudna was awarded the 2020 Nobel Prize in Chemistry with Professor Emmanuelle Charpentier for their pioneering work in CRISPR genome editing. The first genome editing therapy (Casgevy) was just FDA approved, only a decade after the CRISPR-Cas9 editing system discovery. But It's just the beginning of a much bigger impact story for medicine and life science.Ground Truths podcasts are now on Apple and Spotify. And if you prefer videos, they are posted on YouTubeTranscript with links to audio and relevant external linksEric Topol (00:06):This is Eric Topol with Ground Truths, and I'm really excited today to have with me Professor Jennifer Doudna, who heads up the Innovative Genomics Institute (IGI) at UC Berkeley, along with other academic appointments, and as everybody knows, was the Nobel laureate for her extraordinary discovery efforts with CRISPR genome editing. So welcome, Jennifer.Jennifer Doudna (00:31):Hello, Eric. Great to be here.Eric Topol (00:34):Well, you know we hadn't met before, but I felt like I know you so well because this is one of my favorite books, The Code Breaker. And Walter Isaacson did such a wonderful job to tell your story. What did you think of the book?My interview with Walter Isaacson on The Code Breaker, a book I highly recommendJennifer Doudna (00:48):I thought Walter did a great job. He's a good storyteller, and as you know from probably from reading it or maybe talking to others about it, he wrote a page turner. He actually really dug into the science and all the different aspects of it that I think created a great tale.Eric Topol (01:07):Yeah, I recommended highly. It was my favorite book when it came out a couple years ago, and it is a page turner. In fact, I just want to read one, there's so many quotes out of it, but in the early part of the book, he says, “the invention of CRISPR and the plague of Covid will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery beginning just over a century ago, of the three fundamental kernels of our existence, the atom, the bit, and the gene.” That kind of tells a big story just in one sentence, but I thought I'd start with the IGI, the institute that you have set up at Berkeley and what its overall goals are.Jennifer Doudna (01:58):Right. Well, let's just go back a few years maybe to the origins of this institute and my thinking around it, because in the early days of CRISPR, it was clear that we were really at a moment that was quite unique in the sense that there was a transformative technology. It was going to intersect with lots of other discoveries and technologies. And I work at a public institution and my question to myself was, how can I make sure that this powerful tool is first of all used responsibly and secondly, that it's used in a way that benefits as many people as possible, and it's a tall order, but clearly we needed to have some kind of a structure that would allow people to work together towards those goals. And that was really the mission behind the IGI, which was started as a partnership between UC Berkeley and UCSF and now actually includes UC Davis as well.The First FDA Approved Genome EditingEric Topol (02:57):I didn't realize that. That's terrific. Well, this is a pretty big time because 10 years or so, I guess starting to be 11 when you got this thing going, now we're starting to see, well, hundreds of patients have been treated and in December the FDA approved the first CRISPR therapy for sickle cell disease, Casgevy. Is that the way you say it?Jennifer Doudna (03:23):Casgevy, yeah.Eric Topol (03:24):That must have felt pretty good to see if you go from the molecules to the bench all the way now to actually treating diseases and getting approval, which is no easy task.Jennifer Doudna (03:39):Well, Eric, for me, I'm a biochemist and somebody who has always worked on the fundamentals of biology, and so it's really been extraordinary to see the pace at which the CRISPR technology has been adopted, and not just for fundamental research, but also for real applications. And Casgevy is sort of the crowning example of that so far, is that it's really a technology that we can already see how it's being used to, I think it's fair to say, effectively cure a genetic disease for the first time. Really amazing.Genome Editing is Not the Same as Gene TherapyEric Topol (04:17):Yeah. Now I want to get back to that. I know there's going to be refinements about that. And of course, there's beta thalassemia, so we've got two already, and our mutual friend Fyodor Urnov would say two down 5,000 to go. But I think before I get to the actual repair of the sickle cell defect molecular defect, I think one of the questions I think that people listeners may not know is the differentiation of genome editing with gene therapy. I mean, as you know, there was recently a gene therapy approval for something like $4.25 million for metachromatic leukodystrophy. So maybe you could give us kind of skinny on how these two fundamental therapies are different.Jennifer Doudna (05:07):Right. Well, it's a great question because the terminology sounds kind of the same, and so it could be confusing. Gene therapy goes back decades, I can remember gene therapy being discussed as an exciting new at the time, direction back when I was a graduate student. That was little while ago. And it refers to the idea that we can use a genetic approach for disease treatment or even for a cure. However, it fundamentally requires some mechanism of integrating new information into a genome. And traditionally that's been done using viruses, which are great at doing that. It's just that they do it wherever they want to do it, not necessarily where we want that information to go. And this is where CRISPR comes in. It's a technology allows precision in that kind of genetic manipulation. So it allows the scientist or the clinician to decide where to make a genetic change. And that gives us tremendous opportunity to do things with a kind of accuracy that hasn't been possible before.Eric Topol (06:12):Yeah, no question. That's just a footnote. My thesis in college at University of Virginia, 1975, I'm an old dog, was prospects for gene therapy in man. So it took a while, didn't it? But it's a lot better now with what you've been working on, you and your colleagues now and for the last decade for sure. Now, what I was really surprised about is it's not just of course, these hemoglobin disorders, but now already in phase two trials, you've got hereditary angioedema, which is a life-threatening condition, amyloidosis, cancer ex vivo, and also chronic urinary tract infections. And of course, there's six more others like autoimmune diseases like lupus and type 1 diabetes. So this is really blossoming. It's really extraordinary.Eric Topol (07:11):I mean, wow. So one of the questions I had about phages, because this is kind of going back to this original work and discovery, antimicrobial resistance is really a big problem and it's a global health crisis, and there's only two routes there coming up with new drugs, which has been slow and not really supported by the life science industry. And the other promising area is with phages. And I wonder, since this is an area you know so well, why haven't we put more, we're starting to see more trials in phages. Why haven't we doubled down or tripled down on this to help the antimicrobial resistance problem?Jennifer Doudna (08:00):Well, it's a really interesting area, and as you said, it's kind of one of those areas of science where I think there was interest a while ago and some effort was made for reasons that are not entirely clear to me, at least it fizzled out as a real focused field for a long time. But then more recently, people have realized that there's an opportunity here to take advantage of some natural biology in which viruses can infect and destroy microbes. Why aren't we taking better advantage of that for our own health purposes? So I personally am very excited about this area. I think there's a lot of fundamental work still to be done, but I think there's a tremendous opportunity there as well.CRISPR 2.0Eric Topol (08:48):Yeah, I sure think we need to invest in that. Now, getting back to this sickle cell story, which is so extraordinary. This is kind of a workaround plan of getting fetal hemoglobin built up, but what about actually repairing, getting to fixing the lesion, if you will?Eric Topol (09:11):Yeah. Is that needed?Jennifer Doudna (09:13):Well, maybe it's worth saying a little bit about how Casgevy works, and you alluded to this. It's not a direct cure. It's a mechanism that allows activation of a second protein called fetal hemoglobin that can suppress the effect of the sickle cell mutation. And it's great, and I think for patients, it offers a really interesting opportunity with their disease that hasn't been available in the past, but at the same time, it's not a true cure. And so the question is could we use a CRISPR type technology to actually make a correction to the genetic defect that directly causes the disease? And I think the answer is yes. The field isn't there quite yet. It's still relatively difficult to control the exact way that DNA editing is occurring, especially if we're doing it in vivo in the body. But boy, many people are working on this, as you probably know. And I really think that's on the horizon.Eric Topol (10:19):Yeah. Well, I think we want to get into the in vivo story as well because that, I think right now it's so complicated for a person to have to go through the procedure to get ultimately this treatment currently for sickle cell, whereas if you could do this in vivo and you could actually get the cure, that would be of the objective. Now, you published just earlier this month in PNAS a wonderful paper about the EDVs and the lipid nanoparticles that are ways that we could get to a better precision editing. These EDVs I guess if I have it right, enveloped virus-like particles. It could be different types, it could be extracellular vesicles or whatnot. But do you think that's going to be important? Because right now we're limited for delivery, we're limited to achieve the right kind of editing to do this highly precise. Is that a big step for the future?Jennifer Doudna (11:27):Really big. I think that's gating at the moment. Right now, as you mentioned, somebody that might want to get the drug Casgevy for sickle cell disease or thalassemia, they have to go through a bone marrow transplant to get it. And that means that it's very expensive. It's time consuming. It's obviously not pleasant to have to go through that. And so that automatically means that right now that therapy is quite restricted in the patients that it can benefit. But we imagine a day when you could get this type of therapy into the body with a one-time injection. Maybe someday it's a pill that could be taken where the gene editors target the right cells in the body. In diseases like that, it would be the stem cells in the bone marrow and carry out gene editing that can have a therapeutic benefit. And again, it's one of those ideas that sounds like science fiction, and yet already there's tremendous advance in that direction. And I think over the next, I don't know, I'm guessing 5 to 10 years we're going to see that coming online.Editing RNA, the Epigenome, and the MicrobiomeEric Topol (12:35):Yeah, I'm guessing just because there's so much work on the lipid nanoparticles to tweak them. And there's four different components that could easily be made so much better. And then all these virus-like proteins, I mean, it may happen even sooner. And it's really exciting. And I love that diagram in that paper. You have basically every organ of the body that isn't accessible now, potentially that would become accessible. And that's exciting because whatever blossoming we're seeing right now with these phase two trials ongoing, then you basically have no limits. And that I think is really important. So in vivo editing big. Now, the other thing that's cropped up in recent times is we've just been focused on DNA, but now there's RNA editing, there's epigenetic or epigenomic editing. What are your thoughts about that?Jennifer Doudna (13:26):Very exciting as well. It's kind of a parallel strategy. The idea there would be to, rather than making a permanent change in the DNA of a cell, you could change just the genetic output of the cell and or even make a change to DNA that would alter its ability to be expressed and to produce proteins in the cell. So these are strategies that are accessible, again, using CRISPR tools. And the question is now how to use them in ways that will be therapeutically beneficial. Again, topics that are under very active investigation in both academic labs and at companies.Eric Topol (14:13):Yeah. Now speaking of that, this whole idea of rejuvenation, this is Altos. You may I'm sure know my friend here, Juan Carlos Belmonte, who's been pushing on this for some time at Altos now formerly at Salk. And I know you helped advise Altos, but this idea of basically epigenetic, well using the four Yamanaka factors and basically getting cells that go to a state that are rejuvenated and all these animal models that show that it really happens, are you thinking that really could become a therapy in the times ahead in patients for aging or particular ideas that you have of how to use that?Jennifer Doudna (15:02):Well, you mentioned the company Altos. I mean, Altos and a number of other groups are actively investigating this. Not I would say specifically regarding genome editing, although being able to monitor and probably change gene functions that might affect the aging process could be attractive in the future. I think the hard question there is which genes do we tweak and how do we make sure that it's safe? And better than me I mean, that's a very difficult thing to study clinically because it takes time for one thing, and we probably don't have the best models either. So I think there are challenges there for sure. But along the way, I feel very excited about the kind of fundamental knowledge that will come from those studies. And in particular, this question of how tissues rejuvenate I think is absolutely fascinating. And some organisms do this better than others. And so, understanding how that works in organisms that are able to say regrow a limb, I think can be very interesting.Eric Topol (16:10):And that gets me to that recent study. Well, as you well know, there's a company Verve that's working on the familial hypercholesterolemia and using editing with the PCSK9 through the liver and having some initial, at least a dozen patients have been treated. But then this epigenetic study of editing in mice for PCSK9 also showed results. Of course, that's much further behind actually treating patients with base editing. But it's really intriguing that you can do some of these things without having to go through DNA isn't it?Jennifer Doudna (16:51):Amazing, right? Yeah, it's very interesting.Reducing the Cost of Genome EditingEric Topol (16:54):Wild. Now, one of the things of course that people bring up is, well, this is so darn expensive and it's great. It's a science triumph, but then who can get these treatments? And recently in January, you announced a Danaher-IGI Beacon, and maybe you can tell us a bit about that, because again, here's a chance to really markedly reduce the cost, right?Jennifer Doudna (17:25):That's right. That's the vision there. And huge kudos to my colleague Fyodor Urnov, who really spearheaded that effort and leads the team on the IGI side. But the vision there was to partner with a company that has the ability to manufacture molecules in ways that are very, very hard, of course, for academic labs and even for most companies to do. And so the idea was to bring together the best of genome editing technology, the best of clinical medicine, especially focused on rare human diseases. And this is with our partners at UCSF and with the folks in the Danaher team who are experts at downstream issues of manufacturing. And so the hope there is that we can bring those pieces together to create ways of using CRISPR that will be cost effective for patients. And frankly, we'll also create a kind of roadmap for how to do this, how to do this more efficiently. And we're kind of building the plane while we're flying it, if you know what I mean. But we're trying to really work creatively with organizations like the FDA to come up with strategies for clinical trials that will maintain safety, but also speed up the timeline.Eric Topol (18:44):And I think it's really exciting. We need that and I'm on the scientific advisory board of Danaher, a new commitment for me. And when Fyodor presented that recently, I said, wow, this is exciting. We haven't really had a path to how to get these therapies down to a much lower cost. Now, another thing that's exciting that you're involved in, which I think crosses the whole genome editing, the two most important things that I've seen in my lifetime are genome editing and AI, and they also work together. So maybe before we get into AI for drug discovery, how does AI come into play when you're thinking about doing genome editing?Jennifer Doudna (19:34):Well, the thing about CRISPR is that as a tool, it's powerful not only as a one and done kind of an approach, but it's also very powerful genomically, meaning that you can make large libraries of these guide RNAs that allow interrogation of many genes at once. And so that's great on the one hand, but it's also daunting because it generates large collections of data that are difficult to manually inspect. And in some cases, I believe really very, very difficult to analyze in traditional ways. But imagine that we have ways of training models that can look at genetic intersections, ways that genes might be affecting the behavior of not only other genes, but also how a person responds to drugs, how a person responds to their environment and allows us to make predictions about genetic outcomes based on that information. I think that's extremely exciting, and I definitely think that over the next few years we'll see that kind of analysis coming online more and more.Eric Topol (20:45):Yeah, the convergence, I think is going to be, it's already being done now, but it's just going to keep building. Now, Demis Hassabis, who one of the brilliant people in the field of AI leads the whole Google Deep Mind AI efforts now, but he formed after AlphaFold2 behaving to predict proteins, 200 million proteins of the universe. He started a company Isomorphic Labs as a way to accelerate using AI drug discovery. What can you tell us about that?Jennifer Doudna (21:23):It's exciting, isn't it? I'm on the SAB for that company, and I think it's very interesting to see their approach to drug discovery. It's different from what I've been familiar with at other companies because they're really taking a computational lens to this challenge. The idea there is can we actually predict things like the way a small molecule might interact with a particular protein or even how it might interact with a large protein complex. And increasingly because of AlphaFold and programs like that, that allow accurate prediction of structures, it's possible to do that kind of work extremely quickly. A lot of it can be done in silico rather than in the laboratory. And when you do get around to doing experiments in the lab, you can get away with many fewer experiments because you know the right ones to do. Now, will this actually accelerate the rate at which we get to approved therapeutics? I wonder about your opinion about that. I remain unsure.Editing Out Alzheimer's Risk AllelesEric Topol (22:32):Yeah. I mean, we have one great success story so far during the pandemic Baricitinib, a drug that repurposed here, a drug that was for rheumatoid arthritis, found by data mining that have a high prospects for Covid and now saves lives in Covid. So at least that's one down, but we got a lot more here too. But it, it's great that Demis recruited you on the SAB for Isomorphic because it brings in a great mind in a different field. And it goes back to one of the things you mentioned earlier is how can we get some of this genome editing into a pill someday? Wow. Now, one of the things that for personal interest, as an APOE4 carrier, I'm looking to you to fix my APOE4 and give me APOE2. How can I expect to get that done in the near future?Jennifer Doudna (23:30):Oh boy. Okay, we'll have to roll up our sleeves on that one. But it is appealing, isn't it? I think about it too. It's a fascinating idea. Could we get to a point someday where we can use genome editing as a prophylactic, not as a treatment after the fact, but as a way to actually protect ourselves from disease? And the APOE4 example is a really interesting one because there's really good evidence that by changing the type of allele that one has for the APOE gene, you can actually affect a person's likelihood of developing Alzheimer's in later life. But how do we get there? I think one thing to point out is that right now doing genome editing in the brain is, well, it's hard. I mean, it's very hard.Eric Topol (24:18):It a little bit's been done in cerebral spinal fluid to show that you can get the APOE2 switch. But I don't know that I want to sign up for an LP to have that done.Jennifer Doudna (24:30):Not quite yet.Eric Topol (24:31):But someday it's wild. It's totally wild. And that actually gets me back to that program for coronary heart disease and heart attacks, because when you're treating people with familial hypercholesterolemia, this extreme phenotype. Someday and this goes for many of these rare diseases that you and others are working on, it can have much broader applicability if you have a one-off treatment to prevent coronary disease and heart attacks and you might use that for people well beyond those who have an LDL cholesterol that are in the thousands. So that's what I think a lot of people don't realize that this editing potential isn't just for these monogenic and rare diseases. So we just wanted to emphasize that. Well, this has been a kind of wild ride through so much going on in this field. I mean, it is extraordinary. What am I missing that you're excited about?Jennifer Doudna (25:32):Well, we didn't talk about the microbiome. I'll just very briefly mention that one of our latest initiatives at the IGI is editing the microbiome. And you probably know there are more and more connections that are being made between our microbiome and all kinds of health and disease states. So we think that being able to manipulate the microbiome precisely is going to open up another whole opportunity to impact our health.Can Editing Slow the Aging Process?Eric Topol (26:03):Yeah, I should have realized that when I only mentioned two layers of biology, there's another one that's active. Extraordinary, just going back to aging for a second today, there was a really interesting paper from Irv Weissman Stanford, who I'm sure you know and colleagues, where they basically depleted the myeloid stem cells in aged mice. And they rejuvenated the immune system. I mean, it really brought it back to life as a young malice. Now, there probably are ways to do that with editing without having to deplete stem cells. And the thought about other ways to approach the aging process now that we're learning so much about science and about the immune system, which is one of the most complex ones to work in. Do you have ideas about that are already out there that we could influence the aging process, especially for those of us who are getting old?Jennifer Doudna (27:07):We're all on that path, Eric. Well, I guess the way that I think about it is I like to think that genome editing is going to pave the way to make those kinds of fundamental discoveries. I still feel that there's a lot of our genetics that we don't understand. And so, by being able to manipulate genes precisely and increasingly to look at how genes interact with each other, I think one fundamental question it relates to aging actually is why do some of us age at a seemingly faster pace than others? And it must have to do at least in part with our genetic makeup and how we respond to our environment. So I definitely think there are big opportunities there, really in fundamental research initially, but maybe later to actually change those kinds of things.Eric Topol (28:03):Yeah, I'm very impressed in recent times how much the advances are being made at basic science level and experimental models. A lot of promise there. Now, is there anything about this field that you worry about that keeps you up at night that you think, besides, we talked about that we got to get the cost down, we have to bridge health inequities for sure, but is there anything else that you're concerned about right now?Jennifer Doudna (28:33):Well, I think anytime a new technology goes into clinical trials, you worry that things may get out ahead of their skis, and there may be some overreach that happens. I think we haven't really seen that so far in the CRISPR field, which is great. But I guess I remain cautious. I think that we all saw what happened in the field of gene therapy now decades ago, but that really put a poll on that field for a long time. And so, I definitely think that we need to continue to be very cautious as gene editing continues to advance.Eric Topol (29:10):Yeah, no question. I think the momentum now is getting past that point where you would be concerned about known unknowns, if you will, things that going back to the days of the Gelsinger crisis. But it's really extraordinary. I am so thrilled to have this conversation with you and to get a chance to review where the field is and where it's going. I mean, it's exploding with promise and potential well beyond and faster. I mean, it takes a drug 17 years, and you've already gotten this into two treatments. I mean, I'm struck when you were working on this, how you could have thought that within a 10-year time span you'd already have FDA approvals. It's extraordinary.Jennifer Doudna (30:09):Yeah, we hardly dared hope. Of course, we're all thrilled that it went that fast, but I think it would've been hard to imagine it at the time.Eric Topol (30:17):Yeah. Well, when that gets simplified and doesn't require hospitalizations and bone marrow, and then you'll know you're off to the races. But look, what a great start. Phenomenal. So congratulations. I'm so thrilled to have the chance to have this conversation. And obviously we're all going to be following your work because what a beacon of science and progress and changing medicine. So thanks and give my best to my friend there at IGI, Fyodor, who's a character. He's a real character. I love the guy, and he's a good friend.Jennifer Doudna (30:55):I certainly will Eric, and thank you so much. It's been great talking with you.*******************************************************Thanks for listening and/or reading this edition of Ground Truths.I hope you found it as stimulating as I did. Please share if you did!A reminder that all Ground Truths posts (newsletter and podcast( are free without ads. Soon we'll set it up so you can select what type of posts you want to be notified about.If you wish to be a paid subscriber, know that all proceeds are donated to Scripps Research, and thanks for that—it greatly helped fund our summer internship program for 2023 and 2024.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio/video support. Get full access to Ground Truths at erictopol.substack.com/subscribe

Pomegranate Health
[Journal Club] Baricitinib immune therapy for new onset type 1 diabetes

Pomegranate Health

Play Episode Listen Later Apr 11, 2024 40:44


Type 1 diabetes has a very high treatment burden in terms of direct costs, inconvenience and lost productivity for patients and their carers. Further, all the glucose checking, hormone replacement and consults don't abolish the vascular complications associated with poor glycaemic control. Only in the last few years has it been possible to pharmacologically alter the course of type 1 diabetes and other auto-immune diseases without generating intolerable side effects.Teplizumab is an antibody to CD3 which was presented to the world in 2019 as delaying the onset of type 1 diabetes in high-risk individuals thanks to its protective effect on pancreatic β-cells. It has not yet been registered by the Therapeutic Goods Administration but another immunomodulatory drug called baricitinib has. Baricitinib is an inhibitor of Janus Kinases indicated for the for the treatment of rheumatoid arthritis, alopecia areata, atopic dermatitis and even COVID-19.  In December of last year the results of a Phase 2 trial in patients with new-onset type 1 diabetes were published in the New England Journal of Medicine. After almost a year of taking the oral therapy, patients were found to have better glycaemic control and evoked C-peptide levels than those taking placebo, indicating a preserved ability to secrete insulin. In today's episode, Pomegranate's in-house endocrinologist interviews two of the study authors.   Key ReferenceBaricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes [NEJM. 2023. 7;389(23)]GuestsProf Jenny Couper FRACP FAHMS (Women's and Children's Hospital, University of Adelaide) Dr Michelle So FRACP (Royal Melbourne Hospital, Northern Hospital) Guest HostDr Rahul Barmanray FRACP (Royal Melbourne Hospital)ProductionProduced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes ‘Things to Sort out' and ‘Quiet Waters' by Walt Adams and ‘The Appalachian Trail' by Hunter Quinn. Music courtesy of FreeMusic Archive includes ‘I am a Man Who Will Fight For Your Honor' by Chris Zabriskie. Image produced and copyrighted by RACP.Editorial feedback kindly provided by RACP physicians Amy Hughes, Stephen Bacchi, Fionnuala Fagan and Aidan Tan.  Please visit the Pomegranate Health web page for a transcript and supporting references.Login to MyCPD to record listening and reading as a prefilled learning activity. Subscribe to new episode email alerts or search for ‘Pomegranate Health' in Apple Podcasts, Spotify,Castbox or any podcasting app.

iCritical Care: All Audio
SCCM Pod-504 CCM: Baricitinib or Tocilizumab for Severe COVID-19

iCritical Care: All Audio

Play Episode Listen Later Mar 25, 2024 21:43


Host Marilyn N. Bulloch, PharmD, BCPS, FCCM, is joined by Joy Peterson, PharmD, BCPS, BCIDP, Neha Paranjape, MD, MPH, to discuss the article, "Outcomes and Adverse Effects of Baricitinib Versus Tocilizumab in the Management of Severe COVID-19," (Crit Care Med. March 2023 51(3):337-346) which delves into the comparative outcomes, mortality rates, and adverse effects of baricitinib and tocilizumab in severe COVID-19 cases. Dr. Peterson is a Clinical Pharmacy Specialist in infectious disease, and Dr. Paranjape is an Infectious Disease Specialist at Wellstar Health System in Marietta, Georgia.

Ground Truths
Daphne Koller: The Convergence of A.I. and Digital Biology

Ground Truths

Play Episode Listen Later Mar 10, 2024 35:16


Transcript Eric Topol (00:06):Well, hello, this is Eric Topol with Ground Truths and I am absolutely thrilled to welcome Daphne Koller, the founder and CEO of insitro, and a person who I've been wanting to meet for some time. Finally, we converged so welcome, Daphne.Daphne Koller (00:21):Thank you Eric. And it's a pleasure to finally meet you as well.Eric Topol (00:24):Yeah, I mean you have been rocking everybody over the years with elected to the National Academy of Engineering and Science and right at the interface of life science and computer science and in my view, there's hardly anyone I can imagine who's doing so much at that interface. I wanted to first start with your meeting in Davos last month because I kind of figured we start broad AI rather than starting to get into what you're doing these days. And you had a really interesting panel [←transcript] with Yann LeCun, Andrew Ng and Kai-Fu Lee and others, and I wanted to get your impression about that and also kind of the general sense. I mean AI is just moving it at speed, that is just crazy stuff. What were your thoughts about that panel just last month, where are we?Video link for the WEF PanelDaphne Koller (01:25):I think we've been living on an exponential curve for multiple decades and the thing about exponential curves is they are very misleading things. In the early stages people basically take the line between whatever we were last year, and this year and they interpolate linearly, and they say, God, things are moving so slowly. Then as the exponential curve starts to pick up, it becomes more and more evident that things are moving faster, but it's still people interpolate linearly and it's only when things really hit that inflection point that people realize that even with the linear interpolation where we'll be next year is just mind blowing. And if you realize that you're on that exponential curve where we will be next year is just totally unanticipatable. I think what we started to discuss in that panel was, are we in fact on an exponential curve? What are the rate limiting factors that may or may not enable that curve to continue specifically availability of data and what it would take to make that curve available in areas outside of the speech, whatever natural language, large language models that exist today and go far beyond that, which is what you would need to have these be applicable to areas such as biology and medicine.Daphne Koller (02:47):And so that was kind of the message to my mind from the panel.Eric Topol (02:53):And there was some differences in opinion, of course Yann can be a little strong and I think it was good to see that you're challenging on some things and how there is this “world view” of AI and how, I guess where we go from here. As you mentioned in the area of life science, there already had been before large language models hit stride, so much progress particularly in imaging cells, subcellular, I mean rare cells, I mean just stuff that was just without any labeling, without fluorescein, just amazing stuff. And then now it's gone into another level. So as we get into that, just before I do that, I want to ask you about this convergence story. Jensen Huang, I'm sure you heard his quote about biology as the opportunity to be engineering, not science. I'm sure if I understand, not science, but what about this convergence? Because it is quite extraordinary to see two fields coming together moving at such high velocity."Biology has the opportunity to be engineering not science. When something becomes engineering not science it becomes...exponentially improving, it can compound on the benefits of previous years." -Jensen Huang, NVIDIA.Daphne Koller (04:08):So, a quote that I will replace Jensen's or will propose a replacement for Jensen's quote, which is one that many people have articulated, is that math is to physics as machine learning is to biology. It is a mathematical foundation that allows you to take something that up until that point had been kind of mysterious and fuzzy and almost magical and create a formal foundation for it. Now physics, especially Newtonian physics, is simple enough that math is the right foundation to capture what goes on in a lot of physics. Biology as an evolved natural system is so complex that you can't articulate a mathematical model for that de novo. You need to actually let the data speak and then let machine learning find the patterns in those data and really help us create a predictability, if you will, for biological systems that you can start to ask what if questions, what would happen if we perturb the system in this way?The ConvergenceDaphne Koller (05:17):How would it react? We're nowhere close to being able to answer those questions reliably today, but as you feed a machine learning system more and more data, hopefully it'll become capable of making those predictions. And in order to do that, and this is where it comes to this convergence of these two disciplines, the fodder, the foundation for all of machine learning is having enough data to feed the beast. The miracle of the convergence that we're seeing is that over the last 10, 15 years, maybe 20 years in biology, we've been on a similar, albeit somewhat slower exponential curve of data generation in biology where we are turning it into a quantitative discipline from something that is entirely observational qualitative, which is where it started, to something that becomes much more quantitative and broad based in how we measure biology. And so those measurements, the tools that life scientists and bioengineers have developed that allow us to measure biological systems is what produces that fodder, that energy that you can then feed into the machine learning models so that they can start making predictions.Eric Topol (06:32):Yeah, well I think the number of layers of data no less what's in these layers is quite extraordinary. So some years ago when all the single cell sequencing was started, I said, well, that's kind of academic interest and now the field of spatial omics has exploded. And I wonder how you see the feeding the beast here. It's at every level. It's not just the cell level subcellular and single cell nuclei sequencing single cell epigenomics, and then you go all the way to these other layers of data. I know you plug into the human patient side as well as it could be images, it could be past slides, it could be the outcomes and treatments and on and on and on. I mean, so when you think about multimodal AI, has anybody really done that yet?Daphne Koller (07:30):I think that there are certainly beginnings of multimodal AI and we have started to see some of the benefits of the convergence of say, imaging and omics. And I will give an example from some of the work that we've recently distributed on a preprint server work that we did at insitro, which took imaging data from standard histopathology slides, H&E slides and aligned them with simple bulk RNA-Seq taken from those same tumor samples. And what we find is that by training models that translate from one to the other, specifically from the imaging to the omics, you're able to, for a fairly large fraction of genes, make very accurate predictions of gene expression levels by looking at the histopath images alone. And in fact, because many of the predictions are made at the tile level, not at the entire slide level, even though the omics was captured in bulk, you're able to spatially resolve the signal and get kind of like a pseudo spatial biology just by making predictions from the H&E image into these omic modalities.Multimodal A.I. and Life ScienceDaphne Koller (08:44):So there are I think beginnings of multimodality, but in order to get to multimodality, you really need to train on at least some data where the two modalities are simultaneously. And so at this point, I think the rate limiting factor is more a matter of data acquisition for training the models. It is for building the models themselves. And so that's where I think things like spatial biology, which I think like you are very excited about, are one of the places where we can really start to capture these paired modalities and get to some of those multimodal capabilities.Eric Topol (09:23):Yeah, I wanted to ask you because I mean spatial temporal is so perfect. It is two modes, and you have as the preprint you refer to and you see things like electronic health records in genomics, electronic health records in medical images. The most we've done is getting two modes of data together. And the question is as this data starts to really accrue, do we need new models to work with it or do you actually foresee that that is not a limiting step?Daphne Koller (09:57):So I think currently data availability is the most significant rate limiting step. The nice thing about modern day machine learning is that it really is structured as a set of building blocks that you can start to put together in different ways for different situations. And so, do we have the exact right models available to us today for these multimodal systems? Probably not, but do we have the right building blocks that if we creatively put them together from what has already been deployed in other settings? Probably, yes. So of course there's still a model exploration to be done and a lot of creativity in how these building blocks should be put together, but I think we have the tools available to solve these problems. What we really need is first I think a really significant data acquisition effort. And the other thing that we need, which is also something that has been a priority for us at insitro, is the right mix of people to be put together so that you can, because what happens is if you take a bunch of even extremely talented and sophisticated machine learning scientists and say, solve a biological problem, here's a dataset, they don't know what questions to ask and oftentimes end up asking questions that might be kind of interesting from machine learning perspective, but don't really answer fundamental biology questions.Daphne Koller (11:16):And conversely, you can take biologists and say, hey, what would you have machine learning do? And they will tell you, well, in our work we do A to B to C to D, and B to C is kind of painful, like counting nuclei is really painful, so can we have the machine do that for us? And it's kind of like that. Yeah, but that's boring. So what you get if you put them in a room together and actually get to the point where they communicate with each other effectively, is that not only do you get better solutions, you get better problems. I think that's really the crux of making progress here besides data is the culture and the people.A.I. and Drug DiscoveryEric Topol (11:54):Well, I'm sure you've assembled that at insitro knowing you, and I mean people tend to forget it's about the people, it's not about the models or even the data when you have all that. Now you've been onto drug discovery paths, there's at least 20 drugs that are AI driven that are in the clinic in phase one or two at some point. Obviously these are not only ones that you've been working on, but do you see this whole field now going into high gear because of this? Or is that the fact that there's all these AI companies partnering with big pharma? Is it a lot of nice agreements that are drawn up with multimillion dollar milestones or is this real?Daphne Koller (12:47):So there's a number of different layers to your question. First of all, let me start by saying that I find the notion of AI driven drugs to be a bit of a weird concept because over time most drugs will have some element of AI in them. I mean, even some of the earlier work used data science in many cases. So where do you draw the boundary? I mean, we're not going to be in a world anytime soon where AI starts out with, oh, I need to work on ALS and at the end there is a clinical trial design ready to be submitted to the FDA without anything, any human intervention in the middle. So, it's always going to be an interplay between a machine and a human with over time more and more capabilities I think being taken on by the machine, but I think inevitably a partnership for a long time to come.Daphne Koller (13:41):But coming to the second part of your question, is this real? Every big pharma has gotten to the point today that they realize they need some of that AI thing that's going around. The level of sophistication of how they incorporate that and their willingness to make some of the hard decisions of, well, if we're going to be doing this with AI, it means we shouldn't be doing it the old way anymore and we need to make a big dramatic internal shift that I think depends very much on the specific company. And some companies have more willingness to take those very big steps than others, so will some companies be able to make the adjustment? Probably. Will all of them? Probably not. I would say however, that in this new world there is also room for companies to emerge that are, if you will, AI native.Daphne Koller (14:39):And we've seen that in every technological revolution that the native companies that were born in the new age move faster, incorporate the technology much more deeply into every aspect of their work, and they end up being dominant players if not the dominant player in that new world. And you could look at the internet revolution and think back to Google did not emerge from the yellow pages. Netflix did not emerge from blockbuster, Amazon did not emerge from Walmart so some of those incumbents did make the adjustment and are still around, some did not and are no longer around. And I think the same thing will happen with drug discovery and development where there will be a new crop of leading companies to I think maybe together with some of the incumbents that we're able to make the adjustment.Eric Topol (15:36):Yeah, I think your point there is essential, and another part of this story is that a lot of people don't realize there's so many nodes of ways that AI can facilitate this whole process. I mean from the elemental data mining that identified Baricitinib for Covid and now being used even for many other indications, repurposing that to how to simulate for clinical trials and everything in between. Now, what seems like because of your incredible knack and this convergence, I mean your middle name is like convergence really, you are working at the level of really in my view, this unique aspect of bringing cells and all the other layers of data together to amp things up. Is that a fair assessment of where insitro in your efforts are directed?Three BucketsDaphne Koller (16:38):So first of all, maybe it's useful to kind of create the high level map and the simplest version I've heard is where you divide the process into three major buckets. One is what you think of as biology discovery, which is the discovery of new therapeutic hypotheses. Basically, if you modulate this target in this group of humans, you will end up affecting this clinical outcome. That's the first third. The middle third is, okay, well now we need to turn that hypothesis into an actual molecule that does that. So basically generating molecules. And then finally there's the enablement and acceleration of the clinical development process, which is the final third. Most companies in the AI space have really focused in on that middle third because it is well-defined, you know when you've succeeded if someone gives you a target and what's called a target product profile (TPP) at the end of whatever, two, three years, whether you've been able to create a molecule that achieves the appropriate properties of selectivity and solubility and all those other things. The first third is where a lot of the mistakes currently happen in drug discovery and development. Most drugs that go into the clinic don't fail because we didn't have the right molecule. I mean that happens, but it's not the most common failure mode. The most common failure mode is that the target was just a wrong target for this disease in this patient population.Daphne Koller (18:09):So the real focus of us, the core of who we are as a company is on that early third of let's make sure we're going after the right clinical hypotheses. Now with that, obviously we need to make molecules and some of those molecules we make in-house, and obviously we use machine learning to do that as well. And then the last third is we discover that if you have the right therapeutic hypothesis, which includes which is the right patient population, that can also accelerate and enable your clinical trials, so we end up doing some of that as well. But the core of what we believe is the failure mode of drug discovery and what it's going to take to move it to the next level is the articulation of therapeutic hypotheses that actually translate into clinical outcome. And so in order to do that, we've put together, to your point about convergence, two very distinct types of data.Daphne Koller (19:04):One is data that we print in our own internal data factory where we have this incredible set of capabilities that uses stem cells and CRISPR and microscopy and single cell measurements and spatial biology and all that to generate massive amounts of in-house data. And then because ultimately you care not about curing cells, you care about curing people, you also need to bring in the clinical data. And again, here also we look at multiple high content data modalities, imaging and omics, and of course human genetics, which is one of the few sources of ground truth for causality that is available in medicine and really bring all those different data modalities across these two different scales together to come up with what we believe are truly high quality therapeutic hypotheses that we then advance into the clinic.AlphaFold2, the ExemplarEric Topol (19:56):Yeah, no, I think that's an extraordinary approach. It's a bold, ambitious one, but at least it is getting to the root of what is needed. One of the things you mentioned of course, is the coming up with molecules, and I wanted to get your comments about the AlphaFold2 world and the ability to not just design proteins now of course that are not extant proteins, but it isn't just proteins, it could be antibodies, it could be peptides and small molecules. How much does that contribute to your perspective?Daphne Koller (20:37):So first of all, let me say that I consider the AlphaFold story across its incarnations to be one of the best examples of the hypothesis that we set out trying to achieve or trying to prove, which is if you feed a machine learning model enough data, it will learn to do amazing things. And the space of protein folding is one of those areas where there has been enough data in biology that is the sequence to structure mapping is something that over the years, because it's so consistent across different cells, across different species even, we have a lot of data of sequence to structure, which is what enabled AlphaFold to be successful. Now since then, of course, they've taken it to a whole new level. I think what we are currently able to do with protein-based therapeutics is entirely sort of a consequence of that line of development. Whether that same line of development is also going to unlock other therapeutic modalities such as small molecules where the amount of data is unfortunately much less abundant and often locked away in the bowels of big pharma companies that are not eager to share.Daphne Koller (21:57):I think that question remains. I have not yet seen that same level of performance in de novo design of small molecule therapeutics because of the data availability limitations. Now people have a lot of creative ideas about that. We use DNA encoded libraries as a way of generating data at scale for small molecules. Others have used other approaches including active learning and pre-training and all sorts of approaches like that. We're still waiting, I think for a truly convincing demonstration that you can get to that same level of de novo design in small molecules as you can in protein therapeutics. Now as to how that affects us, I'm so excited about this development because our focus, as I mentioned, is the discovery of novel therapeutic hypotheses. You then need to turn those therapeutic hypotheses into actual molecules that do the work. We know we're not going to be the expert in every single therapeutic modality from small molecules to macro cycles, to the proteins to mRNA, siRNA, there's so many of those that you need to have therapeutic modality experts in each of those modalities that can then as you discover a target that you want to modulate, you can basically go and ask what is the right partner to help turn this into an actual therapeutic intervention?Daphne Koller (23:28):And we've already had some conversations with some modality partners as we like to call them that help us take some of our hypotheses and turn it into molecules. They often are very hungry for new targets because they oftentimes kind of like, okay, here's the three or four or whatever, five low hanging fruits that our technology uniquely unlocks. But then once you get past those well validated targets like, okay, what's next? Am I just going to go read a bunch of papers and hope for the best? And so oftentimes they're looking for new hypotheses and we're looking for partners to make molecules. It's a great partnership.Can We Slow the Aging Process?Eric Topol (24:07):Oh yeah, no question about that. Now, we've seen in recent times some leaps in drugs that were worked on for decades, like the GLP-1s for obesity, which are having effects potentially well beyond obesity didn't require any AI, but just slogging away at it for decades. And you previously were at Calico, which is trying to deal with aging. Do you think that we're going to see drug interventions that are going to slow the aging process because of this unique time of this exponential point we are in where we're a computer and science and digital biology come together?Daphne Koller (24:52):So I think the GLP-1s are an incredible achievement. And I would point out, I know you said and incorrectly that it didn't use any AI, but they did actually use an understanding of human genetics. And I think human genetics and the genotype phenotype statistical associations that they revealed is in some ways the biological precursor to AI it is a way of leveraging very large amounts of data, admittedly using simpler statistical tools, but still to discover in a data-driven way, novel therapeutic hypothesis. So I consider the work that we do to be a progeny of the kind of work that statistical geneticists have done. And of course a lot of heavy lifting needed to be done after that in order to make a drug that actually worked and kudos to the leaders in that space. In terms of the modulation of aging, I mean aging is a process of decline over time, and the rate of that decline is definitely something that is modifiable.Daphne Koller (26:07):And we all know that external factors such as lifestyle, diet, exercise, even exposure to sun or smoking, accelerates the aging process. And you could easily imagine, as we've seen in the GLP-1s that a therapeutic intervention can change that trajectory. So will we be able to using therapeutic interventions, increase health span so that we live healthy longer? I think the answer to that is undoubtedly, yes. And we've seen that consistently with therapeutic interventions, not even just the GLP-1s, but going backwards, I mean even statins and earlier things. Will we be able to increase the maximum life span so that people habitually live past 120, 150? I don't know. I don't know that anybody knows the answer to that question. I personally would be quite happy with increasing my health span so that at the age of 80, I'm still able to actively go hiking and scuba diving at 90 and 100 and that would be a pretty good place to start.Eric Topol (27:25):Well, I'm with you on that, but I just want to ask though, because the drugs we have today that are highly effective, I mean statins is a good example. They work at a particular level of the body. They don't have across the board modulation of effect. And I guess what I was asking is, do you foresee we will have some way to do that across all systems? I mean, that is getting to, now that we have so many different ways to intervene on the process, is there a way that you envision in the future that we'll be able to here, I'm not talking about in expanding lifespan, I'm talking about promoting health, whether it's the immune system or whether it's through mitochondria and mTOR, caloric, I mean all these different things you think that's conceivable or is that just, I mean companies like Calico and others have been chasing this. What do you think?Daphne Koller (28:30):Again, I think it's a thing that is hard to predict. I mean, we know that different organ systems age at different rates, and is there a single bio even in a single individual, and it's been well established that you can test brain age versus muscle health versus cardiovascular, and they can be quite different in the same individual, so is there a single hub? No, that governs all forms of aging. I don't know if that's true. I think it's oftentimes different. We know protein folding has an effect, you know DNA damage has an effect. That's why our skin ages because it's exposed to sun. Is there going to be a single switch that reverts it all back? Certainly some companies are pursuing that single bullet approach. I personally would probably say that based on the biology that I've seen, there's at least as much potential in trying to find ways to slow the decline in a way that specific to say as we discussed the immune system or correcting protein, misfolding dysfunction or things like that. And I'm not dismissing there is a single magic switch, but let's just say I think we should be exploring multiple alternatives.Eric Topol (29:58):Yeah, no, I like your reasoning. I think it's actually like everything else you said here. It makes a lot of sense. The logic is hard to argue with. Well, I think what you're doing there at insitro is remarkable and it seems to be quite distinct from other strategies, and that's not at all surprising knowing your background and your aspiration.Daphne Koller (30:27):Never like to follow the crowd. It's boring.Eric Topol (30:30):Right, and I do know you left an aging directed company effort at Calico to do what you're doing. So that must have been an opening for you that you saw was much more diverse perhaps, or maybe I'm mistaken that Calico is not really age specific in its goals.Daphne Koller (30:49):So what inspired me to go found insitro was the realization that we are making medicines today in a way that is not that different from the way in which we were making medicines 20 or 30 years ago in terms of the process by which we go from a, here's what I want to work on to here's a drug is a very much an artisanal one-off each one of them is a snowflake. There is very little commonality and sharing of insights and infrastructure across those efforts except in relatively limited tool-based ways. And I wanted to change that. I wanted to take the tools of engineering and data and machine learning and build a very different approach of going from a problem definition to a therapeutic intervention. And it didn't make sense to build that within a company that's focused on any single biology, not just aging because it is such a broad-based foundation.Daphne Koller (31:58):And I will tell you that I think we are on the path to building the thing that I set out to build. And as one example of that, I will use the work that we've recently done in metabolic disease where based on the foundations that we've built using both the clinical machine learning work and the cellular machine learning work, we were able to go from a problem articulation of this is the indication that we want to work on to a proof of concept in a translatable animal model in one year. That is pretty unusual. Admittedly, this is with an SiRNA tool compound. Nice thing about things that are liver directed is that it's not that difficult of a path to go from an SiRNA tool compound to an actual SiRNA drug. And so hopefully that's a fairly linear journey from there even, which is great.Daphne Koller (32:51):But the fact that we were able to go from problem articulation to a proof of concept in a translatable animal model in one year, that is unusual. And we're starting to see that now across our other therapeutic areas. It takes a long time to build a platform because you're basically building a foundation. It's like, okay, where's the fruit of all of that? I mean, you're building and building and building and nothing comes out for a while because you're building so much of the infrastructure. But once you've built it, you turn the crank and stuff starts to come out, you turn the crank again, and it works faster and better than the previous time. And so the essence of what we've built and what has turned into the tagline for the company is what we call pipeline through platform, which is we're building a pipeline of therapeutic interventions that comes off of a platform. And that's rare in biopharma, the only platform companies that really have emerged by and larger therapeutic modality platforms, things like Moderna and Alnylam, which have gotten really good at a particular modality and that's awesome. We're building a discovery platform and that is a fairly unusual thing.Eric Topol (34:02):Right. Well, I have no doubt you'll be discovering a lot of important things. That one sounds like it could be a big impact on NASH.Daphne Koller (34:14):Yeah, we hope so.Eric Topol (34:14):A big unmet need that's not going to be fixed by what we have today. So Daphne, it's really a joy to talk with you and palpable enthusiasm for where the field is going as one of its real leaders and we'll be cheering for you. I hope we'll reconnect in the times ahead to get another progress report because you're definitely rocking it there and you've got a lot of great ideas for how to change the life science medical world of the future.Daphne Koller (34:48):Thank you so much. It's a pleasure to meet you, and it's a long and difficult journey, but I think we're on the right path, so looking forward to seeing that all that pan out.Eric Topol (34:58):You made a compelling case in a short visit, so thank you.Daphne Koller (35:02):Thank you so much.Thanks for your subscription and listening/reading these posts.All content on Ground Truths—newsletter analyses and podcasts—is free.Voluntary paid subscriptions all go to support Scripps Research. Get full access to Ground Truths at erictopol.substack.com/subscribe

Diabetes Dialogue: Therapeutics, Technology, & Real-World Perspectives
Baricitinib & the Potential Disease-Modifying Therapies in Type 1 Diabetes

Diabetes Dialogue: Therapeutics, Technology, & Real-World Perspectives

Play Episode Listen Later Jan 3, 2024 18:18


Hosts discuss a recent study on baricitinib in type 1 diabetes, how these results compare to other data in this arena, and what all of these studies mean for future of type 1 diabetes management. Episode Highlights 00:05 Intro 01:20 Baricitinib Overview 02:30 BANDIT Trial Design 03:30 Trial Results 05:40 Delaying Type 1 Diabetes 14:45 Need for Screening 18:00 Outro

This Week in Virology
TWiV 1070: Clinical update with Dr. Daniel Griffin

This Week in Virology

Play Episode Listen Later Dec 16, 2023 40:18


In his weekly clinical update, Dr. Griffin discusses monkeypox and chickenpox co-infection in southern Nigeria, vaccine effectiveness against influenza A, SARS-CoV-2 neutralizing antibody titers in maternal blood, umbilical cord blood, and breast milk, COVID-19 rapid antigen tests with self-collected vs health care worker–collected nasal and throat swab specimens, four methods for monitoring SARS-CoV-2 and Influenza A virus activity in schools, efficacy and safety of Baricitinib for the treatment of hospitalized adults with COVID-19, a synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong, consistent absence of cerebrospinal fluid biomarker abnormalities in patients with neurocognitive post-COVID complications, and risk of new-onset long COVID following reinfection with SARS-CoV-2. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Monkeypox and chickenpox co-infection in southern Nigeria (JID) Vaccine effectiveness against influenza A (CID) SARS-CoV-2 neutralizing antibody titers in maternal blood, umbilical cord blood, and breast milk (JOP) COVID-19 rapid antigen tests with self-collected vs health care worker–collected nasal and throat swab specimens (JAMA) Four methods for monitoring SARS-CoV-2 and influenza A virus activity in schools (JAMA) Efficacy and safety of Baricitinib for the treatment of hospitalized adults with COVID-19 (EJMR) A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (The Lancet) Consistent absence of cerebrospinal fluid biomarker abnormalities in patients with neurocognitive post-COVID complications (JID) Risk of new-onset long COVID following reinfection with SARS-CoV-2 (OFID) Contribute to our MicrobeTV fundraiser at PWB Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

Evidence Based Hair
Season 6 Episode 4 (Baricitinib for CCCA, LED laser therapy for CCCA)

Evidence Based Hair

Play Episode Listen Later Nov 13, 2023 22:37


STUDIES REFERENCED IN THIS EPISODE: Workman K and Kindred C (starts at 2:10). Hair regrowth in a patient with central centrifugal cicatricial alopecia after a 2-month trial of baricitinib. JAAD Case Rep. 2023 Jul 28:39:109-111.   Cook M et al (starts at 12:07). Use of low-level light therapy in management of central centrifugal cicatricial alopecia: A case series of four patients. Photodermatol Photoimmunol Photomed. 2023 Aug 23.  

Evidence Based Hair
Season 6 Episode 1 (Baricitinib Response Timing, Real World Study of Baricitinib)

Evidence Based Hair

Play Episode Listen Later Oct 24, 2023 41:21


Studies Referenced in This Episode: Season 6 Episode 1 King B et al (starts at 4:07). When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials. Br J Dermatol. 2023 Sep 14:ljad253.   Gargiulo L et al (starts at 30:22). Effectiveness and safety of baricitinib in patients with severe alopecia areata: a 36-week multicenter real-world experience. J Dermatolog Treat. 2023 Dec;34(1):2268764.     Preview of Studies for New Week: Season 6 Episode 2   Krauss A. Why all randomised controlled trials produce biased results. Ann Med. 2018 Jun;50(4):312-322.   Carlisle JB. False individual patient data and zombie randomised controlled trials submitted to Anaesthesia. Anaesthesia. 2021 Apr;76(4):472-479.   Van Noorden R. Medicine is plagued by untrustworthy clinical trials. How many studies are faked or flawed? Nature. 2023 Jul;619(7970):454-458. Listen at https://youtu.be/_QLvzCr6nz4?feature=shared

Cytokine Signalling Forum
CSF Author Interview: Professor Martin Bergman, 2023

Cytokine Signalling Forum

Play Episode Listen Later Oct 11, 2023 27:25


Professor Peter Nash from the Griffith University in Brisbane, is joined by Professor Martin Bergman, a Clinical Associate Professor of Medicine at the Drexel University College of Medicine in Philadelphia, to discuss his recent paper ‘One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.' Detailed summary slides of this paper and many more publications, are free to view and download in the publications section at cytokinesignalling.com.

Dermasphere - The Dermatology Podcast
115. Senior Send-Off! - Baricitinib for LP (Angie Hwang) - EB care (Morgan Dykman) - Isotretinoin & IUDs (Gui Kuceki) - Visual racism (Michael Birdsall) - Rural & underserved derm (Eleonora Marcacci)

Dermasphere - The Dermatology Podcast

Play Episode Listen Later Oct 2, 2023 51:13


Senior Send-Off! - Baricitinib for LP (with Angie Hwang) - EB patients: peds -> adult care (with Morgan Dykman) - Isotretinoin and IUDs (with Gui Kuceki) - Addressing visual racism in medical school (with Michael Birdsall) - Rural & underserved derm health disparities (with Eleonora Marcacci) - Check out our video content on YouTube: ⁠Dermasphere Podcast - YouTube⁠ - and VuMedi!: https://www.vumedi.com/channel/dermasphere/ The University of Utah's Dermatology ECHO: ⁠⁠https://physicians.utah.edu/echo/dermatology-primarycare - ⁠⁠Connect with us! - Web: ⁠https://dermaspherepodcast.com/⁠ - Twitter: @DermaspherePC - Instagram: dermaspherepodcast - Facebook: https://www.facebook.com/DermaspherePodcast/ - Check out Luke and Michelle's other podcast, SkinCast! ⁠https://healthcare.utah.edu/dermatology/skincast/⁠ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at: - ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge) - ⁠https://www.levelex.com/games/top-derm⁠ (A free dermatology game to learn more dermatology!)

Dermasphere - The Dermatology Podcast
113. Best of: Recent Drug Approvals (vol. 1)! - Upadacitinib for AD - Tralokinumab for AD - Baricitinib for AA - Deucravacitinib for psoriasis - Spinosad for scabies

Dermasphere - The Dermatology Podcast

Play Episode Listen Later Sep 4, 2023 70:24


Best of: Recent Drug Approvals (vol. 1) - Upadacitinib for AD (from episode 59) - Tralokinumab for AD (from episode 73) - Baricitinib for AA (from episode 87) - Deucravacitinib for psoriasis (from episode 93) - Spinosad for scabies (from episode 103) Check out our video content on YouTube: Dermasphere Podcast - YouTube - and VuMedi!: https://www.vumedi.com/channel/dermasphere/ The University of Utah's Dermatology ECHO: ⁠⁠https://physicians.utah.edu/echo/dermatology-primarycare - ⁠⁠Connect with us! - Web: ⁠https://dermaspherepodcast.com/⁠ - Twitter: @DermaspherePC - Instagram: dermaspherepodcast - Facebook: https://www.facebook.com/DermaspherePodcast/ - Check out Luke and Michelle's other podcast, SkinCast! ⁠https://healthcare.utah.edu/dermatology/skincast/⁠ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at: - ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge) - ⁠https://www.levelex.com/games/top-derm⁠ (A free dermatology game to learn more dermatology!)

Eczema Out Loud
Eczema Answered: "I was prescribed baricitinib and dupilumab at the same time. Are there studies or information about being prescribed multiple medications?” - Dr. Peter Lio

Eczema Out Loud

Play Episode Listen Later Aug 28, 2023 4:18


From the National Eczema Association, this is Eczema Answered, where world-class experts answer your questions about eczema. Eczema Answered is brought to you by ⁠EczemaWise⁠. On this episode, Dr. Peter Lio answers the question "I was prescribed baricitinib and dupilumab at the same time. Are there studies or information about being prescribed multiple medications?" Do you have a question about eczema that you want answered? Email us at ⁠podcast@nationaleczema.org⁠. ⁠National Eczema Association (NEA)⁠ The National Eczema Association is the driving force for an eczema community fueled by knowledge, strengthened through collective action and propelled by the promise for a better future.

The Counter Culture Mom Show with Tina Griffin Podcast
Deadly Drug Remdesivir Given Without Consent Nearly Kills Mother of Two - Greta Crawford

The Counter Culture Mom Show with Tina Griffin Podcast

Play Episode Listen Later Aug 1, 2023 27:09


TAKEAWAYSGreta's reaction to Remdesivir was extremely painful and caused her kidneys to begin shutting down in a matter of minutesGreta also illegally received the drug Baricitinib - she didn't know this until she saw her paperwork after she was released from the hospitalNO doctor gave her an opportunity to give informed consent which is completely illegalTexas State Senator Bob Hall has diligently worked to protect the Constitutional rights of Texans in his state

TAKEN On Demand
Ep441 Deadly Drug Remdesivir Given Without Consent Nearly Kills Mother of Two - Greta Crawford

TAKEN On Demand

Play Episode Listen Later Aug 1, 2023 26:32


During the Covid pandemic, Greta Crawford was admitted to the hospital with Covid-19 and pneumonia, but the most grueling struggle to reclaim her health came when she was given Remdesivir, an experimental drug that she says nearly took her life. While hospitalized, Greta was repeatedly harassed and pressured to receive the Covid jab, which she refused. In addition, Greta was not given the chance to give informed consent before she was administered Remdesivir by the hospital. Today, Greta is the founder of Protocol Kills, a website dedicated to providing incredible, in-depth resources for those who have experienced or who are experiencing abuse in a hostile hospital environment or lost loved ones who were killed in the hospital. TAKEAWAYS Greta's reaction to Remdesivir was extremely painful and caused her kidneys to begin shutting down in a matter of minutes Greta also illegally received the drug Baricitinib - she didn't know this until she saw her paperwork after she was released from the hospital NO doctor gave her an opportunity to give informed consent which is completely illegal Texas State Senator Bob Hall has diligently worked to protect the Constitutional rights of Texans in his state

Rheumnow Podcast
EULAR 2023 Lupus Highlights

Rheumnow Podcast

Play Episode Listen Later Jun 20, 2023 51:57


Effect of Ancestry on Therapeutic Outcomes in SLE  Dr. Yuz Yusof   https://youtu.be/QqthOjDxePE De Novo Renal Nephritis Flares During Belimumab Trials  Drs. Yuz Yusof and Iaonnis Parodis   https://youtu.be/BYORFgYOdcI Update on CAR T Cell Therapy in SLE & Autoimmune Diseases  Dr. Peter Nash   https://youtu.be/KnHRgaEcqGc  We should put the CART before the T in SLE!  Dr. Janet Pope  https://youtu.be/carHG-5mFmQ Changes in the Causes and Predictors of Lupus Mortality in Spain  Dr. Bella Mehta  https://youtu.be/Yzm4twLAWfI JAK/TYK Inhibitors in SLE  Dr. Janet Pope   https://youtu.be/3wy5pOpbyPY Upadacitinib in SLE  Dr. Peter Nash    https://youtu.be/eqnXUrgpWdM SLE Trial: Dual BTK JAK Blockade compared Upadacitinib Monotherapy Dr. Yuz Yusof   https://youtu.be/yTmQTA7yU8U Efficacy and Safety of Baricitinib in Lupus Nephritis  Dr. Yuz Yusof  https://youtu.be/DgTIdAlhK_s Baricitinib in Lupus Nephritis  Dr. Peter Nash  https://youtu.be/qyhMHyYKuTU

CCO Infectious Disease Podcast
COVID-19 Update: Independent Conference Coverage of ECCMID 2023

CCO Infectious Disease Podcast

Play Episode Listen Later May 5, 2023 36:36


In this episode, Patrick W. G. Mallon, MB, BCh, PhD, FRACP, FRCPI, discusses new data on COVID-19 presented at ECCMID 2023, including:Treatment in special populationsREDPINE: remdesivir in people with renal impairment hospitalized for COVID-19 pneumoniaRemdesivir and readmission for COVID-19 in immunocompromised patientsMolnupiravir vs nirmatrelvir plus ritonavir for COVID-19 with hematologic malignancyManagement of patients with severe diseaseRECOVERY: higher-dose vs standard-dose corticosteroids for hospitalized patients with COVID-19Real-world study of tocilizumab vs baricitinib for severe COVID-19Novel antiviralsEnsitrelvirBemnifosbuvir Novel vaccinesNB2155AZD2816/AZD1222qNIV/CoV2373GRT-R910NVX-CoV2373 in people with HIVFaculty:  Patrick W. G. Mallon, MB, BCh, PhD, FRACP, FRCPIProfessor of Microbial DiseasesCentre for Experimental Pathogen Host ResearchUniversity College DublinDublin, IrelandContent based on an online CME/CE program supported by independent educational grants from Gilead Sciences, Inc. and Novavax.  Link to full program: bit.ly/3niXGJ6Link to downloadable slides: bit.ly/3LUFejG

Evidence Based Hair
Season 4, Episode7 (Tinea with baricitinib, ADHD and AA, Upadacitinib for AA, Baricitinib 52 week data, micro needling for MPHL)

Evidence Based Hair

Play Episode Listen Later Apr 5, 2023 62:02


PCE
Evidence and Guidelines for COVID-19 In-Hospital Management—Expert Answers to Frequently Asked Questions on Supportive Care and Escalation of Therapy

PCE

Play Episode Listen Later Mar 27, 2023 20:04


In this episode, Vikramjit Mukherjee, MD, and Cameron Smith, MPAS, PA-C, answer audience questions on how best to care for hospitalized patients with COVID-19 from a live, virtual question and answer webinar. This episode includes expert insights on:Supportive care management such as oxygen support, glycemic control, and anticoagulationEscalation of therapy in patients with worsening oxygen requirementsUse of remdesivir in patients with renal dysfunctionBrief commentary on long COVIDPresenters:Vikramjit Mukherjee, MDAssistant Professor  Division of Pulmonary, Critical Care, & Sleep Medicine  New York University School of Medicine  DirectorMedical Intensive Care UnitBellevue HospitalNew YorkCameron Smith MPAS, PA-CLead Advanced Practice ProviderMedical Intensive Care UnitBellevue HospitalNew York Health and Hospitals  New York, New YorkContent based on an online program supported by an independent educational grant from Gilead Sciences, Inc.bit.ly/3z52c00

The Lupus Academy
Lupus: Experts Review 2022

The Lupus Academy

Play Episode Listen Later Feb 15, 2023 48:47


In this episode our host, Dr Raquel Faria, is joined by Professors Ricard Cervera and Zahir Amoura who will be providing expert insights from the key lupus research in 2022.  For the full written report '2022 Year in Review' please refer to our online library: https://www.lupus-academy.org/library/congress-reports Disclaimer: ‘During Lupus Academy podcast episodes, participants may refer to off label use of medicines for patients with lupus. Lupus Academy does not make any recommendations about using a medicine outside the terms of its approved licence for use.' References for this episode: Bruce IN, Furie RA, Morand EF, et al. Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials. Ann Rheum Dis. 2022;81(7):962-969. Dörner T, van Vollenhoven RF, Doria A, et al. Baricitinib decreases anti-dsDNA in patients with systemic lupus erythematosus: results from a phase II double-blind, randomized, placebo-controlled trial. Arthritis Res Ther. 2022;24(1):112. Furie RA, Aroca G, Cascino MD, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(1):100-107. Furie RA, Hough DR, Gaudy A, et al. Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study. Lupus Sci Med. 2022;9(1). Furie RA, van Vollenhoven RF, Kalunian K, Navarra S, Romero-Diaz J, Werth VP, Huang X, Clark G, Carroll H, Meyers A, Musselli C, Barbey C, Franchimont N; LILAC Trial Investigators. Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus. N Engl J Med. 2022 Sep 8;387(10):894-904. Ginzler E, Guedes Barbosa LS, D'Cruz D, et al. Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022;74(1):112-123. Jayne D, Rovin B, Mysler EF, et al. Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis. 2022;81(4):496-506. Sun L, Shen Q, Gong Y, Li Y, Lv Q, Liu H, Zhao F, Yu H, Qiu L, Li X, He X, Chen Y, Xu Z, Xu H. Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before-after trial. Lupus. 2022 Jul;31(8):998-1006. van Vollenhoven RF, Hahn BH, Tsokos GC, et al. Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study. J Rheumatol. 2022;49(4):380-387.

CCO Infectious Disease Podcast
Key COVID-19 Studies Influencing My Practice Following IDWeek 2022—Audio Recap

CCO Infectious Disease Podcast

Play Episode Listen Later Nov 18, 2022 37:17


In this episode, Princy N. Kumar, MD, and Paul E. Sax, MD, discuss new COVID-19 data from IDWeek 2022, including:COVID-19 vaccines, including omicron BA.1 bivalent boosterRisk factors for breakthrough COVID-19 infectionsCOVID-19 diagnostics, including digital droplet PCRCOVID-19 therapeutics, including:Nirmatrelvir plus ritonavirTixagevimab plus cilgavimabBaricitinibTocilizumabInhaled interferon β-1aCOVID-19 therapeutics and outcomes in patients with immunocompromiseLong COVIDPresenters:Princy N. Kumar, MD, FIDSA, MACPProfessor of Medicine and MicrobiologyChief, Division of Infectious Diseases and Travel MedicineSenior Associate Dean of StudentsGeorgetown University School of MedicineWashington, DCPaul E. Sax, MDClinical DirectorHIV Program and Division of Infectious DiseasesBrigham and Women's HospitalProfessor of MedicineHarvard Medical SchoolBoston, MassachusettsFollow along with the downloadable slideset at:http://bit.ly/3gkJI67Link to full program:http://bit.ly/3TSVthM

This Week in Virology
TWiV 949: Clinical update with Dr. Daniel Griffin

This Week in Virology

Play Episode Listen Later Oct 29, 2022 45:09


In his weekly clinical update Dr. Griffin discusses progress toward poliomyelitis eradication in Pakistan, polio by the numbers , influenza and COVID-19 vaccination coverage among health care personnel, phase 1/2a safety and immunogenicity of an adenovirus 26 vector RSV vaccine encoding prefusion F in adults 18–50 years and RSV seropositive children 12–24 months, receipt of first and second doses of JYNNEOS vaccine for prevention of Monkeypox, distinguishing SARS-CoV-2 persistence and reinfection, Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages, association between regular physical activity and the protective effect of vaccination against SARS-CoV-2 in a South African case, COVID-19 outcomes in solid organ transplant recipients who received Tixagevimab-cilgavimab Prophylaxis and/or Bebtelovimab treatment, Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralizing antibodies, and Tocilizumab versus Baricitinib in hospitalized patients with severe COVID-19. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Progress toward Poliomyelitis eradication (CDC) Polio by the numbers (JID) Influenza & COVID-19 vaccination coverage among health care personnel (CDC) Phase 1/2a Safety & Immunogenicity of an adenovirus RSV Vaccine (JID) Receipt of first & second doses of JYNNEOS vaccine  (CDC) Distinguishing SARS-CoV-2 persistence and reinfection (CID) Remdesivir fact sheet for providers (Veklury) Bebtelovimab fact sheet for providers (FDA) Novavax triggers potent neutralization of Omicron sub-lineages (bioRxiV) Association between physical activity & vaccination protective effect (BMJ) PAXLOVID patient eligibility screening checklist (FDA) COVID-19 outcomes in solid organ transplant recipients who received monoclonal antibodies (Transplantation) Omicron BA.2.75.2 exhibits escape from neutralizing antibodies (bioRxiV) Tocilizumab vs. Baricitinib in hospitalized patients with severe COVID-19 (CMI) Dr. Griffin's treatment guide (pdf) Contribute to Floating Doctors fundraiser at PWB Letters read on TWiV 949 Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

The St.Emlyn's Podcast
Ep 204 - August 2022 Round Up

The St.Emlyn's Podcast

Play Episode Listen Later Oct 8, 2022 19:09


This is our round up of all that happened on the St Emlyn's blog in August 2022 (yes - we know it's a bit late, but there's been a lot going on!). Listen to Simon and Iain discuss the latest therapies in COVID, particularly Baricitinib, calcium in trauma and how we find balance in our work-life blend. Please do like and subscribe to the podcast and tell your friends and colleagues. We've lots of exciting stuff coming your way over the next few months.

Dermasphere - The Dermatology Podcast
87. Flow cytometry with Dr. Vermeer - Ruxolitinib cream for vitiligo - Baricitinib for AA - Roflumilast for psoriasis - Tapinarof for psoriasis

Dermasphere - The Dermatology Podcast

Play Episode Listen Later Sep 5, 2022 61:56


Flow cytometry with Dr. Vermeer - Ruxolitinib cream for vitiligo - Baricitinib for AA - Roflumilast for psoriasis - Tapinarof for psoriasis - Connect with Dr. Vermeer! https://www.universiteitleiden.nl/en/staffmembers/maarten-vermeer#tab-1 Connect with us! Web: https://dermaspherepodcast.com/ Twitter: @DermaspherePC Instagram: dermaspherepodcast Facebook: https://www.facebook.com/DermaspherePodcast/ Check out Luke and Michelle's other podcast, SkinCast! https://healthcare.utah.edu/dermatology/skincast/ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at: Kikoxp.com (a social platform for doctors to share knowledge) https://www.levelex.com/games/top-derm (A free dermatology game to learn more dermatology!)

BaladoCritique – club de lecture médical
BC 050 – Efficacité du baricitinib chez les sujets hospitalisés pour la COVID-19 (étude RECOVERY- volet Baricitinib)

BaladoCritique – club de lecture médical

Play Episode Listen Later Aug 29, 2022 40:15


Dans cette 50e baladodiffusion, le Dr Luc Lanthier discute de traitement de la COVID-19 avec le baricitinib, en plus de réviser la littérature médicale de juin et juillet 2022.   Quiz clinique (2 min 52), étude principale (3 min 41), critique (20 min 55), autres articles (30 min 54), réponse au quiz clinique (36 min … Continuer la lecture de « BC 050 – Efficacité du baricitinib chez les sujets hospitalisés pour la COVID-19 (étude RECOVERY- volet Baricitinib) »

This Week in Virology
TWiV 924: TWiV clinical update with Dr. Daniel Griffin

This Week in Virology

Play Episode Listen Later Aug 6, 2022 46:24


In his weekly clinical update Dr. Griffin discusses Tecovirimat for treatment of monkeypox, the safety and acceptance of vaccination after multisystem inflammatory syndrome, variants in solid organ transplant recipients, masks for prevention of respiratory virus infections, pre-exposure prophylaxis with Evusheld, the association between Evusheld administration and infection,  if repeat administration of casirivimab and imdevimab is well-tolerated, viral and symptom rebound in untreated infection, extended Remdesivir infusion for persistent infection, Baricitinib in patients admitted with infection, and cognitive impairment 13 months after hospitalization. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Armchair Expert with Malcolm Gladwell Tecovirimat for treatment of monkeypox (OFID) Safety and acceptance of vaccination after MIS (JPID) Is variant less virulent in solid organ transplant recipients (Transplant Infectious Disease) Masks for prevention of respiratory virus infections (Annals of Internal Medicine) Pre-exposure prophylaxis with Evusheld (CMI) Association between Evusheld administration and infection (CID) Repeat administration of casirivimab and imdevimab well-tolerated (ISID) PAXLOVID patient eligibility screening checklist (FDA) Remdesivir fact sheet for providers (Veklury)  Bebtelovimab fact sheet for providers (FDA) Viral and symptom rebound in untreated infection (medRxiv) Extended Remdesivir infusion for persistent infection (OFID) Baricitinib in patients admitted with infection (The Lancet) Cognitive Impairment 13 months after hospitalization (OFID) Contribute to Floating Doctors fundraiser at PWB Dr. Griffin's treatment guide (pdf) Letters read on TWiV 924 Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

Ask Doctor Dawn
Effects of stress on health, protein folding and good and bad chemicals are main themes

Ask Doctor Dawn

Play Episode Listen Later Jul 29, 2022 51:48


KSQD 6-29-2022 (rebroadcast): The roll of stress in chronic hives -- how to detect high histamine levels; The drug Baricitinib for rheumatoid arthritis also works for the hair loss condition alopecia areata; Artificial intelligence general solution to protein folding prediction from just DNA sequence; Using psilocybin to treat depression; How to repel ticks when in the woods; Many body and hair products have deleterious chemicals, especially bad for fetal development; Question about ketamine vs psilocybin use for depression; Pre-adolescents exposed to air pollution show deleterious changes in brain activity measured by MRI; The effect of stress on adolescent brain functions; Therapies to calm the spinal cord to relieve muscle spasms; Using interfering RNA to lower production of the unhealthy Lipoprotein (a)

The Fact Hunter
Dr. Bryan Ardis "Dose of Reality"

The Fact Hunter

Play Episode Listen Later Jul 19, 2022 106:14


My guest appearance with Daniel from "Ba'alBusters" show with Dr. Bryan Ardis. Dr. Ardis gives another tremendous interview as he exposes that hospitals are giving people "Baricitinib" to those individuals who turn down remdesivir. He gives all the alarming side effects. He also breaks down what steps you can take if you are already vaccinated. This was another blockbuster show. Daniels JoshWhoTV channel is here: https://www.joshwhotv.com/channel/BaalBustersHe also has a Roku channel under the same name!Dr. Bryan Ardis' website is: https://thedrardisshow.comFor all things Fact Hunter, go to www.thefacthunter.comemails: thefacthunter@mail.comNever stop searching for the truth.

Ba'al Busters Broadcast
BREAKING NEW Info: Dr Ardis on Olumiant aka Baricitinib

Ba'al Busters Broadcast

Play Episode Listen Later Jul 18, 2022 106:53


Ask Doctor Dawn
Effects of stress on health, protein folding and good and bad chemicals are main themes

Ask Doctor Dawn

Play Episode Listen Later Jul 4, 2022 51:47


KSQD 6-29-2022: The roll of stress in chronic hives -- how to detect high histamine levels; The drug Baricitinib for rheumatoid arthritis also works for the hair loss condition alopecia areata; Artificial intelligence general solution to protein folding prediction from just DNA sequence; Using psilocybin to treat depression; How to repel ticks when in the woods; Many body and hair products have deleterious chemicals, especially bad for fetal development; Question about ketamine vs psilocybin use for depression; Pre-adolescents exposed to air pollution show deleterious changes in brain activity measured by MRI; The effect of stress on adolescent brain functions; Therapies to calm the spinal cord to relieve muscle spasms; Using interfering RNA to lower production of the unhealthy Lipoprotein (a)

Xtalks Life Science Podcast
Eli Lilly's Olumiant FDA Approved for Alopecia + Alnylam's RNAi Drug Amvuttra Approved for Rare Protein Disorder

Xtalks Life Science Podcast

Play Episode Listen Later Jun 22, 2022 23:48


In this episode, Ayesha and the team talked about the FDA approval of Eli Lilly's JAK inhibitor Olumiant for the treatment of alopecia areata, also commonly just known as alopecia. The drug has become the first approved systemic treatment for the autoimmune disorder that causes patchy hair loss. Hear about how alopecia has received mainstream recognition because of a recent infamous Hollywood incident and the importance of raising awareness about rare diseases like alopecia.Ayesha also discussed the FDA approval of Alnylam's RNAi therapeutic Amvuttra for the treatment of polyneuropathy associated with a rare protein disorder called hereditary transthyretin-mediated (ATTR) amyloidosis. Hear about how the drug is also being evaluated for another type of (ATTR cardiomyopathy) and the other big players in the ATTR space including Pfizer and AstraZeneca.Read the full articles here: Eli Lilly's Olumiant Wins FDA Approval as First Systemic Treatment for Alopecia AreataAmvuttra RNAi Therapeutic Wins FDA Approval for Rare Genetic Protein DisorderFor more life science and medical device content, visit the Xtalks Vitals homepage.Follow Us on Social MediaTwitter: @Xtalks Instagram: @Xtalks Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

DocTalk Podcast
Dermatologists Discuss the FDA Approval of Baricitinib for Alopecia Areata

DocTalk Podcast

Play Episode Listen Later Jun 16, 2022 22:38


On June 13, the US Food and Drug Administration (FDA) approved oral baricitinib (Olumiant) tablets for the treatment of severe alopecia areata in adults, which marked the first approval of a systemic treatment for the disorder. The approval has excited patients and providers alike who struggled for decades to treat severe cases of this autoimmune disorder. For this episode of DocTalk, several key opinion leaders in the dermatology field sound off on the implications of this decision, as well as the versatility of Janus kinase (JAK) inhibitors, and how this approval will aid providers in redefining alopecia areata as an autoimmune disorder rather than simply a cosmetic condition, which will help more patients receive proper care. Joining us on the podcast and in written form are the following dermatologists: Brett King, MD, PhD, Yale School of Medicine, New Haven Lisa Arkin, MD, member of the Society for Pediatric Dermatology, University of Wisconsin School of Medicine & Public Health / American Family Children's Hospital. Karan Lal, DO, MS, FAAD, Schweiger Dermatology Group and member of The Society for Pediatric Dermatology Brittany Craiglow, MD, Yale School of Medicine, New Haven

DocTalk Podcast
Dermatologists Discuss the FDA Approval of Baricitinib for Alopecia Areata

DocTalk Podcast

Play Episode Listen Later Jun 16, 2022 22:09


 On June 13, the US Food and Drug Administration (FDA) approved oral baricitinib (Olumiant) tablets for the treatment of severe alopecia areata in adults, which marked the first approval of a systemic treatment for the disorder. The approval has excited patients and providers alike who struggled for decades to treat severe cases of this autoimmune disorder. For this episode of DocTalk, several key opinion leaders in the dermatology field sound off on the implications of this decision, as well as the versatility of Janus kinase (JAK) inhibitors, and how this approval will aid providers in redefining alopecia areata as an autoimmune disorder rather than simply a cosmetic condition, which will help more patients receive proper care. Joining us on the podcast, and in written form, are the following dermatologists: ·      Brett King, MD, PhD, Yale School of Medicine, New Haven ·      Lisa Arkin, MD, member of the Society for Pediatric Dermatology, University of Wisconsin School of Medicine & Public Health / American Family Children's Hospital. ·      Karan Lal, DO, MS, FAAD, Schweiger Dermatology Group and member of The Society for Pediatric Dermatology  ·      Brittany Craiglow, MD, Yale School of Medicine, New Haven

This Week in Virology
TWiV 897: COVID-19 clinical update #113 with Dr. Daniel Griffin

This Week in Virology

Play Episode Listen Later May 7, 2022 47:48


In COVID-19 clinical update #113, Dr. Griffin discusses tocilizumab use in hospitalized Patients, IL-6 inhibitors and mortality, Baricitinib in hospitalized patients, post-infection neurological sequelae, comparative effectiveness of Pfizer and Moderna vaccines, phase 2/3 study of Paxlovid, infection relapse following Paxlovid, pre-hospital administration of Remdesivir, and hospitalization with different variants. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Timing of Tocilizumab Use in Hospitalized Patients (NIH) Interleukin-6 inhibitors reduce mortality (European Journal of Internal Medicine)  Treatment Effect of Baricitinib on Hospitalized Patients (IDSA) Post Infection Neurological Sequelae (Res Square) Comparative Effectiveness of Pfizer and Moderna Vaccines (Nature Commun) Results from Phase 2/3 Study of Paxlovid (Pfizer)  Infection Relapse Following Suppression by Paxlovid (Res Square) Update on Paxlovid Usage (FDA) Availability and Use of Treatments in Outpatients (CDC) Pre-Hospital Administration of Remdesivir (IDSA) Remdesivir and three other drugs for Hospitalized Patients (Lancet) Guidelines on Usage of Anticoagulants (Am Soc Hematol) Different Variants Hospitalization and Morality (Res Square) Contribute to FIMRIC fundraiser at PWB Dr. Griffin's treatment guide (pdf) Letters read on TWiV 897 Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

CCO Infectious Disease Podcast
COVID-19: Which Drug, When, and Why? Anti-inflammatory Agents and Immunomodulators

CCO Infectious Disease Podcast

Play Episode Listen Later Apr 7, 2022 15:06


Anti-inflammatory agents and immunomodulators are key components to treating patients who are severely or critically ill due to a COVID-19 infection.In this episode, Vikramjit Mukherjee, MD, discusses the role and timing of these treatment options, including:High-titer convalescent plasmaCorticosteroidsInterleukin-6 inhibitors (eg, tocilizumab)Janus kinase inhibitors (eg, baricitinib)Presenter:Vikramjit Mukherjee, MDAssistant Professor of MedicineDivision of Pulmonary, Critical Care, & Sleep MedicineNew York University School of MedicineDirector, Medical Intensive Care UnitBellevue HospitalNew York, New York Review the downloadable slidesets at: https://bit.ly/35NNb7QLink to full program: https://bit.ly/35SrxQ0

That's Cool News | A weekly breakdown of positive Science & Tech news.
101. New Alopecia Treatment, New Way for Nuclear Fusion, Saving Dying Organs

That's Cool News | A weekly breakdown of positive Science & Tech news.

Play Episode Listen Later Apr 4, 2022 28:30


News: Scientists Say New Treatment Lets Alopecia Patients Regrow Hair | Futurism (01:14) Scientists at Yale announced this week that a common arthritis medication (baricitinib) appears to help alopecia patients regrow their hair. a potential treatment for a widespread autoimmune condition. Baricitinib is used to reduce pain, stiffness, and swelling in adults with rheumatoid arthritis after other treatments have failed. Helps slow the progression of bone and joint damage. It is a Janus kinase (JAK) inhibitor  Janus kinase (JAK) inhibitors are a group of medications that inhibit activity and response of one or more of the Janus kinase enzymes (JAK1, JAK2, JAK3, and TYK2). These enzymes normally promote inflammation and autoimmunity. Alopecia is a common autoimmune disorder that causes hair loss Affects people of all ages, although it most commonly appears in adolescence or early adulthood.  Affects 1 in every 500 to 1,000 people in the United States. There is currently no FDA-approved treatment for the disease. Dr. Brett King, lead author on the study told Yale news:“This is so exciting, because the data clearly show how effective baricitinib is … These large, controlled trials tell us that we can alleviate some of the suffering from this awful disease.” For the study, the researchers conducted two large, randomized trials involving a total of 1,200 people. For 36 weeks, participants were given a daily dose of either 4 milligrams of baricitinib, 2 milligrams of baricitinib, or a placebo. One-third of the patients who received the larger dose grew hair back. The researchers stated that baricitinib thwarts the disease by disrupting the communication of immune cells involved in harming hair follicles.  Hopefully this medication will be proven to be safe & effective and approved by regulators.   Waymo says fully driverless rides are coming to San Francisco | The Verge (06:47) Waymo plans to start offering rides in its fully autonomous vehicles — without human safety drivers behind the wheel — in San Francisco.  They join a waitlist and, once approved, sign non-disclosure agreements to get access to the company's early technology. As of right now it is only available to employees but will soon grow to include members of the company's “Trusted Tester” program. The Trusted Tester program is for customers interested in using Waymo's robotaxis.  The vehicles will be available 24 hours a day, seven days a week, Waymo says. Additionally, Waymo is making moves in Arizona.Growing to include downtown Phoenix after operating exclusively in the exurban towns of Chandler, Gilbert, Mesa, and Tempe for nearly five years. Waymo has been running fully driverless rides without a safety driver in those towns outside of Phoenix for more than a year now.  They must be confident they have enough data to move forward with autonomous taxis.Last year, the company logged the most miles driven autonomously of all the companies permitted to test in the state: 2.3 million miles, a huge increase over 2020, when it had about 629,000 miles driven, and even the pre-pandemic year of 2019, with 1.45 million. The expansion of Waymo's service area in Phoenix and the imminent launch of driverless rides in San Francisco signal the company's sense of confidence that its vehicles can operate safely and efficiently in more dense, urban environments.    Quantum technology could make charging electric cars as fast as pumping gas | Phys.org (12:10) For a long time, batteries had far lower energy density than those offered by hydrocarbons, which resulted in very low ranges of early electric vehicles.Improvements in battery technologies eventually allowed the drive ranges of electric cars to be within acceptable levels However, despite the vast improvements in battery technology, today's consumers of electric vehicles face another difficulty: slow battery charging speed.Takes about 10 hours to fully recharge at home Even the fastest superchargers require up to 20 to 40 minutes to fully recharge This creates additional costs and inconvenience to the customers. To address this problem, scientists looked for answers in the field of quantum physics.Which led to a discovery that quantum technologies may promise new mechanisms to charge batteries at a faster rate.  It was theorized that quantum resources, such as entanglement, can be used to vastly speed up the battery charging process by charging all cells within the battery simultaneously in a collective manner. Conventional batteries collective charging is not possible, where the cells are charged in parallel independently of one another.  In this most recent study, researchers were able to precisely quantify how much charging speed can be achieved with this collective charging scheme vs parallel. The charging speed increases linearly with the number of cells in classical batteries. The study showed, however, that quantum batteries employing global operation can achieve quadratic scaling in charging speed. To illustrate this, consider a typical electric vehicle with a battery that contains about 200 cells. Charging time at home would be cut from 10 hours to about 3 minutes. Quantum charging would lead to a 200 times speedup over classical batteries,  High-speed charging stations, the charge time would be cut from 30 minutes to mere seconds. Of course, quantum technologies are still in their infancy and there is a long way to go before these methods can be implemented in practice. However, this study creates a promising direction and can incentivize the funding agencies and businesses to further invest in these technologies.   HB11's hydrogen-boron laser fusion test yields groundbreaking results | New Atlas (18:24) Australian company HB11 is approaching nuclear fusion from an entirely new angle, using high power, high precision lasers instead of hundred-million-degree temperatures to start the reaction.The 1st demo ​​produced 10 times more fusion reactions than expected The company started tooting their own horn: “the only commercial entity to achieve fusion so far [making it] the global frontrunner in the race to commercialize the holy grail of clean energy." Just to summarize quickly what is required for fusion: Like throwing powerful magnets at each other in space Most companies try to replicate this by magnetically confining hydrogen atoms in a plasma In order to smash atoms together hard enough to make them fuse together and form a new element, you need to overcome the incredibly strong repulsive forces that push two positively-charged nuclei apart.  The Sun accomplishes this by having a huge amount of hydrogen atoms packed into a plasma that's superheated to tens of millions of degrees at its core. HB11 is using a different approach that doesn't require huge amounts of heat, or tricky, radioactive fuels like tritium.Takes advantage of recent advances in ultra-high powered "chirped pulse amplification" lasers that can produce monstrous, unprecedented power levels over 10 petawatts. An HB11 reactor would be a mostly empty metal sphere, with a "modestly sized" boron fuel pellet held in the middle, and apertures in two spots on the sphere for a pair of lasers. One laser, in combination with a capacitive coil, is used to establish a powerful kilotesla magnetic containment field for the plasma. The second is used to massively accelerate hydrogen atoms through the boron sample. The reactor is not heating things up in the hope that they'll smack together at speed.It is aiming the hydrogen right at the boron and using these bleeding-edge lasers to make it go so fast that it'll fuse if it hits a nucleus. Hydrogen-boron fusion doesn't create heat, it merely creates "naked" positively charged helium atoms, or alpha particles They collect that charge to create energy, rather than needing to superheat steam and drive turbines. Initial experiments on laser-triggered chain reactions returned reaction rates a billion times higher than anticipated, and then seem pretty happy about it and a little cocky:“This is many orders of magnitude higher than those reported by any other fusion company, most of which have not generated any reaction despite billions of dollars invested in the field. The results show great potential for clean energy generation: hydrogen-boron reactions use fuels that are safe and abundant, don't create neutrons in the primary reaction so cause insignificant amounts of short-lived waste, and can provide large-scale power for base-load grid electricity or hydrogen generation." Mitochondrial transplants between living cells could save dying organs | ETH News (23:53) In a technological breakthrough, researchers at ETH Zurich have announced the development of a new technique that can transplant mitochondria.Mitochondria are the tiny powerhouses of the cell where the processes of cellular respiration take place In their research, recently published in the journal PLOS Biology, the group successfully used a ‘nanosyringe' they had previously developed to transplant mitochondria from one living cell to another. In more detail:These cylindrical nanosyringes were specially developed for this study, the researchers pierced the cell membrane and sucked up the spherical mitochondria. They then pierced the membrane of a different cell and pumped the mitochondria back out of the nanosyringe into the recipient cell. The position of the nanosyringe is controlled by laser light from a converted atomic force microscope. A pressure regulator adjusts the flow, allowing scientists to transfer incredibly small volumes of fluid in the femtoliter range (millionths of a millionth of a milliliter) during organelle transplants The transplanted mitochondria have a high survival rate – more than 80 percent. The injected mitochondria begin to fuse with the filamentous network of the new cell 20 minutes after transplantation. The technique could be deployed as a way of treating diseased organs, but may also find use in the realm of anti-aging, rejuvenating stem cells that deteriorate in metabolic activity as we grow older.

Evidence Based Hair
Evidence Based Hair - Season 1, Episode 9 (Alopecia Areata and Androgenetic Alopecia)

Evidence Based Hair

Play Episode Listen Later Apr 4, 2022 46:57


STUDIES HIGHLIGHTED ALOPECIA AREATA King B et al (starts at 3:27). Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022 Mar 26. Fenentinos P et al (starts at 16:24). Assessing the role of stressful life events in the induction and recurrence of alopecia areata: a case-control study. J Am Acad Dermatol.  2022 Mar 24;S0190-9622(22)00526-6. Macbeth A et al (starts at 21:14). The associated burden of mental health     conditions in alopecia areata: A population-based study in UK primary care. Br J Dermatol.  2022 Feb 14. Senna M et al (starts at 29:06). Predictors of Quality of Life in Patients with Alopecia Areata. J Invest Dermatol 2022 Mar 21;S0022-202X     ANDROGENETIC ALOPECIA Ghafoor R et al (starts at 39:15). Association of androgenetic alopecia and severity of coronavirus disease 2019. J Cosmet Dermatol. 2022 Mar;21(3):874-879. Baghani M et al (starts at 40:57). Androgenetic alopecia and COVID-19: Is there a clinical connection? J Cosmet Dermatol . 2022 Feb;21(2):420-425. Veskovic D et al (starts at 42:04). Association of androgenetic alopecia with a more severe form of COVID-19 infection. Ir J Med Sci. 2022 Mar 23;1-6.  

Mayo Clinic Pharmacy Grand Rounds
Overcoming the COV-BARRIER: The Role of Baricitinib in SARS-CoV-2

Mayo Clinic Pharmacy Grand Rounds

Play Episode Listen Later Mar 16, 2022 29:07


Aeryana N. Beaudrie-Nunn, Pharm.D. (@ABeaudrieRx), identifies the rationale for immunodulatory therapy in COVID-19, explores clinical trial data regarding the use of Baricitinib in hospitalized patients with COVID-19, and defines the patient context where Baricitinib use is most appropriate.  For more pharmacy content, follow Mayo Clinic Pharmacy Residency Programs @MayoPharmRes or the host, Garrett E. Schramm, Pharm.D., @garrett_schramm on Twitter! You can also connect with the Mayo Clinic's School of Continuous Professional Development online at https://ce.mayo.edu/ or on Twitter @MayoMedEd. 

Vaccine 4 1 1 - News on the search for a Covid 19 Coronavirus Vaccine
Coronavirus vaccine and COVID variant updates for 03-04-2022

Vaccine 4 1 1 - News on the search for a Covid 19 Coronavirus Vaccine

Play Episode Listen Later Mar 4, 2022 5:11


Hope you didn't sell everything you own to go into the mask business. Data released by the CDC shows Covid levels have dropped enough that more than 90% of Americans can go without masks. The data shows nearly everyone in the country lives in an area with low to medium risk, though that data came out after the CDC tweaked how it measures risk. The new CDC guidance applies to everyone — including school kids and the unvaccinated. It does not, for whatever reason, apply to air travel, trains, or public transit.Yes, Omicron was reported as milder than the Delta variant, but that doesn't mean it's no big deal. Japanese scientists say it's at least 40% more lethal than seasonal flu. The case fatality rate of Omicron in Japan was about 0.13%, while the flu typically has a 0.006% to 0.09% death rate. They say more study is needed once all the restrictions are lifted. If you have arthritis, it's rare you feel lucky but when it comes to the pandemic, you may have been. Baricitinib is an oral drug commonly taken for rheumatoid arthritis, and an expansive study out of Oxford shows it reduced hospitalized COVID-19 patients' risk of dying by 13%. Scientists and doctors welcomed the addition of the pill to the few treatments already shown to help treat severe COVID, especially since the drug comes in generic versions low- and middle-income countries can afford.A couple of good news items for kids. The European Medicines Agency has authorized Moderna's vaccine for children aged six to 11, in addition to recommending boosters of Pfizer's vaccine for those aged 12 and up. And a new study has found Pfizer's vaccine is 91% effective at protecting young people ages 12 to 18 against infection for at least four months after their second shot.You may want to dust off the luggage as well. Rules requiring people to show a Covid-19 vaccine passport to access venues will be lifted in France March 14 and face masks will no longer be needed indoors except for on public transport. And vaccinated travelers to Italy will no longer have to test before entering the country. Unvaccinated travelers must still show proof of a negative test before entering. And once in country everyone must still get a “Super Green Pass” to stay at hotels, take trains, or eat at restaurants. In the United States, cases were down 55%, deaths are down 26%, and hospitalizations are down 43% over 14 days. The 7-day average of new cases has been trending down since January 14. The five areas that had the most daily deaths per 100,000 are Arkansas, Maine, West Virginia, Tennessee, and the Northern Mariana Islands. There are 25,724,877 active cases in the United States.The top 10 areas with the highest number of recent cases per capita according to The New York Times: Saipan, Northern Mariana Islands. Nome Census Area, AK. Bennington, VT. Linn, MO. Roanoke, VA. Pike, KY. Twin Falls, ID. Perry, KY. Fayette, AL. and Jerome, ID.There have been 956,262 deaths in the U.S. recorded as COVID-related.The top 3 vaccinating states by percentage of population that's been fully vaccinated: Rhode Island at 80.7%, Vermont at 80.1%, and Maine at 78.4%. The bottom 3 vaccinating states are Alabama at 50.3%, Wyoming at 50.6%, and Mississippi at 51%. The percentage of the U.S. that's been fully vaccinated is 65%.Globally, cases were down 25% and deaths down 27% over 14 days, with the 7-day average trending down since January 25. There are 61,379,411 active cases around the world.The five countries with the most new cases: Germany 202,338. South Korea 198,802. Vietnam 118,790. Russia 93,026. And Japan 71,570. There have been 5,982,566 deaths reported as Covid-related worldwide. See acast.com/privacy for privacy and opt-out information.

Coronavirus 4 1 1  podcast
COVID, Coronavirus, Omicron, and vaccine updates for 03-04-2022

Coronavirus 4 1 1 podcast

Play Episode Listen Later Mar 4, 2022 5:12


Hope you didn't sell everything you own to go into the mask business. Data released by the CDC shows Covid levels have dropped enough that more than 90% of Americans can go without masks. The data shows nearly everyone in the country lives in an area with low to medium risk, though that data came out after the CDC tweaked how it measures risk. The new CDC guidance applies to everyone — including school kids and the unvaccinated. It does not, for whatever reason, apply to air travel, trains, or public transit.Yes, Omicron was reported as milder than the Delta variant, but that doesn't mean it's no big deal. Japanese scientists say it's at least 40% more lethal than seasonal flu. The case fatality rate of Omicron in Japan was about 0.13%, while the flu typically has a 0.006% to 0.09% death rate. They say more study is needed once all the restrictions are lifted. If you have arthritis, it's rare you feel lucky but when it comes to the pandemic, you may have been. Baricitinib is an oral drug commonly taken for rheumatoid arthritis, and an expansive study out of Oxford shows it reduced hospitalized COVID-19 patients' risk of dying by 13%. Scientists and doctors welcomed the addition of the pill to the few treatments already shown to help treat severe COVID, especially since the drug comes in generic versions low- and middle-income countries can afford.A couple of good news items for kids. The European Medicines Agency has authorized Moderna's vaccine for children aged six to 11, in addition to recommending boosters of Pfizer's vaccine for those aged 12 and up. And a new study has found Pfizer's vaccine is 91% effective at protecting young people ages 12 to 18 against infection for at least four months after their second shot.You may want to dust off the luggage as well. Rules requiring people to show a Covid-19 vaccine passport to access venues will be lifted in France March 14 and face masks will no longer be needed indoors except for on public transport. And vaccinated travelers to Italy will no longer have to test before entering the country. Unvaccinated travelers must still show proof of a negative test before entering. And once in country everyone must still get a “Super Green Pass” to stay at hotels, take trains, or eat at restaurants. In the United States, cases were down 55%, deaths are down 26%, and hospitalizations are down 43% over 14 days. The 7-day average of new cases has been trending down since January 14. The five areas that had the most daily deaths per 100,000 are Arkansas, Maine, West Virginia, Tennessee, and the Northern Mariana Islands. There are 25,724,877 active cases in the United States.The top 10 areas with the highest number of recent cases per capita according to The New York Times: Saipan, Northern Mariana Islands. Nome Census Area, AK. Bennington, VT. Linn, MO. Roanoke, VA. Pike, KY. Twin Falls, ID. Perry, KY. Fayette, AL. and Jerome, ID.There have been 956,262 deaths in the U.S. recorded as COVID-related.The top 3 vaccinating states by percentage of population that's been fully vaccinated: Rhode Island at 80.7%, Vermont at 80.1%, and Maine at 78.4%. The bottom 3 vaccinating states are Alabama at 50.3%, Wyoming at 50.6%, and Mississippi at 51%. The percentage of the U.S. that's been fully vaccinated is 65%.Globally, cases were down 25% and deaths down 27% over 14 days, with the 7-day average trending down since January 25. There are 61,379,411 active cases around the world.The five countries with the most new cases: Germany 202,338. South Korea 198,802. Vietnam 118,790. Russia 93,026. And Japan 71,570. There have been 5,982,566 deaths reported as Covid-related worldwide. See acast.com/privacy for privacy and opt-out information.

Hart2Heart with Dr. Mike Hart
#51: Dr. Mike Hart and Dr. Wes Ely

Hart2Heart with Dr. Mike Hart

Play Episode Listen Later Feb 18, 2022 50:24


Dr. Wes Ely is the author of the new book "Every Deep Drawn Breath" and works as an ICU physician at Vanderbilt University in Nashville, Tennessee. This podcast discusses the importance of physicians treating unvaccinated patients with the same level of care and empathy as vaccinated patients, long-COVID, early treatment (Paxlovid, Mulpinovir and Baricitinib), the efficacy of different types of masks, and everything COVID related.

Hart2Heart with Dr. Mike Hart
#51: Dr. Mike Hart and Dr. Wes Ely

Hart2Heart with Dr. Mike Hart

Play Episode Listen Later Feb 18, 2022 50:25


Dr. Wes Ely is the author of the new book "Every Deep Drawn Breath" and works as an ICU physician at Vanderbilt University in Nashville, Tennessee. This podcast discusses the importance of physicians treating unvaccinated patients with the same level of care and empathy as vaccinated patients, long-COVID, early treatment (Paxlovid, Mulpinovir and Baricitinib), the efficacy of different types of masks, and everything COVID related. Medical Disclaimer: Nothing posted on this channel is medical advice or a substitute for advice from your physician or healthcare provider. Although Dr. Mike Hart is a fully licensed physician, always contact your physician or other healthcare provider with any questions about a medical condition or your personal health.

Rio Bravo qWeek
Episode 80 - Oral Meds for COVID-19

Rio Bravo qWeek

Play Episode Listen Later Jan 28, 2022 25:12


Episode 80: Oral Meds for COVID-19. The US department of human health and services recently launched the COVID19 Therapeutics Locator website to allow providers find locations where they can send prescriptions for Paxlovid and Molnupiravir. Find the COVID19 therapeutics locator online: https://arcg.is/iuuW50Yasmin and Arti discuss oral medications under emergency use authorization for COVID-19: Paxlovid and Molnupiravir. Introduction: Meds for COVID-19.  By Hector Arreaza, MD.  For the last 2 years, humanity has faced the challenge to find an effective way to fight COVID-19. This pressing charge has not been free of obstacles. It has been hindered by politics, misinformation, greed, jealousy, and many other not-so positive human traits. For me, living through the pandemic has been somewhat frustrating and shaming. Stupidity, vulgarity, and mediocrity are a few of the attributes that have flourished during the last 2 years all around us. But not everything about the pandemic has been negative. Many talented people with good intentions have engaged in serious research and have made tremendous contributions to science and humanity. Vaccines have been developed using cutting-edge technology and their efficacy has been very positive so far. Many medications have been tried to fight COVID-19 since the beginning. Some clinicians have tried to repurpose old medications in their honest desires to fight COVID-19. Examples include ACE inhibitors, statins, azithromycin, hydroxychloroquine, and chloroquine, which have not proven to be effective against this virus so far. Ivermectin, for example, has been very controversial since the beginning of the pandemic. Ivermectin is not approved by the FDA for the treatment of COVID-19. Until today, the National Institutes of Health do not have enough data to recommend for or against using ivermectin for COVID-19. “Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin in the treatment of COVID-19.” Ivermectin is still being used by some clinicians in the United States based on personal experience and opinions.At this time, remdesivir (brand name Veklury®) is the only medication approved by the FDA to treat COVID-19. IV remdesivir won full FDA approval in October 2020 for hospitalized patients, and its use has been expanded a couple days ago to include use in non-hospitalized high-risk patients. The NIH recommends against IL-6 inhibitors, such as tocilizumab or sarilumab, in COVID-19 patients who are not in the ICU. At this moment, there is not enough data for the NIH to make a recommendation for patients who are in the ICU. Baricitinib is an oral medication used to treat rheumatoid arthritis authorized in November 2020 to be used in combination with remdesivir for the treatment of COVID-19 in certain hospitalized children and adults who require supplemental oxygen, mechanical ventilation, or Extracorporeal membrane oxygenation (ECMO). Baricitinib is now authorized to be used without remdesivir against COVID-19 in hospitalized patients. We cannot forget the use of dexamethasone in hospitalized patients requiring oxygen.Today we want to give you a little taste of two oral medications: Paxlovid® and molnupiravir. You will listen to two brave medical students presenting what they have found about these medications. This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. Paxlovid®.   By Yasmin Fazli, MS3, Ross University School of Medicine.  What is it?Paxlovid® is the first oral treatment for mild-to-moderate coronavirus disease (COVID-19) in patients over 12 years-old to be issued by the FDA. The FDA issued an emergency use authorization (EUA) on December 22, 2021. It is made up of two different medications: nirmatrelvir and ritonavir. Nirmatrelvir is a protease inhibitor while ritonavir helps decrease the breakdown of nirmatrelvir.  The combination authorized is nirmatrelvir 300 mg plus ritonavir 100 mg. You may remember ritonavir use in combination with other antiretrovirals for the treatment of HIV/AIDS. At the end of the 2021, Pfizer announced that results from a trial comparing between Paxlovid® versus a placebo revealed that Paxlovid® reduced proportion of mortality and morbidity by 88% compared to placebo after a 5-day course. When and how to prescribe it?To use Paxlovid® some criteria must be met by the patient. First, a positive result of COVID-19 viral testing, second, the patient must be at high risk for illness progression to a more severe state, including hospitalization and death; and third, the patient must be 12 years or older.  Paxlovid® should be started as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. It is to be taken by mouth 2 times a day for 5 days straight with or without food. You take 3 pills twice a day. It is not authorized for more than 5 days.  It is not authorized for the pre-exposure or post-exposure prevention of COVID-19. It's not meant to be a replacement for the vaccine.  Side effects?Possible side effects of Paxlovid® include dysgeusia (altered or impaired sense of taste), diarrhea, increased blood pressure, and myalgia (muscle aches). Nirmatrelvir and ritonavir, which comprise Paxlovid®, also interact with other medications, which may lead to serious or life-threatening adverse reactions.  It's contraindicated in patients taking medications that are dependent on CYP3A metabolism for clearance, for example, warfarin, amiodarone, clozapine, midazolam, sildenafil (for pulmonary hypertension), etc. A list of these medications has been reviewed by the FDA and you can find it online.  Liver problems have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering Paxlovid® to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. Furthermore, Paxlovid® is not recommended for patients with severe kidney problems, and if they do use it, the dose should be adjusted.Because nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection. As for pregnancy or lactation, there currently is no data available for it to understand any potential effects on miscarriages, birth defects, or maternal and fetal outcomes. Considering all of this, please review your patients' list of medications and supplements and medical history prior to initiating Paxlovid®.Concerns?Due to its limited clinical data availability, other adverse effects that have not been reported may also occur while using Paxlovid® on top of the side effect list we are aware of. Ritonavir is a well-known medication, but nirmatrelvir is brand new.  Another concern is its limited availability. So even though it has shown positive results, it is not widely available yet, which leads to having to prioritize certain populations such as the unvaccinated patients. This may prove to be a moral and ethical concern.  Effectiveness?There is no long-term data on Paxlovid® yet; however, from what we do know, it is proving to be effective more than placebo by almost 90% which shows much promise. It works against current or previous variants of COVID-19.  EPIC-HR is the randomized, double-blind, 2-arm study done to prove Paxlovid®. It included 2246 patients with laboratory-confirmed SARS-CoV-2 infection, mild to moderate symptoms, and at least one comorbidity with increased risk of developing severe illness from COVID-19. Patients were randomly assigned 1:1 to receive either Paxlovid or placebo orally every 12 hours for 5 days. Results: Paxlovid significantly reduced the risk of COVID-19-related hospitalization or death from any cause by 89% (within 3 days of symptom onset) compared with placebo. Through day 28, 0.7% (5/697) of patients in the Paxlovid® arm were hospitalized compared with 6.5% (44/682) of those in the placebo arm. The study also showed that nobody died taking Paxlovid® while 12 people died taking placebo. These are promising results and Pfizer will be announcing more information on the effectiveness as time passes by.  Pricing?The original pricing was announced to be $530.00; however, it's been added that it'll be at no cost to the people in the United States.  Molnupiravir.   By Arti Patel, MS3, Ross University School of Medicine.  1. What is molnupiravir? Molnupiravir is an antiviral medication that can be used to treat COVID-19. Molnupiravir is a nucleoside analog that inhibits viral replication. The active drug of molnupiravir (N-hydroxycytidine) tricks the RNA polymerase enzyme into incorporating the drug instead of uridine or cytidine. Nucleobases continue to get added to the RNA chain and eventually the new RNA molecule has accumulated enough errors that the virus cannot replicate further.    2. When and how to prescribe it? Molnupiravir is available for Emergency Use Authorization for “mild to moderate COVID-19 disease in adults with positive results of direct viral testing who are at risk of developing severe COVID-19, including hospitalization or death or those in whom alternative COVID-19 treatment options approved by the FDA are not accessible or clinically appropriate.”  FDA provided EUA status on December 23, 2021. It should be taken as soon as COVID-19 is diagnosed, and within 5 days of symptom onset. It is not to be used as a method to prevent COVID-19 disease. Not for prophylaxis.  Benefits of treatment have not been seen after hospitalization, so administration of molnupiravir in patients hospitalized due to COVID-19 is not recommended. Adults above the age of 18 should take 800 mg orally every 12 hours for 5 days, with or without food. Use for longer than 5 days has not been studied.  3. Side effects? Most common adverse effects are diarrhea, nausea, and vomiting.  4. Concerns? Pediatric patients: Molnupiravir may not be used in patients under the age of 18 due to effects on bone and cartilage growth. Studies in rats with repeated doses of molnupiravir showed bone and cartilage toxicity.  Pregnancy: Fetal toxicity was observed when given to pregnant individuals in animal reproduction studies. Risk of adverse maternal or fetal outcomes or birth defects have not been studied in humans as of now. Use of molnupiravir in pregnant individuals may be considered once the prescribing physician has assessed the potential risks and benefits. Prior to initiating treatment of molnupiravir, if clinically indicated, assess whether a patient is pregnant. If a patient is having irregular menstrual cycles, first day last menstrual period is unknown, or patient is not using an effective method of contraception, a pregnancy test is advised.  Females of childbearing age are advised to use an effective method of contraception while under treatment of molnupiravir and for 4 days after the final dose. Effects of molnupiravir on sperm are not known, thus effective contraception must be used while under treatment of molnupiravir and for 3 months after the last dose.  Additionally, breastfeeding is not recommended during treatment and for 4 days after the last dose.  5. Effectiveness? Although molnupiravir is not substitute in patients for whom COVID-19 vaccination and booster are recommended, it can be used for treatment of non-hospitalized patients with COVID-19 who have a high risk of progression to severe disease.  In, MOVe-OUT, a randomized, double-blind, placebo-controlled clinical trial, almost 7% of about 700 individuals who received molnupiravir were hospitalized compared to almost 10% of 700 individuals who received the placebo. During the follow up period, one person who received molnupiravir died compared to 9 people who received the placebo. The safety and effectiveness of molnupiravir continues to be studied.  Availability and pricing?Not available in pharmacies yet, and preliminary pricing for a 5-day course of molnupiravir was about $700. Conclusion of episode:Now we conclude our episode number 80 “Oral Meds for COVID-19.” We hope you got enough information about these two medications: Pax-lovid and Mol-nu-pira-vir. Remember that they are authorized (not approved yet) by the FDA for the treatment of COVID-19. They are both oral medications, taken twice a day for 5 days. Their use in pregnant patients is not recommended yet. Paxlovid can be used in patients older than 12 years old, and molnupiravir in patients older than 18 years old. We'll keep learning together about these medications in the future. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Arti Patel and Yasmin Fazli. Audio edition: Suraj Amrutia. See you next week! _____________________References:F.D.A. Approves Remdesivir for Patients Not Hospitalized, The New York Times, nytimes.com, January, 21, 2022, https://www.nytimes.com/2022/01/21/world/remdesivir-fda-approval-expanded-covid.html. “Frequently Asked Questions on the Emergency Use Authorization for Paxlovid for Treatment of COVID-19”, U.S. Food and Drug, December 22, 2021, https://www.fda.gov/media/155052/download. Accessed on Jan 24, 2022. “Pfizer Receives U.S. FDA Emergency Use Authorization for Novel COVID-19 Oral Antiviral Treatment,” pfizer.com, December 22, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-receives-us-fda-emergency-use-authorization-novel.  Ahmad, B., Batool, M., Ain, Q. U., Kim, M. S., & Choi, S. (2021). Exploring the Binding Mechanism of PF-07321332 SARS-CoV-2 Protease Inhibitor through Molecular Dynamics and Binding Free Energy Simulations. International journal of molecular sciences, 22(17), 9124. https://doi.org/10.3390/ijms22179124 Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults, fda.gov, December 23, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain. Accessed on January 24, 2022. Fact Sheet for Healthcare Providers: Emergency Use Authorization for Molnupiravir, fad.gov, December 23, 2021, https://www.fda.gov/media/155054/download, accessed on January 24, 2022. 

CORONAVIRUS. COVID-19
126-OPCIONES TERAPÉUTICAS POSIBLES PARA COVID-19. ACTUALIZACIÓN ORGANIZACIÓN PANAMERICANA DE LA SALUD (OPS), 11 DE ENERO DE 2022.

CORONAVIRUS. COVID-19

Play Episode Listen Later Jan 23, 2022 19:08


La Organización Panamericana de la Salud (OPS), 11 de enero de 2022. Publica, la 31ª edición de la base de datos de evidencia sobre posibles opciones terapéuticas para COVID-19. Examina 171 opciones terapéuticas. Según el portal de búsqueda de la Plataforma Internacional de Registro de Ensayos Clínicos (ICTRP) de la OMS, se están investigando cientos de posibles tratamientos o sus combinaciones en más de 10.000 ensayos clínicos y estudios observacionales. Treinta hallazgos clave. 1• Corticosteroides: 2• Remdesivir: 3• Hidroxicloroquina, interferón beta 1-a y lopinavir-ritonavir: 4• Antibióticos: 5• Plasma de convalecientes 6• Tocilizumab: 7• Sarilumab: 8• Anakinra: 9• Tofacitinib: 10• Colchicina: 11• Ivermectina: 12• Favipiravir: 13• Sofosbuvir con o sin daclatasvir, ledipasvir, velpatasvir o ravidasvir: 14• Baricitinib: 15• Casirivimab e Imdevimab (REGEN-COV 16• Bamlinivimab con o sin etesevimab 17• Sotrovimab: 18• Regdanvimab 19• Proxalutamide: 20• Dapagliflozina 21• Trasplante de células madre mesenquimatosas 22• Corticosteroides inhalados 23• Fluvoxamina: 24• Lenzilumab: 25• Fragmentos policlonales de anticuerpos equinos (INM005): 26• Famotidina: 27• Anticoagulantes: 28• Antiinflamatorios no esteroideos (AINE): 29• IECA y ARB 30• Molnupiravir: Conclusiones. 1• La Organización Panamericana de la Salud (OPS) hace seguimiento en todo momento de la evidencia en relación con cualquier posible intervención terapéutica. A medida que se disponga de evidencia nueva, la OPS la incorporará con rapidez y actualizará sus recomendaciones, especialmente si dicha evidencia se refiere a grupos en situación de vulnerabilidad como los niños y niñas, las mujeres embarazadas, las personas mayores o los pacientes inmunocomprometidos, entre otros. 2• La OPS también tiene en cuenta las diferencias en el impacto de la COVID-19 sobre las minorías y los diferentes grupos étnicos. En consecuencia, la Organización recopila constantemente información que pueda servir para mitigar el exceso de riesgo de enfermedad grave o muerte de estas minorías. Estos grupos sufren inequidades sociales y estructurales que conllevan una carga de enfermedad desproporcionada. 3• La seguridad de los pacientes afectados por la COVID-19 es una prioridad clave de la mejora de la calidad de la atención y los servicios de salud. 4• Sigue siendo apremiante la necesidad de elaborar ensayos clínicos aleatorizados de alta calidad que incluyan pacientes con COVID-19 a fin de poder desarrollar estrategias de manejo confiables. La importancia de los ensayos clínicos controlados aleatorizados con un diseño adecuado es fundamental en la toma de decisiones basadas en la evidencia. Hasta el momento, la mayoría de la investigación en el campo de la COVID-19 tiene muy baja calidad metodológica, lo que dificulta su identificación y validación. Urge incrementar la transparencia y plantear estudios de más calidad. REFERENCIA. https://iris.paho.org/handle/10665.2/52719 ADAPTACION PARA AUDIO-OYENTES: Medicina en una página. Dirección y Conducción: John Jarbis García Tamayo.

Sinapsis EMPodcast
Recomiendan 2 medicamentos más contra Covid 19, el baricitinib y el sotrovimab

Sinapsis EMPodcast

Play Episode Listen Later Jan 19, 2022 8:00


En el video de hoy revisamos 2 medicamentos más recomendados por disminuir la mortalidad y las complicaciones de la Covid-19, el baricitinib y el sotrovimab.Checa el comunicado aquí: https://www.who.int/news/item/14-01-2022-who-recommends-two-new-drugs-to-treat-covid-19Checa el video aquí: https://youtu.be/0Q9ghcRoHzEVisita nuestra tienda en línea para comprar nuestros libros y material educativo:https://bit.ly/3i6eAnGSi necesitas una consulta aquí nos puedes encontrar:http://bit.ly/3aUSt12Ayúdanos a encontrar los mejores hospitales para estudiar:https://bit.ly/36o82LXUnete al equipo de Mecenas en YouTube desde 1 dolar al mes: http://bit.ly/2O1AtsXSupport the show (https://www.paypal.com/donate?hosted_button_id=2ENWQ7V289PBE)

Habari za UN
14 JANUARI 2022

Habari za UN

Play Episode Listen Later Jan 14, 2022 11:14


Machache kati ya mengi tuliyokuandalia hii leo kutoka UN WHO yapendekeza dawa mbili mpya za kutibu wagonjwa wa COVID-19 ambazo ni Baricitinib ya kumeza kwa ajili ya kutibu wagonjwa mahututi  wa COVID-19 na nyingine ni Sotrovimab ya sindano ambayo ni kwa ajili ya wagonjwa wasio katika hali mbaya sana. Na katika mada kwa kina tunaelekea mkoani  Ruvuma nchini Tanzania kumulika mradi wa nishati salama uliofanikishwa na Umoja wa Mataifa kwa kuwaunga mkono wenyeji.

林氏璧孔醫師的新冠病毒討論會
211105 伊維菌素在日本已做600人臨床試驗得到很好的結果?為何我不知道?

林氏璧孔醫師的新冠病毒討論會

Play Episode Listen Later Nov 7, 2021 31:08


11月2日有這樣的新聞: 抗寄生蟲老藥可治新冠是假消息?專家爆:已很多台大醫搶買 https://www.chinatimes.com/realtimenews/20211102004117-260405?chdtv 同藥廠出品 「伊維菌素」與默克新藥價差1000倍 https://www.chinatimes.com/realtimenews/20211102004134-260405?chdtv 寫在前面,我沒有要攻擊報導中提到的專家。我只想就事論事,就科學論科學。 新聞中有醫師指稱,伊維菌素的相關資料是動態性地不斷增加,轉捩點是2、3個月前日本Tokyo Medical Association(東京都醫師會)做了一個600人臨床試驗,得到很好的結果,之後便建議日本民眾每人隨身自備4顆伊維菌素。 事實查證: 1.目前為止我有找到日本有兩個單位在做伊維菌素的臨床試驗:北里大學240人第二期,還有興和(Kowa)公司的1000人第三期。前者在8月23日NHK報導曾提到,在6月的時點收案到了一半左右就停住了。目前10月底在臨床試驗網頁上顯示似乎已經完成。後者則是在9月才剛剛公布要開始做。這兩個臨床試驗都還沒有結果發表,人數也都不是600人。 2.東京都醫師會的會長尾崎治夫多次推薦伊維菌素,早在印度開始大量使用前就已經推薦,但這應該是他個人的建議。且東京都醫師會是日本醫學會下屬的一個獨立組織。 它不是政府機構,也不反映日本政府或其厚生省的官方立場。 3.目前為止日本並沒有將伊維菌素列入治療指引之中。日本厚勞省新冠肺炎治療指引最新版是8月31日發布的 5.3 版,從第 47 頁開始介紹日本承認的藥物只有瑞德西韋 、地塞米松 (類固醇)、Baricitinib、casirivimab/imdevimab單株抗體這四種藥物。 之後有列舉一些有效性,安全性尚未確認的藥物,第 55頁有伊維菌素的介紹,寫到日本國內正在進行臨床實驗。而從十個隨機臨床試驗的統合分析來看,伊維菌素和安慰劑相比,並沒有改善輕症患者的死亡率、住院時間以及病毒消失的速度。 4.所謂的600人臨床試驗的說法,我想是出自一位在關西開業的開業醫:長尾和宏先生。他聲稱在關西疫情嚴重的時候累積了600例在宅療養的經驗。長尾醫師是腸胃內科,在關西開業。但很確定的是,這不是臨床試驗。這是單一診所沒有對照組的個人治療經驗,且應該根本沒有在醫學期刊上發表。就像一年多前紐約也有開業醫師聲稱自己已經有一千多例奎寧的治療經驗一樣的狀況。這完全不是東京都醫師會做的臨床試驗。 04b碎碎念:陰謀論總有他的市場。整個伊維菌素的陰謀論,就是說西方藥廠很邪惡想賺錢,所以藥物明明有效也要壓下來,要大家打貴貴的疫苗,用貴貴的口服藥。但這有兩個盲點。 1.全世界都努力在找哪些藥對新冠病毒有效,做出來有效的話早就拿出來用了,正式發表在文獻,寫進治療指引。最早做出對於重症有效的類固醇,他也是個老藥呀,沒有什麼賺頭,根本超便宜,為何他沒被打壓?為何全世界的科學家都這麼邪惡要幫萬惡的藥廠隱匿事實?你真心覺得這是有可能發生的嗎? 科學家也很希望這些老藥新用有效呀。抗愛滋藥物,奎寧,族繁不及備載....都被大量試驗過了。啊就大型臨床試驗做出來的結果都讓人失望,能怎麼辦? 2.WHO不可能坐視這種情況發生的。以WHO的立場一定是希望貧窮國家也有藥物可用,如果真有便宜老藥這麼有效,WHO絕對是歡天喜地的撿起來用。能用的話早就用了! 少點陰謀論,這個世界沒有你想的這麼黑暗。 很多科學家的努力,用你的陰謀論一句話就抹煞,太反智了。 --------------- 參考資料: 林慶順教授:抗寄生蟲老藥可治新冠是不是假消息?頂尖期刊曝最新研究成果 https://health.udn.com/health/story/120951/5863014 第一,有關「東京都醫師會」,我曾在兩個月前發表伊維菌素:醫師會長的推薦,良莠不齊的科學證據,指出它的會長尾崎治夫是提倡使用伊維菌素,但日本政府不予採納。 上禮拜五(2021-10-29)美聯社發表Japan has not substituted ivermectin for COVID-19 vaccines(日本尚未用伊維菌素替代新冠疫苗),其中兩段是:「東京醫學會主席尾崎治夫在新聞發布會上表示,伊維菌素可能對 COVID 患者有益,但需要進一步研究,之後出現了關於伊維菌素在日本獲得批准用於 COVID 患者的錯誤聲稱。網上有些人將此誤解為對該藥物的認可,並將尾崎誤認為是政府官員。 但東京醫學會是日本醫學會下屬的一個獨立組織。 它不是政府機構,也不反映日本政府或其厚生省的官方立場。」 第二,有關「東京都醫師會做了一個600人臨床試驗,得到很好的結果」,我查不到有這樣的試驗。 日本厚勞省新冠肺炎治療指引 5.3版 https://www.mhlw.go.jp/content/000829136.pdf NHK報導 https://www3.nhk.or.jp/news/html/20210823/k10013218191000.html 長尾和宏六百例的出處 http://www.genetinfo.com/international-news/item/52255.html https://www.jmedj.co.jp/journal/paper/detail.php?id=17980 長尾和宏開業的綜和診所 只有門診 然後做一些在宅醫療 健檢等等 http://www.nagaoclinic.or.jp/ 北里大學CORVETTE Study 第二期臨床試驗 https://clinicaltrials.gov/ct2/show/NCT04703205 興和(Kowa)公司第三期臨床試驗 https://perma.cc/Y5CA-S37R 【検証】「日本政府がコロナ治療薬にイベルメクチン推奨」は誤り 2021.9.22 https://www.afpbb.com/articles/-/3365969 Japan has not approved ivermectin as Covid-19 treatment 2021.10.30 https://apnews.com/article/fact-checking-079183409501 小額贊助支持本節目: https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

CCO Infectious Disease Podcast
Key COVID-19 Studies Influencing My Practice Following IDWeek 2021—Audio Recap

CCO Infectious Disease Podcast

Play Episode Listen Later Oct 29, 2021 55:39


In this episode, Renslow Sherer, MD, discusses new COVID-19 data from IDWeek 2021, including:Prevention of COVID-19ChAdOx1 nCoV-19Ad26.COV2.STixagevimab plus cilgavimabOutpatients with COVID-19Remdesivir IVMolnupiravirHospitalized patients with COVID-19BaricitinibLenzilumabCasirivimab plus imdevimabLong-term COVID-19 outcomesSustained recoveryPresenter:Renslow Sherer, MDDirectorInternational HIV Training CenterProfessor of MedicineSection of Infectious Diseases and Global HealthDepartment of MedicineUniversity of ChicagoChicago, IllinoisLink to full program and downloadable slides:https://bit.ly/3BCHF2E

Dysevidentia
0018 - The Big Flood (of nonsense)

Dysevidentia

Play Episode Listen Later Oct 13, 2021 72:40


Here are the sources we used this episode:In our intro:SOURCE [1:20] Buoyancy is often taught to 1st grader but we said 3rd to make the insult sound more plausible and therefore more insulting: https://www.brighthubeducation.com/lesson-plans-grades-1-2/129311-first-grade-summer-science-what-floats/When we discussed meta stuff and corrections:SOURCE [6:13] EPA on using HVAC filter - https://www.epa.gov/coronavirus/air-cleaners-hvac-filters-and-coronavirus-covid-19SOURCE [8:19] Baricitinib is a real medicine and here are some other treatments - https://www.unbiasedscipod.com/episodes/covid-19-can-we-treat-it-treat-it-no-one-wants-to-be-defeatedSOURCE [9:06] Last episode we had an emotional interview with someone who lost someone to covid - https://dysevidentia.transistor.fm/episodes/0017-disecting-misinformationSOURCE [9:56] only 100 to 200 in trump crowd - https://www.reuters.com/world/us/us-capitol-high-alert-pro-trump-demonstrators-converge-rally-2021-09-18/When we discussed the Covid minute:SOURCE [12:20] Alaska also has crisis standards of care - https://www.adn.com/alaska-news/2021/09/22/alaska-activates-crisis-standards-of-care-for-entire-state-to-help-covid-overwhelmed-hospitals/SOURCE [12:20] Idaho and the crisis standard of care is one example of a stressor on health care workers - https://www.mtexpress.com/news/coronavirus_covid-19_info/as-covid-19-numbers-stay-high-crisis-standards-kept-in-place/article_600318b4-27bf-11ec-9b43-0ba76e5738cd.htmlSOURCE [13:50] Idaho has 48% vaccination rate and the national rate is 58%, Idaho is the second worst state - https://usafacts.org/visualizations/covid-vaccine-tracker-states/SOURCE [16:29] Merck Covid-19 Pill is good news - https://www.cnbc.com/2021/10/05/merck-covid-pill-who-says-antiviral-is-good-news-as-it-awaits-data.htmlSOURCE [18:37] Our interview with Cognitive Psychologist Sean Toppi in episode 10 - https://dysevidentia.transistor.fm/episodes/hard-to-joke-about-ethicsSOURCE [18:37] Additional Doses from booster shots and you can read about that from the FDA - https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromisedSOURCE [18:37] "Booster shots" for Pfizer were recently recommended for: 18+ who live in high-risk settings - https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html#HighRiskSOURCE [18:37] "Booster shots" for Pfizer were recently recommended for: 18+ who have underlying medical conditions - https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.htmlWhen we discussed the flood myth:SPONSOR [21:05] Get a custom computer, use code evidence for 10% off - https://abk-kustomz.comSOURCE [28:34] Flood Myths - https://en.wikipedia.org/wiki/Flood_myth#MythologiesSOURCE [34:07] K-T Boundary - https://www.lpi.usra.edu/science/kring/Chicxulub/SOURCE [35:53] Wikipedia on Black Sea Deluge Hypothesis https://en.wikipedia.org/wiki/Black_Sea_deluge_hypothesis- https://en.wikipedia.org/wiki/Black_Sea_deluge_hypothesisSOURCE [38:43] Regrettably paywalled but talks about the merits and flaws of the Black Sea Deluge Hypothesis - https://www.sciencedirect.com/science/article/abs/pii/S1040618206001984SOURCE [39:52] Younger Dryas Impact Hypothesis - https://en.wikipedia.org/wiki/Younger_Dryas_impact_hypothesisSOURCE [42:54] Burckle Crater - https://en.wikipedia.org/wiki/Burckle_CraterSOURCE [43:41] Did a comet cause the great flood? - https://www.discovermagazine.com/planet-earth/did-a-comet-cause-the-great-floodSOURCE [44:40] Impact craters as sources of mega-tsunami generated chevron dunes - https://www.researchgate.net/publication/284318503_Impact_craters_as_sources_of_mega-tsunami_generated_chevron_dunesSOURCE [44:40] "Chevrons" are not mega-tsunami deposit: A sedimentologic assessment - http://faculty.washington.edu/jbourgeo/BourgeoisWeiss2009final.pdfSOURCE [50:06] Largest wooden boats in history - https://en.wikipedia.org/wiki/List_of_longest_wooden_shipsSOURCE [50:20] r/AskScience Discussion on max size - https://www.reddit.com/r/askscience/comments/1sbztl/why_is_there_a_limit_to_how_big_wooden_boats_can/SOURCE [53:41] California Academy of scientists on species counts - https://www.calacademy.org/explore-science/how-many-species-on-earthBULLSHIT SOURCE [56:43] Ark encounter bullshit on vegetation mats - https://arkencounter.com/blog/2012/08/31/noahs-floating-farm-of-animals-and-plants/SOURCE [58:08] Pando, a candidate for largest single plant - https://en.wikipedia...

CCO Infectious Disease Podcast
Audio Recap: Timely Treatment for COVID-19

CCO Infectious Disease Podcast

Play Episode Listen Later Oct 11, 2021 43:56


During this episode, Lynora Saxinger, MD, FRCPC, CTropMed, updates listeners on the latest Emergency Use Authorizations and guideline recommendations for optimal clinical management of COVID-19. Gain practical insights on patient identification, risk stratification, and treatment.Key points include:Treatment of COVID-19 can be broken into antiviral and immune-modulating therapiesEach agent should be used at the correct disease stage to maximize benefitAntiviral medications and mAbs show the greatest promise early during COVID-19, before the host immune response is mountedPassive immunization with mAbs can prevent infection and severe disease—and mortality—if given early to hospitalized personsOperational challenges to using these medications exist, but given the epidemic of unvaccinated persons, these treatments become increasingly relevant to reduce burden on healthcare systemsPresenter:Lynora Saxinger, MD, FRCPC, CTropMedCochair, Scientific Advisory Group  Alberta COVID-19 Emergency Coordination Centre  Associate ProfessorDivision of Infectious DiseasesDepartment of Medicine  University of AlbertaEdmonton, Alberta, CanadaContent based on an online CME program supported by an educational grant from Gilead Sciences, Inc.Follow along with the slides at:https://bit.ly/3BxQKtD Link to full program:https://bit.ly/3BwzdlC

Network Five Emergency Medicine Journal Club
Episode 9 - COVID-19 Series: Part 3 - Current Treatment Options

Network Five Emergency Medicine Journal Club

Play Episode Listen Later Oct 5, 2021 61:59


Theme: COVID-19. Participants: Dr Matthew O'Sullivan (infectious diseases specialist), Prof. Sanjay Swaminathan (immunologist), Dr George Zhou (intensivist), Ali Sayeed (ICU registrar), Dr James Tadros (ED consultant), Dr Pramod Chandru (ED consultant), Harry Hong, Samoda Wilegoda Mudalige, Shreyas Iyer, Kit Rowe, and Caroline Tyers.Discussion:Ansems, K., Grundeis, F., Dahms, K., Mikolajewska, A., Thieme, V., & Piechotta, V. et al. (2021). Remdesivir for the treatment of COVID-19. Cochrane Database Of Systematic Reviews, 2021(8). https://doi.org/10.1002/14651858.cd014962.Presenter - Ali Sayeed, ICU Registrar at Westmead Hospital.Summary: Remdesivir is a small molecule pro-drug that inhibits viral replication via its inhibition of RNA polymerase - In Australia, it has been provisionally approved by the TGA for its use in COVID-19.  The theory behind using Remdesivir is really in the early stages of COVID-19 pneumonitis (by reducing the viral load and thereby preventing the augmentation of the inflammatory response).  This was a systematic review with included meta-analyses looking at the use of Remdesivir in COVID-19 compared with placebo or standard care.  It included only randomised control trials, with the primary outcomes being all-cause mortality, changes in clinical status (such as time to liberation from mechanical intervention) and adverse events.  The 5 studies analysed for this review were: the Beigel study (ACTT-1 trial) which enrolled 1,000 patients, the Spinner trial which had 600 patients, the Wang trial with 230 patients, the Mahajan trial with 82 patients, and the WHO Solidarity trial with over 5,000 patients.  Remdesivir was found to have little to no impact on all-cause mortality at 28 days.  The duration to liberation from non-invasive and invasive mechanical ventilation was found to be 17 days in the Remdesivir group compared with 20 days in the control group in the Beigel study, and 7 days in the Remdesivir group compared with 15 days in the control group in the Wang study, although neither of these results were statistically significant.  The Beigel study demonstrated a difference in time to recovery in the Remdesivir group compared with the placebo group, with a median difference of 5 days (however it is unclear whether this result was statistically significant).  The significant heterogeneity in study protocols, methodology, subgroups and settings made it very difficult to compare these studies statistically.   Take-Home Points: Remdesivir likely has very limited or no effect on hard outcomes in COVID-19 (in particular on mortality).  The benefit of Remdesivir is not constant across disease severities; if there is a benefit it is likely to be a subset of patients (which appears to be those on low-flow oxygen).   It does not appear to affect hospital length of stay (there is not sufficient evidence to suggest it does).  All outcomes were based on low certainty evidence, and it is unlikely that there will be further evidence on Remdesivir alone to come, as most patients will be receiving combination therapy in ongoing studies.   Of all the treatment modalities that we have for COVID-19, Remdesivir appears to be the one that has the least impact, but it was the one that was available first, and has very few side effects.   At present in NSW, COVID-19 patients requiring oxygen are being treated with a combination of Dexamethasone, Remdesivir and Baracitinib (or Tocilizumab).  References:  Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of COVID-19 – final report. New England Journal of Medicine 2020;383:1813-26.[DOI: 10.1056/NEJMoa2007764].  Spinner CD, Gottlieb RL, Criner GJ, Arribas Lopez JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivirvs standard care on clinical status at 11 days in patientswith moderate COVID-19: a randomised clinical trial. JAMA2020;324(11):1048-57. [DOI: 10.1001/jama.2020.16349] [PMID:32821939].  Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet2020;395(10236):1569-78. [CLINICALTRIALS.GOV: NCT04257656][DOI: 10.1016/s0140-6736(20)31022-9].  Mahajan L, Singh AP, GiSy. Clinical outcomes of using Remdesivir in patients with moderate to severe COVID-19: a prospective randomised study. Indian Journal of Anaesthesia2021;65:41-6. [DOI: 10.4103/ija.IJA_149_21].  WHO Solidarity Trial Consortium. Repurposed antiviral drugs for COVID-19 - interim WHO solidarity trial results. New England Journal of Medicine 2021;384(8):497-511. [CLINICALTRIALS.GOV:NCT04315948] [DOI: 10.1056/NEJMoa2023184] [EUCTR:EUCTR2020-001366-11] [ISRCTN: ISRCTN83971151].  Living Guidelines [Internet]. Caring for people with COVID-19. 2021 [cited 16 September 2021]. Available from: https://covid19evidence.net.au/#living-guidelines.  The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19. New England Journal of Medicine [Internet]. 2021 [cited 16 September 2021];384(8):693-704. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2021436.   Kalil AC, Patterson TF, Mehta AK, Tomashek KM, et al. Baricitinib plus Remdesivir for Hospitalized Adults with COVID-19. N Engl J Med 2021; 384:795-807.  Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Hebner CM, Sager J, Mogalian E, Tipple C, Peppercorn A, Alexander E, Pang PS, Free A, Brinson C, Aldinger M, Shapiro AE. Early COVID-19 Treatment with SARS-CoV-2 Neutralizing Antibody Sotrovimab [Internet]. medRxiv; May 2021 [cited 16 September 2021]. Available from: https://www.medrxiv.org/content/10.1101/2021.05.27.21257096v1.   Tomazini B, Maia I, Cavalcanti A, Berwanger O, Rosa R, Veiga V et al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19. JAMA [Internet]. 2020 [cited 16 September 2021];324(13):1307. Available from: https://jamanetwork.com/journals/jama/fullarticle/2770277.  Hasan MJ, Rabbani R, Anam AM, Huq SMR, Polash MMI, Nessa SST, Bachar SC. Impact of high dose Baracitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh. BMC Infect Dis. May 2021; 21(1): 427. Available from: https://pubmed.ncbi.nlm.nih.gov/33962573/.  Kit's Corner Signbank [Internet]. Auslan.org.au. 2021 [cited 01 October 2021]. Available from: https://www.auslan.org.au/dictionary/words/COVID-19-1.html. Credits:This episode was produced by the ­­­­Emergency Medicine Training Network 5 with the assistance of Dr Kavita Varshney and, Deepa Dasgupta. Music/Sound Effects Angel by Ikson | https://youtube.com/ikson, Music promoted by https://www.free-stock-music.com. Blue Sweater by RYYZN | https://soundcloud.com/ryyzn, Music promoted by https://www.free-stock-music.com, Creative Commons Attribution 3.0 Unported License, https://creativecommons.org/licenses/by/3.0/deed.en_US.  Nightswim by Scandinavianz | https://soundcloud.com/scandinavianz, Music promoted by https://www.free-stock-music.com, Creative Commons Attribution 3.0 Unported License, https://creativecommons.org/licenses/by/3.0/deed.en_US. Misfits (Instrumental) by RYYZN | https://soundcloud.com/ryyzn, Music promoted by https://www.free-stock-music.com, Creative Commons Attribution 3.0 Unported License, https://creativecommons.org/licenses/by/3.0/deed.en_US.  Sound effects from https://www.free-stock-music.com. Thank you for listening!Please send us an email to let us know what you thought.You can contact us at westmeadedjournalclub@gmail.com.You can also follow us on Facebook, Instagram, and Twitter!See you next time,Caroline, Kit, Pramod, Samoda, and Shreyas.~

Last Week in Medicine
Empagliflozin for HFpEF, Antibiotic Duration for UTIs in Men, Targeted Temperature after Cardiac Arrest, Normal Saline vs Balanced Solution in ICU Patients, Baricitinib and Therapeutic Anticoagulation for Hospitalized COVID-19 Patients

Last Week in Medicine

Play Episode Listen Later Sep 30, 2021 61:52


We're back after a nice relaxing summer taking care of a surge of COVID-19 patients.  To start off season 3 we decided to do a rapid review of some of the best articles over the last three months.  Dr. Brian Locke returns to help us break down some critical care papers, we talk about the miracle of SGLT-2 inhibitors, the treatment of UTIs in men, and the latest in COVID-19 literature. Hypothermia vs Normothermia after Cardiac ArrestEmpagliflozin for Heart Failure with Preserved EFAntibiotic Duration for Afebrile UTIs in MenNormal Saline vs Balanced Solution in ICU patients Baricitinib for COVID-19Therapeutic Anticoagulation for COVID-19Music from Uppbeat (free for Creators!):https://uppbeat.io/t/soundroll/dopeLicense code: NP8HLP5WKGKXFW2R

PVRoundup Podcast
Antiviral efficacy of remdesivir against SARS-CoV-2 still controversial

PVRoundup Podcast

Play Episode Listen Later Sep 21, 2021 5:17


How does Remdesivir plus standard of care compare to standard of care alone in patients hospitalized with COVID-19? Find out this and more in today's PVRoundup podcast.

Saving Lives: Critical Care w/eddyjoemd
Baricitinib: Suppressing the Inflammation and Saving the Lives of COVID Patients

Saving Lives: Critical Care w/eddyjoemd

Play Episode Listen Later Sep 6, 2021 11:23


Baricitinib is a Janus kinase 1/2 inhibitor the has been shown to decrease mortality in COVID-19 patients who are on HFNC or NIV. Show Notes: https://eddyjoemd.com/baricitinib-covid/ Although great care has been taken to ensure that the information in this podcast are accurate, eddyjoe, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom. Website: www.eddyjoemd.com Instagram: www.instagram.com/eddyjoemd Twitter: www.twitter.com/eddyjoemd Facebook: www.facebook.com/eddyjoemd Podcast: https://anchor.fm/eddyjoemd My Amazon store for resources you may find helpful: www.amazon.com/shop/eddyjoemd Citation: RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021 May 1;397(10285):1637-1645. doi: 10.1016/S0140-6736(21)00676-0. PMID: 33933206; PMCID: PMC8084355. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/eddyjoemd/support

The Pharm So Hard Podcast: An Emergency Medicine and Hospital Pharmacy Podcast
Episode 50. The Immune System Needs to Calm Down: Pharmacologic Management with Tocilizumab and Baricitinib

The Pharm So Hard Podcast: An Emergency Medicine and Hospital Pharmacy Podcast

Play Episode Listen Later Aug 26, 2021 24:32


Tocilizumab and Baricitinib Mechanisms of Action COVID-19 Pathogenesis: Late COVID-19 Joost Wiersinga W. eta al. JAMA Review 2020 doi:10.1001/jama.2020.12839 The Road to COVID-19 EUA Approval Tocilizumab 1/8/2010 FDA approval for treatment of moderate to severe rheumatoid arthritis 8/31/2017 FDA approval for treatment of CAR T cell-induced cytokine release syndrome 6/24/2021 EUA authorization for COVID-19 hospitalized […] The post Episode 50. The Immune System Needs to Calm Down: Pharmacologic Management with Tocilizumab and Baricitinib appeared first on The Pharm So Hard Podcast.

Ta de Clinicagem
Episódio 101: COVID - Delta, Novos Tratamentos e Vacinas

Ta de Clinicagem

Play Episode Listen Later Aug 11, 2021 47:51


Pedro, Joanne e Fred discutem as novidades sobre COVID-19, em especial sobre a variante delta, os novos tratamentos aprovados e os efeitos colaterais de vacina. Esse episódio foi em parceria com o Whitebook! Acesse o aplicativo que te ajuda de forma rápida com informação de confiança na hora que você mais precisa! Clique no link para descobrir mais https://tinyurl.com/TdC-Whitebook e use o cupom CLINICAGEM para 30 dias grátis! Minutagem (2:10) Parceria com Whitebook (3:45) Variantes do covid (7:30) Variante delta (8:40) Sintomas da variante (10:45) Transmissibilidade (12:15) Vacina e a variante (16:20) Novos tratamentos (23:59) Inibidores da JAK (25:20) Corticoides (29:40) Anticorpos monoclonais (32:40) Reações vacinais (43:23) Resposta do desafio da semana anterior (44:23) Desafio da semana (45:16) Salves Referências em breve. Referências: Pinzón, Miguel Alejandro, et al. "Dexamethasone vs methylprednisolone high dose for Covid-19 pneumonia." PloS one 16.5 (2021): e0252057. Ranjbar, Keivan, et al. "Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial." BMC infectious diseases 21.1 (2021): 1-8. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Guimarães, Patrícia O., et al. "Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia." New England Journal of Medicine (2021). Kalil, Andre C., et al. "Baricitinib plus remdesivir for hospitalized adults with Covid-19." New England Journal of Medicine 384.9 (2021): 795-807. ALLEN, Hester et al. Increased household transmission of COVID-19 cases associated with SARS-CoV-2 Variant of Concern B. 1.617. 2: a national casecontrol study. Public Health England, 2021. https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ https://covid.joinzoe.com/post/new-top-5-covid-symptoms

AAD's Dialogues in Dermatology
July JAAD: Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy Phase 3 trial in the United States and Canada (BREEZE AD5)

AAD's Dialogues in Dermatology

Play Episode Listen Later Jul 14, 2021


CORONAVIRUS. COVID-19
96-TRATAMIENTOS ESPECÍFICOS APROBADOS Y AUTORIZADOS PARA USO DE EMERGENCIA POR LA FDA. EN EL MANEJO DE PACIENTES CON COVID-19. ACTUALIZACIÓN A LA FECHA.

CORONAVIRUS. COVID-19

Play Episode Listen Later Jul 10, 2021 10:30


Hasta el día de hoy para el tratamiento específico de pacientes con COVID-19, con acción directa contra el virus SARS CoV-2. Estamos usando medicamentos antivirales, anticuerpos monoclonales e inhibidores de proteínas. En este episodio describiremos 2 tipos autorizados por la administración de Drogas y Alimentos de los EE. UU. (FDA). Por un lado, los que son aprobados y por otro lado los que son solo autorizados para uso de emergencia. Además, cuales son para pacientes hospitalizados y los que son para los pacientes no hospitalizados. Tratamientos aprobados y autorizados por las FDA. Primero: El primer tratamiento aprobado para para el tratamiento de pacientes con COVID-19, hospitalizados con síntomas de moderados a graves. Medicamento antiviral remdesivir (Veklury). Segundo: Tratamientos autorizados para uso de emergencia para el COVID-19 por la FDA. Para pacientes hospitalizados: 1- Plasma covalente COVID-19. 2- Baricitinib, en combinación con Remdesivir. Para pacientes NO hospitalizados: 1- Los anticuerpos monoclonales: Casirivimab e Imdevimab. 2- Los anticuerpos monoclonales: Bamlanivimab y Etesevimab. REFERENCIA https://www.fda.gov/news-events/press-announcements/la-fda-aprueba-el-primer-tratamiento-para-el-covid-19 https://www.fda.gov/news-events/press-announcements/la-fda-emite-una-autorizacion-de-uso-de-emergencia-para-el-plasma-convaleciente-como-un-tratamiento https://www.fda.gov/news-events/press-announcements/actualizacion-sobre-el-coronavirus-covid-19-la-fda-autoriza-una-combinacion-de-medicamentos-para-el https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19-0

CORONAVIRUS. COVID-19
96-TRATAMIENTOS ESPECÍFICOS APROBADOS Y AUTORIZADOS PARA USO DE EMERGENCIA POR LA FDA. EN EL MANEJO DE PACIENTES CON COVID-19. ACTUALIZACIÓN A LA FECHA.

CORONAVIRUS. COVID-19

Play Episode Listen Later Jul 4, 2021 10:30


Hasta el día de hoy para el tratamiento específico de pacientes con COVID-19, con acción directa contra el virus SARS CoV-2. Estamos usando medicamentos antivirales, anticuerpos monoclonales e inhibidores de proteínas. En este episodio describiremos 2 tipos autorizados por la administración de Drogas y Alimentos de los EE. UU. (FDA). Por un lado, los que son aprobados y por otro lado los que son solo autorizados para uso de emergencia. Además, cuales son para pacientes hospitalizados y los que son para los pacientes no hospitalizados. Tratamientos aprobados y autorizados por las FDA. Primero: El primer tratamiento aprobado para para el tratamiento de pacientes con COVID-19, hospitalizados con síntomas de moderados a graves. Medicamento antiviral remdesivir (Veklury). Segundo: Tratamientos autorizados para uso de emergencia para el COVID-19 por la FDA. Para pacientes hospitalizados: 1- Plasma covalente COVID-19. 2- Baricitinib, en combinación con Remdesivir. Para pacientes NO hospitalizados: 1- Los anticuerpos monoclonales: Casirivimab e Imdevimab. 2- Los anticuerpos monoclonales: Bamlanivimab y Etesevimab. REFERENCIA https://www.fda.gov/news-events/press-announcements/la-fda-aprueba-el-primer-tratamiento-para-el-covid-19 https://www.fda.gov/news-events/press-announcements/la-fda-emite-una-autorizacion-de-uso-de-emergencia-para-el-plasma-convaleciente-como-un-tratamiento https://www.fda.gov/news-events/press-announcements/actualizacion-sobre-el-coronavirus-covid-19-la-fda-autoriza-una-combinacion-de-medicamentos-para-el https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19-0

Business Standard Podcast
Market Wrap Podcast, June 29: Here's all that happened in the markets today

Business Standard Podcast

Play Episode Listen Later Jun 29, 2021 5:27


Investors booked profits in cyclical stocks as growing concerns about new coronavirus outbreaks in Asian countries, undercutting an economic recovery,  worried investors. Besides, valuation concerns regarding Indian equities flagged by global agency HSBC and economic growth concerns raised by S&P, in the wake of the second wave of Covid-19 pandemic, added to investor woes. In their Asian outlook conference for the second half of 2021, brokerage firm HSBC said on Tuesday that the valuation of Indian stock market has become a concern now after a sharp run up from their March 2020 low. It maintains a 'neutral' rating on Indian equities and opines that the government's latest stimulus measures announced Monday are marginally positive. Relative to the economic dislocation seen in India, the package is not very large, it believes. S&P, meanwhile, cut India's FY22 GDP growth forecast to 9.5 per cent from 11 per cent predicted earlier and said that permanent damage to private and public sector balance sheets will constrain growth over the next couple of years. Against this backdrop, the frontline S&P BSE Sensex ended the day at 52,549 levels, down 186 points or 0.35 per cent while the broader 50-share Nifty closed at 15,748 levels, down 66 points or 0.42 per cent. PowerGrid, HUL, Nestle India, Cipla, Divis Labs, and IndusInd Bank eked out gains of up to 2 per cent to end the day as the top Nifty gainers. On the flipside, ONGC, Indian Oil Corporation, Hindalco, Kotak Bank, ICICI Bank, and Bajaj Auto declined in the range of 1.6 per cent to 2.5 per cent to settle as top laggards. The broader markets too reversed their gains with the BSE MidCap and SmallCap indices closing 0.42 per cent and 0.07 per cent lower, respectively amid losses in Oil India, SJVN, NHPC, Adani Transmission, Vodafone Idea, IFCI, Srei Infra, and Gujarat Mineral Development Corporation. Among individual stocks, shares of HDFC Life slipped 3.4 per cent to Rs 672 in the intra-day trade today after nearly 110.6 million shares changed hands on the counter on the BSE. Standard Life is believed to have sold 3.46 per cent stake. That apart, shares of Bajaj Healthcare zoomed 20 per cent and hit a new high of Rs 863.95 on the BSE in intra-day deal on Tuesday after the company announced that it has moved the Indian Patent Office requesting to grant a compulsory license for manufacturing & supply of Covid-19 drug “Baricitinib”. Shares of Cipla also advanced nearly 3 per cent to Rs 989 apiece on the BSE amid reports that India's drug regulator has granted the company permission to import Moderna's Covid-19 vaccine for restricted emergency use in the country. In a separate communication, Moderna has informed that the US has agreed to donate a certain number of doses of its Covid-19 vaccine through Covax to the Government of India for use here and has sought approval from the Central Drugs Standard Control Organisation (CDSCO), while Cipla, on behalf of the US pharma major, has requested for import and marketing authorization of these jabs. From a sectoral viewpoint, the Nifty Bank, Auto, Metal, and PSB index slipped between 1 per cent and 1.5 per cent on the NSE while the Nifty Pharma and FMCG indices advanced 0.5 per cent each. Global markets   Shares inched back from record highs on Tuesday on emerging Covid-19 variants across the globe, while investors also remained on edge over the United States' exit from accommodative policy. European stocks, as measured by the pan-European STOXX 600 index, were up 0.4 per cent, helped by a jump in industrial, financial and mining stocks. In contrast, MSCI's broadest index of Asia-Pacific shares outside Japan was 0.5 per cent lower as recent positive momentum stalled as some countries re-imposed lockdowns to contain the spread of the Delta variant of the virus. Japan's Nikkei fell 0.8 per cent, while in Australia the ASX/200 index closed down 0.1 per cent. Chinese stocks lost

Unbiased Science
COVID-19: Can We Treat It? (Treat It?) No One Wants To Be Defeated!

Unbiased Science

Play Episode Listen Later Jun 23, 2021 59:44


On this week's episode of the pod, we answer a question that we receive quite frequently: What are the current effective COVID-19 treatments?We spend some time discussing how attempts have been made to repurpose existing medications for treatment which saves time rather than developing new ones from scratch. We kick things off with remdesivir-- the only FDA-approved treatment for adults and some children who require hospitalization. We discuss how remdesivir works and present some real-world evidence of its impact on mortality and time-to-discharge from the hospital. Next, we tackle monoclonal antibody treatments which have received emergency use authorization from the FDA to treat mild/moderate COVID-19 illness in adults and some older children.  We discuss some other treatments (such as Baricitinib plus remdesivir) and Tocilizumab. We also discuss Dexamethasone and present some trial data on its use in improving mortality rates as compared to usual care. Next, we spend some time discussing nutritional supplements such as vitamin C, zinc, and particularly vitamin D which has received a lot of attention (mainly by supplement sellers). We briefly talk about the current status of ongoing clinical trials, using the oral antiviral Molnupiravir as an example. Next, we talk at length about Ivermectin and the mixed and weak evidence that has led the FDA, NIH, and WHO to conclude that there are insufficient data for the use of Ivermectin to treat COVID-19. Finally, we close the episode with a discussion of Hydroxychloroquine and the fact that clinical trials were halted early due to lack of effectiveness. We are taking a break for the summer, but plan to come back with some exciting content in season 2! Stay safe, everyone!

CORONAVIRUS. COVID-19
84-EL BARICITINIB. UN INMUNOSUPRESOR PARA MANEJO DEL COVID-19. LA AGENCIA EUROPEA DE MEDICAMENTOS.

CORONAVIRUS. COVID-19

Play Episode Listen Later May 13, 2021 3:44


Para el 29 de abril de 2021, la agencia europea de medicamentos (EMA) publica en su página de internet un informe donde muestra que ha comenzado a evaluar una aplicación para extender el uso de baricitinib (Olumiant) para incluir el tratamiento de COVID-19 en pacientes hospitalizados a partir de los 10 años que requieran oxígeno suplementario. El baricitinib es un inmunosupresor (un medicamento que reduce la actividad del sistema inmunológico). Actualmente está autorizado para su uso en adultos con artritis reumatoide de moderada a grave o dermatitis atópica (eccema). Es un principio activo que bloquea la acción de unas enzimas denominadas Janus quinasas que desempeñan un papel importante en los procesos inmunitarios que conducen a la inflamación. Se cree que esto también podría ayudar a reducir la inflamación y el daño tisular asociados con la infección grave por COVID-19. El baricitinib se autorizó por primera vez en la unión europea en febrero de 2017. Es un medicamento que se utiliza en adultos para tratar: 1-Artritis reumatoide. Se puede utilizar solo o en combinación con el fármaco modificador de la enfermedad, metotrexato. 2-Dermatitis atópica. Cuando los tratamientos aplicados en la piel no son suficientes o apropiados. El baricitinib está disponible en forma de comprimidos que se administran por vía oral. La dosis habitual es de 4 mg una vez al día, pero puede reducirse a 2 mg una vez al día, una vez la enfermedad está controlada. También puede ser necesario la reducción de su dosis en pacientes con insuficiencia renal, en pacientes con mayor riesgo de infecciones, en mayores de 75 años y que estén tomando otros medicamentos. REFERENCIA https://www.ema.europa.eu/en/news/ema-starts-evaluating-use-olumiant-hospitalised-covid-19-patients-requiring-supplemental-oxygen https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant https://www.ema.europa.eu/en/documents/overview/olumiant-epar-medicine-overview_en.pdf ADAPTACION PARA AUDIO-OYENTES: Medicina en una página. ================================================ PODCAST CORONAVIRUS. COVID-19 Este es un podcast en el que desde el ojo de la ciencia. Aprenderemos del coronavirus y de la enfermedad covid-19. Recuerden al enemigo es mejor conocerlo. Para acabarlo. Esta es una producción de: Medicina en una página. medicinaenunapagina@gmail.com Dirección y Conducción: John Jarbis García Tamayo. Médico y cirujano, Epidemiólogo y Pedagogo Universitario. Portada: Gracias a Sam Balye por compartir su trabajo (foto-portada) en https://unsplash.com/. Música: https://www.youtube.com/audiolibrary/music?nv=1

Business Drive
Eli Lilly Signs Deals to Boost Supply of COVID-19 Treatment in India

Business Drive

Play Episode Listen Later May 10, 2021 1:33


Eli Lilly and Co said it had signed licensing agreements with three Indian generic drugmakers to expand the availability of its arthritis drug baricitinib in the country for treating COVID-19 patients.The three Indian drugmakers - Cipla Ltd, Lupin Ltd and Sun Pharma - will collaborate with U.S.-based Lilly to help make and sell baricitinib in India.Eli Lilly in an emailed statement says Baricitinib has been given restricted emergency use approval by India's drug regulator for use in combination with remdesivir for the treatment of hospitalised COVID-19 adult patients requiring supplemental oxygen.

The Practice of Medicine
Safety of Baricitinib 4 mg for the Treatment of Rheumatoid Arthritis

The Practice of Medicine

Play Episode Listen Later Apr 12, 2021 30:01


Join Drs. Tracey Dabal and Christopher Jackson as they discuss the safety of baricitinib for the treatment of rheumatoid arthritis, a topic they address in their article that will appear in the May 2021 issue of the Southern Medical Journal. In this  podcast, they talk about why they chose to perform their safety-focused meta-analysis and what results were the most surprising to them. They also provide insight into how the findings could impact practice. Additionally, the two of them share their perspective on submitting and having published a research article, as well as touch on the various aspects involved with the publication process.

The Rx Daily Dose
Episode 47 - Oxlumo, Imcivree, & New EUAs

The Rx Daily Dose

Play Episode Listen Later Dec 8, 2020 15:02


Here are the links for everything discussed in Episode 47, I'm also including times here so feel free to skip ahead to the topics that interest you. Vaccines should be approved next week, so keep an eye open for that podcast next week (1:25) Oxlumo approval for hyperoxaluria (4:24) Approval of Imcivree for genetic weight management (8:29) New EUAs for COVID 19 treatment  barcitinib and remdesivir casirivimab and imdevimab CDC updates on COVID-19 & influenza reportingConnect with The Rx Daily Dose:Twitter      Instagram      YouTube      Linkedin       WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter       Instagram       Linkedin  ★ Support this podcast on Patreon ★

MPR Weekly Dose
MPR Weekly Dose Podcast Episode 51

MPR Weekly Dose

Play Episode Listen Later Sep 18, 2020 9:40


This week we cover AstraZeneca and the swift decision to restart their COVID-19 vaccine candidate trial; Pfizer and BioNTech want to expand enrollment for their candidate vaccine trial; There's the janus kinase inhibitor that could help reduce recovery time; An investigative antiviral may ease strain on hospitalizations; Aortic aneurysm, dissection assessed with fluoroquinolones; and a retrospective study compared cardiac events with azithromycin and amoxicillin use.

MPR Weekly Dose
MPR Weekly Dose Podcast Episode 34

MPR Weekly Dose

Play Episode Listen Later May 14, 2020 9:35


This week we cover the latest COVID-19 developments including a triple antiviral therapy that looks promising, Emergency Use Authorizations granted to diagnostics and critical meds, Moderna's investigational vaccine gets Fast Tracked, and the National Institute of Health's remdesivir plus baricitinib trial.

The COVID-19 LST Report
April 28, 2020

The COVID-19 LST Report

Play Episode Listen Later Apr 30, 2020 6:27


Your daily COVID-19 LST Report: — A case series of almost 200 COVID-19 patients found that the frequency of pulmonary embolism in infected patients is 2 times higher than that found during the control period. — Utmost caution is recommended for cryopreserving sperm, which has been found to have low risk of significant virus shedding but there is suggestion that may not be an acceptable risk. — A pilot cohort study with Baricitinib therapy for COVID-19 patients found significant improvement of clinical and respiratory parameters within two weeks. — Visit COVID19LST.org for our full report with links to the articles. — Reach out to us at: contact@covid19lst.org --- Support this podcast: https://anchor.fm/covid19lst/support

The Evidence Based Rheumatology Podcast
E36: Baricitinib for SLE

The Evidence Based Rheumatology Podcast

Play Episode Listen Later Apr 4, 2019 14:04


This week I discuss the phase 2 trial on baricitinib in SLE.  Though it's early times (and the total flop of rituxan in ME/CFS recently can attest to this), this was a large phase 2 and I'm hopeful it carries through to the ongoing phase 3 trials.  Follow me on twitter and find all the papers / links at my new landing page, ebrheum.com!