Educational Webinar: Clinical Benefits of Peptide-Based Formulas Across the Continuum of Care

Good day and welcome to the clinical benefits of peptide-based formulas across the continuum of care conference call. Today's conference is being recorded. At this time, I would like to turn the conference over to Brandon Martin. Please go ahead. Thank you so much. Good afternoon, everyone, and thank you for joining us today. My name is Brandon Martin here at McKesson Medical Surgical, and I'm so excited to welcome you to today's presentation, clinical benefits of peptide-based formulas across the continuum of care presented by Nestle. Before we get started, uh, I just want to direct your attention to our disclaimer. While you're reviewing that information, I will remind you that this presentation is being recorded. Within a day or two, you can expect to receive a link to rewatch this presentation. If you have a question, I do encourage you to enter it into the Q&A panel at the bottom left corner of your webinar window at any time, and we will do our best to answer at the end of the presentation as time allows. Our speaker today is Ann Priest, manager of medical affairs for Nestle Health Science. Anne obtained her Bachelor of Science degree from Texas State University and completed her RD internship at San Diego State University. Prior to joining Nestle Health Science in 2013, Anne worked as an acute care clinical dietician for Sharp Memorial Hospital in San Diego, California. And as a certified nutrition support clinician at Saint Luke's Episcopal Hospital in Houston, Texas, where she provided nutrition support for ICU and GI surgical patients, and also held a position as an account executive for Nestle Health Science, covering the Texas Medical Center for 7 years before her current role. And thank you so much for joining us today. We're definitely looking forward to the presentation. Well, thank you so much, Brandon. Um, it's just such a pleasure to be speaking with you all today. I'm very excited to be able to review the clinical benefits of peptide-based formulas, particularly as they relate to the management of intral feeding intolerance. Peptide-based in feeding predates actually back to the 1980s, uh, with a continuous flow of clinical studies being published over the last 40 plus years. So I'm very happy to share some of the more pertinent studies with you today. And uh this is our sponsor disclosure. Um I am an employee of Nestle Health Science and the material herein is accurate of the date it was presented and is for educational purposes only, and is not a substitute for medical advice, and reproduction or distribution of these materials is prohibited. And thank you very much again, Brandon, for that warm introduction. So, let's talk a bit about our objectives for today. Uh, these are to review the indications, benefits, and the GI tolerance issues associated with the use of enteral nutrition. And after identifying the etiology and the definition of intro feeding intolerance, we will explore some methods of overcoming GI intolerance, where I'll be citing literature that supports those methods. Um, and so, really, for us to get started today, I want to now briefly review the indications, benefits, and the GI tolerance issues that are oftentimes associated with the use of in nutrition itself. So we know or we think of in the literature in nutrition is oftentimes are commonly referred to the term tube feeding. And this is actually defined by the American Society of Parental and Internal Nutrition as a special liquid food mixture that contains proteins, carbohydrates, fats, vitamins and minerals, and it's usually given through a tube either into the stomach or the small intestines. Internal nutrition is indicated, oftentimes when a person cannot or will not maintain oral intake of food or nutrition to support and maintain bodily function uh in the presence of a functioning GI tract. And so if you see on the right-hand side of your screen, uh, the nutritional benefits are in the yellow, and the non-nutritional benefits kind of in that orange color there, shading. We think about nutritional benefits, and this includes the maintenance of bodily function, both systemic and muscle function, as well as the provision of nutrients to really support uh mitochondrial function and protein synthesis. We also recognize non-nutritional benefits, and this can include maintenance of the gut mucosa, the pathobiome, the gut hormone balance, and also could help in decreasing inflammation in our body. So I'm just highlighting a few of these benefits today, um, but it's really like that old saying, if the gut works, use it. All right. So, um, before I really jump into the presentation today, I'd like to share a real-life case study with you all. So this case concerns a 40 year old female, uh, with the diagnosis of idiopathic gastroparesis. And um this patient had significant weight loss all the way down to 60% of her usual body weight. And with much frustration that she was having in terms of getting an actual diagnosis of her problem, uh, and then start treatment, the discovery and the solution to her medical condition actually took around 3 years. So you can imagine that that's very daunting for a patient and their family and caregivers. And so over the course of her treatment, she couldn't tolerate G2 feedings, and she had multiple infections, and the use of parental nutrition was prescribed. And she described her life as being very miserable. So, um, now let's take a look at the timeline. So, uh, once she, um, had a successful placement of a J tube, an appropriate infusion of a 100% weight-based formula was prescribed. And this was after several failed attempts of trials of a standard polymeric formula. And her health then began to improve dramatically. And at this time, she is now at her original usual body weight of around 140 pounds. She is currently a happy, successful businesswoman, and also an active grandmother. And during her course of her treatment, her husband actually was an advocate for her health and the fighting for the failed first rules so that insurance could help and pay for her specialized formula. So I just encourage you to keep this case study in mind, as I discuss more around the benefits of peptide-based formulas. All right. So, um, keeping that in mind, uh, intro intro feeding intolerance specifically, or sometimes you'll see this term EFI in the literature, um, and I might use that EFI acronym throughout the presentation today. So inral feeding intolerance is the most common complication when we look at um inral tube feeding. The challenging thing is that there is no standard evidence-based treatment or definition. And in fact, there's 43 definitions of EFI that appear in the literature. Um, and this is based on systematic reviews. Um, this is by Ryan and Blazer and colleagues that was published in the year 2014. You can see there are 3 main categories or buckets, as you will. First being large gastric residual volumes at 150 to 500 mL with the prevalence of around 8 to 67%. Next, we have GI intolerant symptoms. This includes abdominal distention, nausea, vomiting, diarrhea and constipation, with the prevalence of 2 to 75%, and then inadequate delivery of in nutrition. And this is a range around 36, 37%. So we think about that there is no precise definition of EFI. This certainly can make it difficult to study the prevalence, the association of the outcomes, and the effects of those interventions from a research perspective. So, for example, based on current definitions, it's difficult to oftentimes relate EFI to mortality or to ICU hospital length of stay. And um in this, uh, depiction here, despite many of the benefits I described of in nutrition, DeMeo and colleagues in this publication from the American Journal of Gastroenterology suggested that actually up to 95% of all intraly fed patients have at least one symptom of GI intolerance, uh, and the most often one being diarrhea. Other studies conclude around 31 to 75% of in nutrition patients have at least one symptom of GI intolerance. So you can see it's fairly prevalent. And so, uh, when we think about a number of the probable common causes of inal feeding intolerance, GI symptoms, um, is certainly a top one, but this can also include medications causing that GI intolerance. It can come from infectious sources and sometimes even the ingredients in the tube feeding itself. Two studies out of the Mayo Clinic in Rochester showed a number of underlying conditions in their adult home in nutrition population. Uh, and these were associated with GI intolerant symptoms, including pancreatic insufficiency, fat malabsorption, chile leaks, as well as standard formula intolerance. And likewise, in their pediatric home in nutrition population, they showed that high GI uh intolerance in children, um, was oftentimes occurring in children who had anoxic brain injury, developmental delay, cystic fibrosis, and uh hematological malignancies, among other diagnoses. And so when we think about um this publication by Dr. Ryanton Blazer, um, this one now looking at a publication that she presented in 2021, here she discusses that intral feeding intolerance may arise from different parts of the GI tract. So when we look and we break those down for you here in those three buckets again, um, these certainly can, uh, require very different complexities in terms of the assessment and the management. She breaks those down, uh, so the stomach, the small bowel, and then the large bowel that you see there. And each segment um of the GI tract may be associated with different management techniques uh to treat these intolerant symptoms. And so it really can depend on that etiology and the available management measures. So when we think about, for example, uh, medication like erythromycin or metoclopramide, that may help and support an individual who is having challenges with gastroparesis, very much like our case study patient. Uh, you can also lower carbohydrate feeding, or you can adjust insulin management. This could help and support, uh, delayed gas improving delayed gastric emptying, um, because that's oftentimes associated with hyperglycemia. However, the further you travel down that GI tract, it is more difficult in terms of the management. Uh, we do think that oftentimes and see that diarrhea may be improved with a, uh, a form of fiber, the type of fiber that you might be trying to administer, as well as the type of tube feeding. It really can depend on the etiology or the patient's condition. We also know a lot of times these days, we hear about the microbiome, right? And so the altered microbiome may be supported by uh things such as symbiotics. Um, and then lastly, um, C. diff diarrhea is often a, a, a large challenge for intolerance, and this affects in the colon, and this might require antibiotics or potentially leading to um a fecal transplant. Um, so just again, uh, you know, this, uh, area of EFI can arise from various areas of the GI tract itself. Now, I know this slide looks a little uh complicated. I encourage you to just kind of um as I go through the description to follow your eyes with the arrows. But this is really describing um what we often see occurring in the ICU. So those um practitioners that work in the ICU uh today, um, you know, this is might be more in tune um to the area you work in, uh, and so we oftentimes do see intolerance to tube feeding. So this study by Shaw and colleagues showed us how intestinal edema, that's secondary to high volume resuscitation, um, can be the initiator as well as the propagator of pathways that can then lead to end organ dysfunction. So again, if you follow the arrows from the left to the right, you can see that from resuscitation to edema, we end up seeing a decrease in GI motility, contractility, and barrier dysfunction. This leads to increased mucosal permeability, and finally, this can lead to uh organ failure. So when we think about how complicated this is, uh, these are the patients that are receiving in nutrition and they're experiencing inral feeding intolerance, as well as masabsorption of their nutrients. And so yeah, these are oftentimes the very patients that our nutrition guidelines are suggesting to provide a standard intact control formula for today. All right. Um, and so this pragmatic definition of in feeding intolerance that was suggested by Dr. Pleasure and colleagues is really that inral feeding intolerance is the reduction or the cessation of in nutrition due to clinical manifestations of GI dysfunction. So therefore, individuals that are experiencing inral feeding intolerance are less likely to achieve their nutritional goal rate. This leads to hypocaloric nutrition and negative energy balance. And certainly, uh, we can recognize that in the ICU setting, this can be correlated oftentimes to poor clinical outcomes and increased mortality. And I want to share this study with you. Uh, it's a recent study by Lynn and colleagues, uh, and it was published in Nutrition and Clinical Practice in the year 2022. And um here they found that an elevated feeding intolerance score was independently associated with 28 day mortality. And from the table here, you can see that the, um, they broke this down into abdominal pain, nausea, vomiting, and diarrhea. Uh, and then it was assessed and score. And so the higher the cumulative value of the score, um, in the three categories, the higher the indication of EFI. They also went on to do a sub-analysis of the data, and looking at the patients with the highest nutrix score, uh, which is nutritionally risk, um, critically ill identification score, they found that the mortality was better predicted by the feeding intolerance score than the SOFA score itself. So in this study, the authors concluded that feeding intolerance may substantially influence outcomes and should facilitate timely treatment and incidents. So I encourage any of you that work in the ICU to to maybe go and take a look at that really neat paper. And here we have another retrospective analysis of the data. Um, this was from the year 2009. Uh, for those of you who might remember this international nutrition survey. Uh, this was published by Gunga Basu and colleagues. And again, really, we're looking at the prevalence of intolerance and intruly fed patients. And so the objective of this study was to determine the incidence of inral feeding intolerance, and also factors that are associated with intolerance and its influence of intolerance on clinical outcomes itself. The study looked at 167 ICUs from over 21 countries. It included in this survey, patients had to be greater than the age of 18 years of age, placed on mechanical ventilation within 48 hours of admission to the ICU and they had to have been in the ICU for greater than 72 hours. And they could not have previously been on internal nutrition or parental nutrition during their hospitalization, um, or prior to their ICU admission. Patients that were on prokinetic agents for greater than one day prior to their internal nutrition were also excluded from the study. So of the 1,888 patients, 576 of them are around 31% of those experienced inral feeding intolerance as defined by abdominal distention, subjective discomfort, vomiting, emesis, diarrhea, or high gastric residual volumes. Uh, and that was really dependent upon the um independent facilities threshold in terms of the volume amount of those gastric residual volumes. Negative clinical outcomes, um, included d-free days, ICU length of stay, 60-day mortality, and days to discharge alive. And these were all significantly worse in those feeding intolerant patients. And you can see that on the graph on the right. The Apache scores were almost identical for both groups. So you can't necessarily argue that one group was actually sicker than the other. And um continuing to talk a little bit about prevalence, um, I do want to share with you um that this study took place in a home care setting. Uh, so the objective of this study was to define the prevalence of inal nutrition-related complications, and this included 1600 Mao home enteral nutrition patients. Uh, and the data collection took place between January of 2018. Until December of 2020. And they found that the top indication of in feeding, uh, in general, those that were being inly fed, um, had, uh, diagnosis of dysphagia followed by malnutrition and failure to thrive. And all of the inral feeding intolerant symptoms were of GI of origin, with nausea and vomiting being the top incidents followed by diarrhea and bloating, as you can see on the right-hand side of your slide. OK. So we've kind of talked about prevalence, um, and so when we think about clinical outcomes and the manifestations of intro feeding intolerance, um, we can think that that lends to associated costs. And so there are financial resources that are often expended in an effort to really help to treat in feeding intolerance. And so, therefore, I think the data is very clear that in feeding intolerance must be addressed and managed to really help to promote positive clinical outcomes, as well as to help decrease overall cost of care. Um, and on this slide, you're seeing, uh, our intro feeding guidelines. Um, and so when we think about, you know, how prevalent inral feeding intolerance is, let's take a look at what some of the guidelines suggest. So in Feeding guidelines from Aspen and Spen for the ICU as well as the Spen guidelines for home in nutrition suggest that a standard polymeric or a standard commercial formula be used for most patients. And the Aspen guidelines do go on to suggest that small peptides uh be used for diarrhea or suspected malabsorption. OK. So with that, I would like to take a quick poll. I'd love to hear some of your thoughts here. So, um, if you all don't mind launching the poll for me, I would like to learn from the audience today, how often do you utilize a specialized tube feeding formula to prevent GI intolerance? So keyword here being preventing GI intolerance. Always, often, sometimes or never. So, if we could get that pole launch, that would be fantastic. OK, let's see. We're seeing some numbers coming in. Oh, wow. We have like an exact tie. That is unbelievable. Well, let's see, it just changed. OK. Now I am seeing, let's see, we're at 60%. Uh, as never. And now we have, uh, so we have 20% for both often and sometimes, uh, and then, uh, the always um had a 0%. So, um, really appreciate your feedback today. Um, it's good to know and oftentimes, you know, we may uh always think of that, these types of formulas being an. option for preventing GI intolerance, but certainly with someone who has underlying etiologies of previous intolerance to uh standard formulas, that it might be something to consider in the future. So I'm glad to see that some of you did respond with often and sometimes as your response. So thank you again for, for sharing your thoughts with me today. All right, so now we've kind of gone through first objective. Now I'd like to transition and really discuss the mechanism of action and the clinical benefits associated with peptide-based intro formulas. And um let's take a look. So, you know, oftentimes this, this could be a great area for some, um depending on what area of practice you work in. Um, but when we think about what a peptide-based in formula is, um, and why it is suggested for patients who may have malabsorption. The definition is actually um an inal formula where a protein has been hydrolyzed to produce peptides of varying lengths. Uh, it contains essential fatty acids, um, med medium chain triglycerides, vitamins, minerals, and all in all, the formula um has been designed to be easily assimilated and well tolerated. And we look at peptide-based formulas, and they're not necessarily all created equally. So this is actually an electrophoresis diagram, uh, where you can see that the um protein is broken down into different sizes. So that's kind of on your right-hand side of your screen. And the smaller peptides with the lowest kilodalin weight congregates towards the bottom of the bars, and the larger peptides, um, will, and the intact protein will actually congregate at kind of that higher level above that orange or reddish line you see there. And so in the most very left lane, this is demonstrating a 100% way peptide-based formula. And there are no peptides that are above 14 kilodaltins in weight, with really the majority of the peptides falling below the 5 kilodaltin. And this really represents the high percentage of smaller peptides, such as in the form of dye and tripeptides. And it's important, I will go over here shortly, how these proteins cross the basolateral membrane into the enterocyte in the form of amino acids, as well as dye and tripeptides. And when we look at protein digestion and absorption, um, you know, this is kind of to understand just the intricacies, um, as well as, you know, of those small peptides. When we have normal digestion, mechanical digestion starts and begins in our mouth, uh, the protein is ingested and chewed and into a normal gut, that hydrochloric acid will then denature and break down that protein. We also have Pepsin that breaks down protein into polypeptides. This helps and travels down into the lumen of the duodenum. Here we have pancreatic uh Peptidais enzymes, such as tripsin and chimarypsin, as well as carboxypetilais. These really help to cleave off those polypeptides and package them and make them into these smaller peptides. Then into the microvilla, into the brush border. This is where really the absorption takes place of free amino acids, as well as those dye and tripeptides, and then further cleaving off those peptides as needed. And I think that this is probably the most important slide I'm gonna discuss today in terms of when we think about protein metabolism and inral feeding intolerance. So our small intestine actually absorbs around 95 to 98% of digested uh protein, and this again is primarily in the form of those free amino acids and the dye and tripeptides. And as you can see in the diagram, kind of in the middle, you see highlighted in blue, the PET1 transporter. And that's playing a very important role in helping to absorb, you can see to the left, the dye and tripeptides. It is um also though important to note pancreatic enzymes are necessary to hydrolyze the intact protein, and oftentimes deficiency in pancreatic enzymes can lead to maabsorption. So when we think about that transport of protein across that brush border and into that basolateral membrane, this involves that active co-transport system. And, and the dye and tripeptides are utilizing that PET one transport system for this purpose. And the expression of Pep T1, that transporter, it can oftentimes increase during times of stress and certain types of um infections. Ischemia and electron transport systems can often dysfunction, and this can cause an effect on ATP production. And that's the main transporter for the amino acids. You can see towards the bottom, uh, as they go into the basilateral membrane. And so in such cases, the utilization that occurs with the PET1 transport system really becomes very crucial in helping to increase that protein load as it crosses over to that membrane as you're seeing on the right-hand side. So the key takeaway here today with this is um that more protein will cross that basolateral membrane if it's in the form of dye and tripeptides versus free amino acids. And uh I wanted to share this study, um where uh the authors looked at using a 100% whey peptide-based formula versus an intact protein formula. In terms of this study being a prospective pilot trial from France, 30 patients were included. Um, they had diagnoses of acute pancreatitis, and they were requiring jujunal nutrition. 15 patients received the 100% way peptide-based formula and 15% of the 15 of the patients received an isocholoric polymeric formula. And the tolerance to the intro formulas was actually good in both groups, which is fantastic. However, the length of hospital stay was significantly shorter in the peptide-based formula group, as well as weight loss was less. And so therefore, the authors concluded that the use of a peptide-based formula versus an intact protein formula resulted in more favorable clinical outcomes. OK. So, um, I think it's important to also discuss formula components, and the source of protein and its molecular structure, um could impact the formula tolerability as well as absorption. 100% hydrolyzed whey protein is the major ingredient in the formulas studied in the majority of the peptide-based research that's being reviewed today. And not all semi-elemental formulas contain 100% whey protein. But rather a mixture of different protein sources and different degrees of hydrolization into smaller peptides. Excuse me. And actually around 26% of the protein in whey protein is branch chain amino acids. Uh, for example, leucine, uh, has the capacity to stimulate muscle protein synthesis and is considered a very key anabolic, uh, symbol for protein synthesis itself. In addition, whey protein is also high in cysteine. And for those of you that remember, that's the rate-limiting amino acid for the production of our own bodies, major antioxidant, uh, which is glutathione. Whey proteins also considered as what we call fast acting. This means that it leaves the stomach quickly without curdling. So you can see in the picture on the left-hand side, that's the 100% way hydrolyzed protein, where you're seeing that it's remaining very smooth versus on the right, you see that the intact Kten protein is curdling. In addition, it will, um, the whey protein will be followed by a slower uptake into the small dip bowel, and this really allows for more maximal absorption. Also, it's important to know that uh 100% whey protein has constituents that can also help to modulate the immune function including uh the immunoglobulins. It also has naturally occurring prebiotics, as well as some antimicrobial pro uh properties. And um this is just also describing the DIIS score. Um, this is a score that was adapted in 2013 by the Food and Agricultural Organization. And it, and it describes the measurement and the amount of amino acids that are absorbed into the ileum. And so the DIIS score of whey protein is around 1.09. Uh, and for reference, the protein, uh, DIS score for P protein is around 0.89. Um, so just some additional benefits of whey protein, um, for your review. And this prospective randomized control trial of early in feeding patients that were included in ischemia stroke patients. Here, this shows how a 100% way peptide-based formula enhanced the antioxidant status of these individuals, as well as attenuated inflammatory responses in patients that have had an ischemia stroke. 25 of these patients were entered into the study. They had to have had an initiation of their feeding within 48 hours of their ICU admission and received internal nutrition for greater than or equal to 3 days. And the average age was around 74. By around the 5th day of feeding, a significant increase in the antioxidant glutathione was noted in the way peptide-based group. Patients with a decrease in their serum glutathione typically have increased rates of protein metabolism as well. So, therefore, the glutathione levels may be an indicative of uh going into protein synthesis. In addition, interleukin 6 decreased in the way peptide group, indicating a decrease in inflammation. And we know in uh interleukin 6 typically will directly influence mortality. So, again, some potential benefits here of whey protein in terms of an antioxidant property. Now, I know this slide also looks a little busy, um, but I certainly wanted to mention another important aspect of, um, w weigh benefits. Whey protein also has inertin activities, um, and this helps to lower blood glucose levels. Uh, it's also, I mentioned it's high in branch chain amino acids. Um, it also has a faster gastric entering rate and caseine. Um, this leads to a rapid rise in serum amino acids. And this rise helps to stimulate the secretion um of insulin through um the release of these Aerin hormones and specifically gastric inhibitory peptide or GIP as well as glucagon-like peptide one or GLP one, which I think many of us hear about today. GLP1 enhances insulin sensitivity in the muscle as well as in the fat tissues. And it helps to really suppress the glucagon secretion, which otherwise will then promote glycogen breakdown and increase blood glucose levels. So in addition, uh, kind of the last component, the uh epid Peptidase 4, or DPP-4 will break down these inordin hormones. And we hydro, the way hydrolysates actually will inhibit that DPP4 breakdown. So it preserves this insulinotrophic effect of that GIP and GLP1. So, again, key takeaway here is that whey protein hydrolysates or peptides will help to stimulate insulin secretion and inhibit that breakdown of those Ancherton hormones. And in order to uh demonstrate this, uh this or really to kind of test the hypothesis of this, um, the, this study here uh was a multi-centered, randomized open label clinical trial and it included 102 subjects with the mean age of 62 years with a mean BMI of around 33. And this study took place in 7 academic centers, and all the patients here were mechanically ventilated. They had to have been on in nutrition formula for greater than or equal to 5 days. Those that were on PN were excluded. Uh, patients are randomized to receive either a 37% very high protein, 100% whey peptide-based formula that contained 29% of their car uh formula of coming from carbohydrate, or they received an isoitrogenous polymeric casein-based formula with 25% of the protein and 45% carbohydrate. You can see on the right kind of top uh bar there, the chart. This is the breakdown of the calories and the protein that were delivered. Uh, and the graph on the bottoms of the slide really shows you that the mean daily glucose was much more improved. You can see by the blue line, uh, in those in that peptide-based formula group. And so, therefore, the authors concluded that a very high protein, low-carbohydrate in formula could facilitate glucose control in critically ill, mechanically ventilated, overweight, overweight or obese patients. And so lastly, I do want to discuss uh uh fat in terms of uh formula component. Uh, and, and so this is in addition to the benefits of the hydrolyzed whey protein, uh, in terms of enhancing digestion and absorption. Um, the type of fat can matter. Uh, and so most in formulas contain both long chain, uh, as well as medium chain triglycerides. Medium chain triglycerides come primarily from coconut and palm kernel oils, uh, and these 4 fats typically have a 6 to 12 carbon backbone. And uh it's important to also note, you know, how these fats are metabolized, uh, and so the digestion can be very different. Um, so as you kind of look at the top part of the screen, this is really depicting how long chain fats, um, are, are absorbed. They stimulate pancreatic enzymes, um, to form these fat my cells. They're then absorbed into the introcyte. Then they're converted to yer microns as they then travel down into that lymphatic system, and then they eventually drain into that subclavian vein to really then reach the bloodstream. Those yer microns are are delivered into our cells of the body where they can be oxidized for energy, or they can be stored in our adipose tissue. And then any of those remaining Kyler micron uh remnants can then travel to the liver for dissembly or further utilization. But MCT medium triglycerides are quite different. Uh, so you see that more simply on the bottom. It's rapid, again, it's very simple, and it does not need to stimulate the pancreatic enzymes for production. So they're absorbed right into that portal vein, um, from the GI tract by passive diffusion, and this will produce ketonone bodies as well to really help in to create a very immediate energy utilization. And this makes a very excellent source, the the MCTs do for um providing energy um and being very quick energy, um kind of similar if you think about how carbohydrates do, but this, but it also will not negatively impact blood glucose control. Um, and so this is just quite showing you the difference between, um, the, the, the gestion of those two different types of fats. And um this is just a study that we wanted to show. It's a very small study, uh, only about 10 patients, but it does describe the metabolic effects of a 40% fat that contains um around 78% MCT as compared to a isocaloric long chain triglyceride diet. Um, and here you see that the MCT containing diet increased the insulin-mediated glucose metabolism in all the patients. And so what that means is that the MCT-rich diet really helped to enhance the process by which insulin is helping the body to metabolize the glucose. Uh, you can see that represented in the bar graph on the right. Uh, so just another, um, example of, um, how MCT could help in, um, facilitate fat absorption and improve GI tolerance, um, and, and be considered as also, um, and having an insulinotropic effect. OK. Well, before we jump into our next, or in our last objective today, I would like to take another poll question. So for this question, I'm very curious to learn your thoughts about for which clinical indication do you most often use a peptide-based intro formula. So we've got some example, examples for you here. We also have a, um, if you could launch that poll for us, that would be fantastic. If there are some other reasons, I'm not sure if you can type those in, um, but certainly, uh, I can recognize there might be others, but we'll just take a quick moment and I'd love to see what your thoughts are here. OK, our numbers are changing around a little bit. Um, from what I saw initially. So currently, OK, it's changed again. So currently we have um 50% of you are saying to meet higher protein requirements, and then we have that followed by a tie of impaired GI function and then other reasons. So, um, interesting, I, um, I most often when I do this program, we'll see impaired GI function. Um, I like the thought of using, there are, um, peptide-based formulas that, um, have a higher, uh, percentage of protein that can be supportive of those individuals needing that. So certainly, um, it can lend to more options when you have those needs. So I'm glad to see, um, someone might be using it for that area. And then 25% other reasons. So, um thank you so much again um for your responses here. Uh, and so again, I don't think there was any wrong answer, um, but, um, in any case, I hope that some of the literature I've shared so far as far as some of the benefits, um, is, has been shown through. So thank you again. All right, so let's get back to our slides, and we are now jumping into our last objective of the day, so we're on the home stretch. Um, so really here I'm gonna review current literature that supports the use of specialized intro formulas, really promoting intro feeding, tolerance, and improving clinical and as well as health economic outcome. And what I'd like to do is, um, over there, uh, just a few handful of slides here, I'm gonna start in the ICU and kind of take you on a journey um as we move into the home care setting, uh, as I, you know, conclude in reviewing several pieces of data. Uh, and so the first study I'm gonna share today is a retrospective cross-sectional real world evidence study, uh, by Doctor Nguyen and colleagues. This was actually published, uh, just last year, um, and it is actually the largest study to date looking at almost 20,000 critically ill patients in 67 hospitals in the United States. Uh, and this looked at a time period over 2015 into 2019. And as you kind of look at this slide, kind of start with the left and I'm gonna move to the right. So patients received a median of 6 days of internal nutrition, and then you can see kind of towards the bottom, the breakdown of the type of formula is as follows. So around 3200 patients received a 100% way peptide-based formula. 3100 approximately received another different type of a peptide-based formula. 13,000 patients received the standard intact protein formula. Um, and so, some of the results that we're seeing was that the 100% way peptide-based formula group had a higher severity of illness and frequencies of comorbidities as compared to other peptide-based and standard intact, uh, protein formula groups. So these were kind of the sickest of the patients and that were seen in that 100% way uh peptide-based group. And the outcomes that were observed was that the odds of GI intolerance were 18% higher in the other peptide-based formula group, and that 15%, um, the odds were also 15% higher um in the standard intact protein formula group as compared to the 100% uh weight peptide-based group. So, Again, that was really looking at the GI intolerance odds. The authors went on and they did a sub-analysis of this data, um, and there was around 1280 patients, um, that received a 100% weigh very high protein, low carbohydrate formula compared to a standard intact protein formula, as well as other peptide-based formulas. And here they saw that hyperglycemia was 81% higher compared to the other peptide-based formula, uh, as compared to the way peptide, very high protein we peptide-based group, and that 30-day readmissions was significantly less um in this group compared to a standard intact protein group. Um, so, for those that work in the ICU, um, again, I'd encourage you to maybe take a look at this paper, um, as it is one of the, the very largest, um, number of patients enrolled in a study. Um, it was just recently, um, Uh, was just recently made available last year, so. All right. And then, so as we also continue into, you know, this area of the acute care setting, um, that was really describing adult patients. So when we also think of pediatric patients, um, this is very, the intolerant symptoms is also very frequent. Uh, and so this study is a retrospective study, uh, done by Jared Miner and colleagues, and it was found that switching from an intact protein diet to a 100% way peptide-based diet in hospitalized children with developmental delays was associated with improvement in vomiting, wretching, uh, residual volumes, constipation, diarrhea, and weight gain. And it was also associated with a reduction in GIA tolerance medications, um, and improved growth. And then as we move into the home care setting now, so, um, this study, uh, is a real world evidence study. Uh, so it's a retrospective analysis. This is looking at uh US medical claims data uh for patients that have uh been just uh diagnosed with gastroparesis. These are pediatric patients, and they were prescribed a 100% way peptide-based feeding formula. Between the years of January 2013 through July of 2023. These patients were between the ages of 1 to 17 years, um, and the data was collected for 1 year prior to their initiation of the way peptide-based formula. And then they followed them for 13 and 13, 6 and 12 months following uh that initiation to the way peptide-based formula. Uh, and what they observed, um, were GI intolerant symptoms and healthcare resource utilizations compared, um, for those different time periods. And, um, here you're seeing there were improvements in GI intolerant symptoms throughout that 12 months of the data collection. Um, and just to orient you to this term pre-index, pre-index is a description of kind of the time period before we, um, the one year prior to that use of the way peptide-based formula, and sometime and you'll often hear post-indexes being that, that observed time. So there were improvements also um observed in healthcare resource utilization through that twelve-month post-index period. Um, with a 21% decrease in emergency room visits, um, and inpatient visits. And we're still now kind of, we've moved into that home care space um for those that work in this area. So this is um also retrospective real world evidence study. Uh, this is also based on medical claims from the, this is from the US data repository through the Decision Resource Group. And the objective of this study was to determine uh the demographical, clinical, and treatment characteristics that um are occurring with patients that are receiving in nutrition formulas in that post-acute care setting. Um, and again, it looked at, um, any events one year before and 1 year after, they transitioned to that 100% way peptide-based formula. This study looked at um 1,022 adult patients um that were participated in 39% were around 55 years of age or older, 54% were women, and the most common underlying medical condition was diseases of the digestive system. And after switching to the peptide-based formula, uh, you can see on the right, significant decreases in diarrhea, nausea and vomiting, abdominal distension, uh, improvement in gastric residuals, and constipation were noted. All right. So, um, I think we've got a few more slides, um, and we'll wrap this up, and these include, uh, studies out of the Mayo Clinic in Rochester. So this is also a retrospective study looking at the Mayo Clinic rochester home innutrition Patient Group. They were transitioned to a peptide-based formula. Um, and when they did, they showed a 46 to 78% improvement in GI intolerant symptoms. They also wanted to look at the health economic impact of um this, and you can see that's shown on the right-hand bar graph, where a decrease in the average number of patient-initiated phone calls back to their own home care, as well as ER visits and scheduled provider visits after they transition to the peptide uh based formula were, were less. They further went on to look um at this, this last study. This was presented. Um, most recently at the Aspen Nutrition Practice, uh, Science and Practice meeting, this was in Las Vegas in 2023. This was a retrospective study of 60 patients. This included both their, um, excuse me. Adult and children. Who are followed in that home in nutrition clinic in the Mayo Clinic in Rochester. And again, each of their subjects experienced a form of in feeding intolerance, um, while on a standard formula, and then they were switched to a 100% way peptide-based formula. They looked at the cost of care, and I think this is really eye-opening, uh, and it was collected for 4 weeks before the formula switch and then 8 weeks after. And they noted that enteral feeding intolerance dropped to um from 43.3% during that four-week transition period of time down to 21.6% during that eight-week post-transition period. And this represents a 50.1% decrease in inral feeding intolerance. And so, lastly, they looked at total cost of care and the, this decreased significantly. So with the improvement in inral feeding intolerance during that eight weeks, um, following that transition to the way peptide-based formula, the authors concluded that the use of a peptide-based formula is associated with improvements in in feeding intolerance, as well as reduction in overall and itemized total cost of care. Um, so certainly, there is a role for um in nutrition and, and specialized formulas for helping to support potential reductions in costs. And so I'd like to end by uh just mentioning early on in the case study, um, the question about the fail first rule. So, um, traditional Medicare no longer requires failure on standard in formulas for uh those hicks fix codes of B4150, B40152, uh, for some of the reimbursements. And so, um, You know, before the use of peptide-based formulas could be made, um, but it's really important to continue, uh, to have good documentation as always, um, as it's very much important still and being required, um, in the medical records to showing medical necessities of these formulas. And unfortunately, um, other insurance providers can follow their own plans or policies regarding the failed first rules, um, so, You know, it, it's um gonna be very based on, um, you know, location and where people, um, what type of insurance they may carry, um, but, um, in any case, um, we did want to provide just a resource for you. Um, you can see there, um, some, uh, some places you can go to find out more information about that change in the LCD policy. And with that in summary, um, though, you know, not really officially formally defined as of yet, I think most agree that enteral feeding intolerance, um, originates from gut dysfunction, and it can include a variety of symptoms, uh, and that in feeding tolerance is very prevalent. Uh, it can affect up to 95% of patients on tube feeding in one way or another, um, and it can affect around 30% of intrually fed ICU patients. Uh, and lastly, that a use of 100% way peptide-based formula is associated with improvements in GI intolerance, as we've seen in some of the literature today, um, as well as potential reductions in, um, healthcare cost resource utilization, uh, and cost savings. So, um, I think with that, Brandon, um, if we have any time for questions, I'm not sure where we are on time, so I, um, we'll take any questions if we have a few moments. Sure, thank you so much, Anne. Um, as we near the end of the hour, and I, I know we're a little pressed on time today, but uh I do wanna thank you all for joining us. If you do have a question, um, please go ahead and uh drop one in that um Q&A box to the bottom left, uh. And I was just curious too, so you know, the data looks really strongly in support of peptide-based central feeding for our audience members who may be considering a change in their to their patients formulas. What, what could they do today to sort of facilitate that? Uh, that's a great question. Um, And I think it, you know, understanding your patient's previous medical history, uh, understanding, you know, certainly, um, you know, any surgeries or underlying, um, conditions that they may have that are affecting the potential rise that can occur in GI intolerance. We know, again, you know, kind of describing the ICU population that it's, it's very prevalent. Because of um all the various factors I described with the resuscitation, for example, that occur. Um, and so, you know, uh, it's certainly important to individually, um, you know, evaluate if someone might be at a higher risk for intolerance. And perhaps again, maybe that is someone you might see the benefit of starting that formula for first. We, we do recognize that our critical care guidelines like I reviewed, um, do suggest for most patients, um, to be on a standard formula, however, um, those that have, um, signs of intolerance or diarrhea that they be um considered for a specialized peptide-based formula. Uh, so I think that's important to kind of be very mindful and watchful of those patients. Um, I do think that in addition to that, as we move into that home care setting, we saw in the data from the Mayo Clinic in Rochester that that the intolerance doesn't end in the hospital, right? And that our our patients are still experiencing intolerance as they go home, which can lead to, um, you know, again, those um healthcare resource utilizations that can then kind of go back and affect the institution. So, um, you know, he, if a patient's, if a patient's tolerating a, a peptide-based formula in the hospital setting and you see the necessity to continue that on in the in the home care, I think that's important to evaluate and, and have that good interdisciplinary dialogue with the the healthcare team, the home care team, um, as, as we saw there, you know, there might be some potential cost outcomes and benefits with that. So, I think it's having those open dialogues and, and reading up on some of the newer literature because our guidelines are a little outdated and we, we hope to maybe see some changes potentially with that, but at this time, you know, we're leaning back on some kind of older data um for those guidelines. I hope that helps. Oh yes, absolutely, that's a great summation and um, uh, also, you know, I, we did start a couple minutes late so I wanna be respectful of our audience time and I got some information about the continued education credit. Yes, OK, that's great. So, um, I can show this slide, Brandon, uh, and I, and, um, certainly I believe we have a handout that, uh, so Nestle, um, is providing, uh, one hour of CE credit for registered, uh, dietitians and nurses. Uh, you should. Receive, um, a, uh, again, a PDF of these instructions on how you go to claim your CE credit, but you can also, if you wanted to take a screenshot with your mobile device of this, um, you'll see there's a pin code that's gonna be required for you to enter, uh, to be able to receive your certificate. Uh, yes, and there should be, uh, you'll be receiving, uh, when you receive the link, uh, for everyone in the audience when you receive the link for the, uh, recording of this presentation, there'll be some additional information about the CEU as well. Great. All right, excellent well um. Yeah, like I said, I just wanna be respectful of everyone's time here. I know we're approaching 10 over the hour, so, um, uh, I'll go ahead and thank you all for joining us, uh, today. Um, go ahead and did you have a slide, ah. Uh, just wanted to give you another chance to review our disclaimers. Um, And also for a uh. For a full list of our upcoming events, I encourage you to visit us at mms.mcKesson.com/learning-ebinars. You can register for a future webinar, share events with your colleagues, or sign up to receive regular updates on our webinar schedule. And once again I want to thank you and for joining us today and everyone on the Nestle team for making this presentation available. Thank you so much for your time. This is really a fascinating topic. I really appreciate it. Great. Now, thank you so much for having us. Have a great rest of your day, everybody. Thank you so much. This does conclude today's call. Thank you for your participation. You may now disconnect.