Okay, welcome everybody. If you're here from the Regenerative Medicine Talk, I hate to tell you we're going to be talking about pediatrics here for the next 75 minutes, so if you wanted to continue to listen to pediatrics talks, please stay. If you wanted to talk about regenerative medicine, I think that there is a whole city at your disposal if you'd like to go talk about regenerative medicine. I'm Matt McLaughlin. I'm a Pediatric Rehabilitation Medicine Physician at Children's Mercy in Kansas City. Very thankful to be joined today by my fearless cohort, including Dr. Sruthi Thomas, who's at Texas Children's Hospital in Houston, Texas, Dr. Mary Dubon at Boston Children's Hospital, obviously in Boston. I was just going to have a few things just to go over that's the housekeeping parts of things. First, welcome participants to the session. Number two, thank you, Kayla. Number two, cellularized telephones and audio and video recording. Please keep your phones silent if at all possible. Do not disturb the animals while they're presenting with flash photography, but please, as much as you can, please take pictures if you like, preferably not of me because you may break your camera. Evaluation forms are located online or on your app. That is an application for those of you who also call it cellularized telephones. So if you want to fill out an application, we always appreciate feedback, especially on this session as we try to make some changes year to year. But again, as I'm very thankful to be presenting with my two co-presenters, every year I point this out that, again, I have more than an MD, but I never somehow get any acknowledgement for this because when you present with Sruthi Thomas, who has her PhD, any degree you have after your MD doesn't count, apparently, unless if you're Mary Dubon, which of course means you have a senior after your name. And so when you are Mary Dubon Senior, that comes even before your medical degree. So very well done, again, Mary, that somehow you tricked the AAPMNR two years in a row. Very well done, Sruthi, for making me feel inferior again for two years in a row. But I was just going to say, you know, they have to put up with me throughout the course of the year when we're talking about articles or reviewing articles or pulling different things. And every now and then we do happen to get in some arguments. So as good as I am at research and other things in my life, I'm very poor at Photoshop. And so here is everybody's favorite Swifty. So if you were to see the back of the jersey, which I never could figure out how to Photoshop in, it says Kelsey on the back, or it says Swift on the back, who knows? He may take her name or she may take his name after all is said and done, right? Or neither will take either's name. I mean, they're both professional people. So Kansas City barbecue is better than Texas barbecue is what Sruthi always tells me. So thank you, Bob. That's right. I appreciate that, Bob. And then the other thing is, I always want to say thanks, obviously, to Mary Dubon, who has one of the most interesting hobbies on any fellowship application I've ever read. And this is competing against Mark Fisher, who wrote Bonsai Tree Gardening was one of his favorite activities. And so I had to ask him about that. You guys know how intellectually curious I am. But on Mary Dubon's application to my fellowship program in 2015 or so, right? It said Irish dancing. And so here Mary Dubon is appearing on the Regis and Kelly show. And we will not tell you which one she is, but she's the one in the middle. And on the far right hand side of the screen, almost out of view is the legend himself, Regis Philbin, right? And so this was during your undergrad, I believe. So when you look at these two people that I get to present with, I make jokes and I laugh about them, but I'm immensely proud of them at the same time. And nothing could have made me more proud than seeing Sruthi's announcement on Facebook about becoming NIH funded. And Sruthi could have just said, look, I got NIH funding. But she wrote here, 33 years after my first science fair. So not that we're keeping track to a T, but that's a true researcher to actually keep track to that level. And then if you ever wanted to know how you become a senior, it's by having two wonderful looking kids like this. And so I don't know if you all recall last year that Mary essentially flew down from Boston to New Orleans just to present this session and flew back that same exact day. And that's like the level of commitment that I don't know that I always have personally, but respect immensely from someone like Mary. So very much always appreciative of the two of them for all that they've done for this session and for all that they continue to do for kids where they live. Finally, just a quick shout out for this group of presenters, because this is going to be our last session as a trio in the last time that I'm planning to submit and present this. We have other people who have expressed some interest in doing this, and we'll pass that along. But I wanted to give some shout out, especially to the top three there, Amy, Sue, and Stacy, who started this session, I want to say, more than 12 years ago or something like that. And as far as I'm aware, maybe other than the Molnar Award might be the longest running session continuously in AAPM and our lore. And then throughout the bottom, you see Molly, Mike, Justin, who didn't know he was going to be in my presentation, so sorry about that, Justin, but you're a good looking guy. So anything you can do to include a picture of Justin, you should. And Stacy Stibbs. So all of these people have kind of helped, as far as I know, with this type of a presentation. And so with that, I wanted to say thank you guys for the support and the lineage that you've had for this. This is not a short talk or an easy talk, because you have to spend a significant amount of time reviewing literature from many different journals, and the methodology that we use to do something like this is each of us have specific keywords that we have to search through PubMed within the last year, somewhere in the neighborhood of 15 different keywords, and then each of us are assigned specific journals that we look through to ensure that we're not missing some of those just based on the keywords that we're searching. So for instance, I will look at Pediatrics and GM of Pediatrics, and then each of my co-presenters look at a different one. And so there is some methodology to it. It is not just we randomly choose, but we do assign an ordinal ranking of one to five to determine what's the best abstract that we've read and try to get them in a category so that we generally review the top 10 to 15 actual papers, is usually the goal that we try to limit it to. I have posted the top 15 abstracts online in the Pediatric Rehabilitation Medicine Facebook group, so for those of you who do Journal Club or who are looking for some kind of article to present within your local institution, please take a look at that. I know that the education chair will be looking at inviting some of those high-level abstract or high-level papers to present at national journal clubs throughout the course of the year, too. So I know a lot of you use that, so thank you guys for all of that. With that, moving on to our first article, which was kind of a unique one for us, as I don't think we've ever had any burn-related article presented. But this is Inspiratory Muscle Training Impact on Respiratory Muscle Strength, Pulmonary Function, and Quality of Life in Children with Chest Burns. And so for those of you who have not been involved in burn rehab before, this is one of those areas that I think is ripe for opportunity for us if this is something that you have an interest in yourself. Know that chest wall burns really significantly impact quality of life and quality of inspiration. When you have some kind of burn to that area of your body, it is a constant reminder every single time that you take some kind of breath, how significant it is and how important it is to breathe, obviously, but how significant it is to do so when you're dealing with aspects of pain. After two years after a burn, there's been a lot of evidence saying that you have some kind of aspect of an obstructive pulmonary disease. And subsequently, longer term, because of just this aspect of hypermobility, hypomobility of the chest wall, you end up with much more of a fibrotic or restrictive type of pattern just because of the aspect of not fully expanding your lungs and expanding your thoracic cage, your rib cage to do that. So the goal of this study was really looking at determining the effects of a pulmonary rehab program on muscle strength, lung function, pulmonary capacity, and just the quality of life in that really acute phase to try to prevent, first, this obstructive pattern from happening and, secondarily, potentially prevent this restrictive pattern from happening in the end. So this ended up being a one-to-one randomized controlled trial, which is kind of always interesting to me when you have a therapy trial that gets randomized and what's your sham intervention whenever you're doing something like that. So what they were doing for this inspiratory muscle training is essentially adding on 60 minutes of training three times a week that's really focused on the inspiratory phase of their breathing, so expanding that lung capacity, expanding that thoracic rib cage to really try to prevent that aspect of fibrosis from occurring and allow for more hypermobility or ensure that you still have that hypermobility in the thoracic section while you're breathing. They also got standard of care, which was just a generalized pulmonary rehab program, which was 20 minutes several times a week. And then the control group was that pulmonary rehab, but then also some kind of funny breathing, I guess. I'm not quite sure how they had worked that out. But they looked at children 10 to 18 who had at least 30 to 50 percent of their burns, and those were deep partial full-thickness burns. On the right-hand side of the screen, I have to give a shout-out to the AAPM and our Knowledge Now article, from which I pulled this as well, who had a great review of how they were actually looking at estimating total body surface area. Again, this is kind of how I said that they went through the different aspects of using their protocol. They did an a priori power analysis to determine that they needed 32 individuals per group, but they actually only got to 20 per group. And where that's interesting is that all of the data that they still had was statistically significant at the end of it, meaning that even though that they needed to get a higher number to ensure that they got a significant change or statistically significant change in all these patterns, one of the things that they actually found was that the effect size that they had, so essentially how effective maybe was the treatment and how big of a deal this was, was so significant that they didn't actually need to get to that point, meaning so when you calculate effect size, you have to calculate a power analysis, use an alpha level, which usually we set at obviously .05. You have to look at your sample and how many patients you need. And the third part of that that comes into it is the effect size. So how much does an effect do you need to see a difference between two different groups? So a good example to think about effect size is we can have something that changes a pain medicine benefit from a pain scale of 8 to a pain scale of 7.9. And that's not really important. But if you get enough patients in those two different groups, you can actually tell a difference between those groups if you over enroll. And so that's always a good idea to know what three things go into a power analysis calculation. And so when you're looking at all the things that I was talking about that they were wanting to know is inspiratory function, FEC, FEV1, and those ratios between it, a six-minute walk test, quality of life aspects of stuff, so both the physical, psychosocial things, all of those things were actually statistically significant at the end of all of this. So the question to a degree is how much did that eight weeks of an inspiratory muscle training program during an acute phase of hospitalization really improve several clinical factors? It was a relatively safe and effective treatment option for a lot of these kids when they were actually able to be involved with it. I had the question of what level of PMNR involvement is there at many institutions during this initial phase, as I feel like that's something that we can really look at and potentially affect. I think when we see burn consults at my institution, one of the things that we're majorly focused on is just positioning, range of motion, strength, and we look at the extremities. But when you're looking at what's our work capacity, what's our ability to have quality of life, a lot of that comes into our respiratory capacity and our ability to actually work through therapy sessions and continue to improve with time. And so that was the article number one. The second aspect of that is safety and efficacy of ethanol in cerebral palsy. Some of you may recognize a few names on this paper itself, but this was from the PMNR Journal dating back to November of this last year. Obviously many of us know that there's limitations now in total daily, total body dosing when injecting a botulinum toxin. While we love the fact that medications are now becoming on-label more in pediatrics, that's also somewhat of a double-edged sword because then that's obviously significant limiting the amount of a certain medication we can use. Insurances will look at it and say, well, a drug package insert may say this is the amount of medication that's actually able to be injected to this population. Even if you think you can inject maybe 400 units, the limit may be 340, right? And so trying to find other ways around injecting patients and ensuring that you can decrease their tone to the point that it makes them more, to that it improves their quality of life is very valuable. So with ethanol, one of the things and the benefits with it is obviously it's a longer duration of action, much more potent, and really costs like pennies on the dollar relative to lots of dollars on the penny for a lot of our toxin injections. The real aspect and the benefit of it, like I said, is just to decrease the overall toxin amounts and really allow longer duration of treatment or duration between treatments, which is especially true at our institution where we're not injecting any more frequently than maybe every six months or every nine months, as long out as we can kind of get with toxin treatments. That's kind of our goal. And so they used a hypothesis that using ethanol with some aspects of guidance would result in real safe alternatives related to that. So they prospectively looked at 112 children that received only the onobitulinum toxin, 55 that received that and phenol, and looked at a two-week post-procedure evaluation after injection. And this was performed by a blinded nurse who was not aware, or blinded assistant that was unaware that they were being, that this data was being captured from a survey perspective. And they orderly ranked these improvements from one to five and asking families how well did they think the injections worked versus how they were before. When compared with just the toxin injections alone, the combination treatments had a statistically significant increase in score of 0.35 higher. And that was a pretty good thing to see, but at the same time, they questioned whether or not that was an actual clinical significant difference in the amount of improvement that they actually had. So one of the things that they just summarized is that ethanol and erysis, especially using some aspect of targeted treatment, is very valuable. One of the challenges with it, though, is obviously it's much more difficult to perform this type of injection than just putting a needle in any kind of muscle. And a lot of times, one of the things that they didn't mention is that it's maybe more humane for us to do these sedated than unsedated, right? And so I don't know anyone that I've seen in a while that's doing these unsedated, and I think that's one of those considerations to think about on the other aspect of things is, is doing sedated procedures with risk or without risk? And I would always say that having some risk associated with a sedated procedure is important to be talking about any time we're talking about this level of things. Furthermore, what may change aspects of emerging treatment and procedural techniques that maybe ethanol may be not something that we're doing so much in the future, as we've been talking a little bit at this conference already about aspects of cryoneurolysis and hyaluronidase. And some people may geek out on some of those things. But that's one of those things that when you're looking at what may, what things may not be in vogue in the future. And I always think about that when we're talking about what specific things we need to do when we're training the next generation of pediatric physiatrists. As I don't know as many people who are as old, or I should, sorry, not old. I think Dr. Ratna Singham in the last lecture referred to us as late career. And so, and so those of us in the later career that earned, that learned phenol, is that really going to be the thing that we need to teach trainees in the future, or is it going to be other aspects of targeted intervention and targeted treatment? The third presentation I have, just to go through this a little more quickly, was actually referenced by Dr. Owens in the peds day during the first lecture as well. So this was a zilindrinate study, which was from the journal Clinical Endocrinology and Metabolism talking about non-ambulatory children with cerebral palsy, and it was a randomized controlled trial. They'd previously not had a randomized controlled trial looking at zilindrinate in this level of children with cerebral palsy. We obviously know that just the aspects of fracture frequency is increased as our bone mineral density goes down. They looked at kids who had GMFCS levels four and five, who were ages six to 17. For those of you who don't know, this is a medication that is dosed every six months, and so twice a year infusions, which is different than pamidrinate. And so knowing the differences between the drinates is very important when you're talking about what length of time you may have it. I always like to say about Botox or Dysport or Myoblock, anytime you put a muscle or put something, a medication into the body, you can't just suck it right back out. The same thing is very true for some of these very long, long acting types of medications. So they looked at patients and doing a DEXA at both zero and 12 months. They ensured that these patients had adequate vitamin D and calcium supplementation. They gave a first dose at .025 milligrams per kilogram and a second dose of essentially double that. They were able to look at 32 patients who they randomized 24 into. Two different groups, 14 that were put into the intervention group, 10 that were put into the placebo group and didn't lose anyone to follow up, which was like some kind of a miracle over a course of a year study. But if you get a DEXA on people after a year, apparently they show up. So I think I may start doing that for all my baclofen studies and just offering free DEXAs at 12 months. But one of the aspects that they were looking at is several different areas, the lumbar spine and three different lateral distal femur areas on DEXA. And so that's somewhat of a common aspect. And if you were to look at it, all four of those areas increased in the treatment group on the right-hand side of this graph compared to the placebo group on the left-hand side of the graph. The only thing that they mentioned was that one of the aspects of the lateral distal femur had a confidence interval on the placebo side that was quite large. And especially the treatment group also had that large confidence interval. So that was likely an explanatory aspect of why that was not statistically significant just to look at the graph and potentially be able to see that. So that's essentially what I had talked about, that those Z-scores had increased in all areas. Remember that these medications change both formation and bone resorption. There are some growth and remodeling issues, and we're talking about kids with cerebral palsy from ages six to 17 who will likely have some kind of osteo-related surgery or orthopedic-related surgery during that time period, especially if we're talking about patients who are in that GMFCS four to five category and how do these medications impact and cause all of that interplay to happen. The only adverse effects that were really common were hypocalcemia and also some GI-related side effects. That was just something that they had noted in the 14 patients who actually were treated. One of the limitations where all of the participants were Caucasian and that just overall limited total sample size may have been one of the reasons that that confidence interval was so wide. And so that's just the takeaway that I had from those three papers. Next up, we'll go with Dr. Thomas. All right, well, that's getting pulled up. I think I have to go off on a tangent here where in research, it's really important to be very specific. So if we're going to get into discussions of Texan versus Kansas City barbecue, it's a question of, are we talking about brisket or pulled pork? We got to really break it down because I think brisket, we win. I think any other Texans here would agree with me on that. But I get to take off the second half here with the next three papers. And I was really excited about this super cute baby picture that I found of Matt and I figured everyone would enjoy it. Of course, this year, he chose to be so gracious with me and Mary overall to start this off, but we're ready to troll him. So be prepared. Okay. Because it just wouldn't be the same. I mean, that's really what works in a trio when two of you gang up on one. So the first paper that we have here in my section is functional electrical stimulation during walking in children with unilateral spastic cerebral palsy, a randomized crossover trial. And I will be up front as we dive into this paper. This is from developmental medicine, child neurology. And it's from a very reputable group in the Netherlands who's put out quite a bit of research in different areas of rehabilitation, including therapeutic interventions. We were really excited about this paper because we really liked the methodology, but the conclusions are a little wah-wah. But I do think that it's worth going through the methodology because it applies so closely to what we do in rehabilitation. So for those of you, I think most people are familiar with this territory, but functional electrical stimulation, the entire principle here is that you're using an electrical current to then stimulate contraction in a muscle with the hope that you can produce some sort of functional movement. So here in the picture, you see a walk aid, which is what was used in this study. It is a form of functional electrical stimulation that stimulates the perineal nerve so that you can get ankle dorsiflexion through the tibialis anterior. So this group wanted to know, okay, if we have these kids that are relatively highly functional, GMFCS one to two, and you have unilateral CP, is the walk aid equivalent to something like an AFO? And they wanted to put this into perspective of the international classification of functions. So they wanted to look at body function, activities and participation. So again, something that was exciting to us as the trio. So they created this to be randomized, obviously not blinded because the type of intervention, but allowed for crossover, which is pretty unique. So children were either randomized to a walk aid or to whatever they were using on a regular basis, which was the AFO for 12 weeks. And then there would be a six week washout period. And then they would cross and use the opposite device for 12 weeks. I believe in the washout, they were actually not using anything to be able to truly get rid of the effects of the other orthotic. So for their power calculations, they needed 22 patients to calculate a 30% difference. And we'll talk about what that difference really means in the way they designed this study, but that's a pretty big difference, right? A 30% change is big in a lot of rehabilitation studies. And they wanted to account for attrition. So they chose a sample size of 25 to have a 10% attrition rate. Their outcome measures. So their primary outcome measure that they use, which is used in a lot of therapy interventions, is the goal attainment scale. And for those who are not familiar with it, the goal attainment scale is very nice because it is very patient centric. It puts the patient's goals as the primary objective of the study. Individuals can choose the outcome measure that they want to be focusing on. So if you're using a walk aid or an AFO, what do I expect to happen from this intervention? So you can see here, these are examples from patients in the study. Something like improving forefoot landing or increasing walking distance. So it's very personalized to the patient. Now, from the scientific view, that's also very messy, right? Because that means every individual in the study has a personalized goal that is separate from each other. So it's not as clean. But it is a very sensitive measure as a result. Then they also included secondary goals that were much more quantitative. So they had quantitative gait analysis and they looked at specific kinematic measurements in the gait analysis, the six minute walk test, and then also the cerebral palsy quality of life questionnaire. So I'm gonna talk about statistics. I'm usually the one in the group who glosses over this. So I'm looking at Matt, I'm like, oh, am I gonna get this right? But it's really rare to have a non-inferiority study. And the important thing here is that they're trying to prove that there is no difference between these two interventions. So the null hypothesis is that the treatment is inferior to the comparator by more than the margin that they've set. So in this case, they're expecting a true change to be 30% attainment of goals. So they've set this really large margin. And when you're looking at inferiority, so statistics usually have these two tails, right? Because you're normally looking for a significant change. So that could be a significant change in the positive or the negative. They only care about the inferior. So you only have a one-tailed test, which usually means that you need a larger sample size to detect those changes. But they chose to look at a very large change, so a large effect size, and then they chose a super sensitive outcome measure so they were able to keep the N in a reasonable number. Now, unfortunately for them, out of the 25 patients that they enrolled, seven dropped out. So they actually did not meet their numbers that they needed for their power analysis, as Matt was explaining. But this is also a non-inferiority test, so it's a little bit different. So what they used is, which is really common in clinical trials, is an intention to treat approach. So if you're not familiar with this concept, it's that you include everyone who is originally enrolled and then have to make an assumption about what that outcome would have been. So they were very conservative, and they chose to say that those who dropped out did not achieve any of their goals according to the goal attainment scale. So even with them being that strict, on the left-hand side under the A columns here, you can see the GAS is the goal attainment scale, and one means the first goal that they have. In the goal attainment, you can have anywhere from one to four individualized goals. The first goal is what their primary objective was. And they did not see a significant difference between FES, meaning the walk aid, or conventional, meaning their AFO. And that also was the same for their secondary goals that the children and families had chosen. And when they didn't use intention to treat, and they were like, well, what happens if we just look at the 18 patients who completed the study? And again, there was no significant difference between the FES and the walk aid. Essentially, the way they set up their statistics, meaning that there is no significant difference between the two and their equivalent. Now, the reason I show a billy shoe here, which is when you get to the breakdown that's actually in the paper that we had not seen when we had originally been scanning through this paper, they wanted to test what the patients were using on an everyday basis against the walk aid. So when you look at the breakdown, the AFOs had a whole variety of solid, hinged, dynamic, but some of them were using adaptive shoes. And I felt like that actually made it even muddier because I don't think you can really put those on the same spectrum. And it wasn't like they were telling us exactly what type of adaptive shoe it was either, because obviously we know some that are much more flexible. Some are purely adaptive because there's a big zipper, right? And some are adaptive because they have a hard sole bottom, they're locking out your ankle and things like that. So I think it made the data a little bit muddier. Now, some of the results that they got were sort of obvious. Planar flexion was increased when you were using functional electrical stimulation, but you also don't have a brace blocking planar flexion, right? So you would expect it. When they went back and asked these children, would you prefer the FES or an AFO or whatever you were using on a daily basis, it was about 50-50. And just as many of us who've ever worked with the WalkAid, oh, sorry, that'll be the next one. And they found that the WalkAid could help with some participation, right? Because some of those goals were like, I'm able to walk, I'm able to do specific tasks. So nothing really shocking. And again, the WalkAid was very specific in that it really only worked for children who had essentially weakness with no spasticity. One of the issues that they ran into was that any of their children who were having significant spasticity in the gastrocs were having difficulty with the WalkAid because it wasn't enough to compensate for the spasticity. And then of course, just like any of our older kids, cosmesis becomes a huge issue. They didn't like the look of the WalkAid. And then there was discomfort and even skin irritation from the lead points on the WalkAid. So cool study design, interesting way they set it up, but nothing too exciting to take away from the study beyond what we normally practice. Now, the next paper comes from the Journal of Neurology. It's looking at mortality and causes of death in children with cerebral palsy with scoliosis treated with and without surgery. So this comes from a Finnish group. And we thought this was a really well done study. Their big objective here was, we know that there's a lot of reasons why we choose to do spinal fusions in these patients who are very complex, but there's also a really high post-operative complication rate. Some papers showing as high as 36%, and the re-operation rate is even as high as 14%. So they wanted to know, what is the difference in mortality and cause of death between those kids who have fusions done and those who are managed non-operatively? And because they're coming from a country that has amazing nationalized registries, they were able to use a combination of three registries to put together this data. So they used the medical birth register, the care register for healthcare, and the cause of death register, which are maintained by the Finnish Institute of Health and Welfare and the Statistics Finland group. So first off, when they went through the registrar, now I was not able to tell how far back the registry goes from their paper, but they found 4,571 children with CP, which actually seemed low to me for the registry, but they actually found this beautiful split where when they looked for CP plus scoliosis, they found 236 who had not had surgery and 238 who had been fused in some fashion. So almost a perfectly even split. And they actually did an incredible job of going through lots of different demographic features, comorbidities and treatments, which if you go into the paper, you can see this table that has almost like 40 rows. And there were only three areas where there were actually significant differences. They were actually very evenly matched. One of the things that they were looking at is number of follow-up appointments and how long they had follow-up. And those who had had surgery had longer follow-up. Sort of makes sense. They had more interaction points with the medical system, so that wasn't too surprising. But the two other areas where there was a difference between these two groups was the age of diagnosis of CP was different. Interestingly, those who had undergone surgery actually had a significant delay in diagnosis. So the average age for those without surgery was three years of age, and then 4.2 for those who had had surgery. They didn't have any conjectures as to why this was the case. It was a very surprising finding for them. But then most meaningful to this paper that's looking at mortality, there was a significant difference in the age at death between these two groups. In those children who had not been operated upon, the average age was 16 years plus or minus seven. And on those who had been operated upon, average age was 19.8 plus or minus about six. Also feels like a very young population for death when you look at this. So because they had such a rich data set, they were actually able to create a Kaplan-Meier survival curve. And before you think everyone's dying, it's important to notice that your y-axis here starts at 90 on the bottom for 90% survival and goes to 100% survival at the top. And then it's plotted against 60 months, so five years. The light blue on top is those who had had surgery, and then the navy blue below is those who had not had surgery. And you can see that the lines start to differ, especially as time goes on. They were very curious. Was there any difference with when these children were growing up? Now, they didn't talk about the specifics of how they grouped these patients, like age of the year or how they broke it down, but they essentially broke it down into cohorts of four years at a time. And they show that there's still a difference between the two populations, those who had surgery and those who didn't, but the difference becomes less dramatic as you come to the modern era, essentially. Now, getting into why these children ended up passing away, and young adults. On the left column, you have those who did not have surgery, and on the right column, you have those who did have surgery. So if we focus on those who didn't have surgery, the bulk of them passed away from respiratory causes, most of which were pneumonia. That shouldn't be much of a surprise to us. That seemed fitting, they agreed. Now, those who had surgery, the bulk of them, about 45%, passed away from neurologic causes. And the biggest chunk of that, 17%, was actually anoxic brain injury from aspiration. And they were really quite puzzled by this. And they have some ideas behind this. Now, of course, it's a registry study, so they don't have a lot of details on these children. We don't have any GMFCS classification to be a parallel of health severity. We don't have Cobb angles. We don't have access to the actual spine films. They don't have data on the epilepsy medications that they were on to try to give a level of complexity again. And those who didn't have surgery, they didn't have data as to whether those individuals were deemed unsafe to have surgery, like maybe there were too many other risk factors, or was it really that they were milder, and so they don't know that level of detail. But overall, at least in this finished population, it appears that surgical treatment reduced mortality. And when they did a deeper dive, it was interesting, they noticed that the incidence of pneumonia was no different between those who had surgery and those who did. The difference was that whether you died of pneumonia, which again was an interesting thing that they picked up, because they didn't have an idea of why that was the case. And then when it comes to the aspiration leading to anoxic brain injury in those who had surgery, you know, they were thinking through it, they were looking through the literature themselves, and we know that abdominal contents and thoracic contents shift quite a bit during spine fusion surgery, so that they were wondering, would that play a role? And there are some papers that have shown that there's increased dysphagia and slowed gastric emptying immediately after spinal fusions, so they were wondering, does that play a role? But when you look at the characteristics on the original table, looking at the groups, there's no difference in fundoplication or rates of GERD and things like that. So again, a little bit of a mystery. And is it something that's specific to Finland as opposed to us, something different in the healthcare system, unclear. All right, and then my last paper before Mary comes up. I'm totally nerding out on this. I personally think this is the best, but it's really rare for us to have a basic science paper make it in, so I'm gonna try to make it exciting for you guys, but especially as we were talking about changes and modernizations in rehabilitation medicine, this could be the next wave. So, excuse me. This is titled, Collagenase Treatment Decreases Muscle Stiffness and Cerebral Palsy, A Preclinical Ex Vivo Biomechanical Analysis of Hip Adductor Muscle Fiber Bundles. So this comes to us from Jason Howard's group. He is a pediatric orthopedic surgeon and surgeon scientist at DuPont Children's, and this is a international group of researchers, a mix of, I think, child neurologists and neurosurgeons, not neurosurgeons, orthopedic surgeons, and some basic scientists as well, so it's an exciting group. So to take us through the background of the basic science here, there are multiple studies that have shown that there's increased type 1 collagen deposition in the muscle of children with CP compared to typically developing individuals, and it all seems to be concentrated in the perimesial region, meaning the extracellular matrix or that connective tissue layer that goes around muscle fiber bundles. And the collagen in the extracellular matrix in other situations has been correlated with muscle stiffness. So if you looked at different muscle textures in typically developing individuals, the ones that have more type 1 collagen are stiffer. And orthopedic research shows that collagen deposition is a key piece in muscle contracture formation. So they started to dig on this piece, and multiple people in this group are the ones who've seen this collagen change themselves in their basic science research. So collagenase clostridium histolyticum, or CCH, is one type of collagenase that we are already clinically using, and it can dissolve type 1 and type 3 collagen. The important thing is that it preserves type 4 collagen, which is what gives- which is the primary structural component of smooth and skeletal muscle. And CCH is already FDA approved for dupuytren contractures and peroneal disease, so it's something that's already being used in practice and is known to be safe. So they hypothesized that digestion of collagen in the extracellular matrix, or that perimeceal region, could decrease the stiffness of muscle fiber bundles and therefore reduce muscle contractures. And they went on to conjecture that focal use of a selective collagenase injected into a spastic muscle at an appropriate dose could reduce muscle stiffness and improve clinical range of motion. So this should be where you guys are getting excited. So because they're orthopedic surgeons, they had access to patients when they were having hip adductor releases. So they took advantage of this and got consent to take biopsy samples during this time. So they had 11 patients, it was skewed, it was 9 males and 2 females, but they were GMFCS 4 and 5, which sort of fits with the population you would imagine getting adductor releases. And I have some other details there, but the important thing is that they took four samples from each child. And you can see in this picture it's about a 2 centimeter by half centimeter, so they're like tiny pieces and it's easy to build into the release, so it's not extra, not too much extra trauma. So there were two parts to this study. They needed to know how much collagen do you need to use in the first place to get the effect that you want to see? And then do you see a change in the stiffness? So the first part for the methodology, when they were trying to figure out the amount of collagen that they needed to use, they took those little chunks that I showed you in the previous picture, broke it down into 50 milligram samples, and then incubated it in different concentrations of collagenase, or in this case the CCH, the specific one from Clostridium. So they had a control that had none, then they had 200, 350, and 500 units per milliliter, and they did a two-hour incubation. The reason I say it's not magic, it's science, is that there's a whole description of basic science, like tissue prep methodology, that I'm just ignoring here. Just trust me, it looked good. From using my basic science hat during my PhD, it seemed really rigorous and well thought out. So in the top right, when you see the line graph there, or with a scatter plot, what you're seeing is the collagen reduction plotted against the collagenase dose, which is why you have a measurement at 0, 200, 350, and 400, and 500. And they were able to show that it's a nice linear correlation, which is great when it comes to dosing, right? If we're thinking about dosing in the clinical setting, it's nice to have this nice linear correlation. And they were able to use regression to figure out that about a 50% reduction in collagen happens around 439 units per milliliter. So they decided for the studies that they were going to do to look to see if there's a change in stiffness, they just chose arbitrarily to go below that and use the 350 units per ml to be on the more conservative side, which if you were to plot across is about a 35% reduction in collagen. And then when you look at the microscopy, the top row there, what you're looking at is muscle fiber, and the magenta is the type 1 collagen. And it's important to see that it wraps around the muscle fibers, it's not in the muscle itself, which is important because that means it's easier to target if you were to do something like an injection because you're not having to have uptake into the cell. And the yellow itself is the myosin and the blue is the myonuclei. And then they did a different type of stain that's in the black and white on the bottom, where the type 1 collagen is all white, which again just really highlights how it goes around those muscle fibers. So this was exciting because it was fitting with what they had seen in previous studies, matched other people's studies, and now they had a dose. All right, so then does it work? This is where the nerdiness really starts to come out. So they had to come up with this device on the left side, where the first thing that you see coming down is a force transducer. So that is what is picking up if there is any force being generated, which is being measured in millinewtons. And then it's hard to tell in this, but there is a sample that's connecting. And then the other pipette or metal hook that you see on the other side is the length controller. Fancy term for it's the side that stretches that muscle. And they, for each piece of muscle, they figured out the exact starting point where they stretch enough that it gives a counterforce, which is the passive force. So they'll, you'll see that in this paper they use passive force, stress, strain interchangeably, which is all the same as muscle stiffness. And then they used each of those chunks of muscle, did a control run where they did different amounts of strain, meaning different amounts of stretch on the muscle. So 1%, 2.5, 5, and 7.5% stretch. They even, like, were prescriptive about how fast they were stretching the muscle. And they looked at the forces being generated in that muscle, which is basically a measure of stiffness. So you have a peak force and then a steady force, which you can sort of think of as like a R1, R2, if you want to break it down into terms that make sense to us as rehab docs. Because you have that initial tension that the muscle gives you back, that snap. And then as you have sustained force on it, you get that steady state force in the muscle. And then they repeated that after incubating for two hours in the CCH. So you can see that they plotted peak stress and steady state stress. They used a box and whisker plot. I really like box and whisker plots because they give you a lot of data, but I know we don't see it often, which is why I gave you the descriptor on the right side. But I'm not gonna dive into it unless you guys have questions. The important thing to take away from this is the light blue is pre-treatment, so it's the control. And then the dark green is after collagenase incubation. And you can see that all of the different strains, whether it's peak stress or steady state stress, there is a significant reduction in the amount of stress. And that means you've significantly reduced the stiffness of the muscle. So your takeaways. Collagen reduction in muscle after treatment with CCH displayed a linear dose response. Hip adductor muscle specifically had stiffness that was significantly reduced after CCH treatment. So we have proof of concept of a potential use of collagenase injections for non-surgical reduction of muscle contractures and therefore stiffness. And similar to botulinum toxin injections, you could create muscle specific algorithms with collagenase injection protocols. And it's important to note that different muscle groups naturally have different amounts of collagen. So one of the things that they noted is that in typically developing individuals, we know like hamstrings has more collagen than gastroc. So we would have to get that specific with it. But similar to like recommendations for different botulinum toxins and different muscle groups, there's the potential here to do the same with collagenase for stiffness. And it would be the first thing. And now I'll hand it off to Mary. And it was amazing that I found this cute picture of both of them when they were babies. Yeah. Awesome. All right, you guys. I know we're at the tail end here, so hang in tight there on a Friday afternoon. And thanks for sticking with. So we're gonna go through the last three articles here. So again, I'm Mary Dubonham over in Boston. So first one, actually, I'm not sure if they're in the room or not, but we have some familiar faces there. So this is from Children's Healthcare of Atlanta, and they're looking at early mobilization in a pediatric ICU and WeFim scores. So it was a retrospective study. So what do we know? Our background. So early mobilization in the adult ICUs has shown so many benefits, right? So decreased hospital length of stay, decreased ICU length of stay, decreased hospital-wide illnesses, and improvements in their functional status. But as in so many different areas of rehab and medicine in general, we have less data for pediatric, right? But many of you probably have PICU-EP in your hospital systems and PICU early mobilization programs going on. So the exciting thing is that we're able to start looking at this a little bit more. So that's what CHOA did. So again, it was a retrospective chart review at a single site. Their very first PICU early mobilization protocol patient was in 2014. So they still reported that 2015-2019 was still an uptake period, people kind of learning, getting used to the protocol. So it was still early on for them, but it was well within the period of at least some patients were undergoing this protocol that experts within the hospital system created. So inclusion, so babies through 21 years of age, mechanical ventilation for at least 48 hours, and then that they were ultimately discharged to inpatient rehab. And what they were interested in looking at is the WFIM scores, and was there a difference on admission to inpatient rehab and the WFIM scores in the group that had early mobilization versus those that didn't. Now in terms of early mobilization, probably those of you who have protocols are familiar with, there's different levels of the early mobilization. So they were most interested in looking at level two or level three while the patients were actually intubated. And so that was what was interesting about this study. So that's more degree of mobilization, right? So this is sitting up in bed or things out of bed, like walking and standing while they're on mechanical ventilation, which obviously is impressive, and we've probably all seen those cases and are excited about the potential benefits for that. So they looked at the WFIM scores, they also looked at the PRISM score, so this is a pediatric risk of mortality, and that helped them kind of- their goal with that was that, oh, probably both groups are going to be fairly similar, you know, and they were going to hopefully prove that. They didn't prove that, which is interesting, but looking at how sick these patients were, how stable they were, versus how critically ill were they. So this is that classic figure that you usually see. So of the little over 1,000 patients that were intubated greater than 48 hours, once they actually looked at patients that would meet the criteria for being able to safely do the early mobilization protocol that they had, they basically were down to 78 patients that did do the early mobilization, and then 111 patients that could have done early mobilization but in this retrospective chart review did not for various reasons. And again, this wasn't like, you know, a pick-you-up protocol where like people are- everyone's kind of doing it. It was still early on when there was maybe some docs that had more buy-in than it, some, you know, people that might have been nervous about it for different reasons. So obviously the groups may have had some differences at baseline because it was retrospective, it wasn't prospective. So looking at the groups, there was actually some differences between them at baseline, which is something you can run into with retrospective at times. So you actually saw more trauma patients were not getting the early mobilization, and you wound up seeing actually more primary respiratory patients were getting the early mobilization. And then looking at their age and years on admission, there wasn't anything too significant that I would take away from this in terms of comparison, fairly similar. So I wanted to also point out they were pretty good in terms of the comparison group for age and for sex, except for in the respiratory group there was a little bit of a difference there. But again, this was like a first stab, right? This is not a prospective study where you'll be able to even that out a little bit better. So back to the- now to the results. Looking at that respiratory group. So this is primary respiratory condition as the reason that they're on mechanical ventilation. Looking at the WFIM scores, which again is the big thing that they're looking at, their hypothesis was that across the board the mobility WFIM scores at admission to inpatient rehab were going to be higher in patients that had early mobilization, right? They already started their mobilization, they already started the mobility, and they saw that in the respiratory group. So that was exciting, right? So we could probably debate for longer than an hour about the 0.05 p-value. I'm sure some of you have read the the article about, you know, the pros and cons of using that. But you did see a quote-unquote statistical significance there. What's exciting too is you also saw one for the hospital length of stay, and I wonder if anyone in the audience notices the issue with that. So when you see a p-value, fun fact, you have to look further than just the p-value, right? So there's a significant difference here in the hospital length of stay between early mobility group and comparison group. That's awesome, right? Actually you also have to look at the direction. So Shruti talked about that a little earlier too, but they actually- the early mobility group had a higher hospital length of stay. So again, just a reminder that p-value isn't the only thing you look at, so I thought that was helpful to kind of sneak that piece in. But they were kind of a little surprised by this finding and were like, oh that's kind of cool, or is it because people were around longer that maybe there was more of an opportunity to have the conversation about doing it? Was it that, you know, the comparative group was only intubated for 48 hours, and so therefore they didn't have enough opportunity? I think there probably is data for them to look at that further. It wasn't really delved into too much in the paper, but it was something that they definitely made note of. And then for the neurology group, so we're actually seeing that in terms of the severity of critical illness, you're actually seeing more critically ill in the group that had early mobilization compared to the comparison. So again, kind of cool in a way that actually people were like gung-ho and doing this for patients that were quite sick, but we didn't actually see anything in terms of the WFIM scores between the early mobility versus comparison group. Similarly here, nothing in terms of difference between the WFIM scores at admission to inpatient rehab, but seeing in a couple ways, hospital length of stay, higher in the early mobility group. ICU length of stay, higher in the early mobility group, and then total length of time with an endotracheal tube is also higher in the early mobility group. So again, seemed like it was sicker patients that were getting it in the retrospective chart review, and just in that primary respiratory group were they really seeing that the mobility WFIM scores on admission were improved, were better. So again, this is just all the things that I just mentioned, but the one piece that, you know, I haven't mentioned yet, but I actually think was maybe the most interesting thing is there were no adverse events. So they defined serious adverse events as like a patient, you know, like their tube coming out when they were doing early mobilization, or another significant serious effect that I think a lot of people are concerned about when they're doing this. And of all these cases, there were no serious adverse events that were there, which to me actually I thought that was one of the most interesting findings here. So certainly my thoughts on it are it's exciting, it's exciting that we're starting to have the ability to do this work, it's exciting to see peds rehab doctors doing this kind of work too. No serious adverse events is helpful information when we're talking to our patients, but it needs more perspective work to kind of tease out what those findings were, because there's probably several reasons for the findings that you can't really look at as much in a retrospective study. So next one is optimal volume of moderate to vigorous physical activity post-concussion in children and adolescents. Obviously concussion is a big topic that there's lots of data, lots of research out there on right now. This was another one where I agree with what Truthy said earlier about the study that she presented that kind of looked really exciting, but then when you really tease it apart, there were some things there that I wasn't as excited about the results of this one, but it was an impressive design, a very ambitious design I'd say that they had. So we know you know Dr. Letty years ago was really the pioneer in terms of physical activity being important, specifically moderate to vigorous physical activity cardio for the recovery in concussion, right, and so decreasing symptom burden, resolving your symptoms quicker. So that's known, but the optimal dosing and volume, of course in pediatric patients specifically too, isn't really clear at this point. So that's what they were hoping to look at. So they actually did a prospective cohort study of children and adolescents with concussion. This was in Canada. They collected data at weeks 1, 2, and 4. They looked at their symptom burden with the HBI. They looked at their physical activity actually with an accelerometer. So this is the part that I think is very ambitious. I don't know if anyone else in the room has ever tried to do research with accelerometers. I have. It's very hard to get people to have compliance, and that's the biggest issue with this study. And they also, they considered it data that they would include if they did at least eight hours a day for four days out of a week, which again, that's cool, but you have 24 hours in a day, right? And so it's, it's, I understand why they did this because having done a study with actographs, one of the accelerometers, we had the same challenges, but it also leads to a lot of missing data. And then they also looked at balance, which they didn't focus on as much on the actual study. So the kids were 10 to 17 years of age. They had presented to the emergency room within 48 hours of their concussion, and they exclude, there's a long list of exclusion criteria. They were appropriate kids who had like more neurologic going on than just, or more medically going on than just a concussion alone. So again, the the flow diagram here shows that over 1,000 were assessed for eligibility, and then ultimately 456 were enrolled, and a ton of them were excluded. So 189 were excluded due to missing or corrupted accelerometer data. So that originally just kind of gives you a sense of what's the difference between that group that dropped out versus a group that was there, right? So it already gives you a little bit of a flag on that data, but they didn't wind up including 267. This one is actually, this is probably the most interesting finding. So they had these two groups. So they had one group where they counseled them that said like, it's really important to do moderate to vigorous activity after the first 72 hours, and then they didn't counsel the other group, which I actually think is interesting because we know that that's helpful in terms of the literature, and so I don't know that an IRB would actually approve me for not counseling the other group about it. But again, I think the study, it was done in Canada, might be a little bit different too, but it didn't matter if they were counseled to do cardio. So my biggest question is, are they actually listening to our counseling? So that's what I took away from this study. So yeah, anyway, so they combined the analysis together, and then they kind of like looked at the the spectrum of people's physical activity. And by the way, it wasn't that nobody was doing physical activity, it was that most of them actually were. So take that for what it's worth. So there was a lot of missing data, and so they did some really fancy statistics. They did an imputation model. So they looked, they basically tried to scientifically make assumptions about the missing data to try to piece it together. So I think that it was well done, but I think my concern with it is whenever you have to make so many different adjustments for the data, you just have to make sure that you're keeping that in mind, right? So this was in the supplement, but I thought it's just helpful to show the observed data is the top, the top figures up there, and then at the bottom the graphs are when they actually did the adjustments. So overall it doesn't look too different, but some of the curves are just showing some slight differences there. So just to, you know, full transparency about that piece. Okay, so here basically what we're looking at is all the points for all the different patients, right? And then they create a curve that that goes along those points. So if you can see there, you have these blue dotted lines. The first one for each graph is a 25th percentile for moderate to vigorous physical activity minutes. So the minutes are on the bottom there on the x-axis, and then the second line is the 75th percentile. So you can see the first one is at one week, the second one's at two weeks, and the third one is at four weeks. So you could see at the first and second figures, so figure A and B, which is at one week and two weeks, you have a little bit of a curve that kind of comes up, and it's coming up around 75th percentile. So they were looking at a cutoff of 75th percentile, which is 259 minutes for figure A, it's 565 minutes for figure B, saying that, you know, if they, and the, I should say the y-axis is their symptom burden. So symptom burden seemed to go up after you went above that level, but if you stayed kind of within that 25 to 75 percent, that you seemed to have a lower symptom burden than folks that were outside of that, too little or too much. That's kind of how you interpret that. At week four, it was actually more of a plateau flatline, so not something that there was too much difference really there. So again, this is just showing those numbers and where they got those from for the 75th percentile. Okay, so then they looked more specifically at cognitive symptoms and somatic symptoms, and basically at week one, it seems to follow that pattern for cognitive symptoms, where if you were in that happy place of the physical activity, that you had less cognitive symptoms, but actually for week one and two and four, they did see something when they parsed out the somatic symptoms specifically. So this is direct quotes from them. So they say that their findings is, in this cohort study, volumes of up to 259 minutes in the first week, up to 565 minutes throughout the first two weeks, were associated with lower symptom burden at week one and week two. Again, I wouldn't necessarily write home about all these findings per se because of the missing data, but at least it's a start, and they feel like that suggests that moderate to vigorous physical activity reduced symptoms up to a certain threshold, but then appears to have no further benefit beyond that point. So at least there's a number that can be cited if you're getting asked by your patients, and again, this is how many minutes for the whole week. So again, I don't think for me this is changing practice. It makes me think how much are my patients listening to the counseling that I'm giving them because there was no difference between the experimental and the control group in terms of how much physical activity they did. I think it's great, and I think I'm really excited about all this work that's happening, so I think more study needs to be done, but I don't think this one is gonna actually change my practice, I'd say. All right, so the last one. This is the one I'm most excited about, and again, you'll see some familiar names up there of pediatric rehab, right? So this study was done at Kenny Krieger. Its head control contributes the prediction of emergence from the minimally conscious state in children admitted to inpatient rehabilitation. So background. If we know prognostic factors for pediatric disorder of consciousness, we can make better decisions about how to have those conversations with families because that's what family will want to know, right, is what is next year gonna look like, what is my child's life going to look like, right? And unfortunately, we don't have that much data, right? And so specifically, again, so with disorders of consciousness, we have some data, but still need more. With pediatric disorder of consciousness, even less. So what they wanted to look at is does head control, does neck control, does head control, does trunk control have any prediction value in terms of outcomes in pediatric disorder of consciousness? So the first time that's been looked at. Their hypothesis was that pediatric patients with disorder of consciousness who had better midline control, so head control or trunk control, would have a better prognosis. So it was a retrospective chart review of patients 2 through 21 years of old with a disorder of consciousness. They were admitted directly from acute care to the DOC program on inpatient rehab at Kennedy Krieger, and there was a neuropsychologist that was part of the study team that was able to be part of the chart review to determine their state of consciousness at admission to their inpatient rehab program and then at discharge from their inpatient rehab program. They also just did as part of their protocol, the PAMs, so the physical abilities and mobility scale, that included head control and trunk control. So they had this information available to them. In terms of that famous table one, in terms of characteristics between the folks that did and didn't emerge, they were fairly similar, except one difference that is very well cited in the literature was folks that came in with a lower state of consciousness, so in the vegetative state for instance, were less likely to emerge than those who came in in a minimally conscious state. So that is kind of a little expected information, so the fact that those two are different is what we'd expect. Now this table, so the statistics here are things I'll kind of talk you guys through. So reminder, sensitivity, ratio of true positives to overall disease positive. So for the state of conscious, I'm just going to highlight the ones that I think are important here, for the state of consciousness there was a really high sensitivity. So if the state of consciousness was good when they were admitted to inpatient rehab, they were more likely to emerge. Also when we're talking about state of consciousness, the negative predictive values, so chance of a negative test being a negative test, in this case meaning chance of, okay they're in a vegetative state, meaning they might not emerge, was pretty high too. So good state of consciousness, good prognostic sign, poor state of consciousness, poor prognostic sign. So that's all kind of known already in the literature, but now we have some more information. So head control, positive predictive value, again chance of a positive test being a positive disease. So good head control kind of predicting emergence, okay, for that one, and that was 81.8 percent. So pretty good actually, and that was one of the big things they wanted to look at. So I thought that was really interesting. And then the head control for PAMs greater than three. So head control greater than one, so they were able to maintain some midline head control. If they were able to lift their head and to have head control for 30 seconds or greater, there was a hundred percent positive predictive value. That's really cool, right? Again, it's smaller numbers, it's retrospective, we need to do more data, but that was really cool information to see. In terms of trunk control, there really wasn't anything to take home for that one. Okay, so here we can just see that we also have to remember the fact that, okay, if they were unable to maintain their head up, so they weren't able to do that with their head control, it didn't mean that none of them emerged. So we have to keep that in mind too. So if you look at the very first bar here, you will see that the folks who emerged are in black here. So if you were unable to maintain your head up at all when you came in to inpatient rehab, there were still some of them that emerged. All right, so that's kind of where we're thinking about all these different statistical terms that some of you may have not thought about in a while, but that's just, I'll go over that in a little bit more in a minute here too. And then if you're looking at the trunk support, it's, like I said, that one was a little bit less helpful. They think in part because a lot of these patients are- so if they needed maximum assistance, a ton of them still emerged. And obviously it's because, as we all know, usually you're able to start working on your head control and then you're kind of able to do trunk control. So they kind of felt like this one maybe wasn't as good of a factor to look at. So now we're going to look at the ROC curve. So I know it's interesting that we kept this one for last, but here we are. We'll get there. So on our x-axis is 1 minus our specificity. That is our false positive rate, okay? So positive, but it really shouldn't have been positive. And then our true positive rate is going to be our sensitivity, and that is on our y- axis. So for a receiver operating curve or an ROC curve, a perfect test, a perfect curve would look like this. It would come up and across, okay? So that if you look at what's the area under the curve for an ROC curve, everything would be shaded in, okay? That's a perfect test. I don't know if a perfect test exists. It probably, I mean, sure. None of the ones that we're using in medicine are perfect, right? So with that, you want a curve that's going to be as close to that as possible. Now, if you see a curve that looks straight like this, that's about 50% area under the curve, which means it's a flip of a coin, right? So that's not a good test. So you want it to look less like that and more like the first line that I showed you, okay? So what I'm going to go through, so when we look at the area under the curve, for trunk control, the area under the curve, so that basically means, like, when you get a result, you can kind of trust it in both ways, right? You can trust that it wasn't a false positive and then it wasn't a false negative. You're kind of looking at both parts of it, right? So with trunk control, the area under the curve is about 57%, so it really wasn't helpful in terms of, like, prognostication. When you look at admission head control, the area under the curve was, so, sorry, this one here is our trunk control, this one here is our head control. So it's not bad, but we're kind of still missing a chunk of the graph there, right? And that's because what I showed you earlier was if you had poor admission head control, that didn't mean that you didn't emerge, right? So that's the piece that's kind of missing on this area under the curve there. But we also remember that admission state of consciousness was actually super helpful, right? And so looking at admission state of consciousness here, okay? So now what they did was they actually said, okay, if you combine the admission state of consciousness plus the admission head control, what does the area under the curve look like there? And it's 87%. So that's kind of what they had suggested. So it's kind of interesting, all that to say, you're not using head control as the only thing you're looking at, and of course it's the first study on it, we need to repeat that. But maybe it's something that if you're, you know, it's a factor that you'd look at. So you would look at your state of consciousness on admission, but you'd also look at your head control. So in conclusion, admission state of consciousness had the highest negative predictive value, admission head control had the highest positive predictive value, and then 50% of those who emerged didn't have independent head control at admission, so don't forget that. Don't, you know, don't get too disheartened or counsel your patients, oh, they don't have good head control, that means they're not gonna emerge. It doesn't actually mean that, right? It just means that they do have good head control, that's a good sign that they may emerge, right? So I thought this was a really compelling study. I think that it's gonna be helpful in our conversations, right? And, you know, we are the docs that follow these kids more long-term, so we should be having these conversations, and it's awesome to see that there's peds rehab doctors that are working on some factors that we could talk about for these conversations, and then next up with some prospective data would be much needed. So with that, that is the last article that our threesome here is going to present, and I just, I don't know, Matt, was it like a few years ago? I don't even remember how I got roped into this. Do you know, like, I feel like, did we have a conversation at some point? Did you invite me? I heard that I had a conversation with Matt, but I really, I don't remember having a conversation with Matt that roped me into this for a few years. Also, as we know, we all joke with each other a lot with these talks, but this is also what happens when it's during the pandemic, and you're giving a virtual lecture with glasses on, and you have blue PowerPoint slides. So I noticed two things today. Matt has learned from that, right? So he's not wearing glasses today, and his PowerPoint slides were not blue, so good job with that. But all kidding aside, thank you so much, Matt, for the opportunity, and it's been wonderful working with Matt and Shruti over the past few years, and as Matt pointed out, Dr. Thomas is federally funded, as is Dr. McLaughlin, so it's just wonderful to be able to work with these wonderful human beings who are adding so much to our literature as well. So, thank you. Well, thank you very much. I know the reason why the AAPM&R really likes this lecture every year is that we ensure that you get the full 1.25 hours of seeing me that you pay for. So with it actually being 4.15, I don't know we have a significant amount of time here really for questions, but I think all of us will sit up here in that meantime. I guess two final comments, just because I went first, so I never got a chance to fire back. I did win a cute baby contest at Kmart when I was a kid, and so that was not that far away from saying that I actually did look really cute as a kid. I think I won $150 worth of diapers for my parents, so that was a big deal at the time when I grew up. And then the other thing, as I just have to say, the last article where Stacey was listed last means that she is very much keeping with her pen name of et all. So anytime you see et all, that's essentially Stacey's name. So, you know, well done everybody. Thank you guys very much, and I hope you guys enjoy the rest of the conference. Go enjoy a happy hour or two.

pediatric rehabilitation

functional electrical stimulation

unilateral spastic cerebral palsy

head control

disorders of consciousness

early mobilization

pediatric intensive care

muscle stiffness

collagenase treatment

spasticity management

AAPM&R conference