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#113 - Journal Club 44

Hello Friends,

Lots of new articles were waiting for us to be reviewed this week. We covered a variety of topics including the use of anti-reflux medications, resident training for neonatal intubation, using transcutaneous bilirubin in preterm infants, discontinuing antiseizure medications in HIE patients, and much more. Thank you to all of you for tuning in each week and for helping us make this show possible.

Do not forget to secure your spot for the DELPHI CONFERENCE taking place on March 27-28-29 in South Florida. Our discounted rate for hotel room reservations at Le Meridien will expire on Feb 27. Make sure you take advantage of that, transportation to-from the conference venue will be provided. Delphi offers opportunities to submit abstracts for poster presentation and will offer CME credits. Register at use the code INCUBATOR for a special discount for our listeners at checkout.


The articles covered on today’s episode of the podcast can be found here 👇

Wolf ER, Sabo RT, Lavallee M, French E, Schroeder AR, Huffstetler AN, Schefft M, Krist AH.Pediatrics. 2023 Mar 1;151(3):e2022058330. doi: 10.1542/peds.2022-058330.PMID: 36756736

Rumpel J, O'Neal L, Kaukis N, Rogers S, Stack J, Hollenberg J, Hall RW.J Perinatol. 2023 Feb;43(2):233-235. doi: 10.1038/s41372-022-01553-9. Epub 2022 Nov 11.PMID: 36369530 No abstract available.

Gariépy-Assal L, Janaillac M, Ethier G, Pennaforte T, Lachance C, Barrington KJ, Moussa A.J Perinatol. 2023 Feb;43(2):215-219. doi: 10.1038/s41372-022-01546-8. Epub 2022 Oct 29.PMID: 36309565

Sankar MN, Ramanathan R, Joe P, Katheria AC, Villosis MFB, Cortes M, Bhatt DR, Truong H, Paje V, Tan RC, Arora V, Nguyen M, Biniwale M.J Perinatol. 2023 Feb;43(2):220-225. doi: 10.1038/s41372-022-01477-4. Epub 2022 Aug 5.PMID: 35931798

Sewell EK, Shankaran S, McDonald SA, Hamrick S, Wusthoff CJ, Adams-Chapman I, Chalak LF, Davis AS, Van Meurs K, Das A, Maitre N, Laptook A, Patel RM; National Institute of Child Health and Human Development Neonatal Research Network.Arch Dis Child Fetal Neonatal Ed. 2023 Jul;108(4):421-428. doi: 10.1136/archdischild-2022-324612. Epub 2023 Feb 2.PMID: 36732048

Starr MC, Schmicker RH, Halloran BA, Heagerty P, Brophy P, Goldstein SL, Juul SE, Hingorani S, Askenazi DJ; PENUT Trial Consortium.Pediatr Res. 2023 Aug;94(2):676-682. doi: 10.1038/s41390-023-02514-4. Epub 2023 Feb 9.PMID: 36759749 Free PMC article.

Kaur S, Manerkar S, Mondkar J, Kalamdani P, Patra S, Kalathingal T.J Perinatol. 2023 Feb;43(2):203-208. doi: 10.1038/s41372-022-01597-x. Epub 2023 Jan 5.PMID: 36604581 Clinical Trial.

Lakshminrusimha S, Murin S, Lubarsky DA.J Pediatr. 2023 Apr;255:1-6. doi: 10.1016/j.jpeds.2023.01.013. Epub 2023 Jan 31.PMID: 36731717 No abstract available.

Monson BB, Ambrose SE, Gaede C, Rollo D.J Pediatr. 2023 Feb 1;262:113344. doi: 10.1016/j.jpeds.2022.12.042. Online ahead of print.


Find some of our notes here 👇

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The transcript of today's episode can be found below 👇

Ben 0:54

Welcome Hello, everybody. Welcome back to the incubator podcast. It's Sunday. It is Journal Club week. How you guys doing today?

Unknown Speaker 1:05

And tired.

Ben 1:09

It's not Sunday, but it is. When are we recording this Tuesday? Monday? Your POST call? I'm pre call. That's right. That's right. But you know what?

Speaker 1 1:18

We were getting it done. So happy to be here. Journal collabing. With everybody today.

Ben 1:23

That's right. Priya, how's life for you? Good, good.

Speaker 3 1:28

It's busy. But everybody's busy. So but I'm glad to be here.

Ben 1:32

Yeah. We are finalizing the preparations for the Delphi conference. We're so excited to have some to have so many speakers. I saw, I saw that I didn't want to brag. But like I saw on Twitter that people were having a discussion with Fumihiko from like, chord management and all that stuff. And I was like, in the like, oh, how do you guys do it in Japan. I'm like, man, like he'll be here in combat. And when I didn't want him. I was like, Yeah, he'll be here like, you can talk to him about like, how they like this is literally why we invited him because he'll be here to talk about some of the ways they approached some of the same things that we do in Japan, and how are their outcomes different from ours. And this is going to be basically the theme of the entire conference, we wanted to give our listeners who are considering registration, an opportunity to have some sort of perk. So if you are a listener, and you are registering for the conference, please. Starting today, you can go on the registration and use the discount code incubator, and you will get I think, 30% of the price of registration. So yeah, the code is incubator, spelled like an incubator. It doesn't matter if it's, it's not lowercase, lowercase, uppercase, everything works. But yeah, so we wanted to give something to our listeners. And so here here it is

Daphna 2:51

not to put the pressure on. But for people who want to come and stay using the hotel block at the local hotel where we have transportation back and forth. The last date we said February 27. So

Ben 3:03

yeah, so if you want to take advantage of our discounted rates. Yeah, absolutely. You shouldn't, you should register soon. And we look forward to seeing everybody there. It's going to be a fun one. All right. So I guess we can start. Priya, you want to you want to get us started?

Speaker 3 3:21

So yeah, the first paper I'm looking at today is the overuse of reflux medication in infants. And the author here is Elizabeth Wolf. This was published in pediatrics, and she is from the Children's Hospital of Richmond. So in Virginia, and I think this is a familiar topic to all of us. We all know that. You know, there's a distinct difference between gastro esophageal reflux, which occurs in many children, so two thirds of healthy infants and usually resolves by one year of age, versus gastro esophageal reflux disease or GERD. So that reflex really can involve poor weight gain pain or mucosal injury on endoscopy. And so what we're finding is that often it's difficult for providers to distinguish between reflux and reflux disease, especially given the assessment of pain which is much more subjective. And so the use of acids depressants obviously decreases gastric acidity, but it's not effective in against reflux, and the use of these acids depressants. Histamine receptor agonist and PPIs is really linked to this higher risk of serious infections and fractures, and therefore choosing wisely and the AAP have recommended against their use and infants with gastro esophageal reflux. So the question the authors are posing here are what are the individual and healthcare system characteristics associated with acid suppressing overuse using a statewide all payer claims database from the most recent years available with the newer ICD 10 codes and the reason and why they're using these newer codes is that these codes actually can distinguish between reflux and reflux disease. And so for the study's design, they're using data from the Virginia all payers claim database. They also use the zip codes to identify and classify the education demographic and geographic estimates program. So the study included infants zero to 11 months of age with at least 30 days of continuous enrollment between 2016 and 2019. And they excluded any diagnosis of pediatric complex chronic conditions at any point in the patient record. So the they actually did two separate analysis here, one in which GERD was an exclusion criteria and one in which it was not. And the way they define GERD is they looked at a soft vaginas, ulcers and weight loss, along with other exclusion based criteria in an earlier claims based study, and those were identified by ICD nine or 10 codes. And when they were applied one to two days before, h2 receptor antagonists or PPI prescriptions, and the statistical analysis they used here was a multivariate binomial regression model, the model the rate for h2, RAS and PPIs, using sex insurance type rurality, and indicators for low birth weight and prematurity. So what the results were is that they analyzed 270,000 infants aged zero to 11 months, those were identified. And after they removed those with medical complexity, and no prescriptions for the acid suppression. They were left with 16,910, which is 7% of the patients were prescribed these acids suppressants after removing the medical exclusions. So those with GERD we, we then had 5433. So 2% of the patients in this database were included in the analysis. And when you compare that to earlier studies, they really showed something similar two to 6% that were prescribed and acid suppressant. So the this is really on the lower end, and the authors said that maybe it's because of that Choosing Wisely recommendation or some of the other literature that's out there, or that you know, the exclusion criteria did did exclude those patients with GERD. So what we found here is that the odds of being prescribed these acids suppressants were higher than males, and those with commercial insurance compared to those with public insurance, and in rural settings, versus both urban and suburban settings. Removing the GERD as an exclusion factor did not meaningfully or substantially change the estimates. And so, you know, there are several limitations here. We went from using ICD nine codes where you couldn't differentiate to then using ICD 10 codes. And so there's really not a one to one mapping that makes comparisons from new to older data. And then there was a thought that maybe clinicians might be up coding from the diagnosis of gastro esophageal reflux, yep, to gastro esophageal reflux disease, to sort of justify the medical management. And of course, like me being the pharmacist here, I would have been interested to see the difference between h2 receptor antagonists versus ppi. So I think there was a thought at some point that you would start on the h2 and then move to the PPI. And you know, so that, do you lump them together? Is there a difference in those two patient populations there. But overall, the conclusion by the authors was that acids depressant overuse remains a persistent problem, particularly among commercially insured infants and those residing in rural areas. reduction efforts should include providers and patients outside of urban academic children's hospitals, to achieve maximal benefit. So it is interesting in the sense that there are two main populations that they saw in terms of insurance and in terms of where folks live. And so they really say, you know, maybe if you're not affiliated with an academic center, that's where you need to start working on this reduction.

Ben 9:29

Right. I have a few questions for you. So can you I'm thinking like, if I'm listening in the car to this, can you walk me through again, why GERD is like an exclusion criteria? Because it's a bit I think I understand what they're trying to do. But you're thinking if if you aren't, like, wouldn't you want to not exclude babies with GERD so why why would they? Why would they have that as an exclusion criteria?

Speaker 3 9:54

Well, they did the analysis two different ways right? So that one was because that piece of pain is so subjective. So one, they did the analysis, one excluding the patients, which were good, and then one in which it was not just to see if there was any difference in the rates. And then if there were any differences again in the patient population, but yeah, I, you know, they didn't really explain why or why not they they did that.

Ben 10:27

I think I think yeah, I mean, I think so. So the problem, I think, with this study is that, while it is extremely valuable information, then it's always what you were describing in the end in the discussion, which is something that they also mentioned, the authors are mentioning in their conclusion, which is, is it a chicken or the egg, right? Is it? Is it that you then because it's a coding, an analysis of a coding database? The question is, if a parent presents with a baby, and Sal and my baby is fussy, and so they, they really give you a story of GERD and you maybe you are pushed to prescribe a PPI or an HRA, then are you going to then code because you prescribe the medication because of the irritability that was presented? So I think it's, it's a bit cyclical. And so it's hard to know, which one is driving which, but I think the idea behind the exclusion, if I understand what you said correctly, is that they wanted to take at face value, the fact that if you had good then the prescription was justified, I guess. Right? Okay. And then and then if you removed it, then it was like, Well, if you don't have good and you shouldn't be really on a ppi, and then why, why are they being prescribed? But overall, it's kind of cool to see that like, I like that we're publishing, I guess, quote, unquote, negative results were so well, actually, it's not that bad. Like, it's actually following the recommendation. So that's, that's kind of neat.

Speaker 3 11:48

Ya know, and I do think like this, this topic has come up several times. And, you know, they're doing due diligence by looking back and saying, Are we doing a good enough job here? Absolutely. So yeah,

Ben 12:01

absolutely. And then something that that is something that in the NICU, we are extremely big players in this, in this in this phenomenon, where they're aware, it's been well described, that we, we are using these medications quite routinely, and the baby, the babies do go home on it. And God knows that, as parents take their babies home, they're very reluctant to stop or modify any medication that was started in the NICU, because that's sort of what's that's gets assumed to be something that saved the baby's life. And so, yeah, so we have we have a duty to make sure that we, we are prescribing these carefully.

Speaker 3 12:40

And do you think then, so the commercial insurance piece of it, like, Is there a problem with coverage in terms of you know, sometimes these medications are compounded? I know that there are some now that come in a kit that's easier to be dispensed or readily available in the pharmacies? Do you think that plays an issue in terms of why they're, you know, I,

Ben 13:04

you know, I was thinking of, I think it's such a, it's such a loaded piece of data? Because is it? Is it like you said, is it the insurance that's not going to cover your Nexium or whatever, whatever other brand name medication, technically, or map results, there they are, they are good medications that have been that are very cheap. But also you wonder if it is something where people with commercial insurance are more likely to are more likely to have the social luxury of going to their pediatrician to say, my baby is a little bit fussy after feeds and braid or, and this is something that with public insurance, where that's a complaint that unfortunately doesn't cross the threshold of parents taking their car or taking public transportation to go to the pediatrician and to bring that up, and, and that just sort of falls by the wayside. I think these are all assumptions. But but but I think I think technically could all play a role. So I don't know the answer. I was thinking about that when you mentioned the finding. Okay, I guess I am next. I'm going to start with a brief communication in the Journal of parasitology. And we will see why it is interesting because I have two papers that are following one another. And this one is called mannequin to patient intubation. does it translate? Question mark? first author is Jennifer rumble rappelle. I'm not exactly sure how to pronounce it. But and this is coming out of a group in the US. And the question that is being asked and the background is actually quite interesting. We've talked about this on the podcast before many trainees do not successfully demonstrate procedural competence, and there's less and less opportunities for them. To perform endotracheal intubation, and when you compound these two things where the frequency of intubation is reduced and their opportunities to perform them is reduced, you are creating a framework where many, many trainees are leaving fellowships and other training, other training periods with without potentially the competency to perform these interventions on successfully on a consistent basis. They're recording some data from the anesthesia world that mentions that you would need at least 47 intubation attempt to be to require what's called procedural competence, defined as like 90% success rate. And as we'll see, it's something that's super difficult to come by when you are in the NICU. So the question that they were that the authors were trying to address was to determine if simulation training with instructors using video laryngoscopy to guide residents who were using who were using direct laryngoscopy would improve intubation success rates of their residents beginning at the at the beginning of their NICU rotations. So they looked at participating residents who were PGY, one through four, and who rotated through the NICU in one month increments and basically were quasi randomized according to the month of service to either receive the control or the intervention plus control. And they had like 51 residents in each cohort. So what's the control the control was that they had an intubation practice for 15 minutes during orientation, with a mannequin intubation head. Basically, it's like this full term infant head that we've all seen. And they will use direct laryngoscopy with a miller one blade under the supervision of a neonatologist or a faculty member. And then the control group then had real world intubation experience during their NICU month, and pick you months as well. So that's sort of, that's how I get it. And that's how that was their control group. Now, the intervention had a bit of more sophisticated setup where they basically had a 30 minute educational session facilitated by one unit ologists within the first three days of their NICU rotation. So now like this happens now, just before they entered the NICU, and they discuss various things, equipment needed for intubation, ET tube size, depth of insertion, correct mechanics and verification, ways to verify the placement of the ET tube, then they had like one on one training with the mannequin, but this time, it wasn't like the, the old, crummy philtrum head it was like a 25 week mannequin, like you know, I think it's called Little any, and they have the they have the model and the paper, and they used the C Mac video laryngoscopy. So now they actually had video laryngoscopy and they could see what the residents were doing on the screen. And they were using a mailer as your blade. Now, they had like the camera connected to a monitor. And they were able to give real time feedback to the residents. They made the the instructors made corrections while viewing the video. And, but and then and then the resonance were able to practice again using direct laryngoscopy. They could repeat and they could practice on this for however long they needed until they were consistently able to intimidate a baby within 15 seconds. And obviously your six successful intubation was just passed the tube through the cord. So what are some of the things that they found? And so surprisingly, they found that it this this intervention did not significantly increase the first attempt or overall success rate of intubation. On Live neonates, the control group had a first attempt success rate of 28% Compared to 35% in the intervention process control, so technically a little bit higher, like 7%, higher, but definitely not a statistically significant difference. The control group had an overall intubation success rate of 55% versus 50% for the intervention and control. Now, what's interesting is that and that's something that's mentioned that the result is that the intervention group had more intubation encounter. And they're saying, huh, that's interesting that the people who got more thorough and extensive training had more encounters, and they hypothesize that the intervention itself made the residents probably more comfortable and confident with the procedure that's sort of led them to proactively seek out these opportunities to intubate like neonates. And I think there's no real way to prove that based on the data that they're showing. But if that's the case, I think that's that's pretty neat. Interestingly enough, they're looking at the overall opportunities and they're saying that residents had limited opportunity to perform intubations on live neonates during their NICU rotations for the entire cohort of 102 residents, right? There was a median of two intubations that were performed by each residents on live neonates during their month long rotation. So that's, that's extremely small. And finally, residents in their program perform for Nikki rotations, meaning that they will mostly all graduate with fewer performing fewer than 10 neonatal intubation during the residency. And so when you compare that to some of the data that was presented in the background, where we're talking about, like close to 50 intubation in according to anesthesia data that leads to performance, success and competence. This is this is quite frightening. And so the conclusion of the paper is that in this one on one simulation training of residents using a neonatal mannequin and video laryngoscopy really did not increase the residents, intubation success rate with like neonates, there's a potential that maybe the intervention could have an effect if residents had more opportunity. But we unfortunately, the system is set up in a way that this was not feasible. And so they're proposing a few changes, which is allowing trainees to view laryngoscopy feeds on the large screen during intubation of like neonates to consistently use premedication for intubation, to offer weekly simulation training in the NICU, and to use a validated competency assessment tool during simulation training. So yes, this

Speaker 3 21:19

is really interesting, I have two things to say here. I mean, this, this concept of simulation is obviously not new, especially for intubation. However, this the use of video learning, lowering the scope, I think, is it's really variable. So some units have it, some say it's not easily accessible when they're going to intubate. And while you think like, this is a tool that's supposed to help with the comfort of intubation, what if when they, when they're like, in practice, they don't have that? So are they are you now becoming a dependent on technology that may not always be available to you, which is, you know, sort of a double edged sword there. And the other piece of this, I think that was interesting is that, well, now that I know I forgotten what I know, there's something else I wanted to say about this, because I do. Oh, was the challenge of intubation with all of the people in the unit that want to learn, right, so we have source practitioner,

Ben 22:21

I'm gonna get to that kind of second, okay. Because I have a follow up paper than that. I think it's always interesting when you find papers in different journals that are sort of addressing some of the similar things and I think this is the beauty of doing the journal club. So the second paper I want to present then, is published in the Journal of parasitology. It's coming from Canada, and it's called a tiny baby intubation team improves endotracheal intubation success rates, but decreased residents training opportunities. first author is Dr. Gahan UPSL, and colleagues, and it's a great follow up to the paper that we just reviewed. In the background, they mentioned a lot of things that we've talked about on the podcast again, that intubation of ELB W's is extremely dangerous, and it presents an increased risk of neurological injury related to the intubation multiple attempts is associated with worse outcomes. Increased physician training level is associated with increased success rate of the tracheal intubation, which emphasizes the value of the intubation being done by the most qualified person. But the problem is that there are multiple obstacles like pre act like you just were mentioning, there's more use of non invasive ventilation, there are a few medical fewer medical indications for intubation in neonates, and then like you said, there's the presence of other health care professionals in the NICU. There's residents, there's fellows, there's pas, there's nurse practitioners, there's RTS, and that creates a crowded field. And so there's an right and and the implementation of reduced work hours, have led to trainees reduced exposure to potential opportunities. And so all that really contributes to the opportunities of trainees having decreased. Now, I must say, they don't mention the reduced work hours directives in the background as like something that needs to be changed back, but they're making a sweeping assessment of all the different factors that have led to trainees having less opportunities. And we'll see that in the protocol that they've outlined. That's not something that they are trying to change. The question that they had was the question is the goal of this study, I guess, is to assess the impact of implementing a tiny baby intubation team on the quality of care surrounding endotracheal intubation, as well as the educational impact. So this was a retrospective study at St. Justine University Hospital in Quebec, Canada. And historically, they had they have about 600, neonatal endotracheal intubation in the NICU and delivery room each year. Now, what they're noticing is that in the past few decades, the number of intubation has decreased. So it went from 500 You In 2009, to 220, and in 2015, to approximately 160. In 2021. I thought like, right, we know this, but when you actually see the numbers, you're like, oh shit, this is this is a dramatic reduction. So I have to close my notes are popping up in there. Okay, there we go. Now, during the three year core training pediatric residents complete for one month rotations to cover calls in the NICU. Now, all intubation performed in the delivery room or the NICU during the three time periods were evaluated. In the following way, they had a first time point first epoch from 2012 to 2014, which is before they implemented this tiny baby integration team. Then they had 2014 2015, which was six months after the inflammation of a tiny baby integration team. And then finally, from 2018 to 2020, which is four years after the intubation team was set up. And what they noticed was they had to create an action plan after the second so six months after the inflammation of the of the of the tiny baby intubation team, they realized that they needed to effect some changes to make sure that their residents were going to get better opportunities and better success rates. So what are what is this action plan looking like? Number one, intubation goes to the resident first, and they try to use the person who has the least experience so like they try to prop up the person who needs to practice. They all carry a logbook, so that they can log their procedures, and they use video laryngoscopy for the first five intubations and they have simulation training prior to real life attempt. What's the tiny baby intubation team is for basically any baby that is born below 29 weeks or with a birth weight less than 1000 grams. And the tiny baby team includes a resident, a fellow a neonatal nurse practitioner, and neonatologist and the respiratory therapist, the primary outcome of the study is to look at first attempt success rates and proportion of endotracheal tube intubation attempted by residents. The secondary outcome is second attempt success rate and number of attempts by and residents success per endotracheal intubation. I feel like these papers are extremely valuable because these are things we all struggle with between balancing the safety of the patient and make sure that the BBS doesn't get exposed to negative outcomes, all the while fostering an educational environment for for for trainees. So I'm very much fascinated by these papers. So 646 injured tracheal intubations were included in this analysis. They had 250 in the first epoch 196 in the second epoch, which was six months after the integration team was set up and 201 in the third epoch, which is when four years after the integration team was set up. So the results are quite interesting. First attempts first attempt success rates. So how successful were they on the first try, in tiny babies increased between period one and period two from 44 to 59%. So that was a significant improvement, and was stable thereafter in the 30 Park to 56%. So setting up a team that's dedicated to these babies specifically improves their first attempt success rate. The number of attempts per intubation for tiny patients decreased right after the inflamation implementation of the tiny baby intubation team from a median of two attempts to one attempt in the second epoch. The number of attempts per intubation for non tiny baby patients decreased several years after the to be in after the implementation of a tiny baby intubation team from a median of two to median of one in epoch three. So interestingly enough, the expertise learned from the tiny baby unit, the tiny baby intubation team sort of almost seems to have crossed over to the non tiny baby where the success rates are even higher than now let's talk about our residents. So the proportion of endotracheal intubation performed by residents decreased after the implementation of the tiny baby intubation team. And it went down from 53% in epoch one to 37% in epoch two, regardless of patient's weight and gestational age at intubation, so less opportunities for the residents. After the implementation of these action plans that we talked about, including training logbooks and so on, the residents overall and non tiny baby intubation success rate improved going from 60% to 79% for overall endotracheal intubation and from 60% to 82% for endotracheal intubation is performed in non tiny babies, so they had less opportunities, but they were somehow more successful at it. There Residents success rate remained stable for tiny babies between period two and period three at around 60%. The conclusions of the paper is that the development of a tiny baby intubation team decreases the number of endotracheal intubation is performed by residents in training. And conscious effort must be made in order to find other ways to ensure appropriate exposure to the procedure. And they're mentioning that prioritizing residents intubation experience in non tiny baby video laryngoscopy use and simulation based training are important elements that need to be emphasized to ensure adequate procedural training. So these two papers are showing interesting things. One of them is struggling with a way to actually increase competency while this one is showing that there are there system seems to increase competency but they still haven't figured out how to increase exposure. And so I leave that question to the audience I guess to you too, I guess I'm but I'm not going to step foot in that landmine

Daphna 30:54

you know, it's interesting. The the breadth of Pediatrics is growing exponentially, right? And, like, do all pediatric residents need to learn how to intubate? It's an interesting question, right, depending on what they're going to do with their careers right now, that's that's the criteria. But there's definitely a proportion of them that really do need the practice, right, those of them going into the procedural subspecialties. But so it's interesting, I

Ben 31:25

wonder I'm gonna be devil's advocate here. And I'm going to tell you, you may be a pediatrician. And this study is coming from Canada, like they are they are underserved area where you are the only you're the only sort of children's physician. And, and you may be faced with an intubation, I think,

Daphna 31:41

yeah, and I think those people learn to do a lot of stuff that they didn't do in residency, right.

Speaker 1 31:48

Yeah, so our world Doctor really? Yeah, jack of all trades. Right, right. Yeah.

Speaker 3 31:54

And I know like the NRP now for resuscitation has some wording or recommendations about the use of LMA in Baker kids. But I do you know, maybe there will be technology out there that should help us with this ease of intubation successful

Ben 32:10

Tesla like a self intubating

Speaker 3 32:14

driving yourself, you know, just Yeah, I know, I know there there are institutions are working on this too is you know, how can you coach How can you do that without being right there? And so I think it's an important area but I you do here like we're doing less intubations How can we train and when there are so many people who want to do this, right, like every, every discipline may have some sort of role in intubate Shen So yeah, that's good articles.

Ben 32:48

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Daphna 33:11

So I'm going to present this paper from the journal Perinatology. You now I love TC belly, so the Transcutaneous bilirubin levels and extremely preterm infants less than 30 weeks gestation, the lead author, Mira Sancar, and the trailing author Minaj Ben walay. So they really want you to determine the relationship between Transcutaneous bilirubin levels and total serum bilirubin levels in extremely preterm infants. Because at most places, we're using Transcutaneous Billie's to help us screen for increasing bilirubin levels in the term population, but general not in the preterm population. So I thought this was a an interesting study. So the primary outcome was really how well did the Transcutaneous measurements approximate the serum Billy Rubin measurements? And the study design was a prospective multicenter study of extremely preterm infants less than 30 weeks gestation across eat NICUs in California. They looked at the differences between paired Transcutaneous bilirubin in total serum bilirubin values, and then they kind of stratified it based on gestational age, birth weight, race and ethnicity chronological age as well as during an after phototherapy, which is kind of a controversial question because in general, we don't follow suit Transcutaneous Billy measurements after phototherapy has been initiated. So, then 141 Extremely preterm infants between 22 and four sevens and 30 and 07 weeks of gestation. They had 755 paired Transcutaneous belly ribbons in total serum bilirubin measurements obtained from these infants somewhere between a day of live zero and day of life 18. So I will post these graphs, but I think they're really, really useful. So really the the primary outcome was looking at the variation, so they took three values for each Transcutaneous bilirubin measurement, and the mean coefficient of variation among the three values recorded with the Transcutaneous measurement was 10.9%, or Transcutaneous bilirubin values greater than five. And to minimize variability related to dispersion they use the highest measure Transcutaneous bilirubin levels for all comparisons, they took three they took the highest measurement when comparing it to the serum bilirubin. It's interesting, they had an institution using the Billy check Billy meter, and then most of the other institutions were using the Drager Billy meter and there were some differences so the mean Transcutaneous Billy Rubin using Billy check Billy meter read 2.85 milligrams per deciliter higher than total serum bilirubin. This was statistically significant, and they found a pretty poor correlation. So the Pearson correlation coefficient comparing the TCB and tsp in the Billy check group was point 506. However, with the Drager Billy meter, they found a strong direct linear correlation and our point 786 between the toto seal, Billy and the Transcutaneous, Billy ribbon values, and so their graph is literally almost like a perfect fit. So that is definitely something to take a look at. Total sealer Billy values range from zero to 12.6 and the Transcutaneous Billy values range from zero to 14.2. Total serum Billy was predicted with a high degree of accuracy, and they give us an equation at total total serum Billy equals 2.37 plus point five four times a change cutaneous bilirubin level. I told you about the bland Altman plot that showed a significant agreement between total serum bilirubin and Transcutaneous bilirubin values, and the bias line does show that trans total serum bilirubin was point three three milligrams per deciliter higher than the Transcutaneous bilirubin with the majority of points falling in plus or minus 1.96 standard deviations of the difference between serum Billy and Transcutaneous Billy they wanted to look at the difference between the stratification of gestational age subgroups, and the subgroup analysis showed that the strong correlation persisted across all three gestational age subgroups. They looked at different birth weight groups, which also showed good correlation between TSB and TCB levels. All race and ethnic groups including Asian infants who are at high risk for elevated bilirubin levels showed strong correlation. And in that group, in particular, the R equals point 808. Interestingly, the correlation was stronger in infants more than one week of age compared to younger infants. And then they did do this subgroup of infants who were receiving phototherapy. So they had 274 Transcutaneous bilirubin measurements taken during phototherapy and the correlation was still similar, whether infants were receiving phototherapy or not. And then finally, they said, Okay, what what were the results that were kind of too abnormal? So they found disparities and only 2.5% of peered TC bellies, and total serum Billy measurements in which the Totus total serum Billy read higher, and two milligrams per deciliter from the Transcutaneous Billy levels, and that infants would have qualified for phototherapy based on the total serum Billy levels but not with the Transcutaneous. Billy levels. They didn't mention which levels they were using. Maybe I I'll go back and check one more time if they're using the new, the updated Billy Rubin guidelines for that. But overall, the study supports the use of a transcutaneous Billy meter as a screening tool for monitoring jaundice and extremely preterm infants. Thoughts.

Ben 39:38

I have tons of thoughts. Okay. I think it is. This is earth shattering because yeah, how many? I think

Unknown Speaker 39:46

the how many times do we stick them?

Ben 39:48

How many times do we stick them in? I also think I think it's more pervasive than this. I think the serum belly checked and preterm baby is an open invitation to draw more lines, right. So you're like, well,

Speaker 1 39:59

if abs like Listen, I gotta get a Billy. So I might have That's exactly right. Right?

Ben 40:03

How many times have we said, Well, I'm sticking the kid for the Billy might as well get some other stuff. And now, also, there's always the concern with Transcutaneous, especially in fourth term, they go, you know, above a certain level, then it's sort of no longer reliable. But how many times have we seen in very tiny babies bellies of like 1214? It's extremely rare. It's extremely rare. So the fact I'm not surprised that it correlates at low level. And, and so I think I think this is something I definitely want to want to try out and see if we can reduce our because this, this has the potential to affect the amount of blood that we draw the number of transfusions we give,

Daphna 40:42

and it's a lot of blood, right? Yeah, these are the smallest babies,

Ben 40:46

it's a large proportion. Yeah, it's a large proportion of their blood volume, even though we're using the micro micro containers, but still, it's like, I could now get away with doing these is that epoch whatever people call them? Well, I can do with point three ml, I can do a gas a pretty much a BMP, get a crit. But that's it. And, and to get just get an additional Billy would be an additional point five ml. That's, that's a lot of that's a lot of blood. Sorry, Korea. You

Speaker 3 41:14

know, I was just gonna ask you, so this may change your clinical practice in the sense that you feel a little more comfortable just doing the Transcutaneous. Billy, do you think there's going to be an overlap, where people are gonna say, Oh, well, I've got to see if I trust this, or do you think it would be a shift automatically? I mean, it's gonna take some time, right?

Ben 41:32

I'm gonna I'm gonna test it out. I think I think you don't really have to be. And also, I mean, I'm sorry to say, like the management of bilirubin. hyperbilirubinemia in preterm babies, is a crapshoot, right? We don't have we don't have guidelines, we it goes up, we start the photo, then we stop it. And we know it's going to go back up a little bit, and so on. So it's like, I mean, do we really need to have such an accurate measurements to make a decision? I don't know. So that's, that's, I'm very excited about that paper. Thank you for reviewing me

Unknown Speaker 42:01

too. For sure.

Ben 42:04

All right. Priya, you want to you want to go last. So you want to you want to squeeze in your your next paper here?

Speaker 3 42:09

I don't care. Let's go. Okay. So the next paper I have is one on anti seizure medication at discharge and infants with HIV. It's an observational study. The first author here is Liz Sewell, who's from memory. But this is really the NIC HD group that NRN that published this article. And I think it's an interesting Yep.

Ben 42:32

I want to give a few mentions of the list of authors number one, Sita, Sita Shankar on is second author. So, a massive name in the in the context of cooling and he I think Natalie metric is also on there. Ravi Patel is last author Abbott lab talk is on there. Shannon Hamrick who was on the podcast as well. I always very much appreciate to see IRA, Adams Chapman on there as well. Her work continues to live on. So this is, yeah, this is a paper that that's worth checking out.

Speaker 3 43:05

Okay. So I'm just yeah, the background here is that obviously, I think we're all aware that these anti seizure medications that we use in the NICU can be neurotoxic, and the duration of for treatment of acute symptomatic seizures in newborns is really variable. So the article does a great job showing the variation of this within centers, and the in 2011, the who recommended to consider early discontinuation of anti seizure medications in newborns with normal neurological exams, and EGS. However, there's a lot of variation like we talked about, that occurs. And this this topic actually has been studied by another author, Hannah glass published in 2021, looking at data from a neonatal seizure registry, for varying ideologies of acute symptomatic seizures that suggested that discontinuation prior to discharge did not increase the risk of functional disability or epilepsy at 24 months. So the author group here the question they asked is, What is the association between discharge with or without anti seizure medications and death or moderate to severe disability in infants with HIV and seizures? So the study design is is unique. They looked at three different trials combine them together, this is over a 14 year span. So it's a retrospective study of infants enrolled in the induced hypothermia, which is 2000 to 2003. The optimizing cooling 2010 to 2013 and late hypothermia 2008 2014. And these trials were conducted at 22 of the NIC HD network centers. The inclusion criteria for all three trials were pretty similar. So two of the studies that It was gestational age of greater than equal to 36 weeks presence of acidosis, or a sentinel event with moderate or severe encephalopathy within six hours. And then the other study was identical, but the randomization could occur at six to 24 hours postnatal age. And the analysis included infants with documented clinical or electrographic seizures, treated with anti seizure medications who survived to discharge, it was regardless of hyperthermia treatment. And one thing to note here is that the continuous use of continuous EEG and seizure management was per the individual center or clinician, there was no protocol to standardize that. And also that the specific type and dose and duration of the anti seizure medications were not collected. So obviously, they excluded all patients that didn't have documented anti seizure medications at discharge, or if there was any missing documentation. And they did a very robust statistical analysis, they accounted for, you know, the severity of the HIV hypothermia treatment, the five min Apgar score, birth year discharge on tuberc lavage feeds, any use of EEG and then the center, so there was some control for that. And they also had an expanded model that included sex and your abnormal neurologic discharge exam. And they went even further and did a sensitivity analysis, including only infants who had an EEG performed, adjusting for the presence or absence of electrographic seizures, and then a secondary sensitivity analysis that was the same, including the sex and abnormal neurologic discharge exam. So the results were, they had some 140 infants that were enrolled in these NRN hypothermia trials, 302 met inclusion criteria, and of the 61% or 184, were continued on anti seizure medication at discharge. And so one of the nice figures that they have there is they they mapped out all 22 centers, and there is a range from 13 to 100%. In terms of what what centers, you know, kept their kids on anti seizure medications at discharge. And that's a huge range. So it just shows the variation of care. They also looked at maternal and neonatal characteristics. And when you look at that table, the intrapartum partum, complications were slightly higher in those discharged home on anti seizure medications. They also had a table looking at the hospital course that showed pretty similar outcomes, but severe HIV presented in 24% of those discharged on anti seizure medications, compared with 22% of those discharged without so there really was no difference in severe Hae, when they looked at the abnormal neurological exam 57% were discharged home on an anti seizure medications versus 46%. Without and where there was a little bit of a difference is discharged with lavage or tube feeds occurred and 27% of those discharged home on anti seizure medications versus 19%. Without the primary outcome was death after discharge, or moderate or severe disability. And that occurred in 44% of the infants with anti seizure medications at discharge, versus 28%. Without so actually higher in those that were discharged home on anti seizure medications. And then, you know, one of the other outcomes that they looked out, obviously, they looked at the combined death or or moderate slash severe disability, but then they also looked at death alone. And then the outcomes looking at the Bailey two and Bailey three scores for cognitive and motor and there was really no difference when you looked at those separately. I thought it was very interesting. They looked at parent reported post discharge seizures. So with the parent report there 36% of infants discharged on anti seizure medications reported a seizure versus 13% Without anti seizure medications. And then among infants with EEG performed, the adjusted odds ratio between anti seizure medication at discharge and the primary outcome was 1.79. And in the sensitivity analysis limited just 96 infants with the electrographic seizures, the odds ratio was 1.42. So in the discussion, they talk about you You know, the WHO recommendation that came out, it said, you should really discontinue anti seizure medications without a taper after 72 hours with a without a seizure and infants with a normal EEG and neurologic exam, and they sort of dug in deeper and said, well, some of the data we're looking at was prior to this recommendation. So that could have played a role. And then also, the, the the fact that some of these anti seizure medications, such as fina BB make that neurological exam, sort of challenging that, and that could have played a role there. So the limitations to the study, really, I mean, they did not look at the type, dose or duration of any of the anti seizure medications. They didn't look at seizure burden, burden on outcome because of the lack of data. And then, of course, the seizures that were reported by the parents were subject to bias. And we really couldn't differentiate between the type and frequency of post discharge seizures. But in conclusion, infants with HIV and seizures, discharged home on anti seizure medication really varies throughout centers, and it's substantial, and it could be associated with a higher risk of death or disability. And the important thing to note here is that this patient population has a really low risk for epilepsy. And the data here suggests that some of the infants with resolve seizures associated with HIV may not warrant potential risks of continuing the anti seizure medication at discharge. But as all good studies there, we still need more. So further studies are needed on the efficacy, long term effects of anti seizure medication, as well as identifying which patients are at higher risk of epilepsy that may warrant that continuation of medication. And the research on the factors that impact clinical decision to continue or discontinue medication would be meaningful. And this could be an opportunity for some evidence based practice recommendations. So I thought, yeah, this was an interesting study where, you know, we sort of have have a recommendation like, are we in line with it? It really is variable percenter.

Ben 52:27

I want to any thoughts. Yeah. Yeah. I want to just just emphasize something, you said that the risk of seizures is increased in HIV. But what you mentioned is that the risk of epilepsy, right, so that that's, that's really a critical difference. And, and you mentioned it correctly, but I want to just make sure people don't misunderstand what we're talking about, because it's the risk of epilepsy that we're looking at now. I think this is a this is, to me a very interesting paper. I think you read the title, you read some of the paper and you're like, Okay, so maybe like the babies who get discharged home on anti seizure medications are just a kid with severe HIV, you know, and there's the secret ones. But when you look at table two, when you look at your hospital course, the comparison groups are pretty much very much similar, right? So similar numbers of kids with severe HIV in both groups, similar numbers of kids who had hypertension, similar number of babies with persistent pulmonary hypertension and similar groups and in their length of stay in there. So on and so forth. So that's something that's that's that was very interesting. I do think that the biggest weakness of the study is really the fact that they were limited in having access to the the presence of EEG seizure among the infants who received who had an EEG, so obviously, not everyone has an EEG, and and some of them who do then may have seizures on EEG. And then they were seeing how they were missing data for 68 infants, because obviously, if a baby still has seizure on an EEG, then maybe that's a reason to send the baby home on anti seizure medications. However, I think what's interesting to me is that each is so traumatic for patients and families that as soon as we reach some stability, we're very inclined to say oh, you notice like just just get this family to take this baby home and finally end this ordeal, right. And you're like, and if you are still on Capra, or if you're still on phenol BB depending on what you use, you when you when this as an outpatient, right? And you're like, at least now this family gets to come, but you're looking at this data and you're like, maybe, maybe not, maybe, maybe we should just do a make an effort to win them before they go home. Especially if there's not I think if you have a complex baby that's seizing that potentially could have epilepsy, then that's a whole different ballgame. But how many times you start them because they get cooled because they initially have a seizure? And then you're like, Well, you know, like, we'll, we'll sort everything else out and this you'll figure it out with a neurologist as an outpatient. Very interesting, very interesting data from the Achd. What do you think? And they

Speaker 3 54:58

did, I thought, you know, we did this seizure article a few weeks ago when we did this may may have been last month, but they did include clinical and, and electrographic seizures, which I do think is important. I mean, there's a shift right in this. This the the earliest study here was 2000. That's like 23 years ago, there's been a shift in management, there's been a shift in the use of medications and what medications we're using. And so I do think that that that was the difference here with the compared to the other studies that have previously been done. Yeah, I don't

Daphna 55:33

have much to add, except that, you know, we don't want to we don't have a consensus. I've worked with like a dozen neurologists, and they all have a different idea of how to tackle it. So I do think I think we are developed, we have enough information to start developing some guidelines. But to your point about families, Ben, I think it makes us feel better not to rock the boat. But in my experience, the impact, when we say to a parent, you have to go home on this seizure medication is actually not one of relief, I find that they do not want to go home with seizure medications. And I think it adds an additional stressor and burden on them. We, you know, we say, Oh, the seizures should resolve, right. They're part of this acute situation. But we're going to send you on all these medications, just in case. And so, in my experience, parents do not like going home.

Ben 56:28

I don't know, I agree. I don't think that's that's what I meant to say. But saying that parents are happy to go home on anti seizure medication. I think that when we offer the prospect of saying, hey, everything is good, we're just on these medications. You can go home now and win this with a neurologist as an outpatient. Or we can keep you an additional seven days as we win your Barbie doll or something. Parents are like, no, I'll take my baby home right now. And I'll win this. So while I don't think I don't think they rejoice at the idea, they definitely sees very often and my experience has been that they they do seize the opportunity of going home right there and then and figuring out the winning of this medication once they go home rather than just keep staying in this dreadful place that the NICU is for seven days just so that we can titrate slowly there phenol BB but yeah,

Speaker 3 57:13

well and the WHO recommendation said without a taper, so I mean I do that's like that's also a controversy as I remember those fina BB wanes and then having to teach the parents like, Okay, we're gonna do this time in this time, and then we're gonna go down. And so it is complex. It's not like, you just start it, and then you stop. And so there's another question that's posed as do Yeah, I mean, for fina bark, do you have to We? I mean,

Ben 57:40

I think I think I think what you did mention that in the presentation, it's how long you've been on it. I think you said 72 hours and off. I think it's just like steroids, just like everything else. I think if you are on it for two weeks, then maybe maybe I will consult the pharmacist and the neurologist about a slower when but it's true. If it's just 48 hours, 72 hours, then then let's do it. Let's just stop it. Okay. I have two more papers. I'm leaving one for last. It's actually a lot of fun. This one you guys are going to enjoy. It's a short one. The next one I have is published in pediatric research. It's called premature infants born premature infants born before 28 weeks with acute kidney injury have an increased risk of bronchopulmonary dysplasia. first author is Michel Starr, who we say hi to who was on the podcast and who is is just a great researcher. So the background is interesting. there's mounting evidence to show that BPD is actually a systemic issue. It's not just an issue of just your lung being underdeveloped and and they're mentioning that Aki acute kidney injury is is a very common comorbidity and premature infants and it happens in in reported 40% of yabby W's. Now, Aki was initially thought to be an isolated organ dysfunction. But there's recent work that has shown that it's an actually an inflammatory, there's an inflammatory condition that contributes to the dysfunction of other organs, including the lung. And the authors have reported some association between Aki and a higher likelihood of BPD with some papers saying four times more likely to develop BPD in patients with Aki to something 70% more likely. The mechanism of a source of disassociation, however, is unknown. Now the authors are saying Could it just be altered angiogenesis, something that's been observed in animal models that is seen in premature infants after kidney injury. Now there are biomarkers that we could test to identify these angiogenic disruption. So they did a few things. They evaluated the relationship between Aki and BPD in prematurely born infants and they actually use data from the peanut trial, which is a paper that we reviewed on the podcast, which is the preterm erythropoietin neuro protection trial, which is where they give Ico for neuroprotection in preterm infants. They also had an additional question which is, is severe Aki independently associated with moderate to severe BPD. And then they measured some urinary biomarkers of angiogenesis to see if they could establish any correlation. So they looked at the peanut trial, which basically included infants who were born between 24 and 27, and six weeks of gestation in the participating NICUs. They were enrolled at less than 24 hours of age, and they all had central access. Now, they excluded babies with major life threatening brain cardiac or chromosomal anomalies they had if they had any sort of coagulopathy DIC if they had high hematocrit or if they had hydrops, or congenital infections, so they use the que que digo like the kidney disease improved global outcomes definition of Aki, which basically looks at the change in serum creatinine, and basically stages it from zero to three, we'll have the table in our in our notes in the supplemental material, I pulled it out and it's in my notes that will post on the website. The Define severe Aki or stage two or three, the primary outcome was great two or three BP BPD defined by the Jensen criteria. Now in an exploratory analysis, they measured urinary biomarkers in a sample of infants with known Aki and BPD status available. And that was in 106 infants which is much smaller than the overall cohort that they looked at for these other primary outcomes. The vascular and the biomarkers that they looked at were vascular endothelial growth factors, the VEGF A and D. They looked at ti e two, they looked at angiopoietin One angiopoietin, two erythropoietin placental growth factor and fibroblast growth factor in the first available urine sample obtained in the first week of life. Now, the urinary angiogenesis biomarkers or potential early indicators of BPD in preterm infants, and as angiogenesis is involved in vascular development of both the kidney and the lung, which is why the the looked at these specifically, now 885 infants were included in the study 70% of which had grade two or three BPD. So that was a large proportion of these infants. Infants with moderate to severe BPD grade two or three, or death had significantly lower birth weights, lower gestational ages, and were more likely to be small for gestational age than those who had no BPD or grade one BPD. That is actually good to know, just to make sure that the like this is data that's consistent with other published reports. So this just this just important that I guess to report in those results. Now, of the study population 33% had acute kidney injury within the first 28 days. And again, I would have, I mean, it's it's remarkable that it's such a large number, I think, again, we tend to overlook Aki, infants with Aki were more likely to be born at lower gestational ages and have lower birth weights. They were also more likely to have complications during their neonatal course, including higher frequency of necrotizing, enterocolitis, Payton, ductus, arteriosus and sepsis. So let's look at some of these outcomes that were interested in infants with Aki were more likely to have the composite outcome of grade two or three BPD or death 74% versus 63%. What's super interesting in our poster graph this week on Twitter, there was a dose response effect of both the exposure and the outcome. That is that infants with higher stages of Aki were more likely to develop BPD and infants with Aki had a higher risk of moderate or severe BPD. So quite interesting, that sort of correlation between the degree of kidney injury and the severity of BPD. When they looked at some of these urinary biomarkers, and those 106 infants, what they didn't really notice anything interesting. Basically, they saw that infants in the babies who had Aki, the ones who develop BPD had a higher, though insignificant, so not statistically significant levels of urinary biomarkers, compared to those who did not develop PPD, the ones that were elevated were VEGF a veg, F, D and T, ie two with an area under the curve of point six. So not really something that's earth shattering that I think we should all tomorrow, start testing, but interesting, nonetheless. And so the conclusions are that in extremely preterm infants, Aki is associated with grade two and three BPD or death. They also report that infants with grade two or three PPE have differences in some of these urinary angiogenesis biomarkers. And so what they're saying is that the impact of this work really is its potential to drive more work to decrease BPD development through better understanding of these angiogenesis mechanistic pathways. And I think that's definitely something that's not been explored as readily as Should and so I agree with Michelle on these on these outcomes and conclusion.

Daphna 1:05:07

Yeah, it's interesting, right? Is it that the sicker babies are just sicker? Right? They have all this inflammation and then so they have all these long term consequences, or is it part of the pathophysiology that we just don't really understand? Yeah.

Ben 1:05:24

And, or and or is that inflammation and injury then suddenly changes? Changes the makeup of your, of your angiogenesis? Potential. Exactly. That's super interesting.

Daphna 1:05:36

Yeah, yeah, it's kind of terrifying. But, but But bless the neonatologist, who are how are doing the kidney research? You know, I think it's such an elusive organ. It's nice to have Neos that are helping us bridge bridge the divide between us and nephrologist.

Ben 1:05:53

I think there's I think there's, this is a new frontier. And I think there's a lot of shared researchers working on that. And I'm curious to see either kind of come up with something that is going to become like, so obvious. 10 years down the road, they were like, Oh, my God, I can't believe we were not doing you guys have

Daphna 1:06:06

been ignoring the kidney all this time. Especially these tiniest babies and our BPD baby like we know that fluid management. We know it's really great. We just don't know how or why. All right. I have one more. Well, I have two more. I have one and a half more. And you have one more Yeah. Okay. Ivan. Next, I have another journal opinion etiology paper the dilemma of feeding during the treatment of Payton ductus arteriosus. With oral ibuprofen in preterm infants less than or equal to 30 weeks of gestation, a randomized control trial. I do love a paper that tells you exactly what the paper is. It title lead author, Sama, deep cower and trailing author sliema. Kala, bingo. I think I'm getting better.

Ben 1:06:54

Yep. You just fantastic.

Daphna 1:06:58

So they really wanted to look at the effective and minimal quote unquote minimal enteral feeding versus what was their unit practice withholding feeding on time, withholding feeding during treatment with ibuprofen to target a quote unquote hemodynamically significant PDA and what was the effect of the different types of management on the time to reach full feeds. It was a single center randomized controlled trial of 126 premature infants born less than or equal to 30 weeks gestation. They had to be less than seven days of age with a hemodynamically significant PDA which I'll tell you what their criteria was. And they compared like I said, continuing minimal enteral feeding versus no feeding during treatment. Their inclusion criteria were all intramural preterm infants less than or equal to 30 weeks gestation on any form of respiratory support, diagnosed with a hemodynamically significant PDA for which the team thought they needed early treatment with oral ibuprofen exclusion criteria contraindications for use of ibuprofen, such as active bleeding, GI bleeding, intracranial hemorrhage, grade two or higher or thrombocytopenia lesson 60 significant impairment of renal function with creating greater than 1.5 congenital heart disease with duct dependent pulmonary systemic circulation, major congenital or chromosomal, or gastrointestinal anomalies, severe shock, the need for treatment of PDA after the first week of life or infants that were already on a pretty significant and more significant feed volume greater than 60 mils per kilo per day. So let's get to some of the definitions. Obviously, there is debate about what is the hemodynamically significant PDA and obviously there is debate about whether or not we should treat it or not anyways, so that is not the point of the article. And we know that PDAs are still being treated worldwide. And and there's this discussion around what do we do with feeding. So their criteria for hemodynamically significant PDA requiring treatment in the study were the presence of all of the following a PDA size greater than 1.5 millimeter, a left atrium to aortic ratio of greater than equal to 1.4 and a left pulmonary artery and diastolic velocity greater than or equal to 30 centimeters per second. Their treatment regimen was oral ibuprofen at a dose of 10 Five and five milligrams per kilogram at zero 24 and 48 hours respectively. And then the definitions for the feeding groups so the feeding group infants received 20 amounts per kilo per day of feeds advancement, typically, and then for the three days of treatment. And they were they just stayed at the top 20 mL per kilo per day. So they were enrolling babies very early on an admission, so they'd stay at 20 miles per kilo per day of feeds. And then they would advanced by 20 mL per kilo per day of feeds. And the non feeding group, they'd get no feeds for three days. And then they were advanced by 20 mils per kilo per day to full feeds. So these 12 These some other details at the end, they required a second course they continued to receive feeding depending on their group. So if you were in the know feeding group, you didn't feed for six days. And if you're in the minimal enteral feeding group you fed for the 20 miles per kilo for those 60s. If I repro, Finn was substituted with paracetamol, Tylenol due to gi concerns in Benson, both groups were kept NPO. And then they continued in their original group. They gave some criteria for feeding intolerance, and when they would stop, and they define neck as Bell stage two or greater. And they also even had parameters for checking and repeating residuals, which is also a hot topic.

Ben 1:11:08

And they're not afraid of controversy. I mean, first of all, the paper in and of itself is there, they're there. They're not afraid. So kudos for them to them to just

Daphna 1:11:17

listen, I think I think they're, I think there's so much confusion that that centers are saying, well, like, if we've decided to like what are what are we going to do so they you know, they're just trying to figure it out in their in their center. So their baseline characteristic Oh, sorry, the primary outcome was the time to reach a full feed volume of 150 miles per kilo per day. secondary outcomes were episodes of feeding intolerance, sip, late onset sepsis, GI bleed neck and other comorbidities ivh PVL BPD are okay. In the year prior to the study, their policy was to stop feeding during treatment, which is not uncommon, and even to the some of the places that we've worked at them. And then the average days to full enteral feed was 15 plus or minus four days. In this group, they had a median gestational age and birth weight of 29 weeks and 1200 grams respectively. In both groups, the mean aged enrollment, I thought this was very interesting 16 hours in the feeding group, 16 hours of life, and 14 hours of life in the no feeding group. In 54 infants in the NPD Group and 46 infants in the no feeding group that reached the primary outcome to be analyzed a total of 16 infants in the feeding group and 20 infants in the no feeding group died, of which 10 infants live in group and 16 infants and the no feeding group died before reaching the primary outcome of full needs. However, the prac for the primary outcome, there was no significant difference in the primary outcome between the two groups of getting to full feeds, the median time to reach full feeds was 16 days in both groups. I thought that in and of itself was very interesting. So they standardized starting feeds, and they still didn't get there faster. And the secondary outcomes, there was no significant difference in secondary outcomes such as feeding intolerance before reaching full feeds. There was no difference in incidence of feed interruption due to causes other than feeding intolerance like sepsis, apnea as respiratory deterioration, hypotension, blood transfusions, the incidence of next stage two or more sip, late onset sepsis, total duration of respiratory support, duration of hospital stay weighted discharge ivh BPD, ROP and mortality all similar in both groups.

Ben 1:13:39

So So basically the same I wanted

Daphna 1:13:42

to say one more thing, I want to say one more thing. Overall, the PDA closure rate was 100%. With medical management, which I also thought was very interesting.

Ben 1:13:51

I need to get there, we need to get there manufacturer of ibuprofen to come towards oral Yeah. So So it's interesting. So I just want to go back to something you said they, they they had some deaths, and then they excluded these and then analyzed, but somehow, for people who may have missed this point that you you mentioned, like only 10. So 10 and 16 died in each group. That's right. 10 in the feeding group 16 in the non feeding group. Right, crazy. So I mean, you would think, like there's all this stigma around feeding during breast feeding, but it turns out that it's the ones who were made NPO, who had a I don't know if that ends up being significant that didn't look in the paper, really, but crazy. I mean, it doesn't translate into data analysis at the end because they were excluded. But so 10 versus 16 is pretty

Daphna 1:14:43

well, and I think we're learning more and more about the importance of, you know, a, a non leaky gut if which feeding helps with that. Right. And there's some preliminary studies about reducing inflammation feeding during a Qi things like that are during therapeutic hypothermia. So, I mean, I thought it was an interesting study. We don't do either of those things that are you. And I'm sure other units are doing all sorts of things. It's another place where we just don't have

Ben 1:15:15

we're probably like every other unit, there are some of us who would like to keep moving up. There's some of us who would like to stay where we're at. There's some of us who would like to just stop them. And it's just, I guess it's it's interesting to see that, I mean, still still relatively small numbers, but 60 versus 60 years is 24 for normal distribution purposes and stuff. So no interesting stuff. Of

Speaker 1 1:15:36

course, there are some units that aren't treating the PBA at all, so they don't have to have this discussion.

Ben 1:15:43

Okay, what do you want to do your next paper tougher? Since you're on a roll?

Daphna 1:15:46

Oh, you you want to go save the best for last? That's what you're saying?

Ben 1:15:50

Yes. I think I mean, it's not my paper. I didn't write it. But I mean,

Daphna 1:15:54

I know you're very excited about this period. Okay. Okay. Well, I'm not going to do a full review. But I think this is a very interesting paper. It's a total hot topic. So it's a pre proof in the Journal of Pediatrics. And if you were at the AAP Scottsdale conference, like you need a perinatal medicine, like I was the honor of attending, and this was the discussion around what is your clinical FTE and productivity? And why don't we what, what is our pay structure? And why is our pay structure? This was the topic of many discussions, and some of those were standing room only. And I'm Dr. Satya, and I'm gonna say his last name, right? Luck Shamin. Through Seema, I think I did it has written on this topic extensively. And we've had on the women in neonatology group to talk about some of these really important workforce factors that affect our day to live day to day life. So and this article was low is entitled low compensation for academic, pediatric medical sub medical specialists role of Medicaid productivity, work hours and gender. So I think it's a great paper just to review if this is a topic that can that is of concern to you. And interestingly, Dr. Sathyan, when he gave this lecture, he doesn't leave out all of the private practice Neos, but and this particular article is talking about academics and in particular, but we have parallels in both types of, of workforce. But the gist is really talking about like, what are the main differences for why the pediatric medical specialties are getting paid less than, say, our adult counterparts, and they he lists four major factors, the first of which is low Medicaid reimbursement, the second of which the productivity benchmarks are different in general, the pediatric specialties have lower patient volumes, potentially lower disease complexity, varying procedures, and this much greater added time for interaction with parents and guardians and talking to the parents separately from the kids can potentially contribute to lower pediatric productivity. However, for those of us in neonatology, we are an exception with the lowest dollar per work RVU value among all medical subspecialties. And neonatology contributes to a large proportion of web of work related RV use to academic pediatric departments.

Ben 1:18:53

So we bring in the big bucks, basically,

Daphna 1:18:55

we bring in the but the big bucks we work more we'll chat tell you about we work more than most of the other sub specialists. So but it's our pay commensurate with that it's not the second the third factor that may contribute to lower compensation and pediatric subspecialist is, quote unquote, fewer work hours. So relative to say Family Medicine, work hours, including all medically related activities were lower for general pediatrics by minus 288 hours per year. However, work hours were much higher for neonatologist plus 564 work hours per year, but not necessarily different than the other pediatric subspecialties. So, you know, we are lumped in with all of the pediatric subspecialties, but actually our work and our pay and the amount of time we work is a little bit different. And the final factor we've been talking about this is is gender distribution among us providers. So active pediatric providers are predominantly female 64% compared with family medicine, 41 per sent an internal medicine 38%. And we know that there are gender inequities in salary and contribute to low compensation to pediatric providers. And this graph is striking. So when you talk about a picture's worth 1000 words, there are maybe I should have counted six, eight graphs at the end of this pre proof, which describe all sorts of things. Where are we in terms of our adult sub specialists? And where are you in terms of state reimbursement. And then in particular, this one about the percentage of female providers in a field is like inversely related to the pay. Even though this is interesting, there's a general perception that female physicians earn less because they work fewer hours or see fewer patients. But even when adjusted for these factors, female physicians still earn less than their male peers. And the data shows that for patients, they haven't done this study and pediatric patients, but for elderly patients treated by female internist, they have lower mortality, they have less readmission rates. And so is it possible that they're they're making less money for the hospitals because the patients are our health are staying healthier because of their care? And so is there better care potentially by female physicians contributing to low productivity measured by our view generation? So a lot of things to think about? A lot of graphs that I think are a good jumping off point and points of discussion, but I think he makes some they make some good recommendations about what can we all do when talking about pay equity. So obviously, discussion about Medicaid parity with Medicaid is with Medicare is urgently needed. New measures are being adopted by CMS to enhance Medicaid and address health related social needs to expand access to quality, affordable care, but doesn't necessarily discuss Provider Reimbursement. Increased pediatric representation on agencies that determine coding and RVU assignments is needed in a coordinated effort from physician leaders, patient advocates in organizations to address comparatively low compensation among pediatric specialty physicians is direly needed. So definitely we'll post some of these graphs. But definitely take a look. Definitely don't look wait. If I was,

Ben 1:22:42

I would say, do not look at this paper before last week, before you go on service. Because you're gonna feel like oh, man, after after you come off, you can look at it.

Daphna 1:22:53

And it was really interesting how, like you said neonatology makes a lot of money for hospitals. But the the reimbursement is not, does not evidence

Ben 1:23:04

is not commensurate is not commensurate.

Speaker 1 1:23:09

Okay. That is interesting. All right. All right. scrotum

Ben 1:23:13

rollin. So Sathyan is going to be on the podcast. I mean, he's sort of, I mean, we're saying this, the invitation has not formally gone out, but he's informally

Unknown Speaker 1:23:20

agreed. But he still had to accept he's

Ben 1:23:23

informally agreed. I spoke to him in person and I said, sat down, you're coming on the podcast be like, that'd be great. And so it's going to happen. Just we have to find it.

Daphna 1:23:30

The hard thing is we have so many things to talk about, not just this paper, so many things that he does

Speaker 3 1:23:36

are amazing. Yeah. Like how did you even get started in that?

Ben 1:23:41

Maybe we'll do like a Lex Friedman podcast like three hour long. He hasn't signed up for that yet. Oh, my All right. Last paper for today is a paper that I got hooked by the title. It says language exposure for preterm infants is reduced relative to fetuses. first author, I loved this paper. I know. First off, there is Brian Munson. It's in the Journal of Pediatrics. It's from a group out of the US. And the background is super interesting. They mentioned how auditory function begins as early as 23 weeks of gestation, and that preterm infants undergo a rapid and premature change in auditory experience as they transition from the intra uterine acoustic environment to the neonatal intensive care unit. The intra uterine environment is quite unique, unique, with constant primarily low frequency sounds of mother's cardiovascular and digestive system, and voice transmitted to the fiddle to the fetal ear via amniotic fluid. Extra uterine sounds are modified by transmission through abdominal tissue, which provides some attenuation, possibly more pronounced at higher frequencies. Now, when you contrast this with the NICU, where infants are exposed to high sound levels, electronic and mechanical noises and periods of silence transmitted via air rather than fluid. Now it is presumed that These auditory exposures in the NICU differ from fetal exposure, the extent of which is unknown. Now, their goal in this study was to analyze the auditory exposures for typically developing fetuses compared to NICU infants. It was a prospective study, and they included pregnant mothers who were 19 years old are more, who were 20 weeks or more of gestation, but less than 32 weeks, and who had no pregnancy complications. The families of preterm infants were approached by practitioners in the NICU, and they included similar patients where mothers were above the age of 19. The babies were less than 32 weeks, or 32 weeks or less of gestational age, and the obviously excluded babies with congenital anomalies, infection or any type of prenatal brain lesion. So what was the intervention so they basically use this thing called the Lena for the Federal exposures. And it's basically like a little, it looks like if you're listening in the car, it basically looks like a good old pager. So it's like a small rectangular device with a small school LCD screen. And basically was placed in a fabric pouch it was attached almost like as a necklace, but worn around the neck and it dangled pretty much around the abdomen, so that it would capture the sounds around the mother's abdomen. And it was placed for a 24 hour period. And during sleep, they would place it at the bedside so that the mother would not really fall on it. And they would just be close by but not on the on the mother. Recording took place twice per week and throughout the third trimester and basically the parents were allowed to pick the day but it just had to do twice per week. And now for the NICU exposure, they use the same device, and they attached it to the inside wall of the crib near the infant's head. And the only the recordings were made inside the infant incubator only open cribs were used for a variety of reasons. So 27 pregnancies and 24 NICU babies were included, and it's accumulated to more than 23,000 hours of auditory exposures. So that's quite impressive. The participation was approximately 12 weeks for the fetal group and about five weeks for the NICU group. The post menstrual age during data collection range from 22 weeks to 41 weeks postmenstrual Age across fetal participants. And the postmenstrual age in the NICU was 26 to 44 weeks. So very preterm infants received an estimated point five, three hour per day, so half an hour. So yeah, that's, that's always tricky, right? When you say point five, three, so it's about half of an hour of exposure to adult language, nearly five times less than the 2.6 hour per day estimated for fetuses. So right away, this is already quite significant. These exposures resulted in an adult word count estimates of 7000 Something words per day for preterm infants compared to 36,000 for fetuses. So language exposure dramatically reduced for fetuses. 69% of adult language exposure was female, whereas 88% of adult language exposure was female for very preterm infants. So interestingly enough, the breakdown of male versus female voices is completely skewed when they end up in the NICU, and they end up being exposed to more female voices. And they're not really trying to go into what is the implication of that. But I think in at face value, it's an interesting finding. very preterm infants had more exposure to electronic sounds 5.1 hours versus 1.3 hours, compared to fetuses and airborne noises 4.4 hours versus 2.8 hours, then fetuses. Finally fetuses. Well, that's something that was just mind blowing to me. While fetuses never experienced silence, owing to the presence of mother's heartbeat and other biological sounds in utero, preterm infants spent an estimated 4.7 hours per day in silence. Want to let that sink in for a second. Whereas language and total extra uterine sound exposure cycles for fetuses showed the expected marked Day Night pattern with low exposure during nighttime hours, preterm infants in the NICU showed less change across a 24 hour cycle, which is not surprising the NICU is busy 24/7 And so they never really had that that decrease in the cycle. And so, the conclusion was that some preterm infants may incur deficits of over 150 hours of language exposure over the preterm period. And given the known effects of prenatal slash preterm language exposure on neurobehavioral outcome, this magnitude of deficit is alarming. They have some pie chart which will post on Twitter, but men crazy.

Daphna 1:29:50

I mean, I don't even have anything to say because the data speaks for itself like I mean, and this is this is again, something you could take to the bedside there Are there are ways we can change this up?

Ben 1:30:02

Right? super interesting.

Speaker 3 1:30:03

But don't be too loud. Right? Like that's the other thing is like we don't want the decibel exposure to be too loud either. It's a very it's an it's a fascinating study that I Yeah. Is mind blown, I would say in terms of what they looked at and how they were able to accomplish that. The data getting that data. Yeah.

Ben 1:30:25

Yeah, fascinating. Okay, I guess we went over time. Priya. We always do, but that's okay. Now now with the journal club shorts. People can just listened to whichever article they want. By the way, people people to know the journal club shorts do not include every article. It's sort of like the three four big articles that we reviewed. But yeah, this was fun. Priya Daphna. I'll see you guys later. Have a good Sunday. And yeah, we'll be around on Twitter.

Unknown Speaker 1:30:55

Yeah. Yeah. Sounds great. Thanks so much. Thank you. Hi, everybody.

Ben 1:31:01

Thank you for listening to the incubator podcast. If you liked this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcasts, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you. So feel free to send us questions, comments or suggestions to our email address NICU You can also message the show on Instagram or Twitter, at NICU podcast or through our website at WWW dot v dash This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns. Please see your primary care professional. Thank you

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