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#015 - 📑 Journal Club 8

NICU journal club the incubator podcast

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

Effect of Systemic Hydrocortisone Initiated 7 to 14 Days After Birth in Ventilated Preterm Infants on Mortality and Neurodevelopment at 2 Years’ Corrected Age: Follow-up of a Randomized Clinical Trial. Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia. Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth. An assessment of dexmedetomidine as an opioid-sparing agent after neonatal open thoracic and abdominal operations. Association of time of day and extubation success in very low birthweight infants: a multicenter cohort study. Caffeine citrate for apnea of prematurity—One dose does not fit all a prospective study. Early High-Dose Caffeine Improves Respiratory Outcomes in Preterm Infants. Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

Effects of single family room architecture on parent–infant closeness and family centered care in neonatal environments—a single-center pre–post study. Asynchronous telemedicine for clinical genetics consultations in the NICU: a single center’s solution. Cortical hemodynamic activity and pain perception during insertion of feeding tubes in preterm neonates: a randomized controlled cross-over trial.


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


babies, hydrocortisone, infants, study, bpd, nicu, outcomes, early, caffeine, neurodevelopmental, trial, dose, dexamethasone, precedents, looked, discharge, day, question, units, thought


Daphna, Ben

Ben 00:04

Hello, everybody, welcome back to the podcast. Daphna. How are you?

Daphna 00:46

Better than you? I'm still on vacation, and you're stuck in the unit. But I'm excited for all of these great articles we have.

Ben 00:55

Yeah, at some point, you're just gonna have to stay to stop saying you're on vacation. Because pretend like you're on service just sound tired. Like, it will all sound so much better. What you've been up to on vacation.

Daphna 01:10

We're just hanging out at the beach. My daughter is obsessed with the podcast. So that's also probably outside the door right now. Because my excuses always. I got to work on the podcast stuff.

Ben 01:28

Very cute. Yeah. Well, well, I've been doing good. I wanted to thank everybody who gave feedback on the episode from last week we've done raffle. It was really good. And the feedback we've got was really excellent. We'll try to do more of these. And I guess I wanted to start the podcasts, we should tease who our next guests are. Right.

Daphna 01:51

Okay, let's do it.

Ben 01:53

Now. What do you think?

Daphna 01:55

Yeah, go for it.

Ben 01:56

So next week,

Daphna 01:58

we're obviously excited.

Ben 02:00

We're obviously excited. But next week, we will be having a one on one, one on two or two on two discussion with Camilla Martin and Dara Brodsky, authors of the famous neonatology review books. And we're so excited to talk to them. It's gonna be a lot of fun. Yeah, can't wait can't wait. Okay, definitely. Let's start. Let's start reviewing some articles. There was a lot of cool stuff, and let's not waste any more time. I wanted to start with the one sort of brief research letter that was published in JAMA called effective systemic hydrocortisone initiated seven to 14 days after birth and ventilated preterm infants on mortality and neurodevelopment are two years corrected as a follow up of a randomized clinical trial. It's one of these things that could have you could miss easily because it's buried inside of these Research Letters. And it doesn't feel like a big deal. And it is a big deal. It's a follow up of this study, that you guys probably have read the stop BPD trial. For the people who don't remember the stop BPD trial was published a few years ago, and it really looked at giving hydrocortisone to babies that were born prematurely. And hydrocortisone was initiated, seven to 14 days after birth and their doses regimen was was pretty standard, I think it was five milligram per kilo per day divided to six, and then we would divide that up, they would they would reduce that dose afterwards over the next few days. And we taper off basically what they were looking at is the risk of death, or BPD at 36 weeks, and it didn't show any difference. And so it was really not really good in terms of the potential question as to should we use hydrocortisone to reduce BPD in these babies, that were really not able to see a difference. But this the stop DVD trial was performed in Europe, right, the Netherlands and Belgium and it involves 16 units, or the babies were less than 12 150 grams. I think we already mentioned that. And and they were all receiving steroids. And so when they followed up these infants, we're not going to go into too much detail because this topic at trial is not new, and you can check it out yourself. But when they looked at two year outcomes, they were able number one, kudos on the 356 out of 371 follow up 6% Follow up for two years. Yeah, very hard to do. If you've done any research on follow up, you know that 96 is pretty, pretty awesome.

Daphna 04:42

It's almost impossible.

Ben 04:47

The occurrence so let's go straight into the main results. The occurrence of death or neurodevelopmental impairment was 56.7% in the hydrocortisone group versus 62% in the placebo group. That was not significant P value was 0.28. The rate of death was 21.5% in the hydrocortisone group and 29.5% in the placebo group that was also not significant P value was 0.08, northern mental impairment 44% or 3.9 in the hydrocortisone group 46.5%. In the placebo group, again, not really significant P value was 0.68. And so it didn't really I mean, what, I'm going to stop right there, what do you take away from this?

Daphna 05:33

Well, you know, the point of follow up, the real follow up studies for neurodevelopmental outcomes is obviously this kind of long held concern that do steroids cause worse neurodevelopmental outcomes, and they didn't find that. So that's reassuring, you know, for the times that we do need to use steroids. I think that brings me some comfort. You know, obviously, I would have loved to have seen a huge decrease in mortality, which they did not see. But I'm glad that you know, I didn't expect the I mean, maybe the neurodevelopmental outcomes could be better if we have less lung disease, but I'm glad to see that they weren't worse. Right.

Ben 06:19

Yeah, I mean, it's interesting, right? Because so the initial study, the trial was published in 2019. And it came at the time where really all these trials sort of work published regarding the use of hydrocortisone, used as a blanket medication for babies that were born very small to try to prevent BPD. And the start up trial was one of the trials that was actually very well conducted, and showed that it did not benefit. It's a big deal, though. Because whenever we have these initial trials that come out, stop BPD. And then we wait for the two year follow up. And it's out here now, and it's not really showing any harm of the hydrocortisone, which I think is good, but still based on their initial findings about death and BPD. Are you going to use hydrocortisone? I don't

Daphna 07:03

know but you may use you may need it for some other indication. Right. So it's nice to know that if you have a baby on long term hydrocortisone, you have a prolonged wean for some reason that that that's doesn't mean we should leave it on forever, but but I'm glad at least to see that.

Ben 07:23

Did you mention I guess just for the sake of clarity of completeness in the discussion, you do mention that there's there was a high proportion of open label hydrocortisone treatment in the placebo group. We have diluted possibly the effect of hydrocortisone in this day, although the modulating effect of open label steroids on long term outcomes is probably limited. So yeah, overall, a very valuable piece of information. And I think a good way for us to open up the podcast.

Daphna 07:51

Well, I think that takes us right into the paper postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia, and in neonatology by Dr. Lex Doyle, and out of Australia. And so this was really

Ben 08:08

a in case you didn't know where Lexol was from. That's right, this point, right.

Daphna 08:15

So this is really a review, or meta analysis, I should say, of the options that we have for postnatal steroid therapy. And so there is a lot of data in this meta analysis. So I really encourage everybody to take a look, I think it was really easy to read, really easy to understand, and it helps kind of give a synopsis of where we've come in terms of steroids, so certainly, especially for our trainees, I think it's particularly valuable. So the major outcomes looked at in the review include BPD, at 36 weeks, defined as obviously, oxygen dependency at 36 weeks in most but not all studies looked at mortality at 36 weeks, and then the combined mortality or BPD at 36 weeks, and then in when possible looking at long term outcomes, cerebral palsy, mortality before follow up and a combined mortality or cerebral palsy. So we won't be able to go over all of that today, but we'll give you will give you some snips. So certainly, he was looking at both their early exposure. So in the first few weeks of life and then late exposure, so for inhaled steroids differentiated for early is less than 14 days. So found that inhaled corticosteroids lower the rates of BPD at 36 weeks, and combined mortality or BPD at 36 weeks. Mortality itself at 36 weeks is not substantially different between the groups found that cerebral palsy is not substantially different between the groups, but evidence that mortality before follow up and combine more time. With your cerebral palsy is higher in the inhaled cortical or corticosteroid group.

Ben 10:06

Yeah, and I think, yeah, I think, first of all, I think he would call, I think we should call this like a systematic review. I know it's called the review. I don't think it's a meta analysis. But I think you would agree that this is a systematic, systematic, systematic review. What's interesting is that, like you said, there's not much on inhaled corticosteroids early on. And but he seems to really underscore the promising aspects of that, of that pharmacology, I think that's quite exciting. Because if he feels like it might work, means we're close to something.

Daphna 10:37

Well, and certainly that work is is being done. So we'll get we'll get more information. Then, moving on to systemic steroids. So again, looking at early use, so less than seven days of postnatal age, so 32 trials in regards to this, and again, some of those are the Cochrane Reviews also. So lots of babies included 43, almost 4400 participants. And so showing that early systemic corticosteroids reduce the rates of BPD at 36 weeks, combined mortality or BPD by 36 weeks is also reduced, but does not appear to affect mortality rates at 36 weeks alone. Also, he took the opportunity to look at the effects of dexamethasone and hydrocortisone on these findings. So mostly care about

Ben 11:39

right after what we read from this web trial. That's the that's the outcome that we're interested in

Daphna 11:44

that we're looking at the today at least. So most of the reduction of early systemic steroids on BPD at 36 weeks arises from dexamethasone, rather than hydrocortisone. So that was interesting, I think, especially when we're trying to decide what steroids to use. Both dexamethasone and hydrocortisone contribute to the reduction of BPD at 36 weeks, but early systemic corticosteroids overall do not reduce rates of mortality at the latest age reported. And then certainly, he wanted to describe some of the long term outcomes, but showing that early systemic corticosteroids do increase the rates of cerebral palsy and later childhood. Here, corticosteroids 11%, control 7% And most of the effects were felt to be found due to dexamethasone therapy as opposed to hydrocortisone therapy. The the p value. It was a trend, not a statistically significant point oh nine. Early dexamethasone increases the rate of combined cerebral palsy, or mortality. So dexamethasone 45% Control 38%. And he takes the opportunity to talk about the work in the primo lock trial where hydrocortisone early hydrocodone orally, prophylactic hydrocortisone reduced the rate of the primary endpoint of BPD, or mortality at 36 weeks. But again, that study was stopped and at follow up at 22 months corrected age, the rates of cerebral palsy were similar in those two groups hydrocortisone 6%, and control 5%. So that was reassured that's

Ben 13:33

so that's the big question, right? I mean, there's all these studies that are not really showing much effect, but then you do have the premiere lock trial that is showing an effect. And I don't know how you feel about that. But obviously, the Primaloft trial, it was interesting, because it did show benefits of using early hydrocortisone on the outcomes of BPD. But their definition of BPD was not the one we're used to. And it goes back to this really dilemma of using different definitions where we're not really speaking the same language. And you wonder, is the fact if I remember correctly, they were using a physiologic definition with a with a winning trial. And and then you wonder, does that influence the fact that they were able to see a positive outcome compared to all these other trials, like the stop BP trial, which didn't really see a benefit? So let's do it doesn't really take a stand either, right? I mean, he sort of puts the information in front of us and tells you like, well, this is what most of the data show and that notably, there's this large trial called the criminal trial that is not showing the same outcomes. You do with it.

Daphna 14:35

You decide, and certainly, you know, I think he does a good job of going into some of the concerns about early steroid use some of the adverse events, such as spontaneous intestinal perforation, for example. And so, I think, I mean, the answer is we probably but we still need more, probably still need more studies, unfortunately, still

Ben 15:03

need more studies. But it's at least at least it's reassuring that when we don't really know what to do, there's the safety of knowing that at least if you are using it, the long term outcomes of early hydrocortisone are not terrible, right. I mean, that's what the Jama sort of research letter really highlights, and that it's almost protective to know that at least, I'm not going to give something that if I'm wrong, if the data is wrong, within at least I'm gonna, I'm gonna, I'm gonna want to cause a lot of damage down the road, at least it's reassuring to see that.

Daphna 15:32

So then just to kind of finish up so everybody gets the kind of whole picture. So looking at late systemic steroids, greater than seven days after birth 23 trials, looking at about 1800 infants, so late systemic corticosteroids reduced the rates of BPD, at 36 weeks, mortality to 36 weeks, and combined mortality and or BPD at 36 weeks. And so again, he looked at differentiating between which systemic corticosteroid and felt that most of the effects beneficial effects were coming from dexamethasone versus that from hydrocortisone. And then

Ben 16:14

she's she's the one who published all these darts, protocols and so,

Daphna 16:19

but he does he does have all of this all the data here. So everybody can come take a closer look. also looked at again long term data so late systemic corticosteroids reduce the rates of mortality at the latest stage, reported, and noted that hydrocortisone reduces mortality at the latest age reported. So again, not at 36 weeks, but at the latest stage that they had for those babies. And then since we like to the question is really what about neurodevelopmental outcomes? There's little evidence that late systemic corticosteroids affect the rates of cerebral palsy in later childhood. In those randomized study, only one of those studies looked at long term outcomes with hydrocortisone. So he couldn't differentiate between the two. But similarly, rates of combined death of cerebral palsy at follow up were similar between late corticosteroid and control groups. So again, that that that's the finding in the stock VPD trial on the leat corticosteroids. So there's a lot more data here, we don't have the time to go through all of those. But definitely, definitely everybody has to take a look.

Ben 17:37

But and it does sound because we are trying to present a lot of data from this review, it does sound like it's a 15 page PDF. But it is not a six page PDF. It's very well organized, very concise, very easy to read. And it's kind of nice, because as all these trials are coming in, you start losing, you start losing the plot a little bit as to what is the evidence, and let's do has disability to put everything together in a very concise fashion and really give you what matters. He did give a talk that sort of covered the same topic at a conference I attended to not too long ago, I forgot which one it is. But it's nice to see that he was able to this talk was amazing. And I took so many pictures, but it's nice to see that he has actually put all this together in one document, and you should check it out. It is an amazing, amazing review.

Daphna 18:29

What would you like to do next?

Ben 18:30

So then the next one I really liked since we were talking about long term outcomes and repeating, I want to talk about long term outcomes. And I want to talk about this paper from Jama peds called temporal trends in neurodevelopmental outcomes to two years after extremely preterm birth. And right, we're like so smooth today because guess who's the senior author on this paper, legs Doyle himself. So this was a, a review of the outcomes of babies born preterm between 1991 and 2017, within the Victorian infant collaborative study group, which is right, which is this collaborative group from Australia, and they looked at infants born between 22 and 27 weeks, and like I said, 99 he wants 2017 They looked at survival to two years. And they looked at neurodevelopmental outcomes at two years of age corrected. And they looked for CPE, blindness, deafness and developmental delay, their their method of assessment, their tools, were very thorough, they were using the Bailey's and they were using pretty much the most up to date barely, depending on on which timeframe they were looking at. neurodevelopmental disability was defined as having cerebral palsy, blindness, deafness or any detrimental delay and categorized as mild for mild CP walking at age two years. gross motor classification system level one or model of mental delay, it was categorized as moderate, if you had moderate CPE, and deafness or moderate developmental delay and severe if you had severe cerebral palsy blindness or severe mental delay, major neurodevelopmental disability comprise either the moderate or the severe category. So what I was very interested in is that when you look at the figures that are being provided, it's interesting, there's figure one, which looks at the outcomes of babies from all age groups, right. And you see that the percentage, so you have a bar graph, that's pretty much three bar graphs. First one looks at patients who died. And you can see that between 1991 and 2017, there's a significant reduction in death. And then in terms of survival with no major disability, it's a beautiful graph, it's a stepwise increase in outcomes where less and less patients survive with major disability. So it's, it's kind of amazing. And in terms of patients who survive with major disability, it's sort of remains the same. And again, this is for the entire cohort. And then when you move on to figure two, which is interesting, because it now breaks down these outcomes by gestational age you have, you have six separate graphs, 2223 24 weeks, 2526 27 weeks. And what you see is that the trends that we observed before, sort of are translated, when it comes to 27 week, infants survival, we know major disability really increases over time, same thing with 26 weeks. So if I think without major disability increases over time, 25 weeks still, and there's a significant pronounced change from 1991 to the 2000s. And then you get into 2423, and 22. And it really doesn't look the same. And you can clearly see that I'm not gonna say we even do I don't practice there. But I feel like it's the same issues in the US and all around the world, there's a drop off. And so I feel like these graphs tell a very complete story as to where we are right now, which is that our care over the past 20 something years has significantly improved for babies that are 25 weeks and above. And there's a lot of work left to be done for 2223 and 24. I mean, the 22 week graph looks atrocious, right, I mean, most of them die. And survival with no major disability is I mean, I can't, I will not really be able from the graph, you can't really estimate the number, I would have to pull it up from the table. And for 23 weeks. What's interesting is that when you look at survival with no major disabilities, it is going down, meaning we're actually doing less of a good job, it's increased from 1991. But in 9097, that number is rather high, close to 30%. And then it drops off to like 24 2005 and below 20% for 2016 2017. And when it comes to 24 weeks, it's almost feels very flat. So I thought that was a good reminder that we're not perfect, and that there's a lot of work that list has left to be done. I mean, we will post these graphs on the Twitter account. And I'm curious to see what you think about this study?

Daphna 23:11

Yeah, well, absolutely. And I think the graphs are quite dramatic, but to some credit to the neonatal community. So in terms of the 23, and 24, weekers, certainly, the babies who survive has improved significantly, but we know that, you know, quality of life is important to parents. And so so we are making strides, but now we need to say, okay, these babies are living, and we need to do what we can to protect their developmental outcomes. And so what do we have to do particularly in the 23 and 24? weekers, our most fragile infants, how do we improve? How do we improve those neurodevelopmental outcomes? But I'm hopeful that that will come in time. I mean, I imagine if if, you know, we looked at these graphs much longer ago that it would look this way for the 2526 and 27 weekers also.

Ben 24:16

So yeah, I guess also, there's this idea that the Victorian Collaborative has a very high reputation to and I look up to them personally. And so it's quite it's quite daunting to see such a large timespan and seeing the trend that would I was really hoping that I was really hoping when I pulled up the article, that the trends would be much more positive. And I think like you said, babies are dying less, which is which is amazing, but we need to improve. Die.

Daphna 24:51

Yeah, well, certainly these are the babies right at highest risk for ivh. And we know that you know that singular event has a huge jump tacked on on long term outcomes. And certainly, you know, spending an extra month in the NICU doesn't help either. So lots of comorbidities to overcome for sure. But yeah, I found this to be a hopeful study.

Ben 25:17

I think, to me, it, it makes me motivated to get to work, right. I mean, it shows you that we're not we haven't solved everything, and there's a lot of work that's left to be done. They don't really discuss the morbidities that you're referring to, obviously, ivh, it's probably available in the supplements, I didn't get a chance to look at the supplemental material. But it's also not the point of the article, right. I mean, at the end of the day, the article is just to show you like a two years, this is what happens. And these are the outcomes that we're seeing. And, and this is what truly truly matters to parents and as secondarily to, as it should to clinicians too. So it was a very interesting article, and we'll post those graphs on the on the Twitter page so that people can check them out.

Daphna 26:00

So shall we shall we talk about

Ben 26:02

precedents? Oh, yes. Let's go.

Daphna 26:07

So this article is from the journal Perinatology, entitled, an assessment of decks method. Never say

Ben 26:15

can't pronounce it either. You can say precedents. I was reading Listen, let's take a break for a second. I was reading a paper and I was like, I'm gonna need like, How can I pronounce this out loud? Right. And I don't know. dexmedetomidine?

Daphna 26:30

That's exactly right. I've been practicing and I still got. That's exactly right. That's just the president acts as an opioid sparing agent after neonatal open thoracic and abdominal operations. Lead author, Alicia Sykes, and this is coming from Rady Children's Hospital in San Diego. So this was a retrospective review of neonates who are post operative from a variety of abdominal and thoracic operations, which, which I'll talk about who received IV acetaminophen, with or without precedents in the post operative period. So the primary outcome was opioid dosage within the first 10 post op days, and the secondary outcomes included times extubation, full feeds and discharge. So they looked at 112 infants, which infants they looked at, I thought were kind of interesting. So all of these babies were less than four weeks of age, the mean gestational age was 37 weeks. So these were older infants. And it it really, it included, really anomalies more than anything a treasures malrotation esophageal atresia, trachea esophageal fistula, it excluded. A lot of babies that I had imagined would were in the study when I first read the title, so excluded babies with neck CDH gastroschisis, congenital heart or lung disease. So it's definitely in a select group of babies. The results so they had 112 babies, and what they found is that those so all the babies got IV acetaminophen, but those manage with precedents received more opiate on post operative days one through three had longer times to extubation, and at a trend towards longer lengths of hops hospital stay than infants who were not. And the difference in opiate dose was was large. It's really a lot of opiate. So I have a few thoughts about that. Their conclusion was that precedents may not be opioid sparing after major operations in neonates and its use could potentially delay recovery. My first thoughts are that I'm glad they looked at it. My second thoughts are that I'm glad all of the babies in their unit were receiving IV Tylenol postoperative. So I think that's something we could discuss in and of itself. We know that, especially from adult surgical literature that Tylenol postoperatively can reduce opiate use. And so that's what they wanted to look at is would using precedents also reduce opiate use, but this was a retrospective review. And so I wonder if if, you know, they they don't really describe what their unit practices what you know what sort of algorithm to to get depressed, it acts as you know, not a first line agent. And so I wonder if those were the babies who were having the most pain were the most difficult to control in terms of pain and so they required precedents and still required a lot of opiate. I'd love to To see this as a randomized control trial, because I think if we randomize babies to receiving precedents, maybe, maybe maybe we have seen something differently. I don't know. You know, I like precedents. So,

Ben 30:16

right. And the question is, was was this was his precedents really an agent to prevent opioid use? Right. I mean, I think the frame, they're the Favorites frame to ask the question, will the use of precedents really reduce the amount of opioid use? Right, and you can question the question, you could say, well, maybe that's never what I intended to use precedents for. And I think it would be interesting to see the same type of study when it comes to decreasing the use of benzos. Right. I mean, we use less versus and stuff like that, because maybe the sedate of effects might be better than the analgesic effects. So that's interesting. But it's it's good that we're talking about precedents, right. I mean, at the end of the day, it's an agent that is widely used in many other areas of the hospital. And it's still a little bit taboo in the in the neonatal ICU. So yeah, it's not opioid sparing, but it may have a role to play. And I was happy to see the paper too.

Daphna 31:15

Yeah. And they didn't. They didn't see in terms of adverse events, which, you know, they didn't comment on a lot of but they did look at things like liver function tests, mostly in regards to, you know, an acetaminophen toxicity, but they're there were no, they didn't have any problems with any of the neonates on precedents, which is a common reason that clinicians don't start pressing X. So that was interesting, more about check this out precedents.

Ben 31:47

And these were, I mean, as you said, right, I mean, just to clarify, these were major surgeries. Like they they didn't press it, right, they give out these were babies with open abdomens or open chests. So um, yeah.

Daphna 32:02

Yeah, absolutely. Shall we talk about extubation success?

Ben 32:07

That Go ahead, let's go. So this paper was published in the Journal of parasitology. It's from first author, Brittany, guy, and it's called association of time of day and extubation success in very low birth weight infants, a multicenter cohort study, it is out of Vanderbilt. And it's a cool study, the idea is to determine the association of overnight extubation with extubation success. And I'm always interested in that, right, we always try to avoid extubation at night. And it's interesting to see whether or not that has any role to play. So they had a cohort of very low birth weight infants that were weighing less than 1500 grams at birth, and that received mechanical ventilation for any period of time. And what was shocking to me is that the study lasted from 2016 to 2020. So it's a four year of study period. And it was done across three NICUs, including van Vanderbilt and and some others that I'm not familiar with. One of the NICU. That's the other thing that was interesting is that one of the NICU the Stormont NICU was a 20 bed unit that houses preterm and eel term infants. And then you had the Jackson Madison County General Hospital NICU, that is a level 330 bed, NICU, so they were the 30. Bed NICU, I think I'm assuming is a relatively high acuity, high intensity NICU, but it's nice that they had a lower one as well. Because Weren't you wonder if it's a big institution, then maybe you have all the resources extubation. Overnight, extubation was defined. I think this is important as happening between 7pm and 6:59am. And for infants with more so then you look at the definitions that they use. And that was interesting, because they, for infants with multiple exhibitions, only the first attempt was evaluated. I was very appreciative that they did that. Because obviously, if a baby fails multiple times, is it the time of day, or is it just the baby's pathology? So that was taken into account? The other thing that I was wondering was that is it? Was there any difference in staffing between day and night, and obviously, in order to perform the study, there was none. It's nursing and respiratory therapy. Staffing does not differ between day and night shifts. And the extubation timing was determined by the clinical team in each NICU. And there was no formal extubation criteria that was put in place, which I think opens the door for a little bit of variability. But that's important for people to know. And then the other question that we had that I had was when you excavate them, do you what do you excavate them to because maybe the kid you activate to roomier will fail more likely than the kid who's on an IV, but no, they extubate only to CPAP or an imp. And so when they looked at the number of babies that were was 535 VRB W's that received mechanical ventilation in one of the NICUs. And from this study, they were able to select 379 that met inclusion criteria. 80% received their first extubation attempt during the day shift. And this was similar across all NICU. So it's interesting, right, because it tells you a little bit about the perception from the neonatologist standpoint that we would much rather do this in the middle of the day. And the one thing that I feel

Daphna 35:30

like is the trend in most units this time of day 10 To 10am to 3pm.

Ben 35:37

Right. And we talked about staffing. But if nursing and respiratory therapy staffing was identical, they did not mention whether physician staffing differ that night with that, which I'm assuming might have been the case. And obviously, that might explain a little bit why more more exhibitions happened during the day, the rate of exhibition success, let's get to the to the meat of this paper did not differ for infants exhibited during the day. And the rate of extubation success was 76% for the day versus 75% for the evening. And I think that was interesting. I mean, that's the main conclusion, obviously, this is the number that you want to take home. And in our in their cohort overnight. extubation. We're not we're this we're not dissimilar to what's happening during the day and extubation rates did not differ. And they they're they're acknowledging that there is smaller study, obviously, because of how many exhibitions did happen overnight, which was only 76 out of out of the almost 400 ones. And they're recommending larger multicenter study. But it's interesting, right? I mean, you, you always wonder if there's variation, temporal variation in what happens in the NICU depending night? They?

Daphna 36:55

Absolutely. And they did, they did comment on that they said of, of note, both in nursing and respiratory therapy, at least in their units. And I think this is not uncommon, that sometimes the experience level is generally higher during the day shift. So you know, more of your senior team, for one reason or another is on Amazon during the day shift. So could that have been kind of a potential factor. And then what I thought was interesting, which, which I think is true in most units, but the babies excavated during the day, were the babies they were most worried about, right. So they were younger, slightly more severe respiratory disease after birth, higher oxygen requirements, more use of surfactant, and we're older at first excavation attempt. But they could have also failed more often than they and they didn't. So but just like you said, they had no formal extubation criteria. And if we show that it doesn't really matter, when we activate babies, then certainly it is an opportunity to have formal extubation criteria. So that we're, we're working on

Ben 38:11

the paper to take with you at sign out when you're going to sign out that you need to activate this baby for the night shift.

Daphna 38:16

Or oh, so and so was just excavated today about 45 minutes ago.

Ben 38:23

6:55pm. And it really makes no difference.

Daphna 38:28

You'll be fine. So that's probably it. Right? It's not that we think babies are gonna fail more at night. It's that nobody wants to be woken up if they do, but if it's the right thing for the baby, it's the right thing for the baby.

Ben 38:43

That's exactly right. That's exactly the point of the paper. The point of the paper is do not delay an excavation to the next day because you feel like oh, we shouldn't do that at night when in truth, there's really no evidence to suggest that because you're going to activate at night, there should be a difference. Again, like you said, taking into consideration that if it's the orienting it who's covering that baby that night, maybe maybe you want to spare that person, or if it's more junior staff or less less staff to patient ratio, you know that stuff matters, but if everything is the same, go right ahead.

Daphna 39:17

That's right. Well, speaking of babies in their in their respiratory needs, we have a few papers on caffeine, this this few weeks. So the this first article of journal Perinatology caffeine citrate for apnea of prematurity one dose does not fit all a prospective study. So lead author have a rosin. This is a study out of the Sheba Medical Center in Israel. And so they did a prospective observational study looking at preterm neonates less than 33 weeks and they're kind of treatment with their caffeine protocol. So overall, they had 66 Babies less than 33 weeks. They looked at babies, they split them into kind of their Fallout core her 30 infants defined as responders. So these were babies, basically who weren't having acne as a breeze, that required actually pretty significant intervention. So they needed to have less than five within the 24 hour period. And then non responders, so babies who are having more than five adna Brady episodes within 24 hours of starting the their caffeine protocol. So they started with seven and a half Meg's per kid, caffeine citrate. No mention of a loading dose, which is something we can talk about. And then, if needed, if babies continue to have events, they would do a dose escalation to 10 milligrams per kilogram. And so then they looked at the two groups, so infants in the non responder group, not surprising were born at an earlier gestational age than responders. 29 versus 31 weeks, the non responders required a significantly longer hospital stay longer supplemental oxygen support needs. And then they looked at babies, specifically the subgroup of babies less than 29 weeks. And so I thought this was interesting. 14 of the 17 Babies 82% of these infants continued to be non responders, even on their high dose of 10. Meg's per kilogram of caffeine citrate, compared to infants born at 29 weeks, where they had only 40% of non responders to higher dose caffeine. And so they followed levels on all babies, they did have a protocol to continue dose adjustment. But one thing that was interesting is looking at the monitoring of the levels. So despite being on different doses, the levels, the plasma levels of caffeine was not significantly different between groups. And I think that's just a good reminder that these babies all metabolize caffeine differently. And even, you know, regardless of the dose that they were on, I thought it was interesting that how quickly they escalated the doses. So in general, my practice for caffeine is that I give babies and this is not based on evidence, but you know, I give babies some some time on the caffeine dose I consider acne as in Brady's early on in the very little baby to not be out of the norm. And potentially, after some time, I would would, would increase the dose. But I've been in multiple centers all who did caffeine differently. Some who followed levels, some who didn't follow levels. And I think it's both of these papers that we'll talk about her are interesting, because there are a lot of questions that we haven't answered about caffeine.

Ben 43:14

Yeah, to clarify, I think they did mention in the methods that they were loading with 20. Meg's per kilo. So it's, it's one of these things these days where the methods are written in smaller character. And it's so hard. No, I missed that. It was there. I just, I just thought that this was this, this sort of legitimizes a little bit what they were doing in terms of that was pretty much routine. Before we discuss this further, I will just want to mention that other article that was published in the journal called children, and this was from the need to member and senior author is Prem fourth was a friend of ours. And it talks about early high dose caffeine improves respiratory outcomes in preterm infants. This was done at all children's, Johns Hopkins All Children's in Tampa, and they conducted the single center trial where they were prospectively reviewed about like 300 babies that were born in less than 32 weeks, and they started these babies on initial dose of caffeine of 10 milligrams per kilo. compared to a regular dose infants in the early high dose caffeine had less hours of mechanical ventilation up until 36 weeks. And in that group, it lowered the odds of developing moderate to severe BPD compared to the sort of normal six milligram per kilo per day dose. Obviously, this is data that is not completely new in the sense that if you do look for studies with that, look at early high dose caffeine there are out there, and it's the same story again, over and over again. All these studies are finding benefits but they're saying they're retrospective. So we need more prospective randomised trials, so we'll see when those come out. But the question then, is posed right, do we need to start higher doses and would you start I mean, the question that I have for you is, do you think that there's enough evidence to say that if you have a very small baby, you should start them on higher doses? Right off the bat, just give them five per kilo?

Daphna 45:10

Yes. So I think the evidence is trending that way. In my personal experience, I worked at a unit that exclusively did high dose. And we were rarely increasing the dose in babies for acne abrading events. And then you and I both worked at a unit where we monitored caffeine levels, and we started with a more moderate dose. And I feel like we were increasing caffeine all the time. And those babies. So you know, if you're going to be following the levels, you're going to be increasing it all the time. Anyways, when I see that potentially a higher dose to start with is, is reasonable.

Ben 45:52

And for people who are monitoring level, right, it's the dilemma of when you get a low level and you bolus and you bolus them that day, and you go up by one or two milligrams per kilo. Sure. You may not be at 10 milligrams per kilo early on, but what is the cumulative dose? And what is the difference between that and just starting them off? 10 mils per kilo per day, right off the bat? I don't know the answer. Because on these days that you get when you get those weekly caffeine levels, if you give a baby six milligrams per kilo plus the 10 bullet 10 of bolus that you're gonna give that day that's 16 for that day, and how does that averages out over the course of a week? Over a month? I don't know. But it does seem that high dose caffeine may be something to look into for babies that are at least small, like the less than 30 weeks, you know?

Daphna 46:41

Yeah. And I think that's why we looked at that group specifically. And then one might argue I have a baby who's caffeine level is low, but they're not having events, right? So so what do you do with those babies? Or you have a baby who has a normal caffeine level, and they're still having events. So what do you do with those babies? And that's what I thought was so interesting about the first paper was that there was no difference in plasma concentration between responders and non responders to the same dose. So

Ben 47:12

you can tell doctors passionate about something once you've been to the table

Daphna 47:15

being on the table. You guys can hear me being so anyways,

Ben 47:21

yeah, and I think it's time I think the time has come to reevaluate. Catherine seriously, Dr. Bank, Laurie at the University of Miami always made the point. If you're on a ventilator, and you're on the way to 45, can you really have apnea as lasting 20 seconds, right. I mean, technically no event is going to kick in. So who needs caffeine at what dose which gestational age? It's up in the discussion. And I think what we're seeing coming out of the evidence is that yes, caffeine is beneficial. I'm not dismissing caffeine, but it looks like high dose caffeine for lower gestational ages might be more beneficial. And standard dosing for babies of higher gestational ages might be the way to go. We'll see what the data shows.

Daphna 47:59

My very first mentor as a resident and probably the reason I went into neonatology doctor are the Douglas Escobar. She used to come around and say this baby needs more coffee, so

Ben 48:14

And sometimes the doctors too.

Daphna 48:17

That's what she would say both the baby and I need more. I know we wanted to talk about this pre proof journal, though. PDAs. Yeah. Did you take that one?

Ben 48:33

Sure. So this was a pre proof again, complaining about the format of the pre proven Journal of Pediatrics if anybody's listening. It's called low rate of spontaneous closure and premature infants discharged with a patent ductus arteriosus, a multicenter prospective study. This is a study out of Baylor done in conjunction with the pediatrics group. So the first author is Virol. Talia, and senior author is Kenneth Schaffer and Rhys Clark. This is a question that is on everybody's mind. The objective of the study was to assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a PDA, I think that was a very valuable question to ask because there's so many babies who are sort of ready to go home and they still have a PDA and you wonder, Am I going to put them at high risk of pulmonary hypertension? Should we get it closed before what is the right thing to do? The study was a prospective multicenter trial, and they enrolled 200 201 infants between 23 and 32 weeks of gestation at birth. They look at them at the time of discharge and they were followed for their PDA status at six months interval all the way up to 18 months of age. The primary outcome was the rate and tightening of spontaneous closure with a secondary outcome that included the use of assisted closure and the incidence of serious adverse events. So The rates. So that's those are let me see, I want to I want to do this justice because I did go through this article thoroughly. So let's look at the results. Because I don't want to give you the abstract this study is pretty cool. So 18 participating sites, that study covered 2016 to 2019. Approximately 1/3 of the babies were treated with at least one course of PDA medical therapy during their NICU stay. And as we mentioned earlier, we are talking about 200 or so baby over the babies who were treated 47% received indomethacin 42%, acetaminophen and 8% received ibuprofen 3% receive more than one type of pharmacotherapy. I was, let's stop right there for a second kind of shocking how Ibuprofen is getting no more love and ICME offend is like the big player.

Daphna 50:53

Well, we've had you and I had two real late success stories as registered in the last month

Ben 51:00

to discharge 75% of the babies were reported to have a small ductus arteriosus. So that's also important to know and almost all reported a left to right shunt at the doctor level, that's 95% 29% of the infants were discharged home on respiratory support. So the rates of closure at one year 95 infants, which is 47% reported spontaneous closure, which then increased to 58% at 18 months. So that's lower than I would have hoped. Just FYI, 17 infants so that 17 infants, which represents 8.4% received the system closure, and of the remaining 67 Wishes are 33% of the group 35 reported a persistent PDA at 18 months of age, and 32 infants report the persistent hidden doctors through nine months of age but were then lost to follow up. Three infants 1.5% died during the study. Let's look a bit at the demographics Who are these babies right? Because I mean, now you want to know do I send this baby home tomorrow or do I just get their ducks close? Well, demographic and in hospital treatment characteristics are detailed in table one and infants with a PDA spontaneously clothes were more mature and larger at birth, they were more often male, and they were less often on positive pressure, high flow nasal cannula CPAP, or mechanical ventilation at 36 Weeks was menstrual age. They had shorter hospital stays. And then infants who had prolonged PDA, or those who had assisted closure of their PDA, major morbidities, severe ivh cystic PVL, necrotizing enterocolitis, and severe ROP were uncommon and did not differ between all the three groups. A greater proportion of infants who received the SR closure of the PDA had a moderate PDA at hospital discharge compared with the other groups, some infants PDAs, increased in size and left ventricular enlargement became more common. That was, you don't want to know the comment I wrote next to that is not PG 13. readmissions to the hospital occurred in 70 infants and that represented 35%. A lot of them were for respiratory stuff, a lot of RSV, and then they go over the patients that die. A lot of them had to do with pulmonary hypertension. But the bottom line is right. I mean, it's 47% and 58%. At best at 18 months. What did you make of that? dhafra?

Daphna 53:28

Yeah, I agree with you. It's less than I thought. And you know, almost 10% of them needed them closed. Which I you know, feel bad that I have not been including that in my anticipatory guidance other than you know that the cardiologists would follow it. And we'd make a decision if needed. But I don't think I don't think it changes my practice. But it changes my counseling for sure.

Ben 54:02

It and that's, that's for

Daphna 54:03

those babies. I want I would want them to be seen. Maybe more sooner than the routine cardiac follow up,

Ben 54:10

I was interested to see that smaller babies with longer hospitalizations were at higher risk of not having it closed. So I think that for me, who deals with complex medical babies who have BPD, who have been in the hospital for a very long time, if it hasn't caused by the time of discharge, you can bet that may not close. So it's very important to establish proper follow up and to and to maybe do not stop demystifying this process right we tend to tell parents Oh, don't worry, it closes in time.

Daphna 54:43

That's right. Well, well,

Ben 54:45

not so much. So

Daphna 54:48

that's what I said I was feeling guilty about my my discharge anticipatory guidance related to the PDA but it's obviously a group well known for their PDA work. And so, yeah, and I think they follow more babies. Yeah,

Ben 55:04

yeah, I think the idea to have small preterm babies born between 23 and 32. And to be able to get echocardiographic data, even if it's indirect data up until 18 months of age after discharge, it's, it's crazy good. Yeah. So kudos to Rhys Clark and his peers. All right. Anything you want to, you're leading the way this this,

Daphna 55:32

just, I'm just keeping us on track, you know. So there was this article, also in journal a Perinatology, called effects of single family room architecture, on Parent Infant closeness and family centered care in neonatal environments, a single center pre and post study, lead author at Emma chi Namie. This is a study out of Finland. And so the aim of their study was to evaluate the effects of changing NICU environment. So they went from a kind of large bay environment, to a single family room architecture and their NICU. And so they were already collecting data on skin to skin care, and the quality of family centered care. So they were looking at their data pre and post that change in their units. So the parents in their units use daily diaries to, to report their presence at the bed, how much skin to skin care, they do. And they have a system where they respond to daily text messages about the quality of family centered care. And so in brief, the results that they found were that parents in the single once they moved to single family rooms, that parents did spend more time at the bedside. And that they really didn't have a difference in either skin, the skin care or the quality of, or how the parents read the quality of their family centered care. So I thought this was really interesting. Because one might anticipate that if you had a single family room, and the parents are at the bedside more, that they may have the opportunity to do more skin to skin care. But that's not what they found. And, you know, that's kind of my feeling having worked in multiple types of units, or at some of the units, we worked out where babies were in a big bay and then moved to single family to single baby room. That they're, they're just families that do a lot of skin, the skin and their families that don't do as much skin to skin.

Ben 57:55

you summarize the paper very well. The question that I was wondering reading the paper is, is the as the the fact that with a single family room model, or when you're providing the privacy to the families to be in a room by themselves, right baby? Does that remove that incentive to do skin to skin because you feel like you're bonding with your baby. But rather than when you are in a big bay openbay unit, you're saying, Well, you know, this is not very private, I want this this bond with my babies, I'm going to do more skin to skin. I don't know. And the authors also mentioned the fact that they were really pushing skin to skin before the move. And so they're wondering if they were wondering if had basically they were asking themselves have we peaked in terms of skin to skin, and that's why we didn't really see an improvement. It's possible to I mean, it I think they use the move as a as a nice as a nice time point to study the effects of changing models. But the images have been doing a great job from the beginning. And it's not doesn't really hold true. But I was wondering that is the privacy of the single room enough to not really push for skin to skin. Interesting stuff. Interesting.

Daphna 59:02

Yeah, I don't know. I always was under the impression that once they got into the private room, maybe they'd feel more comfortable doing skin, the skin for some families. But maybe not. What I will say the other things that I thought was interesting was obviously how much time parents were already spending in the NICU, which is different than my experience. Obviously, we're here in the states we have different healthcare systems, different parental leave, but mother presents increased from a median of 5.2 hours to 9.1 hours a day. And Father's presence increased from a median of 3.6 hours to 5.9 hours a day. You know, after the move to single room, which I thought was really phenomenal and their skin to skin care was a median of three hours a day before the move and four hours a day after the move. So, you know, how

Ben 1:00:03

you do think about? That's right.

Daphna 1:00:05

And certainly, right, that's a whole nother point of discussion is how, how in the States? Can we get parents to the bedside? More often? And certainly our parents are doing, I think the best that they can get

Ben 1:00:19

at an upcoming episode right about talking about these issues of equity and, and how do we get people to be able to even do these things. So we're going to have want to talk you want to tell people about our guests from chop coming up on the podcast.

Daphna 1:00:33

And sure, Dr. Montoya Williams, is coming to us from chop and certainly looking at health disparities in neonatal care. So super excited.

Ben 1:00:47

For sure, yeah. All right, back to journal club. quick mention of this paper in Journal of parasitology, called asynchronous telemedicine for clinical genetics consultation in the NICU, a single center solution. First author is Emily booth. Last other is Brian currency, I'm going to not go into too much detail this was done from the University of Mississippi. And what they were trying to do is to see if they could palpate the lack of genetics consultant by just able to just take pictures of the baby at the bedside, draft a little arm the family tree, and and then get a history submit that to a geneticist who not in real time. That's important. Not that's what they mean by asynchronous. We then review the studies, review the pictures, and then we'll give an opinion. And what they found was that asynchronous telehealth for clinical genetics is a feasible and successful alternative to an unsafe clinical geneticist and should be considered in areas with a genetic workforce shortage. I think it's very good, because it opens the door to a geneticist from maybe different states, different towns to consult on more patients and provides genetic services to areas that are harder to reach. And it's nice to have that evidence out there. Because I feel like without this paper, you wonder like, what are we going to do? We're going to just submit the case by email, like that doesn't sound right. But at least now you see that people have looked at it, it has been peer reviewed. And and it is a viable option. And if you don't have a geneticist, it's definitely better than nothing. So I was

Daphna 1:02:23

right. Well, and I thought that they had such a nice, I mean, their flowchart was really simple. But but really, when you talk about what are the logistics, and again, this genetic testing, parents have a lot of concern about getting this awaiting the tests and then getting the tests. And certainly, they met with parents, regardless. And if they were net negative genetic tests, then they were able to do that potentially remotely. And then if they were abnormal, they were still bringing the families in to do their outpatient consultation. And so it's just, I think, a great way for us to use telemedicine that won't kind of alienate parents saying, well, you're just not coming in to see me and I, I'm not sure the parents care if we come in to see them. We being certain specialists, as long as they get seen, and as long as all of the important information is is is transmitted, and

Ben 1:03:26

for the new Intel, just to be able to offer that service to the patients. And then when you look at the type of genetic diagnosis that they had there, nothing to laugh at. And they

Daphna 1:03:33

were they were still able to get what did they say? 20 25%? I think it's 21% received a genetic diagnosis before discharge. And so I don't think there was any delay in care. I think that's a pretty good number for getting a giant a genetic confirmation.

Ben 1:03:54

All right, the work we're getting close to the end of the podcast, you want to go over one more article, maybe.

Daphna 1:04:00

Yeah, I wanted to talk about this article, cortical hemodynamic activity and pain perception during insertion of feeding tubes and preterm neonates a randomized control, crossover trial. Lead author, giant loop a day two, this is a an article out of India. And I thought this was even the way they did the study, I think was interesting. So they did a true randomized crossover study. So they had 50 infants, the mean gestational age of about 31 weeks, birth weight of about 1500 grams. So they were randomized either into getting an OG to placed first or an NG to place first and then when that device fell out, they were replaced with the alternate native device. So I thought that was a kind way to do their randomized crossover trial. So the mean age and assessment was about 33 weeks. And basically, they looked at a few criteria. So they looked at the mean oxygen saturation during insertion, they looked at the PIP pain scale scores. They looked at heart rate variability, the time for the infant to normalize their oxygen saturations after insertion. And then duration of cry, I thought was an interesting marker to use.

Ben 1:05:44

They looked at that thing that I was actually not aware of, they looked at threads, and they looked at at oxygenation in the brain through nears. Right, they looked at several regional oxygen saturation years. And And my first question was, does that assess pain? And there in the background, there are quoting a bunch of studies who are mentioning that this could be used as a marker of pain. I was not aware of that.

Daphna 1:06:05

Well, and certainly, you know, fluctuations in our blood pressure will change our oxygen saturation. And so, you know, it's hard to parse out how much is, is? Is it pain leading the blood pressure fluctuations, I don't know. But regardless, I think it shows some dysregulation in the in the neonate. And so what they found is that, during fair trial, their outcomes were significantly lower with nasal gastric or NG tubes compared to orogastric. Tubes. So the mean, pap scores, the mean heart rate variability, the mean time to normalize their nears markers, and the duration of CRI. Were higher with ng insertion. So that was not a fracture. Yeah.

Ben 1:07:07

That was not expecting that. And that was very interesting that they found that ng so they were, like you said, I think the one thing that you have to highlight is how elegant the design was. And when they did all these measurements, they made sure that the babies did not have any painful procedures for a minimum of two hours so that there would not be any confounding factors. They had mostly healthy babies. So that's really good, meaning there was no other things like ventilator or other thing that could have confounded the results. And, you know, I feel like when you play synergy, an OG or an NG, it's always less gagging when you put the NG. And I was, I always think it's it was the I was expecting to see that ng were better. And it turns out that actually, no, oh, geez, reduce yield to less painful sort of response from the baby. Right, then that's interesting, right? I mean, I think at the end of the day, it makes you think about placement of OG as a true procedure, should we medicate that or even with non pharmacological agents. And the other thing is, I have so many times in the NICU, a baby that's an OG feeds, and that that may appeal. And so let's put the OG in the nose so that we could actually allow the baby to pee. Oh, and then you wonder, should that rethink those types of decisions a bit more carefully? Considering that it does generate a significant amount of pain? The baby? It's in a very interesting paper, I think people should check it out.

Daphna 1:08:30

Yeah, I think the next time the nurse asked me, What do you want me to put in the mouth of the nose? And I may, you know, at least have me think about that question a little bit. A little bit,

Ben 1:08:39

right. And if we do put it in the nose, are we going to, like I said, we're going to try to make sure that this can be done as in the least painful way possible. Which is not something I'm thinking about these days, when I'm putting an NG I just just put it in.

Daphna 1:08:53

No longer. No longer do you have one more you wanted to do?

Ben 1:08:57

No, I think that's it for me. There was there was a lot of that was a lot of Article, lots of articles. And then there's some others that we can definitely talk about next time. But I think we had the main ones. Yeah.

Daphna 1:09:09

Yeah, there were a whole slew of articles this time.

Ben 1:09:13

Well, that was fun. Thank you. Definitely thing that we didn't read the review this time around. We'll do that next time. It's okay. But yeah, check out look out for next episode. Martin and broadsky coming on, very excited about that.

Daphna 1:09:29

We're very excited. We are loving, you know, the feedback we're getting on Twitter and to our messages. So certainly, if you've got any comments, questions, things that you'd like to see, just let us know.

Ben 1:09:43

Yeah, check out episode 14 with Don raffle. I think it's kind of neat that our field of neonatology did not start in some big fancy hospital but at a broad walk in an amusement parks. I think that's kind of fun. And the story of Martin Cooney and preterm babies being displayed Coney Island is something all neonatologist and neonatology enthusiast should be aware of. That's it for me. Thank you Daphna. Have a good evening. Yeah,

Daphna 1:10:08

for sure, for sure. And for people who didn't read the book, I think you'll still learn a lot about the book and the and the experience that Coney Island so definitely, definitely check it out. Get table. I know I'm being

Ben 1:10:26

by. Thank you for listening to this week's episode of the incubator. 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. Personally, I am on Twitter at Dr. Nikhil spelled Dr. NICU. And Daphna is at Dr. Dafna MD. Thanks again for listening and see you next time. 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 practitioner. Thank you


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