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#023 - 📑 Journal Club 12

NICU journal club the incubator podcast

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

Parent Preferences for Transparency of Their Child’s Hospitalization Costs.

Monitoring of carbon dioxide in ventilated neonates: a prospective observational study.

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010-2018.

Early-Onset Sepsis Among Very Preterm Infants.

Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia.

Survival prediction modelling in extreme prematurity: are days important?

Association of time of first corticosteroid treatment with bronchopulmonary dysplasia in preterm infants

Burnout and Perceptions of Stigma and Help-Seeking Behavior Among Pediatric Fellows.


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


babies, sepsis, paper, weeks, nicu, co2, infants, group, therapeutic hypothermia, patients, neonatal, fellows, corticosteroids, included, morphine, cost, number, steroids, parents, survival


Daphna, Ben

Ben 00:04

Hello, everybody, welcome back to the podcast. Definitely. Has it been going for you?

Daphna 00:45

It's been going well, I think I get less sleep preparing for a journal club than I do on call.

Ben 00:54

You procrastinate for Journal Club?

Daphna 00:56

Well, but I get it done.

Ben 00:59

No, I'm not saying you're not not saying you're not.

Daphna 01:02

But do you have different we have different styles? I would say

Ben 01:05

that's, that's right. Well, I'm a foreigner, I panic if I have to read massive amounts of English stuff. A few hours before recording.

Daphna 01:16

That may be your I mean, your English proficiency is just

Ben 01:23

we want to start the show by highlighting a poll that we ran on our Twitter account. We asked you guys if you would be interested in podcasts and episodes and guests addressing healthcare worker burnout slash moral injury. And we were stunned by the response. Thank you for for taking the time to answer the survey. About 80% of you said yes, 60% of which said absolutely. 11% of you were I guess indifferent, saying why not and only 10%. Were not interested. So taking into account this this overwhelming enthusiasm for addressing this issue of moral injury and burnout in medicine, we will be putting out a few episodes with special guests to talk about that. And we think you will you will really like them. In other news, we have some major announcements that we want to share with you. And it probably will be it won't do it justice to do it at the opening of a journal club. So we'll record a little episode midway through the week that we will share on the podcast page, and you can listen to it and then we'll announce some of the changes that are happening. Again, making the podcast better growing using our growing reach to provide more content and more tools for the neonatal community. Duffner anything else to add to that?

Daphna 02:49

No, I think that's it. I think we were we're really loving how people are engaging with us and providing us, you know, suggestions and feedback. And we're really trying to take that all in and really run with it. So I think we have some exciting, exciting things coming up.

Ben 03:05

Yeah, yeah, we do. Yeah, we do. Let's start Journal Club. And we have we have a loaded loaded week of articles and so we should not waste too much time. I guess the most the thing we should really start with are these new ACOG recommendations right for antenatal steroids. Do you want to tell us about that?

Daphna 03:24

Yeah. So I think people should just know that ACOG put out a new practice guideline regarding the use of antenatal corticosteroids at 22 weeks. So I'm sure you've all dealt with this in your clinical practice. But previously, they were not recommending the administration of beta methadone at 22 weeks gestation. So apt 20 and zero weeks to 22 and six weeks of gestation. The previous studies that had been done, which were few demonstrated no significant reduction in neonatal death and neurodevelopmental impairment with the administration of antenatal corticosteroids, but obviously, our practice is changing. And our ability to do what we do in the NICU is changing, and so they have reevaluated that in this last year, so, a 2021 systematic review and meta analysis included 31 retrospective observational studies of 2200 infants who are delivered at 22 and zero weeks to 22 and six weeks of gestation found that survival among infants born to pregnant individuals receiving antenatal corticosteroids was twice that of infants born to pregnant individuals not receiving antenatal corticosteroids, so 39% survival in the babies whose Mommy's got corticosteroids versus 19 and a half percent. One of the observational cohorts that analyzed over 1000 live births at 22 and zero to 22 and six found that infants who receive antenatal corticosteroids with postnatal life support so coming to the NICU than being at least evaluated, were more likely to survive than infants who received postnatal life support alone. So many of us were seeing this in our practice, we were speaking with families and being asked to resuscitate babies at 22 weeks. But our obstetric colleagues were following the ACOG guidelines which were not providing steroids. So what they found were that infants who received steroids with postnatal life support had a 38.5% survival versus those who received life support without antenatal steroids 17.7%. That's

Ben 05:40

huge, right? I mean, 3038 to 17 is

Daphna 05:43

astronomical. So while survival without a major morbidity was improved with antenatal corticosteroids, the absolute rate of survival without major morbidity still remains very low. So 4.4% to 1%. So obviously, this is something we'll have to take into account in our discussions with families and that's exactly what they're saying. So based on this new literature, the ACOG and the Society for maternal fetal medicine are revising their recommendation regarding antenatal corticosteroid administration at 22 weeks of gestation. Thusly, antenatal corticosteroids may be considered at 22 and zero to 22 and six weeks of gestation, if neonatal resuscitation is planned and after appropriate counseling.

Ben 06:28

And that's the key, right? Yep. That's the one thing that's the thing that I'm interested that was very interested about is the fact that they're tying into OB and neonatal and saying this is a shared decision process.

Daphna 06:40

And that's, that's what they're saying. So if they should be linked, so if you're going to resuscitate if that's the plan, after you've met as a multidisciplinary team, with the family, and that is in line with the family's wishes, well, then we should, then we should be giving the steroids and if we're not planning to intervene, well, then maybe we don't need steroids and to put mommies at any of the at that time, additional risks right associated with the an antenatal steroids.

Ben 07:11

And you may and you may give it down the road if the mother elects to resuscitate closer to 2324 weeks. But But yeah, I mean, this is this is nice. I feel like there's so many silos between OB and neonatal when it comes to delayed cord clamping and suctioning the baby at the at the shoulder, there's always recommendations that are coming and, and the relationship is never clear. Here. I really like it. Well, they have to give steroids if neonatal has been consulted, and there's a plan for resuscitation. Love that,

Daphna 07:44

for sure. And that always, that was always a struggle, right? Where we say, Well, you were going to do this, right? We the family and I and we have made this decision. But are we are we given the baby everything that we can and before that the data, again, the studies were small, there weren't a lot of babies included, our survival rates alone and 22 weekers were were different than they are even now just in the last five years, really. And so I'm glad that we have, you know, some data and that at least we can all be on the on the same page. And I really experienced this. You know, for example, we didn't even get to counsel these parents at 22 weeks. But when they came in, they signed a consent for C section. You know, and so I what really changed at some of my previous institutions was doing this joint counseling and saying, These are the range of options, including fetal monitoring intervention for fetal distress and in Natal steroids. And it doesn't have to be all or nothing. But let's take a real thoughtful approach to individualizing. This individualizing is for families and if we are planning to resuscitate then, let's give the babies everything, everything in our arsenal, so to speak.

Ben 09:03

That's right. That's right. Well, thank you for going over that. I think I think these are the type of articles that from the neonatal community may slip by unless somebody mentioned them to you because they're published on the ACOG. website. And even on the ACOG website. This was not front and center. So

Daphna 09:17

that's right. That's right. The premise was potentially some of our obstetric colleagues don't know, a new statement. point for discussion.

Ben 09:26

And I think if I remember correctly, this was actually highlighted to us from a Twitter follower. So again, this is where the community is getting together and providing providing good resources. Anyway. The next paper I really wanted to talk about was a paper that actually does not really involve the NICU but it's it's in The JAMA Network open and it's called Parent preferences for transparency of their child's hospitalization costs. The first author is Hannah Bassett. And the last author is As a pediatrician I actually worked with in the past Alan Schroeder, who's who's brilliant. And this paper was aimed to quantify parental preferences for experiences with an perceived barrier to cost transparency. And a secondary objective of the paper was to identify association between patient and family characteristics and cost transparency preferences. I think this was fascinating, because I, I it was timely for me. I was in the NICU on call, I went to a to the room of the baby and the well baby nursery, or I guess in postpartum area, because the baby was with the parents. And I spoke to the family about doing phototherapy. And the father, who was a former Navy officer told me how much is that going to cost? And I was baffled, I was like, I have no idea. It was definitely the right thing to do the baby met criteria and so on. But it felt like such an appropriate question, right to say, How much is that going to cost us to have this baby placed on phototherapy? And me having not only not the answer, but having also no idea where to get them? The answer from Totally. That'll I thought that's

Daphna 11:10

exactly how I felt when I read this is like, well, we'll get to the punch line. But I don't we don't know. And in fact, I've tried to get the data. I tried to do that project as a resident in the NICU, just to see what are the costs for some of the simple things like extra days on pulse oximeter, administration of certain medications, and nobody could tell me what.

Ben 11:36

And so this is from a group out of Stanford in California, and they looked at, they conducted a survey between November 2017, and November 2018, and six, geographically diverse university, Ophelia Children's Hospital. This did not include neonatal intensive care units. So that's why I said it doesn't really involve the NICU. But I do think that parents all around are the same. The reason why they said they did not involve the NICU was because of confounding issues of mothers often being admitted concurrently. And so they just didn't want to deal with that potentially having to include the mother's cost in there. They had a survey that was available both in English and Spanish and had 40 items in there. And their primary outcomes were parents cost transparency preference, which were measured descriptively through survey items, assessing their agreement with the importance of knowing this, of knowing I'm sorry, first knowing discussing, and considering their personal cost and their child's medical care. And these were answered on a five point Likert scale from strongly disagree to strongly agree. And I think their findings were were very important. So they they had about 523 completed survey surveys. And most of their sample were categorized as male, non Hispanic, Latino, most parents, and this is some of their findings. So most parents 76% of them strongly agreed that knowing the cost of their child's care was important. So far very expected. 75% strongly agreed or agreed that a hospital employee should talk to them about the cost, they will have to pay for their child's care. In comparison, almost half of the parents 49% strongly agreed or agreed that the physician should consider the parents cost when making medical decisions for their child. I think this is something that we always say that we always say we take into account. And on the other hand, we still I mean, there's the blue book where you can look at cost of things, but I have no idea how much of the stuff I'm ordering costs. I'm assuming imaging is more expensive than the CDC. But I really don't have any idea. 48% strongly agreed that they consider their own costs when making medical decision for their child, and 75% reported, they're concerned about how much their child's hospitalization would cost them personally. And I think that's terrifying. And it's so tragic that when a baby or child is in the hospital, that has to be an additional concern. I'll just finish up some of their findings. 19% were worried about discussing costs and that this would hurt the quality of their child's care. terrifying, terrifying, that's that should never enter a parent's mind. 56% prefer a financial counselor to be the source of information. And I think that's very important, right? I mean, that totally reasonable. Totally reasonable. I do think that the physician is not a financial expert, and they finish the physician should have the tools to make decisions as to what is the less cost prohibitive methods of actually achieving the management that the patient needs. And it shouldn't be we shouldn't become financial counsellor for these parents. These parents deserve financial counselors, people who actually know what they're talking about.

Daphna 14:48

And, and so that they don't think we're making decisions exclusively about cost and so that they don't feel like we feel like they're making decisions exclusively about cost. It's really so

Ben 14:58

that brings that's a great segue because you brings me to their last resort 48% indicated that they would want to have cost conversations before their child receive tests and treatment, as if, if I mean, because I mean, if you get the treatment, it's like, well, how's that helping me now, I have no decision to give it already, we're gonna get built. Parents whose child was in the intensive care unit, during their admission, had higher mean agreement that it was important to know their child's cost of care compared with families whose child was not an intensive care unit. Compare it. And then there's some some interesting things, obviously, about education, which I think are important for us to know where they said compared with parents who had not finished high school, all parents educate all parental educational levels, were negatively associated with wanting the child's physician to consider costs and medical decision making. IE, the more schooling you got done, the less concerned you were with medical costs, which probably you were probably making more money, which obviously then becomes less of a concern as your as your more and more well off, I guess. So. Anything else? The perceived barriers, right? I mean, so what are the barriers to this discussion? So perceived barrier to cost discussions were not knowing who to talk to. She's exactly. of it and fear of affecting the quality of their child's care. Although cost transparency has not been part of the traditional family centered care model, Our results suggest that perhaps it should be and I'm going to leave it at that because heck, yes, right. We pretend to be family centered, patient centered, but we have no problem racking up the bills behind their backs. So yeah, Daphna, I'm sure you love that paper?

Daphna 16:42

I did. I think it's so important. Well, it's here. Here are my thoughts. Firstly, this is this is obviously based in the American healthcare system, which I have my own feelings about. And what we know is that like, for when, when I did this project to see what the cost was, what struck me was it's and I misspoke, it's not that they didn't know what things cost, it's that it cost different amounts of money for different patients who have different types of insurance or no insurance. So that's really the crux of the issue and why it's so hard to tell parents exactly what things cost is because it changes over time. And it depends on who your provider is, or if you have a provider for insurance. So it's almost impossible to get a final number before within the timeframe to make a clinical decision. But I think what we can do is we can be sensitive to the extra trauma and financial burden that families have, we can't just ask them to ignore that, when they're already having trouble meeting, you know, making ends meet, and they're gonna get this catastrophic bill. We had very close friends who the mom was on bed rest for about six weeks, with twins who are delivered at 32 weeks. I mean, their bills and their bills spanned two years, right. So the babies were born in, let's say, January. And so But Mommy was admitted in December, and so they got like a double double hit. And I mean, they had racked up millions of dollars that how could they ever pay that we know they're not going to pay that our system doesn't expect them to pay that. But even what we expect families to pay is a real a real burden. And so, you know, the other my other thought is, what can we what can we actually do about it? And so I think there are things that where we can take costs into account, can we do maybe in the nursery at home bilirubin monitoring instead of staying in the hospital for one more day? So I think there are ways we can have the conversation with families. But it speaks to how provide providers need to have transparency of what things cost, so I can't even make a recommendation for families. Because I mean, I don't actually know,

Ben 19:05

Ashley is there's grocery sort of open in my neighborhood, and we went there, and they just still hadn't put the price tags on every item. And my wife and I were like, What are we supposed to do here? I'm not gonna just put stuff in the in the bin until I know that how much things cost? And if you wouldn't accept it from your grocery stores? Can you imagine medical bills? This is nuts.

Daphna 19:22

Yeah. Well, and you know, I think we can, I think, I don't think parents are asking us not to do things for their babies based on cost. I think they're trying to say, is there a different way where we can be effective and safe? That's less expensive, and that's totally reasonable. I just wish I knew where to find the answers for them.

Ben 19:47

So that was that was that was a very cool paper. Do you want to go next or should I should I should I keep going? Yeah. Oh, okay. Go ahead.

Daphna 19:57

I wanted to do this because this came up again in the unit this be monitoring of carbon dioxide and ventilated neonates, I was hoping you were gonna pick that one that prospective observational study, lead author, Toby is Werther. And so this is coming to us from the archives and a group in the Department of Pediatrics at the University of Vienna and Austria. And so what the group set out to do was to assess the reliability, the accuracy and the precision of distal entitled capnography. In neonates compared with Transcutaneous carbon dioxide measurements, and again, as it correlates with the baby's blood gas measurements. And so they did this on not very many babies. But I still thought this was a very valuable work. So they had 25 babies. The mean gestational age was 32, and six with a range of 28, and three to 40. And zero weeks, mean weight of 1.4 kilos, with a range of one kilo to about 2.9 kilos. And what they did was they obtained numerous measurements, so they got the blood gas measurements, and they did three measurements of the end tidal co2 and three measurements at separate time points of the Transcutaneous monitoring. And they looked at how did these things correlate. So I'll get you the data, the mean, standard deviation of arterial co2, and titles YouTubes and Transcutaneous, co2 was 4542 and 50, respectively. So say the average blood gas co2 was 45. The mean, the end tidal co2 is 42. And the Transcutaneous was 50. They also looked at intraclass correlation. So they looked between the arterial co2 And the end tidal co2, and then the arterial co2 and the transfer taneous youtubes. And they reached point eight and point five nine, respectively. So really, what they found was that repeated measure correlations between the blood gas co2 And the end tidal co2, had better reliability, accuracy and precision than those with the Transcutaneous. co2 in ventilated neonates on conventional mechanical ventilation without really severe lung disease. And so I thought this was interesting, because I've often had that question, how can we do less blood gas monitoring is Transcutaneous, the best way to do that our adult colleagues and even our PICU colleagues are using end tidal co2 with much higher frequencies than then we are, I think one of the concerns people have is that we don't use cuffed tubes. And they talked about that in this and they, the babies did not have cuffed shoes. And in fact, if they had cuff tubes, they were excluded from the study. And in 14% of the babies, the tube leak was greater than 20%. And I'm sure we've all had that experience. And still, it didn't really change the accuracy of the end tidal co2, and so we're not using internal co2 in our unit, I think it's something we should definitely consider.

Ben 23:33

So that's, yeah, I have a lot of thoughts on this paper. So number one, they did something really cool, which I was not familiar with. It's called the bland Altman analysis. And basically, this statistical analysis provides a measure of bias and precision. And so what was interesting is that the bias gives you how off the values you're trying to compare are on average. And so when they looked at the comparison for for entitle co2 and Pa co2, the bias was minus 2.7. And when they compared Transcutaneous, and Pa co2, it was 5.4. And then they do something called precision, which is basically looking at the range of values that you could get in and around. The control value in this case will be the pH co2. And when they compared entitle with pure co2, the blender Altman precision was 10.6 millimeters of mercury. And when they compare Transcutaneous to Pa co2, it was actually 17.2. So as you said, transmit end tidal co2 was better at correlating with blood measurements of co2. Now, like you said, there's a few knotty issues, but there's a few items with this study that we need to highlight for our listeners. Number one, you mentioned the fact that it was small right 27 patients. The other thing They did is that they used double lumen attitudes, where basically one of the lumens was connected to the entitle and the other to the ventilator. I'm not sure what that means, practically speaking, if we were to do the same thing with a single loominatee tube, which is what I've always used when I was in the NICU. And so from a technical standpoint, I'm not sure if that makes any difference. So again, like I said, they're not issues, but just little caveats that we have to highlight. And then obviously, the big big topic of discussion is hot. So the end tidal co2 is related to a little cannula that goes into a sampler that increases that space significantly as the baby gets smaller and smaller, or as the baby gets more and more into that VPD range. And they address it, right. I mean, they talk about that in their limitation in the discussion, they said, As for the end tidal co2, we did not explicitly exclude patients with severe lung disease that could augment physiologic Deadspace, which in turn may lead to low and tidal co2 values. So having the machine there, influences your measurements, at extremes of patient care whether you're extremely small. And if you're pulling from the tube to three MLS to measure to make your sampling that's very significant tidal volume, or if you have severe VPD. So that's something that people have I'm not, I'm not coming up with that issue. Obviously, this is something that the authors were very aware of, and they are addressing it. But this is always the ongoing issue with the use of entitled co2 in the NICU. I'm not sure if technology is going to provide at some point a manner in which we can measure in tidal co2 without having to really on a continuous basis, pour so much, pour so much volume from the tube, however, we may have a need to do so just because of the fact that the Transcutaneous number one is expensive, if you guys have used it, it works

Daphna 26:57

50% of the time, that's about accurate. Yeah. And, and then you have an Artis hate having to put it on,

Ben 27:06

right, they always fall off, and then they heat up, right. And for people who don't know this, right, the Transcutaneous, co2 has to be at a specific temperature in order to measure the Transcutaneous levels of co2, and that's 41 degrees Celsius, which, which is hot,

Daphna 27:22

which if you take your shower, just have the temperature of the babies

Ben 27:25

know which if you take your temperature, your water, your shower at water at 41 degrees Celsius, it's burning hot. So obviously, the therapists are aware of this. And that's why they have to constantly rotate the probe from one area to the next, we have to use these rings that are stuck on to the baby's skin, which again, can provide damage whereas they get removed. So there's definitely a need to think more creatively when it comes to Transcutaneous co2, and maybe entitled is the way, but I also don't. So I think what they're showing is that for specific category of patients, it works, I don't know how we're going to be able to on to roll this out to the rest of the patient population. Very cool paper.

Daphna 28:06

Yeah, I mean, I think what it shows is that actually Transcutaneous co2, when it's working is is is reasonable, it works pretty well. But right, it needs to be recalibrated every four hours, it's time intensive. For the smallest babies who are in humidity, it's almost impossible because the things just don't, they just don't stick. So we can't really get good measurements. But you know, there are babies where, where it really works for and it saves us time. And I think you're right in the smallest babies in the biggest babies. It's not may not be the right technology, but we have a whole bunch of babies who are living in between who you know, people are getting gases multiple times a week gases with no other lab needs. And you know, like everything in medicine, the trend is valuable. And when we talk about trauma informed care if we can do something that is reasonably effective, without having to stick those babies as often I think we definitely have to look into it. Absolutely. The only other thing I wanted to mention about this study is they did indicate that they had 27 Babies enrolled, but at some point in time, two parents withdrew their consent. And I thought it was interesting that they mentioned that and I think since we're a team of people who who looks at studies I think we It begs the question, how do we how do we really talk about do we do a good job of talking to parents about these studies? This is a what I perceived myself as a neonatologist a low risk study right with potentially potentially a benefit to the baby right maybe better monitoring not for these babies they were gonna get the same number of of lab drawers but but potentially for those babies after enrollment, things like that. And and yet parents withdrew their consent. I think neonatologist, especially pediatricians, we, we don't feel like, you know, maybe we're not the best at enrolling patients into into studies, you know, we're we're focused in care, we're focused on knowing that parents are having to make decisions for their children. They're totally overwhelmed in the ICU, especially for their critically ill babies. But so I just thought I would mention it something.

Ben 30:31

I think there's there's something to be said, when the studies involve therapeutics, where you say, Hey, we're gonna give you a baby a medication that might help, versus we're going to do some tests on your baby. Yeah, I think regardless of what you're talking about, if you're a parent, and you say, Hey, we're going to do some tests on your baby, it's like, yeah, I don't want it. I'm much more reluctant. Yeah. When I want to get to so many papers, I'm gonna Is it okay, if we move to the next? Yeah, please. All right. So I want to talk about this one, again, which is not going to change your practice, but it's called, it's from the Journal of Pediatrics. It's called medication use in the neonatal intensive care unit, and changes from 2010 to 2018. First author, Ashley Stark, this comes from the pediatrics group. Rhys Clark is one of the authors in the group as well. And so this paper just goes over the pediatrics registry and looks at the changes in medication use over the past over eight years, right, from 2010 to 2018. And it reminded me when I was a kid, and on the weekends, I would just look at the standings of the NBA teams, right. And you can just like, look at what people are doing. And, and it's the data itself, like I said, is not very useful from a practice standpoint, right? Because it's just what people are doing all across these pediatrics unit. And so why some things were ordered, and not others, you don't have that information, but it's interesting as to what the trends are. So and they present the data, again, like like, like the top 100 of hit records, right? It's just, it's just cool. That's great. I know that the charts the top of the charts and table two, table two is the medications most commonly used in the NICU ranked by exposure and wanting to take the lead the pack with antigens, which are fine. Number three is caffeine. Number four is surfactant. And then number five is morphine. And I was surprised by that right I mean, I was not expecting that. least six is seven. Fennel is eight. And the one that surprised me the most was ibuprofen, right? I mean, ibuprofen I thought we we use it pretty often for PDAs we don't use indomethacin as much and Tylenol is still being worked up. I profund is number 55 falling below phenol Efrain

Daphna 32:50

that's great and, and some things I have never used.

Ben 32:53

I know I know. So it's very cool. The so there's you can go through this list and and it's kind of an it's kind of neat. Then there's more information being provided. So they have the table three is the most commonly used medications in the NICU for E RBW. And this is where again, you can find some things that are a bit puzzling number one and pungent and caffeine still top three. Number four is vancomycin over surfactant. And I was surprised by that really, I mean, if you're an ER W surfactant, I was expecting to really be competing for number one spot. Again, I'd be profaned on this list for ELP W's is number 40, which is which was surprising. And eco is number 27. You have dobutamine number 32. Nitric oxide is number 34. And the one that wanted to mention was dexamethasone was number 16. So that's also again, some interesting, some interesting aspects of of the patterns of use of these medications. And then they had the relative and absolute increase in exposure. And I thought these were also really cool. All right, so they had the absolute increase in exposure between 2010 and 2018. And the first one was surfactant. Number two was morphine, which was surprising. Number four was glucose gel, which was nice to see. Number seven was clonidine number eight was acetaminophen number nine was dexamethasone. But then when you look at the relative increase, so meaning the percent change, not just in absolute numbers, but from what they were in 2010 versus what they are in 2018. Number one is precedents. How funny was that percent change 5,000% Number two was clonidine. Number three was rocky rhodium, which was puzzling. Number four was not as surprising it was Keppra right? I mean, we We've seen the shift between phenol BBQs and Keppra. In the NICU. Number five was atropine, which I thought was interesting. Why? Because I'm assuming this has to do with intubation. And that means that people are pre medicating their baby, which is, which is good, great. And then SEF Triax on had a large relative increase, which I was surprised to see. I'm not sure how you felt about that one. Well,

Daphna 35:23

in one of our upcoming papers, maybe not so surprising.

Ben 35:27

That's right. And then the, again, the surfactant is on there, obviously. But anyway, I'm going to stop talking. It's just if you haven't seen this paper, check it out. It's just cool to peruse the table and be like, Huh, that's an interesting and to see which, which of your favorite meds or where, how high or how low on the table? What do you think about Yeah,

Daphna 35:49

well, I thought, especially some of these little one offs, were interesting that amp and gent are still the first and second most used medications, but also the greatest absolute decrease from 2010, and two to 2018, which just goes to show you how many babies still get antibiotics, right? It's still, it has the greatest decrease over time. And yet, it's still one and two. And then

Ben 36:14

even for ELB W's initially, you can think well, there's maybe more full terms in the baby that are here for without sepsis. So maybe I'm Punja and makes sense. But even in the high risk category of ELB W's they still are number one, gen two being first, by the way. That's right, Jen's being first How crazy is that?

Daphna 36:31

And you know, I really like

Ben 36:32

those nephrons one at a time.

Daphna 36:35

I really appreciated their discussion on nearly all infants admitted used in medication that was off label. And it's just a reminder of the state of neonatology. Right, that that, so much of what we're doing is, is still off label, it works. But you know, we don't necessarily have have all the data that we would have expected to use a medication in any other population. And so, you know, it's it complicates our work. I think. They don't study the medication interactions. But but we're, but we're giving them we're giving them and for some of our babies, they're getting a lot of medication. And so I thought it was a it was a good study, just to see.

Ben 37:24

I know, I actually enjoy browsing this paper.

Daphna 37:28

I can tell. Well, maybe that brings us to talking about this other paper in pediatrics, early onset sepsis among very preterm infants, lead author, Dustin de Flannery, and

Ben 37:45

this is a Twitter friend of ours. And so if you're not following Dustin, on Twitter, go right ahead. He's a great follow.

Daphna 37:50

And so this came out of chop. And so what what they're looking at is to determine the kind of current state of the epidemiology and microbiology of early onset sepsis among very preterm infants. And so they looked at Babies weighing 401 to 1500 grams and or 22 to 29 weeks gestation. So you either qualified by weight, or by gestational age, and you were admitted between January 2018, to December 2019. So relatively recently, in one of the 753, Vermont Oxford Network centers. And so what why were they doing this? So obviously, early onset sepsis is a significant cause of morbidity and mortality. And could the epidemiology be changing, such that we may need to change our empiric antibiotic therapy. So I thought this was

Ben 38:45

really was right in line with what we just talked about.

Daphna 38:47

Exactly. And so I told you about the makeup of the babies, there were 753 senators included in 49 states. And again, this is using the bond database. Early onset sepsis was defined as a culture confirmed infection of the blood or CSF by a pre specified bacterial pathogen. In the first three days after birth, the primary outcome was survival to hospital discharge. They also looked at two secondary outcomes survival without morbidity by using, again, the Vaughn manual of operations definition so that includes survival without any of the following neck, chronic lung disease, severe ivh pneumothorax, late onset sepsis, cystic PVL and survival with major neonatal morbidity. So again, chronic lung disease, ivh PVL, and severe retinopathy of prematurity. And they did define all of those, so that's something for you to look at. And subsequently, they looked at covariance covariates, including race and ethnicity, maternal health, comorbidities, chronic hypertension, preeclampsia, diabetes choreo. Did mommy get prenatal care anti natal steroid administered? issue SGA length of stay and congenital anomalies. So they had a total of 84,000 infants, medium birth weight of 1100 grams median gestational age of 28 weeks, median length of stay of 66 days. And so what they found was that a 1139 infants had early onset sepsis. So that was an incidence rate of about 13.5 per 1000 births. Obviously highest for infants less than or equal to 23 weeks. So let me tell you, I guess, let me get to the major punch line, right. So what were the pathogens, so E. coli number 140 6.5%, early onset sepsis, GBS eight down to 18.8%. And then 34% were other included Hammar flesh species, and predominantly the staph aureus species, either MSSA or MRSA,

Ben 41:08

then this was scary.

Daphna 41:11

Yes, and, and I'll get to the probably the scariest point, but let me tell you about some of the other data but comparison of infants with and without early onset sepsis. So not surprisingly, infants with early onset sepsis were more often born vaginally to mothers without with choreo. And without some of the other comorbidities, hypertension, multiple gestation. Infected infants were also less often to be SGI, less often to be SGA. There were no major differences in sex, race or ethnicity between the two groups. length of stay or longer for infants with early onset sepsis compared with uninfected infants 92 days versus 66 days. That is that's a lot. And then looking at some of their other outcomes. Infants with early onset sepsis had lower rates of survival to hospital discharge 67% Compared to 90%. Infants with early onset sepsis were more than twice as likely to survive to hospital discharge without morbidity compared with infants with early onset sepsis. And then, those babies with early onset sepsis, who did survive to discharge words significantly increased risk for at least one or greater major neonatal morbidity. And again, those are chronic lung disease IBH PVL, ROP when compared to babies without early onset sepsis. The other interesting details that the incidence of early onset sepsis was inversely related to gestational age. So almost one and 20 infants born at less than 23 weeks had early onset sepsis. So obviously a major cause of preterm labor. In contrast, one of every 100 infants born at 28 to 29 weeks were infected. And then greater babies born at greater than 29 weeks, the incidence declined further to one in every 200 to 250 infants. Same incidence of early onset sepsis was also inversely related to birth weight. And so in general, babies who were smaller had Earl had higher incidences of early onset sepsis. This was not true for babies, very preterm babies who are born weighing greater than 1500 grams. So if you were small, but have a good size, you are less likely to have early onset sepsis. And then what I think was probably the takeaway point is that previous studies, not necessarily this study, they didn't actually do the sensitivities. But E. coli is becoming resistant to both amp and gems. So in other studies, almost eight to 10%. And so if we have, you know, almost 50% of babies infected with E. coli, and 10% of them are resistant to our empiric antibiotics. It's definitely something for us to consider, you know, broadening our coverage in those very sick, sick babies.

Ben 44:08

What did you think? Well, I agree with everything you said. And I want to jump on the last point you made, because that's the only thing really that I wanted maybe to add something to is, you realize that we may not have as much room to make errors when it comes to early onset sepsis and our choice of antibiotics in these babies. Because what we treat them with is highly real. We need to treat these infections effectively with the proper antibiotic, especially when you consider that in relationship to any see. And you see that in the cohort. There are patients who had early onset sepsis were more likely to have neck 6.1% versus 4.7%. And so if you think about bacterial translocation as a mechanism of NEC, it makes sense that if you're equalize resistance and you poorly treated you expose the baby to more and more severe potential infections down the road So I think this was this was a again, there's not much to add, you went over everything and the paper is very robust. It doesn't pretend that that's, that's why I think Dustin is really good. The paper doesn't pretend to be something it's not right. It's just telling you what it's going to do. It does it very, very well. It gives you enough information to think about stuff. And it gives you it leaves you wanting more studies to be done to find out like, what's the next step? So that's really,

Daphna 45:24

yeah, and I think it, you know, all of us have different resistance patterns, right. And so that's something that we can we can all do today is see what are the resistance patterns in our area in our NICUs? And in determining, you know, are you a high resistant NICU or a low resistant NICU, and maybe maybe in in certain groups, until we have more data, we may still have to be changing some of our empiric antibiotics, or in the babies that are getting worse and not better? Changing our our antibiotic choice. Very interesting. Yeah. Your turn,

Ben 46:03

my turn fine. Um, let's talk about there's many, there's many articles, I guess. We can talk about precedents. And that paper from NYU, since we spoke about that medication earlier. And this should be a short one, because it's, it's again, it's a small study, that's well done. And it's so this is a paper called in the Journal of parasitology called Dex method. Okay, we're gonna say press X, again, this is our usual, we've been practicing

Daphna 46:31

the next

Ben 46:33

comedy, comedy, because that's the only time we're gonna say that we're just gonna move on

Daphna 46:39

our upcoming guests Kalyana, our pharmacist will be quite proud of us.

Ben 46:45

For you, so dexmedetomidine versus intermitted morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia. first author is Anna Cosner. Han from NYU in New York. The objective of the study was to basically the since March to 2019, the sedative of choice for therapeutic hyperthermia at Bellevue and NYU was changed from intermittent morphine to President during calling and so they wanted to evaluate the impact of this change on the efficacy and safety parameters in neonates undergoing therapeutic hypothermia. Hypothermia. This was a retrospective study chart review, and this was conducted between January 2018 and April 2020. You can go over their cooling protocols. It's very standard, meaning there's nothing fishy about it. And our patients showed evidence of moderate to severe encephalopathy. So there's no no mild encephalopathy business to discuss. And the patients were then either on continuous precedents from March 2019 to April 2020, or on intermittent scheduled morphine in the previous epoch from January 2018 to march 2019. So they go over the different doses and they assessed the baby's pain and agitation. Using the new neuropathy and pain, agitation and sedation scale, the end Pass and Pass scores greater than three were significant for breakthrough agitation and merited breakthrough morphine or administration. So both groups are always eligible to get breakthrough morphine, whether you were on morphine, intermittently or unprecedented. And they had this whole protocol about titrating, the dose of precedent depending on side effects, heart rate, lack of response to stimuli and so on, so forth. Yeah, I

Daphna 48:28

thought that was very helpful.

Ben 48:30

Yeah. And again, it's very standard things that you can look into the paper, the primary outcome was to determine if President is an effective agent for sedation and analgesia for neonates undergoing therapeutic hypothermia for HIV. The efficacy was defined as a reduction in pain scores during therapeutic hypothermia and overall requirements for cumulative dosage of morphine and milligrams per kilo. clinically significant reduction in enpass was defined as a reduction in pain score by one, their secondary outcomes, including impact on hemodynamics measure respiratory support tolerance of interval fees after rewarming and short term neurological outcomes. So let's go into their results. So they had 72 patients that were admitted, and they were able to include 70 of them 34 In the precedents, group, and 36, in the schedule of morphine. They talked about the average dosing of precedents and so on so forth, there were no clinical clinically significant differences in pain scores at any time points and median pain scores, that majority of time points was zero, the President's group received higher breakthrough morphine, but the total morphine requirements was significantly higher in the morphine group. So I thought that was very interesting. So basically, the breakthrough morphine, and were more required in the president group, but at the end of the day, looking at this in a retrospective fashion, they were exposed less to opioids than if they were on intermitted morphine, and I think that was a that was a very valuable point. In terms of their hemodynamics measure, there were no difference in heart rates between next up to unprecedented morphine patients at most time points. And then, except for 3640, to 48, and 72 hours of therapeutic hypothermia, where the morphine group tended slightly higher, but within normal range across both groups, so they're really defining all these different changes, even though they're all remaining. within the normal range, there were no difference in mean arterial pressures between the two groups. There were no differences in oxygen saturation between the two groups, no patient had bradycardia severe enough to turn off precedents completely, meaning they were able to manage it with just titration. And there were no real differences in requirements of vasopressors. During therapeutic hypothermia, the number of as oppressors or the type of Feza presses that needed to be used in terms of feeding outcome time to trophic, some enteral. And for enteral feeds was similar between the two groups. There were no differences in video EEG patterns, post therapeutic hypothermia, and there were also no detectable differences on MRIs post therapeutic hypothermia. And so their conclusion is that precedent is effective and safe for sedation analogies are during therapeutic hypothermia and reduced and that I think, is the main point to opioid usage, with no increased incidence of adverse events. So a very small study that does a very, very good job and brings a very valuable point to the discussion about management of sedition analogies in Ha babies.

Daphna 51:17

Yeah, I think this was a very important paper. You know, I like pressing X, we were I trained, we were using it as a first line, especially for babies with HIV. And I found, in my personal experience, that it was very effective for those babies that were kind of the mild to moderate, versus a moderate to severe babies. Some of our moderate to severe babies don't seem to need any sedation. But these kinds of hyper irritable babies, the Shivering babies, it really seemed to reduce some of that kind of irritability. And we really didn't have to make many accommodations for like this cardio respiratory changes. And so we found that very valuable, parents could still interact a little bit with their babies, which they found very valuable. So in my experience, it's great. I think a lot of places don't know how to start. And so I think this is a valuable paper because they basically gave you their titration protocol. And so I think if people are looking to start incorporating it, that this is one way to do it. Obviously, the major concern is long term nerd, dirt neurodevelopmental outcomes. I think it's valuable that we have EGS and MRIs on this baby to at least make kind of a shorter term comparison. And we do have some animal data. So hopefully, we will. And we do have the data that opiate, long term, opioid use is no good. Right? So we know that. So

Ben 52:51

older version of the meta analysis, it's no good. It's a technical, technical terms of use, no good.

Daphna 52:58

And so I hope we'll get some more long term studies. But I think this is a good start. Especially, I mean, so many of the things we use for sedation, and our babies are, quote unquote, no good, right. So we have to find something that works. And maybe we'll be able to use it in other populations of our of our NICU babies.

Ben 53:20

Yeah, I have two more papers, we're coming to the end. So I'm going to start we're going to two papers, I know you have definitely one that you want to talk about. So I'm going to talk about two and maybe I'm going to start with one and then now that you will see if we get to the last one. The one I wanted to talk about was published in the Journal of parasitology. And it was called survival prediction modeling and extreme prematurity. Our days important. First author is Timothy Schindler. And this is a paper out of Australia. Interesting question they're asking you objective of the study was them to demonstrate that observed survival rates in extreme prematurity increase with each additional day. And to show that these observed differences are important when creating survival prediction models based on gestation? It reminded me of my mentor, again, recently passed away who used to nail you if you didn't have the weeks and days of everything, right. And, and that's just the way he was paying attention to details. But here, this is a study where they looked at baby 23 plus zero to 27 plus six admitted to level three neonatal intensive care units in both Australia and New Zealand. And those units are part of the Australian and New Zealand neonatal network, which is a famous network that has published excellent data over the years. And they looked at data from 22,009 to 2016. You can look at their different criteria. And again, because we're short on time, I'm going to go to the meat of the paper. So they created a prediction model that was created based on the probability of survival. And they created this model and it's it's quite sophisticated and then they plugged into these models, the different gestational ages of the babies based on their outcomes, and they compare to whether using weeks alone versus weeks and days made a difference. So they had a total of that 8000 infants that met criteria 84% of which survived to hospital discharge. The two models estimating the probability of survival were created. One model was based on gestation in weeks and days and the other based on completed weeks only the model based on weeks alone over estimate survival near the beginning of a gestational week, but underestimated later in the week, which sounds very obvious, right? If you're 22, and zero, it's going to be lower than 23. And six, find the area under the receiver operating characteristics of the AUC was point seven to two for the weeks and days model compared with point 712 for the weeks only model and so the one. So the one thing I wanted to highlight is those differences because it comes at a critical juncture when we talk about prenatal counseling as we discussed at the opening of the episode with the 22 week ACOG recommendation. Comparing survival prediction models based on gestation, the model with weeks and days performed better than the model with weeks only. This is more likely to be clinically significant at lower gestations, which is probably by the way when you need that model to be more precise when parents have to make decisions regarding resuscitation or not. When rates of survival are lower and difficult decisions are made around provisions of intensive care, for example, and listen to this 23 and zero weeks, the week's only model gives a predicted probability of survival of 54.6%. So over half, compared with a predicted probability of survival of 47.7%. In the weeks and days model at 23, plus six, the model only gives an estimated probability of 54.6 compared with 61.7, when you use the weeks and days model, so just to recap that a little bit, they have table two. First of all, they have the figure, which is kind of nice, because you can see how the curve is so much more comprehensive when you include days. And then you have table two, which goes over the estimated survival when you use only weeks versus when you use weeks and days. And so I'm going to give the example of the baby at 23 weeks just so that you can get a sense because it's so dramatic. You have a baby, that's 23 weeks, you don't know how many days he estimated survival based on weeks alone is 55%. Which if you're a parent, you may say well, that's over half. And some people may say that's enough. And I will pursue intensive care. Some people may say it's not enough, and I'm going to pursue palliative. But then when you look at Whitsundays estimated survival, when it's 23 weeks plus zero days, it's 48%. So now less than half estimated survival when it's weeks plus six days, 62%. That's a dramatic difference. So I think for a parent, I mean, again, I like numbers. If I were in this situation, I would want to have precise numbers. And so I thought that was very interesting that we can augment our level of sophistication when we talk about gestational age and outcomes. And I thought that was really neat.

Daphna 57:58

Yeah, I think it's it's valuable. I think anytime we can provide more information, that's good. I think like with any discussion with family, it's a with a grain of salt that not everybody's a numbers person, you know, like, maybe you were you were me. And so asking our families, you know, are our numbers helpful? And if they're helpful, then I think this paper, you know, is very valuable for those types of families. And if they're not, and maybe now need to find another way to communicate, you know, we're all at risk and benefit. But

Ben 58:31

I've had, I've had these these parents where, exactly that is like an engineer. And when you give them the estimate, the like, is that point zero or you have decimals.

Daphna 58:41

They want to know that

Ben 58:43

4.5 or 54.2. And what's your confidence interval there?

Daphna 58:46

That's right. I thought that was useful.

Ben 58:50

The last paper I want to talk about and I'm going to let you close the show, because I think the people you want to mention is an important one. This is a paper that I have to talk about because it's pushed off from the prior week. It's called association of time of first cortical corticosteroid treatment with bronchopulmonary dysplasia in preterm infants. This is coming from the Children's Hospital neonatal consortium, severe BPD focus group. And what was very interesting is that this paper looked at variation in timing of corticosteroids, initiation and BPD in a recent multicenter cohort of preterm infants treated with corticosteroids, their hypothesis, which I thought was interesting was that among preterm infants treated with corticosteroids after seven days of life, they assumed that later treatment is associated with increased risk of EPDs 36 weeks postmenstrual age. So they looked at Babies between 2010 and 2016. They were all less than 32 weeks, and they identified them based on whether they received steroids whether it was dexamethasone or hydrocortisone, the primary outcome was BPD. And it was defined based on the Jensen criteria, which we've had on the show now it's very cool to say that the looked at the exposure based on Timing and they created several groups. So you either receive steroids from between day eight and 21, between the 22 and 35, between day 36 and 49. And beyond 50 days. And this was based on postnatal age in days when the first dose of corticosteroids was given, right, so we're talking about their first initial course. And because we don't have time, I'm not going to go into the details too much, but I'm going to give you the main results. So they identified six about 600, corticosteroids treated infants, of these 47% were treated at eight to 21 days. 25%, were first treated at 22 to 35 days 14% at 36 to 49, and 14%, were treated beyond 50 days. So obviously, we have a majority of babies treated early. And that decreases as time goes on. Infants treated at 36 to 49 days and beyond 50 days had a higher independent odds of developing grade two or three BPD when compared to infants treated at eight to 21 days after adjusting for birth characteristics, admission characteristic center and comorbidity. And so I think that was interesting, because I think this paper doesn't tell you that everybody should be on steroids, right. But I think we do have risk assessment calculators that can assess the long term risk of BPD. And I think that has definitely to be used more readily in the first two weeks of life to assess whether it may be maybe a candidate for early steroid treatment, because you can see that sometimes you think, Oh, if this baby doesn't need steroids, it will be better. But delaying it might actually not be as beneficial for that child. Again, they're not really teasing apart. Which one is better? Obviously hydrocortisone versus dexamethasone, which again, that's not the point of that of that paper. But it was very interesting. They have nice graphs. And I suggest you check out check out that paper.

Daphna 1:01:57

Yeah, lots of graphs. I thought that were were useful to look at.

Ben 1:02:01

And I would have, I would have killed myself if I hadn't. If I had to push off again, that paper.

Daphna 1:02:05

That's well, I mean, it's I mean, it's just it's a changing discussion, right. And we're all trying to decide when is the right time.

Ben 1:02:15

And whether whether it's not really telling you whether you should do it or not. I think he's just telling you, you must have the discussion early rather than later. I think that's that's an important point to point to that side. Okay, now, go ahead. Because that's that paper is cool that you want to talk about?

Daphna 1:02:28

Yeah. So this paper, also in pediatrics, burnout and perceptions of stigma and help seeking behavior among pediatric fellows for software, Anna Kay Weiss. And so, you know, we told you that we were going to start including more discussions about about burnout and how what we could do as a neonatal community. So I thought that this was interesting. This is not specific to neonatal fellows. But it included a lot of pediatric fellows at CHOP. And so they actually offered this to all of their fellows over the course of a six week window. So it was a survey basically using the Maslach burnout inventory. And so that's probably the most common used inventory in medicine to look at burnout. And so it's a it's an almost 50 item inventory, using Likert type matrices, to assess attitudes towards behavioral health treatment, and the MBI. And inventory includes three sub skills, which had been well documented in the medical community, they look at emotional exhaustion, so II, depersonalization and low personal accomplishment, which they entitle, or they substitute for P. And so like I said, they offered it to 288 of their trainees, so fellows across disciplines, and about 52% responded, they had 152 fellows participate. And I think one of the things that they tried to do very well, is that they really tried to reassure anonymity in this testing, because I think that was important to get an accurate data.

Ben 1:04:20

And it was important for the answers as well, when we find out what people answered

Daphna 1:04:24

her act. Exactly. And so if you've ever worked with trainees, they're highly suspicious of getting surveys about anything. And, you know, in my experience as a chief resident, it didn't matter what we asked or how often we told them that it was safe and anonymous and depersonalized but they always assume there was some sort of backdoor way to for us to find the data. So

Ben 1:04:52

I guess there is right there is right.

Daphna 1:04:55

For many things, there is a way but all of that as to say, I think that the data I'm about to tell you is probably even more impressive than we have reported here. And so they showed that between the subgroup analysis that there was strong positive relationships between emotional exhaustion and depersonalization in between emotional exhaustion and self reported stress. So not surprisingly, the more tired that fellows were, the higher these other indices were, on average, they reported a stress level of 6.8 out of 10. And a 53% of their fellows met the criteria for, quote, unquote, burnout, more than a half people more than half. And and that that wasn't even I think, the most striking part of the data. So most fellows reported believing that people in their administration, their superiors, would have negative attitudes about mental health, illness and treatment. So they thought 78% of their program directors or chairs, 72% of their attending physicians, and 82% of their patients would hold negative attitudes about mental illness and its treatment. A total of 68% of fellows agreed or strongly agreed that potential employers would pass over their application if they were made aware that they had sought help for mental health problem during their training. 75 Yeah, 75% would hide the fact that they have received counseling. And then this one this this really bummed me out. 56% agreed or strongly agreed, that that that they thought their patients wouldn't want them as their doctor if they were treated for mental health concerns. The other thing they did is they looked at the groups of fellows who didn't meet criteria for burnout 53% of them versus the fellows who didn't meet criteria with burnout. And those fellows who met criteria for burnout had even higher held beliefs of stigma. So odds ratio 1.2, meaning that they're probably even less likely to get help than the fellows who who didn't meet criteria for burnout. A total of 79% of fellows with burnout agreed or strongly agreed that future employers would pass over their application if they knew they had sought help for mental health problem. And 59% of fellows with burnout agreed that most people think less of a person who has sought mental health care. So I mean, I think this really just introduces the problem, the the, how deep the problem is, especially for our trainees who are early in their careers. And unfortunately, those feelings don't tend to get better as we move into attending hood. And so I thought this was a really valuable paper. I think it shows how much work we have to do as a medical community to reduce reduce stigma, especially for trainees. And they talk about, you know, ways we can do that. We don't we don't really have all those answers, but it's a good place to start.

Ben 1:08:11

Yeah, frightening stuff. I think this is a perfect paper to end the journal club on. Because if you are eager to hear more about this, stay tuned for our guest next week, who is an expert on dealing with burnout, and dealing with physicians who feel trapped in medicine. And I think you guys will really like that episode. And we're going to also talk about ways in which the incubator is going to try to make a difference when it comes to trainees and mental well being and so on and so forth. But my two cents on the paper is that this every program director should read that and find ways to implement things to support the mental well being of their fellows, which, who are at a very crucial moment in their training and who are in a very fragile emotional state between imposter syndrome learning and dealing with work life balance. It's just it's just something that program directors have to take seriously.

Daphna 1:09:10

Yeah, it's such a vulnerable time. Right. And I think it sets the stage for how you respond to your own mental health needs for the rest of your life, the rest of your career and whether you seek help or not. So we have work to do.

Ben 1:09:28

Well, definitely. Thank you so much. We're 10 minutes over. It's not the end of the world. I think these were good. 10 minutes. And thank you all for listening. Thank you all for engaging with us on Twitter. We'll see you next week. Definitely have a good one. You too. Bye. Bye. 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 Questions, comments or suggestions to our email address the queue 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 Dafna 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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