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#117 - Journal Club 46

Hello Friends 👋

We have an amazing episode of journal club for you this week. We review some super interesting papers but most notably, we are piloting our first segment with the EBNEO to review their commentary on the article of the month. This month we have the pleasure of chatting with Dr. Bri Liberio, who authored the commentary. Finally we cover articles about parental preference regarding PDA treatments, use of ondansetron for NOWS and a QI initiative looking at social risk screening in the NICU. We hope you enjoy this episode.

Have a good sunday!


Do not forget to secure your spot for the DELPHI CONFERENCE taking place on March 27-28-29 in South Florida. Delphi offers opportunities to submit abstracts for poster presentation and will offer CME credits. Register at use the code INCUBATOR for a special discount for our listeners at checkout.


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

Mitra S, Hatfield T, Campbell-Yeo M, Dorling J, Johnston BC.JAMA Netw Open. 2023 Mar 1;6(3):e232273. doi: 10.1001/jamanetworkopen.2023.2273.PMID: 36892840 Free PMC article.

Cordova-Ramos EG, Jain C, Torrice V, McGean M, Buitron de la Vega P, Burke J, Stickney D, Vinci RJ, Drainoni ML, Parker MG.Pediatrics. 2023 Apr 1;151(4):e2022058975. doi: 10.1542/peds.2022-058975.PMID: 36919445

Liberio BM, Rose RS.Acta Paediatr. 2023 Jun;112(6):1354-1355. doi: 10.1111/apa.16754. Epub 2023 Mar 16.PMID: 36929493 No abstract available.

Starr MC, Griffin R, Gist KM, Segar JL, Raina R, Guillet R, Nesargi S, Menon S, Anderson N, Askenazi DJ, Selewski DT; Neonatal Kidney Collaborative Research Committee.JAMA Netw Open. 2022 Dec 1;5(12):e2248826. doi: 10.1001/jamanetworkopen.2022.48826.PMID: 36580332 Free PMC article. Clinical Trial.

Peltz G, Jansson LM, Adeniyi-Jones S, Cohane C, Drover D, Shafer S, Wang M, Wu M, Govindaswami B, Jegatheesan P, Argani C, Khan S, Kraft WK.J Perinatol. 2023 Mar;43(3):271-276. doi: 10.1038/s41372-022-01487-2. Epub 2022 Aug 27.PMID: 36030327 Free PMC article. Clinical Trial.

Grinberg G.N Engl J Med. 2023 Feb 9;388(6):486-487. doi: 10.1056/NEJMp2213031. Epub 2023 Feb 4.PMID: 36744804 No abstract available.

Slagle C, Gist KM, Starr MC, Hemmelgarn TS, Goldstein SL, Kent AL.Neoreviews. 2022 Mar 1;23(3):e189-e204. doi: 10.1542/neo.23-3-e189. ----

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

Ben 1:01

Hello, everybody, welcome back to the incubator podcast, it is Sunday, Daphna. How are you?

Daphna 1:07

I'm doing great. We've had, we've had a crazy couple of weeks. Coming down to the wire here for the conference, but we couldn't miss Journal Club, because there's just too many articles in the folder forgot

Ben 1:21

to mention in fellowship, that organizing a conference is really a lot of work. This was in the textbook,

Daphna 1:28

it does require a number of skill sets for which we have no training.

Ben 1:32

That's it. Yeah, it's exactly right. But it is very exciting. And, and, you know, it's it's something that it did require a lot of work, we're talking about what is going to be the frequency of this conference, we're thinking maybe every two years. So, you know, if you're, I hate to say this, but like, if you're thinking like, Oh, I'll go in 2024. It may be 2025. So,

Speaker 1 1:56

but if you want to do it in 2025, let us know. I will force ben to do it.

Ben 2:04

We have a lot of very cool. sessions, one of the sessions we're organizing that's going to be quite nice is that we're going to have a discovery session, as we call it, where we're going to have a panel of physicians. And we're going to walk through a relatively complicated case. And we're going to have a bunch of physicians, I think we have a neonatologist from Brazil, from Canada, from the US from Japan, from Norway. And we're going to basically stop somewheres some at some intervals through the case and ask them, hey, in your country, how would you approach this situation? Whether it is it is a viability, whether it is visitation, or whether it is management of the baby? And so we'll be very cool to see the differences between how to do it in Japan, how to do it in Scandinavia, how to do it in Latin America, it's going to be it's going to be quite interesting. Obviously, we don't we're not representing every country, obviously. But we're doing the best we can. So this could be a recurrent theme after that. There's podcasts being released today in Spanish and Portuguese, check them out if you are a if you're not a native English speaker, and these podcasts are more helpful than I think that's all the announcements I have for today. Agreed. All right. Okay, I have an article that I'm super excited to present. Is it okay, if I started? Please go ahead. Alright. It's a long review that I have, but the paper is super, super interesting. It's called evaluation of health related values and preferences of adults who were preterm infants and parents of preterm infants concerning the use of prophylactic cyclooxygenase inhibitor drugs. First other issue Vic Mitra has in The JAMA Network open. The study is taking place. I mean, he's writing from Canada, but it's looking at data from the UK and Canada. So this is a super interesting article, it starts off with some basic background information that infants born extremely preterm are at high risk of ivh and EC BPD. And that a common contributor for these pathophysiological mechanisms is postulated to be the PDA and that the current available pharmacotherapy therapeutic options to prevent the PDA and related complication include the cyclooxygenase inhibitors, such as indomethacin, ibuprofen and acetaminophen. So far, really nothing new. COX inhibitors themselves are associated with some adverse events, such as an EC gastrointestinal tract perforation. Sorry about that, as you're reading them, so sorry, too many emails coming in. Now, obviously, and then this is where the introduction gets a bit interesting is that there's variations in clinical practice regarding how COX inhibitors are used so far, nothing new. Now, what they're talking about is that the decision on Koh cyclooxygenase inhibitors pharmaco prophylaxis is likely driven by the perceived benefits versus the potential risks as determined by the treating physician with usually little input from families regarding their values and preferences. cyclooxygenase inhibitors prophylaxis involves such a trade off between long term benefits and serious short term adverse effects, that there's probably a discussion that needs to be had. And so the objective of that study was to explore the health related values and preferences of either former preterm infants, or the families of preterm infants regarding the use of COX inhibitors prophylaxis for the prevention of PDA related morbidity and mortality. So basically, what they're asking is saying, What if we don't know what we're supposed to do regarding the PDA? What is the perception of parents and what would they want to do if they were presented with the data themselves. So the data is a cross sectional study. And they did the study in two phases. So they conducted first a Phase One pilot feasibility study where they basically, really were trying to see how their questionnaire was, and really giving themselves the opportunity to modify anything in terms of the methodological issues that they could encounter, so that then they could move to this phase two, which is basically the formal study of values and preferences used in the pretested interview questionnaire to describe the variability in health related values, preferences of former preterm infants and their and families concerning the use of COX inhibitors for prophylaxis in the context of a PDA. So who were these patients, they were either adults born very preterm and their gestational age less than 32 weeks, or they were families of very preterm infants currently in the neonatal intensive care unit, or having graduated from the NICU in the last five years. These patients were included from across Canada and the United Kingdom. The participants were contacted while their infants were admitted to the IW K health health NICU through the IW K health perinatal follow up clinic, and through representatives of local national, Canadian premature babies, foundation, parent, partner organizations. This study basically was done through the communications between the study team and these families through zoom basically. So again, an interesting way of how the technology that really became mainstream during the pandemic is now being used to conduct research studies. So what was the study procedure? They collected a lot of data that was super interesting, because they collected baseline demographic questionnaire, they had standardized description of health state. So in this section, basically, they gave the information about what are the complications of having a PDA and they told them, hey, you could have an EC, you could have BPD, right? They told them, hey, here's the risk of having a PDA. Then they looked at the importance of outcomes. And they said, Hey, what, how would you rank these outcomes? In terms of how would you rank the the outcome of having severe ivh? How would you rank the outcome of having NEC? Then they did a direct choice elicitation of treatment preference. So basically, they did a directress experimental design to assess the proportion of participant willing to accept prophylaxis using any of the three COX inhibitors. So basically, what they did is that they walked through each single one of the medication. So they went through indomethacin. They said, Hey, here's the risk of using an MSN, here's the benefits, would you consider using it in your baby? Then they did that for ibuprofen than they did that for acetaminophen? And then at the end, they said, Well, now that you've seen all three, which one would you pick if you could pick one of the three? And then they had something specific for indomethacin. Knowing that indomethacin with hydrocortisone has issues. They said, If you picked into medicine, what about now the fact that you couldn't use hydrocortisone because of the associated risk of intestinal perforation? Would you prefer another medication instead of in the medicine so that you could use hydrocortisone or no, you would rather just keep indomethacin on and even if that means you're not getting hydrocortisone. Then they had a semi structured interview on determinants of treatment preference. So they basically did a qualitative review of like, Hey, why did you pick what you picked? And then they did relative importance of having family values and preference including decision making. So they said given the risk of information overload in the first 24 hours, participants were asked how important it was for them to have their values and preferences included in the decision making for use of these medications. They were asked to choose between one to four option whether it was not important someone important, important or very important. The outcomes that were measured were the relative importance of the clinical outcomes the willingness number two willingness to use each cyclooxygenase inhibitor when presented as the only option. Number three, the preference for using prophylactic hydrocortisone versus indomethacin. Number four, the willingness to use any cyclooxygenase inhibitor when all three options were available. And number five, the relative importance of having family values included in the decision making process. I think this is a phenomenal study design. It is super innovative. And it's such a it's such a shoo Vic type of paper that takes a very interesting approach. Like, of all the PDA papers we've read. This is super interesting.

Speaker 1 10:26

Yeah, interesting, innovative and complicated. Oh, yeah.

Ben 10:30

But he's, he's, he's has this. He has. I mean, we've talked to him on the podcast, and he made an appearance to review to help us review one of his papers. And he has this ability to juggle with study methodology at a level that is quite sophisticated. So it's not surprising. So listen to the results. So they had 44 participant that were enrolled in during the study period between March 3 2021 And February 10 2022. So what did they learn from this pilot phase one study. So the phase one to remember is just like using a few patients to test out their their their questions, make sure that the questions are appropriate, and that they're they don't want to make any adjustments based on the feedback that they could receive from the families. So in that phase one study, the median age of participant and their children at birth was 20, was about 24 months. In the pilot study, they were asked to rate five clinical outcomes, severe ivh development, severe mental delay, BPD, NEC and GI tract perforation on a numeric scale of zero to 100. Assuming 100 was the worst possible state of health, while zero was the best possible state of health. Now, they chose these outcomes based on consensus of the study team and input from partners from the Canadian premature babies Foundation, because they were perceived as the most clinical and most important clinical outcomes related to the use of prophylactic cyclooxygenase inhibitors. And what was super interesting is that death was initially not included in these five outcomes, as it was assumed that you don't need to ask parents about death because obviously, it's the worst possible outcome. And the participants believed that for some parents death may not always be the worst possible state of health. My God, right. I mean, I was so shocked to read that because it is true, right? I mean, we've all been in this position, where is death really the worst outcome in babies who are really being put through the wringer and who are going through complication after complication? And so there's

Daphna 12:25

Well, and that's the benefit of allowing some qualitative, you know, analysis in your in your work for sure. Giving people the opportunity to freestyle, what they can you imagine

Ben 12:36

this this input coming from parents saying, well, that's right. So they said, Therefore, death was an added as one of the clinical outcomes to be rated. So the added death as then the participants furthermore believed that evidence on too many outcomes was presented, and that the unanimous consensus was from the seven participant that were included in this pilot study, to choose only death severe ivh, NEC, and chronic lung disease as the for outcomes to be presented in the direct choice experiments, which hints at the theme of parents being overwhelmed by information and their willingness to to deal with maybe more concise or narrowed and narrowed spectrum information. Okay, so then they gathered all this information, they went on to the phase two study. So 40 participants were recruited in that form of phase two that took place from October 2021 to February 10 2022 77.5%. Were parents of infants born preterm and 920 2%. Were adults who were born preterm. So that was also super interesting that they were going to ask adults born preterm what their perceptions was, were perceptions were the overall median gestational age of the participants, whereas 26 weeks, and very interestingly, 67% had a university degree. So they were, they were well educated, the majority of the population was quite well educated. And I'm saying, and I'm saying this, because it's interesting that despite having close to 70% of people who have a university degree, we're going to look at how much that information can still represent information overload. So I think that's interesting.

Daphna 14:22

Listen, my husband has a doctorate, right. And we've been together through my entire medical training, and there's still some days where might you have literally no you know, and with our own family, it just, I have family that's in health care, but they're not physicians, or they're not in certain areas of expertise, and it's just totally overwhelming. It's totally overwhelming. What we ask families to do. This is such an interesting like you said design to really get to the heart of that.

Ben 14:55

Yeah, yeah. Okay, so um, So that rating, the importance of outcomes. So on the numeric on the numeric rating scale, death was rated as the most serious outcome. So it's funny that in the pilot study, parents voiced a concern that maybe death is not the worst outcome. But yet when, at the end of the day, the families ended up right on the face to ended up reading this says as the worst possible outcomes. And so what was the second one, and it was severe ivh. So severe ivh really took took the last year with over BPD and over NEC, in terms of direct choice, elicitation of treatment preferences and the rationale for choices. So this is actually the crux of the paper. What would parents choose when they were offered the treatment for the PDA? So when they were offered as the only available option, so they were just presented in for an indomethacin? And they said, would you use it? Yes, no. Most participants chose indomethacin 90% and ibuprofen 85%. And only a small proportion choose acetaminophen. So when they presented them with the information on acetaminophen, they said would you use it? They're like 10, only 10% said yes. among participants who initially chosen the medicine when prophylactic hydrocodone was offered as a potential therapy, with the caveat that both cannot be used simultaneously. 33% still preferred in the medicine. So a third of that population said, we will stick within the medicine and forget about hydrocortisone. Now when they looked at the thematic analysis, it showed that for indomethacin reduction in death in severe ivh, with moderate certainty was the primary driver for the participants choice in favor. So that's what drove them to sit on the we're sticking with the medicine because the effects on death and severe ivh is really something I care about. However, when prophylactic hydrocortisone was offered to those who chose indomethacin, two thirds of the participant indicated. That's what I just said, I'm so sorry. Similar to indomethacin, the primary motivation behind choosing ibuprofen over no treatment was the possible reduction in the critical outcomes of death and severe ivh. Most participants opted against acetaminophen as they believed that the evidence was highly uncertain. So when you think that families maybe don't cannot understand everything that we have to explain, Well, listen to us. Now, when all three cyclooxygenase inhibitors options were available, 47% chose 47.5% chose indomethacin 40%, chose ibuprofen, and 12.5%. opted for no cyclooxygenase inhibitor prophylaxis. When they asked them in the thematic analysis, it showed that those who chose in the medicine believed that the overall certainty for benefit was better within the medicine. And those who chose ibuprofen indicated that there seemed to be no overall harm. And in addition, they would like to keep the option of hydrocortisone open. So basically, they were saying, it seems like Ibuprofen is pretty benign, and it leaves the door open for me to give a hydrocortisone to my baby if I need to, which is not something I have within the medicine, so which is pretty sophisticated reasoning. And then for the remaining participants who opted for no prophylaxis, the primary motivation was a preference for hydrocortisone. So parents did understand that the benefits of hydrocortisone to the extent that it would supersede their preference for PDA access. Now looking at relative importance of having family values and preferences included in the decision making that was very interesting. Most participants believed that it was somewhat important. So 55%, or interest are just important in 35%, to be informed of the benefits and harms of the pharmaco prophylactic options prior to making a clinical decision to use the drug or refrain from use. And so I thought that was that was obviously very interesting. Now, if you have time, you should look at the supplemental material, because it has the slides that they showed the parents, and it's basically super well done. I mean, the slides you can't really zoom in very well, I'm sure sure we can share with us the slides if we were to ask him, but it basically has the medication and it says alright, like death. When we did the study, it showed that 24 fewer babies will receive the medicine had death. And what else chronic lung disease, there was an increased by 36 More infants, right. And so it was very well depicted. Now, despite that, those who indicated that it was somewhat important believe that in the first 24 hours after birth, that these first 24 hours were quite overwhelming. And therefore, though they would like to be informed about the benefits and harms of the therapies, they will trust the clinicians judgment. And so it's interesting how it's going to be this balance right between this is decisions that are being made early on in the course of the hospitalization. And so we should not dismiss the fact that it's a very difficult time for these families and they may not be in a position to make these decisions all the time. Finally, in the postdoc exploratory analysis, they failed to demonstrate any statistically signal differences in the responses between either the parents of preterm infants or former preterm infants who are now adults, so there was no real difference between the two was pretty much the overall consensus. And so, the results of the conclusion of the article is that the results of the study showed that death and severe ivh are the two most serious outcomes that participants would consider in relation to prophylactic cyclooxygenase inhibitor use in preterm infants. And this finding the findings of this cross sectional study of former preterm infants and parents of preterm infants suggest that there was minimal variability in how participants evaluated the main outcomes with death and severe ibhs, which are set as the two most important undesirable outcomes. While indomethacin was the most preferred form of prophylaxis. Variability was noted in the choice of COX inhibitor interventions when participants were presented with the benefits and harm of each drug. A super interesting paper about how we take evidence to the bedside. And if you are, if this is a subject you're interested in, I'm sorry to be again, an advocate of or a conference, but Shauvik will be at Delphi and will be presenting exactly on this subject. And, and his title of his talk will be doing right things right. Can evidence based medicine, parental preferences and quality improvement initiatives ever coexist in the NICU? I'm super excited about listening to this talk. So yeah, surely congratulations. What a phenomenal paper.

Daphna 21:26

Yeah, I think for people, this can be like a career changing talk, right? The way the way you counsel, parents because we know in studies about physician counseling, like physicians are very much not great at handling uncertainty themselves, right? Like we don't like. But we have to make decisions every single day that are potentially uncertain. And how do we convey that to parents? So very interesting article, thank you. Thank you, thank you. Okay, I'm gonna move in a little bit of a different direction, but still very much family centered. All right. So this article is called implementing social risk screening and referral to resources in the NICU. I'm the lead author, Erica Cordova, Ramos and senior author, Margaret Parker, is coming to us from Boston. And I think the background is kind of important. Because you know, we've been taking on this advocacy series, which will be rolling out those episodes. And at some point in time, you can't, you can't separate what a family is going through outside of the NICU, from the clinical care inside the NICU, and its impact on long term outcomes. So I'm going to read from the paper in the United States 44% of children less than three years of age live in poor or quote unquote, near poor households, which places them at risk for worse health and developmental outcomes than their more privileged peers. families with young children who live in poverty are more likely to have unmet basic needs, such as food or housing insecurity. systematic social risk screening and referral is particularly relevant in the NICU setting. Because families of preterm infants are disproportionately low income and the burden of unmet needs is higher than the preterm compared with the term population. unmet needs are exacerbated during the prolonged NICU hospitalization owing to the costs associated with frequent meals, transportation childcare for other children, and forgone income from last time at work. So this is was really a QI initiative, using kind of they adapted a screening tool and they provide their pathway for their PDSA PDSA cycles. But the end goal is to integrate screening and referral to resources into their day to day clinical workflow. So I think lots of teams are starting to realize the importance of this or we're talking about it in the literature, but how can we actually make it happen in our units. So during the pre implementation period, the team conducted interventions related to the selection of a social risk screening tool and the development of this one page resource guide for unmet needs. The screening tool was adapted from an existing tool called Thrive, which is already being used in outpatient settings, and creatively was already integrated into their health systems EMR, which I think is very valuable. To develop the resource guide, they follow the guidance from AP. They have a child poverty website, which uses publicly available community resource aggregators. They engage their units, social workers and family navigators who had previously participated in development of other types of resource guides. And this process entailed weekly meetings over two months. Their smart aim was to one Increase systemic social risk screening of eligible families included families who were anticipated have a length of stay greater than one week. And to to increase the rates of family connections with resources, each from baseline to greater than 50% over 14 months. In addition, they aim to achieve no disparity in the implementation of screen by race, ethnicity and primary language, which is really a new component with a real kind of equity lens to it's not just enough to just say, Are we rolling out screening, but are we rolling out screening in a disproportionate way. So I'm gonna kind of give the overview their cycles. So the first PDSA cycle, they trained six champion nurses to conduct social risk screening. So I think this is valuable. These were nurses at the bedside, using just kind of a structured conversation to evaluate it, and the nurses documented the responses into the EMR. So they weren't using their social workers to do this part. Cycle two, and cycle three focused on increasing the screeners capacity and improving the quality of the resource guide. They also trained residents, and then subsequently all the bedside nurses to perform the screening, leveraging the original group of nurse champions as kind of teacher teaching the teacher kind of system, and ongoing problem solving support PDSA for cycle, I think was a big, major turning point because they started to engage community providers. So this meant that families in the NICU, were able to then reach out to specific people in the community providing guidance on how to actually enroll in various services for housing, food, utilities, and childcare. PDSA cycle five, they created a quote unquote, thrive station in the NICU. So they just had access to copies of the resource guide, a one page resource cheat sheet with information that people could use in their discussions. The team also got additional funding, which is important to this type of project to launch, basically a transportation program. And finally, in PDSA cycle six, they introduced an additional community based organization that specialized in programs for employment and education just so cool and very well rounded for the program. The primary outcome was to look for families screened and secondary connection with resources. And then they examined screening by maternal race and ethnicity and primary language. They wanted to look at process measures, which were time from admission to screening and percentage of referrals provided to families reporting unmet needs, and requesting assistance. So the hospital baseline, they weren't doing kind of unmet needs screening, they did have a social worker, and the plan was for the social worker to meet with each family within seven days of admission. And that happened about 72% of time, and then on a as needed basis for the remainder. So they had a total of 212 infants who were eligible for screening, median length of hospital stay was 31 D is non Hispanic Black and Hispanic mothers of any race represented 41.5% and 29.3% of the population respectively. 45% of mothers had a non English primary language, so very diverse population based in their across their cycle screening increased from 0% because they weren't doing any to 49%. And among 103 families screened at 4.4 reported greater than one and 64% reported greater than two unmet needs. Overall 221 unmet needs were reported and families desired assistance for 86% of them. So they may not want to ask us for help, but they definitely need the help of education, transportation, employment and food. For the most prevalent reported needs. The median time to screening was 10 days and 98% of families who reported greater than one unmet need and requested assistance, received referrals, which is amazing rates of connection with resources increased from a mean of 21% to 52%. Over time, and in the way that they did this no significant differences in screening rates by maternal race or ethnicity or primary language and zero families to claim screening. Other interesting findings, I think, they talked about what made this rollout easier for them. Definitely they needed staff buy in, they were able to leverage the EMR and they were able to streamline the procedures which reduce the time burden on the clinical staff. It was really important that they had this engaged group of nurse champions. They frequently solicited and incorporated feedback from nurses and families. So continuous a reassessment of their process, critical to ensure the clarity of roles and to establish procedures whereby screening results and referrals were communicated then to the social worker. And they underscore that they viewed this intervention as an augmentation, not a replacement of the crucial work that the social workers do in their NICU. So anyways, we like to highlight Qi initiatives, from time to time when we can, I think this is something that lots of units are trying to do. And this is a nice framework for doing that. But I thought some of the data was important about how many families do really have unmet needs, that they'd like our help in achieving them. And when you can identify unmet needs, then you can work towards securing those resources. Thoughts.

Ben 30:54

Um, I think it's, it's, it's going back to something that we've mentioned on the podcast many times, which is that unless you do value, this aspect of care, and making sure that we do leverage, I guess, I'm not exactly sure how we want to call these things. But like, we can focus on what medication we give, and so on, and so forth. But if you're not looking at social determinants of health, and you're not doing these, the same risk assessment you would do for a baby that's at risk of developing BPD. If you're not doing the same thing, from a social standpoint, you stand to lose all the ground you've you've gained in this sometimes unrealistic world that is the NICU where all the variables are sort of erased a little bit because you are in this bubble, and then But then when they when babies leave the NICU, all these pressures and suddenly fall on these families, and it's, it has dramatic effects. So I think this was this was a very, this was a very impressive Qi.

Daphna 31:52

Yeah, and even so, when you think about how much work goes into any one patient, and we know their outcomes are better if say, their parents can be at bedside if say their parents can provide milk and soy, you know, it's really about tackling these unmet needs early on, and I mean, can even change outcomes in the in the unit before discharge? So

Ben 32:19

this episode is proudly sponsored by Reckitt Mead Johnson recognized Johnson is dedicated to the research and development of nutrition products that help support baby development at every stage, including an extensive and familiar portfolio for premature and low birth weight infants learn more at HCP dot meet Okay, so we have a new segment for our listeners that we're very excited to to introduce today.

Unknown Speaker 32:45

Are you gonna play the drumroll? No, we

Ben 32:47

have a jingle.

Unknown Speaker 32:50

The jingle is better than

Ben 32:52

we are going to have once a month on that doesn't we're not exactly sure which, which Journal Club, it will be, but it will be one journal club month, we'll have some members of the EB Neo team if you're not familiar with the video team, look them up on Twitter comm and present the commentary that they that they write about what is voted as the Article of the month. And we're super excited to to introduce the segment today. So without further ado, let's let's play the jingle

Speaker 3 33:24

Article of the month commentary brought to you by the evidence based neonatology team. Make sure to follow EB Neil on Twitter at EB Neil or on the web at EB

Ben 33:42

Okay, Daphna so we have today on our first segment with the EB Neo team. Dr. Bree Liberto, who's an attending physician at Riley children's health in Indianapolis. Bree, how are you?

Unknown Speaker 33:54

I am great. How are you guys this morning? Doing well

Unknown Speaker 33:56

doing? Well.

Ben 33:58

We're doing well. Thank you for coming on and for reviewing some of the literature with us. Bree, we are super excited to have you because of the commentary that you wrote on the paper titled fluid balance as a critical factor in neonatal outcomes. And this is a and this is a paper commentary that you wrote in, in relationship to this paper that was published in JAMA Network open and authored by our good friend Michelle Starr. The paper is called association of fluid balance with short and long term respiratory outcome outcomes in extremely premature neonatal secondary analysis of a randomized clinical trial. We have not had the chance to review this paper on the podcast yet so do you mind walking us through what the paper is about what is what are they're trying to show and what are some of their their results?

Speaker 4 34:50

Yeah, happy to thank you for having me. I think this papers really important. I mean, we know in the adult literature, and even PD hattrick literature the importance of a positive fluid balance or what people kind of used to call fluid overload and how that is associated with poor outcomes. And I think there's now mounting literature in the NICU about how, you know, this positive fluid balance can impact things as well. So I was really excited to see this paper. And so yes, as you mentioned, this is a secondary analysis of the peanut trial. And just as a reminder to people, the peanut trial enrolled 24, to 27, and six weekers. In this study looked primarily at the first two weeks of life, and looking at fluid balance as it relates to some of the respiratory outcomes. And so they had the hypothesis that a more positive fluid balance during the first two postnatal weeks would be associated with mechanical ventilation on postnatal day 14, and then some of their secondary outcomes we'll get to as well. But the thing you know, how do we measure IV fluid balance and babies? Is it ins and outs? Is it Do they look puffy? Is it their weights, it can be really hard babies can hide a lot of their positive fluid balance, before we even realize that they're fluid overloaded. So this study defined fluid balance as using an equation and essentially using the daily weight and the birth weight. So daily weight minus the birth weight divided by the birth weight, so kind of like the percent change in weight is how they defined fluid balance. And then not only do they have that equation, but they looked at fluid balance at five different in five different kinds of time points. So they looked at the maximum percentage of weight gain, or like your peak positive fluid balance in that 14 day period, your maximum percentage of weight loss or your peak negative fluid balance, and then the, you know, fluid balance on postnatal day three postnatal day seven, and then whatever day the baby returned to birth weight.

Ben 37:03

And the measurement of the fluid balance is not like a statistical or methodology trick, right? I mean, it is the preferred method of following a following that that fluid balance, right. I mean, it's, it's the preferred method. It's not like the I think it's important to mention that this is the, I guess, quote, unquote, gold standard to follow that metric.

Speaker 4 37:26

Yeah, definitely. And definitely in babies to where, you know, ins and outs are always reliable, you have just diaper weights that are sometimes mixed with stool and things like that. So yeah, I think in the neonatal nephrology community, this way to measure fluid balance is kind of the gold standard for babies, right. And so they looked at the primary outcome of mechanical ventilator invasive mechanical ventilation on postnatal day 14, then their secondary outcomes were the composite outcome of severe BPD, or death, between postnatal day 14 and 36 weeks postmenstrual age. So hitting on both kind of short term and longer term outcomes. And so if you are looking kind of at the paper at our table, one looking at the patients that we have, so the total core cohort that they included was 874 infants. And what I thought was really interesting that they had weight that was recorded on 96, you know, almost 97% of possible patient days. And the ins and outs, data was way less than that. So you know, something important to know, like, how, how good is the data, and they had values for almost 97% of the possible patient days. So that was really good. And so then looking kind of at what kind of babies are making up this cohort. I think the babies that required mechanical ventilation, as I would expect, sounded a little bit sicker just looking at table one. So they were more likely to have a lower birth weight, lower Apgar scores, lower gestational age, more likely to require some vasopressors have a PDA that was treated and have IV H. So kind of not not very surprising there. And then we can go ahead and get into the primary outcomes if you guys are okay with that. Yeah, so the primary outcome, like I said, was the need for mechanical ventilation on postnatal day 14, invasive mechanical ventilation and they found that out of their cohort 52.4% received mechanical ventilation on postnatal day 14. And kind of the takeaways from that when they looked at how does fluid balance play into that those that had this primary outcome of requiring mechanical ventilation were more likely to have a higher peak power Did IV fluid balance on postnatal day 14, or just kind of over the course of those first 14 days of life, a less negative fluid balance on postnatal day three and a shorter time to regain their birth weight. So essentially, they were more kind of fluid positive fluid balance, they didn't lose as much by postnatal day three, they took a shorter time to get back to their birth weight. And again, over that first 14 days of life, they had a higher peak positive fluid balance compared to those who didn't require invasive mechanical ventilation.

Ben 40:33

And that's interesting, right? Because what it tends that is this this sort of trend that we know to expect in full term babies where you expect them to, to lose weight in the beginning, in the first life and then slowly regain their birth weight. And it seems like what Michelle and her colleagues found in this analysis is that for the babies who didn't follow this path where they were actually staying about birth weight, and they never lost that weight, while their outcomes seem to have been worse from a from a respiratory standpoint, is that

Speaker 4 41:02

yeah, definitely. Yeah. I thought it was also interesting that when they use the logistic regression analysis, they noted that babies who had a peak positive fluid balance of greater than 5%, greater than 10%, and even greater than 16%, they all had very similar odds of requiring invasive mechanical ventilation. So even like a baby that is just 5% positive, in that first 14 days of life, they have a very similar risk of invasive mechanical ventilation compared to baby who's 16%. So meaning 5% is sounds very, like meaningful, like a meaningful number that we need to be paying attention to. Whereas, you know, prior to reading this, I would have thought 5% wasn't that big of a deal. But so I thought that was interesting. And then they even adjusted, you know, for multiple factors, they tried to, you know, keep track of everything that could be confounding this just overall sicker babies, but when they even corrected for gestational age, Apgar score, vasopressors, having Aki ivh and a PDA, they still found that your peak positive fluid balance in that 14 first 14 days of life, as well as your fluid balance on day three, and seven still remained independently associated with this need for invasive mechanical ventilation. So I thought that was interesting.

Daphna 42:27

Yeah. And that was so important, because those groups really were different. And obviously, given the study group who did the paper, you know, focusing on Aki was, I think, really valuable, because you often wonder, like, is it the baby? Or is it us, right? That we're managing the fluid, you know, inappropriately? Or is the baby managing the fluid and appropriately by, by evaluating for that, that makes the picture slightly slightly clearer.

Ben 42:59

And one more point is that you mentioned the 5%. Change. And I think some people may say, Well, isn't that kind of ridiculous? Like how, like, these babies are super tiny to begin with? 5%? How am I supposed to control for that, but when you actually put it in perspective, I think the mean birth weight for these kids was around 800 grams. Yeah. But if you were talking about a 5%, change, then you're talking about like that 40 grams on a day to day so like, even like if you walked in, and the kid who was 800 is now 840 Be like, whoa, that's that's kind of a it's kind of a large gain you with this? They'll be surprised when actually, when you read the paper 5% seems like almost like a negligible number. But it really isn't it it is something that you can actually notice, even clinically without too much statistical support.

Speaker 4 43:42

Right, right. Yeah. And I think that that was one of my takeaways like, oh, gosh, 5% does actually make a difference. And it is something that I think could catch our eye. Yeah. So then they looked at the secondary outcome, which again, was the composite outcome of severe BPD, or death. And they looked at that between postnatal day 14 and 36 weeks of postmenstrual age. And when they compared, you know, those that had that, so that that secondary outcome occurred in 33% of their cohort, and compared to those events who had survival with just mild or no BPD. Those with this outcome of severe BPD or deaths were also more likely to have a higher peak positive fluid balance, a less negative fluid balance on postnatal days three and seven in a shorter time to regain their birth weight. So similar to kind of what we were seeing with their primary outcome, that those that are kind of keeping on the fluid or not losing as much are having worse longer term outcomes in this sense. And then in this, in this secondary outcome, they also use their logistic regression and notice that a 5% 10% and 16% Peak positive fluid balance all So should it increase odds of severe BPD or death? And they? And I think, you know, that was kind of both most of the takeaway points for the secondary outcome. So again, I think this is probably one of the first studies looking more more so at the longer term outcomes and just this short term outcome of meeting mechanical ventilation in the first two weeks, so a couple of the things that they mentioned, you know, in their discussions, obviously, they're, they have some limitations. They're limited to just the first two postnatal weeks. So this did not track fluid balance throughout the course of the NICUs day, there's still some residual confounding that might remain, although, you know, they they definitely tried to account for those variables in their models. And then, yeah, this idea that fluid balance is probably a proxy for critical illness and premature neonates. And you know, these two groups are different kind of at baseline, potentially. But I think they did a really good job of working with the awesome amount of data from the peanut trial. You know, obviously, there's been a lot of sub analyses of this trial. So that was amazing that they were able to collect so much data and have it be so useful and informative to us.

Ben 46:20

Yeah, and I really appreciated the commentary that you wrote for Ibnu. Specifically, because as I was reading through the discussion, I was like, What about the freaking sodium? And I was like, I did not talking about like, I mean, because we've all we've all managed fluid balance in our, in our neonates, and especially the lb W's. And we've all had to deal with it. When you walk in the morning, the sodium of 147. And it's like, okay, now now, what am I supposed to do? And, and it's, it sort of puts things in perspective, because it also, it also creates a little bit of a pause as to how practically, can I take this evidence from this paper and bring it to the bedside? Considering that, as you mentioned, in the commentary, this new treatment is really a concern that we deal with everyday. So Can Can you talk a little bit about about what what you meant by that? And also, like, how does that moderate a little bit of the evidence as it is today, and maybe points in future direction as to where we need to go?

Speaker 4 47:16

Yeah, yeah, definitely. So as I read this paper, you know, I was like, Okay, well, I shouldn't really be excited when a baby gets back to birth weight. Like, I feel like during training, you're always like, oh, and they're back to birthweight, it's like a happy day, but really, this careful consideration of their fluid balance, especially in the first two weeks, you know, that's maybe not the goal right away. And so then I was thinking, Okay, well, then should we kind of fluid restrict to these babies, and really be thoughtful about how quickly they get back to their birth weight. And, you know, there's, there's definitely some evidence out there of later, you know, much prior studies about some careful fluid restriction, and how that could reduce risks of PDA and neck and a trend towards reduced risk of BPD. And that was in the 2014, Cochrane review. But then my mind went to well, then was this they began to then become hypernatremia, and have all the risks with that. And I think it's so hard, right? And these premature babies who their kidneys aren't super mature at all. And so they have issues with sodium handling, they have issues with concentrating their urine, and how do we balance all of that, and we're, we're giving them a lot of their electrolytes and fluid. And so it seems like the onus is on us to really be thoughtful and paying attention to this. And in preparation for the writing the commentary, I had looked through some papers about Disney trivia, and, again, something that's definitely in the adult literature. And there are some studies in pediatrics in neonates as well, that shows, you know, high hypernatremia. And even this combination of hypo and hypernatremia, in the first week of life is a Sodhi, associated with increased risk of mortality in neonates. And so it really is this walking a fine line between providing enough fluid and maybe the right type of fluid to prevent hypernatremia. But then also, not not allowing them to have too much of a positive fluid balance based on you know, this present paper that we're talking about. It's really, really difficult. Yeah,

Ben 49:32

I mean, I wonder if we're, if we're going to end up in a place where we're going to optimize our fluid balance at the expense of what we used to consider to be a normal sodium level. So maybe, maybe a sodium of 155 will remain abnormal, but it will tolerate higher sodium in the first week of life to actually allow for the benefits of of more negative fluid balance. I mean, that's going to be very interesting to see it. Obviously there's not enough data right now to to come up with any conclusions But I think this is where this is where we're heading. And yeah, and I think for anybody who's studying kidneys and fluid balance, this is super exciting. Yeah.

Daphna 50:08

Well, it's interesting, I think, again, the takeaway is always that these preterm babies are just not the same as the term baby, right, you know, they're in this was in some of the data, the moms were more likely to have hypertension, preeclampsia, you know, they're sitting over there getting tons of fluid, getting magnesium boluses. And so, I mean, that's something you remember about those, those, even the term babies, when the moms got lots of fluids, babies had more fluid on them, and they, you know, they didn't weren't losing weight expected. And that's most of our babies that we get at that gestational age, so much about their prenatal course, is still kind of nebulous. And we're not always including those factors in her data. But they did include some of those in this. Yeah, I had, oh, go ahead. Oh, I

Speaker 4 51:02

was just gonna bring up this paper that I a new review article from last year that I read that I kind of liked, because I was like, Well, where do we go from here? Like, what am I supposed to do with this information? And Dr. Slagle, who's in Cincinnati had written a new review article about kind of fluid management in preterm infants. And she, I don't know if she made up this term, but I kind of liked it. Kind of a fluid stewardship program, like similar to like an antibiotic stewardship program, and being very thoughtful, where, you know, you work to concentrate all your medications, looking at ways to minimize the volume with flushing, different medications, obviously, following daily weights and strict ins and outs and, and just having it be a point of discussion every day on rounds. And maybe that's the point to start. And, you know, as hopeful that this paper too, could potentially inspire some creative thinking and innovative thinking, you know, Ben, like you're saying, like, should we, you know, rethink where limits of someone's sodium should be given this new information. But I'm hopeful that it will kind of bring to light this issue and have more and more people thinking about it, and potentially come up with some innovative and creative ways to both, you know, support our babies, and whatever fluid management that they need from like an intravascular volume standpoint, but also not losing the bigger picture that this article pointed out.

Daphna 52:30

I love that you bring that up, because that that is something that we can start doing, you know, today in our units at a previous institution where I worked, we added up, what were the just the flushes for these ELB W's. And I mean, we had not been accounting for that in their in their daily volumes, and it was significant, you know, a substantial, substantial. Right? And I

Speaker 4 52:52

don't think, go ahead, go ahead. Oh, I just think I don't think I you know, fully appreciate that and target a really sick, you know, HIV baby, that you're trying to keep that 40 per kilo or being on ECMO, where you're really particular about their fluids. And we should really be thinking about that just in our preterm infants, too.

Daphna 53:08

Yeah, you're almost like, we literally can't fit it all in. And then when you think about these, these other little babies, you're like, Well, that makes sense. And, you know, they do give a nod about what are the next steps. So I'll just read this further work should focus on defining gestational age specific fluid fluid balance thresholds, and development of fluid balance and weight curves in prospective cohorts to better understand the contribution of fluid balance to short and long term, respiratory outcomes. And I guess I wanted to pose this question to the two of you, because this group was the 24 to 27, age, and gestational age, and the mean birth weight was not that small, 800 grams. And, you know, we've had a slew of these really little babies really growth restricted babies. And it seems like they're like almost at the other end of the spectrum where we are pouring in fluid in we can't get these babies to gain weight. And so I just wonder what you guys thought about the these kinds of nano preemies calling them now the 21 to 24. weekers.

Speaker 4 54:15

Yeah, that's, uh, that is I was thinking the same thing. When I was reading it. I was like, oh, shoot, there's no like, 22 or 23, weekers in this paper? And yeah, maybe they're kind of their own thing. But I think what this paper posed is like, we need to prospectively collect some data and generate these curves, I think that would be important to include, like 22 and 23, weekers. Right, because their, their skin losses are different than you know, 27 weaker and they just definitely have different needs. And one would say even their renal function is is quite different than like a 20 weaker. So yeah, I think that would be an amazing future effort to help us all take better care of these 22 and 23 weekers.

Ben 54:58

Yeah, I mean, I think there's no not enough of them to do these studies quickly and generate data in a timely fashion. So I think at the end of the day, we're going to have to be creative in how we combine as much of the data that we can collect in a in a not just non invasive way, but in a thoughtful way. So obviously, the solution is not going to be to draw tons of blood from these kids. And just but if you combine, because right now, I mean, you're looking at the fluid balance equation that you mentioned, bringing the paper, we're looking at percent change in birth weight, and that's kind of that's kind of, it's not very refined. I mean, this is, this has a lot of imperfections as well. But maybe if you start combining point of care, ultrasound point of care, echocardiography, you start combining nears, you start combining some of the tools that we have, maybe we'll be able to create a framework where we can treat each baby individually. Because these studies are super hard to do. You don't have enough 2120 You don't have enough 22 and 23, weekers. And then even when you do have them, one of them is born because of preeclampsia. One of them is one because of sepsis, and they're all even the small number you get together. They're all very different from one another. And so I think that's where the scientific creativity of the community is going to be very important. Yeah, definitely. A great thing that you mentioned, Bree was it's called fluid hemostasis and diuretic therapy in the neonates, it's published in Neil reviews, actually, Mr. Star in that paper as well. And I'll post it on our, on our on the episode page for people who are interested in reading that as well. So thank you, thank you for bringing

Speaker 4 56:21

Yeah, that was a really a really good paper. So yeah.

Ben 56:26

Bri this was this was great. I'm looking forward to more reviews with you. It's this was actually super interesting discussion. We thank you for making the time. And I wanted to congratulate you again on the publication of that commentary. And yeah, thank you. Thank you so much.

Unknown Speaker 56:41

Thank you, I appreciate it.

Ben 56:44

Okay, this was this was awesome. I am very excited about the partnership that we are establishing with EB Neo. And I guess we should give a We should give a shout out to Clyde right, who is in the shadows behind the scenes,

Speaker 1 57:06

make doing a lot of work to make this collaborative

Ben 57:09

fide. Thank you for your diligence. Thank you for your patience in our delayed response to your emails. We're trying trying.

Daphna 57:20

But we should mention that people can get engaged with voting for the article of the month, every month, right? And so they can do that right on the website, whether you're on Twitter or not on the EB Neo web.

Ben 57:32

So yeah, this is super exciting. All right, let's get back to I have one more paper I wanted to present today. It's actually a paper that caught my eye because it's the it's it involves a medication that we're very familiar with be Adric residency and something that we never use in neonatology. So the title of the paper is called Odense drawn to reduce neonatal opioid withdrawal severity. A randomized clinical trial first author is Gary pelts. It's in the journal appearing intelligence data coming out of the US. And obviously, it was like Zofran for our babies. Let's let's take a look. So neonatal opioid withdrawal syndrome now as we, which we now call nows, which we used to know as NES. So in the background, they're talking about the fact that while meta analyses and expert opinion have identified opioid as a primary pharmacological therapy to reduce symptoms of nows, there are concerns about the long term consequences of their use, especially in the form of they're in the form of primary therapy. Now, they had done this group had done some study showing that through computational genetic analysis of the measured severity of neonatal opioid withdrawal syndrome, they were able to identify in some animal model allelic variation within the gene, H T, R three a encoding for the five HT three receptor, as most likely correlated with a response pattern. And so they thought, consistent with this genetic finding, maybe if we administered an eight, five HT three antagonist Zofran, maybe we can decrease the severity of symptoms in animals, which is something that they demonstrated now. This is quite cool, because we're doing now translational, we're looking at translational work. Obviously, if you want to look at the animal data, it's it's quite interesting. The I think it was an intraventricular administration of Zofran. So definitely not the same methodology that I'm going to present to you today. Thankfully, yeah. But interesting nonetheless. So the underlying hypothesis is that a short course of Odense run treatment administered in the perinatal period could reduce the severity of nows in at risk infants. So this was a double blind placebo controlled multi site clinical trial. And basically after consented they randomized patients in a one to one fashion to either Odense run or placebo. The primary endpoint was the fraction of infants requiring pharmacology trickle therapy with morphine. The secondary endpoints were now severity defined as the duration of hospitalization, the severity of symptoms as measured by a Finnegan scores. The total dose of morphine required in the first 15 days of treatment and the need for adjunctive phenol BB or clonidine therapy for now as treatment. Mothers were included because they be a well we'll discuss how they did this, but there were maternal inclusion criteria, which were a daily opioid use for at least three weeks prior to delivery estimated gestational age of 37 to 42 weeks. The exclusion criteria were ingestion of attention within 24 hours prior to delivery, known prior acuity see prolongation, or other medical concerns for the investigator. The infants were ineligible if they had a prolonged QT interval medical condition or administration of a concomitant drug that would impact the attention metabolism. And so what did they do in the active treatment, the mothers received an eight milligram dose of advanced on IV within four hours prior to delivery. If the delivery somehow extended, they could repeat one more dose. And then infants had an EKG done before receiving their first dose of the study drug if the QT interval was not elevated and no contraindication for participation were identified. Then, these infants who were born to mothers who received the intervention received a daily oral dose of Zofran point one milligram per kilo daily for five days. Duration at which symptoms of nows requiring opioid therapy should manage should be manifest. The first infant dose of Odin, stron, or placebo was initiated within four to eight hours of delivery, and the EKG was performed within two to five hours after each dose of the study drug. Now, now symptoms were monitored using the local sights modified Finnegan scoring instrument and the threshold for pharmacological therapy with morphine was according to local protocol with standardized rater assessment. If you know Barbara clonidine was added as an adjunct based on local protocols as well. So if you wonder why they give, or then strong to the mother, they had already preliminary data in adults to show that it does pass to the neonate. And so they were thinking about using that data, obviously, to see if giving it to the mother could actually help almost prime the baby. I don't want to get into too much of that data, I wanted to focus on this particular paper. So the results are that 98 mothers provided consent 90 infants receiving at least a single dose of Odin strong or placebo. In terms of efficacy for the primary endpoint 49% of the denstone treated infants compared to 63%. In the placebo treated infants required pharmacological treatment for nows. So while it's quite a striking difference 63% In the placebo 49% in the 10 strong group that was not statistically significant. However, the mean modified Finnegan score, defined as the mean of all the modified Finnegan scores for that infant was significantly reduced in the audience strong treated infants compared to placebo. Now, they looked at a graphic analysis that provided a graphic analysis of the length of stay. And it was quite interesting that for the attention treated neonates, whose duration of hospitalization was either five days or less, or between six to 10 days, the denstone actually increased their length of stay. However, for the kids who stayed more than 16 days in the hospital, when they compare the groups, the kids who were in the audience from treatment intervention actually had a lower length of stay. You could say a lot of things about using technically continuous variable as a categorical variable, but I'm just yeah, this is you'll do with this data what you wish. There was no statistically significant difference between placebo and treatment arms in the amount of morphine administered to infants in the first 15 days of treatment or in the need for adjunctive, phenobarbital or clonidine therapy. Among the infants who did not require pharmacological therapy, the maximum Finnegan scores in the attention treated group were below those in the placebo treated group. But these reductions did not reach statistical significance. They looked at safety obviously, they had six infants with serious adverse events to in the attention group and four in the placebo group. And none of the severe serious adverse events were judged to be due to the Odin strong treatment. And there was no significant difference in the QT interval of infants in the attention versus placebo group. So the conclusions are that with instant treatment reduced the severity of now symptoms, and that there was an indication that it could potentially reduce the length of stay. I thought this was very interesting data because this is a medication that I I would not have even thought of for the treatment of neonatal abstinence or neonatal opioid withdrawal syndrome. I think you could make a lot of arguments for and against this study. So what I mean by that is, you could say, for example, that well, is the reduction of Finnegan scores by like 20%. Is that something that's really significant? Is that worth the trouble? That is a that is up to you to decide. I also want to say that even though the study did not find a difference in the Yeah. In the, in the amount of morphine administered, you have to remember that. And you mentioned this in the in the discussion, like these are protocolized. And so I think once the baby gets on a protocol, there's usually sort of on on tram tracks and the weaning is done in a specific way. And so it'll be interesting to see if having more than strong can allow you to deviate maybe from protocol. But so it's even though there was no difference, you wonder, could there potentially have been a difference if this aspect of care was not so protocolized? Like, it has no institution, for example. So I think the data is interesting. And, you know, if you are committed to doing this, and if you are committed to maybe getting an EKG before starting, you would have support to maybe try this on the baby, you know, that's just just miss made me beneficial. I think it's very interesting. It just opens the door to something that I had not considered previously.

Daphna 1:05:59

Yeah, and I think you bring up a good point, like in the in the units where they have really good, you know, environmental interventions are doing eat sleep console, you know, and they're already minimizing how much opiate they give. Could this be an adjunct? Or, I wonder in these babies who have been exposed to kind of polypharmacy, might there be a role in that? So I was hoping we'd see a bigger difference, but it's exciting, nonetheless.

Ben 1:06:28

Agreed? Agreed. Yeah, I have one

Daphna 1:06:33

of one more paper, but I'm not sure we have the time for it. I did want to mention a different paper, though. So I will do that. Instead, I wanted just for people to take a look. And the New England Journal of Medicine, there was a perspectives piece called, please look at my baby, when clinicians should say the word hospice by Golda Grinberg. And like I said, it's a prospective article that details this family's journey to move in from ongoing, almost prescriptive intensive care, into hospice care, and how the family broach the subject of hospice care, not the medical team. And I think that speaks to what you were saying, Ben, in our first review, about how parents feel about certain outcomes, you know, given different clinical scenarios, and it really highlights I think, the need for a team, along with the family, to occasionally take a step back with kind of a more bird's eye view of the long term plan to say is this pathway still consistent with the goals of the family? And not only that, but maybe given how a child's clinical course has progressed? Might the goals of the family have changed? And we really don't know if we don't ask, because not every family can have the insight that the Grinberg family had. And so I thought it was a really interesting article about just readdressing goals of care. Sometimes it seems like once the dominoes have been laid, and they start to fall, like we're just stuck on a certain clinical pathway. But we we have opportunities at multiple time points to reassess with them. Right.

Ben 1:08:15

And you said that we will most likely we will most likely try to record this as a separate little journal club short,

Daphna 1:08:25

we'll do in an audio review. Absolutely. We want it to say we will, we will most likely track.

Ben 1:08:32

Most likely. The bottom line is we're gonna

Speaker 1 1:08:34

get it done. We'll get it done, but maybe not until Monday.

Ben 1:08:38

And yet, yeah, it's no, it's it's one of these things where maybe we'll do it as soon as we're done here, but can't can't promise anyway. Definitely, this was fun. We will continue to see each other for board review this week. If anybody has any questions, concerns, we have our email addresses open. We're always responsive. So feel free to reach out to us if you have any questions or concerns. This was a fun Journal Club thanks to the EB Neo team for allowing us to collaborate with them. Definitely have a good Sunday feel better. You have to feel better for the conference. We need you if you're not if you're not showing up,

Unknown Speaker 1:09:21

Abby. I'll be all healed by

Ben 1:09:23

Awesome. All right. Have a good one. Thank you for listening to the incubator podcast. If you like 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, Nikki You can also message the show on Instagram or Twitter, at NICU podcast or through our website at WWW dot d dash incubator dat org This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns, please see your primary care professional. Thank you

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