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Right. So, good evening, everyone and a warm welcome to Tonight's First Gas Journal Club of 2025. Thank you for taking time out of your evenings to come and listen to some really important updates from the field of global obstetric research. And thank you to those joining from all over the globe. A reminder that tonight's Journal club is live and recorded. Tonight's Journal Club will focus on updates in global obstetric research. We'll be hearing from three clinicians. Doctor Alice Beardmore Gray, a specialist trainee in obstetrics and gynecology and coordinator of the Cradle for Trial and Dr Sinu Natarajan and and Lean Beeson who are involved in running the emotive trial. So a little bit of background on tonight, um with 95% of all maternal deaths that's 800 women a day occurring in low and middle income countries and the majority of deaths being preventable. There's a huge discrepancy between settings and this can largely be explained by poor recognition of illness and lack of timely interventions, obstetric hemorrhage, pregnancy induced high BP and severe infections directly cause the majority of maternal deaths worldwide. And effective interventions are readily available but due to poor access and training and low resources are often not instigated. So, knowing and doing the basics is key and measuring vital signs is definitely key to early recognition, allowing timely management and prevention of adverse outcomes and having the ability to measure maternal blood loss and recognize PPH, which is critical to then activating PPH protocols. Tonight, we're looking forward to hearing about how emotive and cradle are tackling PPH in hypertension and preeclampsia respectively head on and thank you to those speaking this evening, we are really grateful. The plan for the evening is um we'll start with a 30 minute talk from the cradle team and then a 30 minute talk from the emotive team and then 30 minutes of Q and A from our chat box. Um So please do put your questions in the chat um for Alice's talk and Sin and Lean's talks. We'll then just close for a couple of minutes and that will be the end of the evening. So without further ado, um I'm going to introduce to you Dr Alice Gray. She's a clinical lecturer in obstetrics and gynecology. Um She was the trial coordinator of the Cradle four trial which evaluated the optimal timing of birth for women with preeclampsia in India and Zambia and is currently leading the empowered study which aims to better understand long term health outcomes for women affected by severe preeclampsia in Zambia and Sierra Leone. So welcome Alice. The stage is yours? Ok. Hi everyone. Thank you, Cathy for that lovely introduction and, and thanks to, to gas for, um, inviting me to speak. It's a real pleasure to be here. Um I'm currently in Sierra Leone, so I'm gonna turn my camera off. Um, but hello, everyone, um, and hopefully the, the internet holds. Um, so as Cathy said, I'm here sort of on behalf of the cradle team, um, and gonna focus specifically on providing an update of the cradle four trial results, but then hopefully talk a little bit about how that fits into the broader picture um of preeclampsia research in low middle income countries. Um And you know, the wider wider program of work um that is going on. Um And um here also on behalf of my, my colleague, Doctor Katie, who couldn't make it tonight. So I will be speaking for both of us. Hopefully, this slide moves along. Um Yes, so I'm sure you're all familiar with preeclampsia. Um But just as a, as a small reminder and I'm conscious that not everyone here will be um an obstetrician um hypertensive disorders of pregnancy of which preeclampsia is the most serious form. Um the second leading cause of maternal death globally. Um and responsible for around 21% of all direct maternal deaths. Um So it's a, it's a very um serious condition and it's very rapidly progressive and very unpredictable. Um And of course, we know that 95% of these deaths are happening in low and middle income countries and primarily that's Sub Saharan Africa and South Asia. Um It's responsible for about 46,000 maternal deaths every year. Um And a huge number of, of stillbirths. Um So 200,000 every year, it's only real cure. The only way to ultimately make sure that it starts to resolve is by delivery of the baby and the placenta. Um And therefore it requires early detection and early treatment if we're going to reduce the adverse outcomes that are associated with it. And again, just as a reminder, you know, preeclampsia is a multisystem disorder. So we know that it's related to um poor perfusion of the placenta. But what happens from that is really, really widespread. Um So this poorly perfused placenta becomes ischemic and starts to throw out lots of really harmful toxins um and inflammatory molecules throughout the maternal vasculature. Um And so we know that this is what then goes on to affect um the woman's renal function, liver function, cerebral edema, pulmonary edema, eclampsia, and so on. Um And of of course, by the time that you start to pick up the signs of preeclampsia, so high BP and protein in the urine and a lot of the damage being done at that point, let me try and advance the slide. So the background to the cradle four trial really came off of the, the previous cradle trials um which looked at how could we better detect preeclampsia? Um And they really focused around the development and design of a low cost um BP device that was calibrated for use in pregnancy. Um And the cradle three trial looked at implementation of that device um across multiple different settings in different low and middle income countries. Um And whilst it was helpful in many ways, um it kind of led to the next question, which is, of course, well, it's all very well, if you've detected high BP and you've detected preeclampsia. But actually, what do you do once it's detected? Because, you know, although we were picking up potentially more women with the condition, um those adverse outcomes were still happening and it is the safest time to offer delivery for both mom and baby. And again, it looked at quite a specific time point. Um because if you look at what the current wo we have evidence that from 37 weeks onwards, the safest thing for mum and for baby is to deliver, irrespective of the severity of the preeclampsia. And we also know that before 34 weeks because of the complications that are associated with early preterm birth, unless there are severe features and severe complications. It's preferable to wait and to manage the woman expectantly if you can. But between 34 and 37 weeks is really a gray area of clinical practice because actually beyond 34 weeks, most babies are sufficiently developed from a, you know, a lung maturity point of view, um, that actually birth at this stage wouldn't cause any of the, the long term complications associated with an earlier preterm birth. Um, and, you know, there's still a, a huge number of, of women and babies in this time window who are dying because we've not intervened early enough. So the cradle four trial, um, was looking at the specific time period and it looked at it in um two countries, India and Zambia. And it's so nice to be back here um today because it's, I've been back here once before and that was in 2019. So it forced me to sort of look back and, and reflect. And at that point, I was presenting the feasibility study that we did for this trial. Um which again, I think for anyone that is involved in global health research or wanting to go into it is such an important step. Um So, you know, we found out so much valuable information from doing this feasibility study in terms of whether the intervention was acceptable, both to women, their families and to health care workers. Um and also crucially, you know, the resource availability and, and all of the other um sort of research infrastructure that we would need to make the trial happen successfully. Um So where are we now? The trial I'm pleased to say has been completed and it was published in the lancet in 2023. And so, um you know, a vast team effort um with a huge number of, of collaborators um and particularly the research midwives who were incredibly dedicated. Um so, a huge, huge, huge team achievement. Um And I'm delighted to share the results with you today. Um I have tried to summarize them because if you want to go through them in, in excessive detail and the paper is there for you to read. And I'm always happy for people to get in touch and ask questions. Um But I will try and give a brief summary. Um And um hopefully also take any any additional questions at the end. Um So we were able to recruit 565 women and these were pregnant women with a clinical diagnosis of preeclampsia at that time period I mentioned. So between 34 and 37 weeks of gestation, they were enrolled from nine sites in total. So we had four in India and that was in the State of Karnataka and five in Zambia. Um And the trial took place between December 2019 and March 2022. And you can see that we had 282 women allocated to planned delivery, which was the intervention and 280 who were allocated to usual care. So watching and waiting until either they reach 37 weeks or they develop a complication, needing emergency delivery and this is just a slightly more detailed trial profile. And so again, you can see the total number randomized and the numbers allocated. And then you can see at the bottom here are per protocol analysis. So clearly there were some women in the planned delivery arm who didn't quite receive the um the intervention which was initiation of delivery within 48 hours after randomization. So some women around 25 or so, there were delays in them um having their delivery initiated for various different reasons. Um which again, happy, happy to talk about. Oh, wait, I also just wanted to say again, this is a testament to our amazing team that we had only one, the whole trial lost to follow up. So I think um my learning point from that is that particularly when you're doing sort of global health research, people will tell you it's impossible to do to do follow up. Um And it is a challenge but um it is entirely possible um to, to make it happen as well. Um And then again, just a brief summary of maternal characteristics at enrollment. Um So, um you know, well balanced between the two groups as you would expect. And I think the interesting things to highlight here um if you look at the um characteristics at enrollment, so you can see. So again, for those of you not working in syna aspirin is um a really key intervention for us because we know that it's really effective at reducing the risk of developing preeclampsia and particularly the risk of developing preterm preeclampsia. Um So, there are different ways of um risk stratifying women, but for those who are identified as being at high risk of developing preeclampsia, and that would include things such as previous preeclampsia or family history, um chronic hypertension. Um It's really important that they take aspirin um from the first trimester onwards. Um And you can see here just how low the use of aspirin was. Um And then again, another sort of challenge that we had was in accurate determination of gestational age. So again, you can see that the vast majority of women were dated according to their last menstrual period. Um because of a real lack of access to obstetric ultrasound. Um And these are two areas which, you know, we're now looking at going forwards in terms of improving that early pregnancy care. On the other hand, steroids were pretty widely available and that was very reassuring. Um particularly knowing that that these women were often gonna be delivering um preterm. So coming on to our main outcome. So our maternal primary outcome was a composite outcome um with of maternal mortality and morbidity with the addition of severe hypertension. Um And you can see that our overall outcome, although um the intervention reduced, um the um the composite outcome, it wasn't statistical statistically significant. However, we did see a significant reduction in severe maternal hypertension. And again, that's really important because we have very good evidence. Um linking obviously the risk of severe hypertension to stroke. And in these settings, sadly, women were dying as a result of stroke, which is not something that we, you know, we're not used to seeing young pregnant women in the UK um having a stroke, but unfortunately, in these settings, it, it does happen. So that was a really important finding. Um And then we look at our primary perinatal outcome, which was a composite of stillbirth neonatal death and neonatal unit admission for more than 48 hours due to neonatal morbidity. Um And this was a non inferiority analysis. Um So we found that the um which, which was significant. Um And again, I can, it's quite a complicated um thing to get. Well, at least I found it tricky to get my head around the noninferiority analysis. But we wanted to show that there was no statistically significant increase in risk um which we were able to do. And so that was again, very, very reassuring. The kind of most impact for the most surprising finding was us, for us was as you can see this very significant reduction in stillbirth by 75%. Um And the number needed to tweak that was 33. Um And just to kind of make a comparison in the UK, we offer women a Postdates induction of labor at around 41 weeks gestation um on the basis that it prevents stillbirth. And the number needed to treat for that intervention, which is widely implemented in, in all of our guidelines is 544. Um So, you know, quite a, quite a stark uh finding and that's just um a graphical representation of the same outcomes. Um So again, you can see the planned delivery group here in the beige um significant reduction in severe maternal hypertension um and a a similar um outcomes in terms of the composite perinatal outcome, which is what we wanted to find. And then just to go through some of the um individual components of that composite maternal outcome. And again, happy to um kind of show more slides um on that if people are interested because there's about 21 different individual components. Um But again, you can see um although not, not significant, there was a reduction in eclampsia abruption, PPH um no real difference here in platelet count. And again, we found the same thing when it came to things like renal dysfunction and liver dysfunction. And really that speaks to the lack of availability of lab resources in those settings. So there were much um fewer numbers of, of women who we were even able to test this outcome on. Um And again, this is now just showing a summary of those key perinatal outcomes. So um a really drastic reduction in in stillbirth um for the planned delivery group. And when you look at when those stillbirths are happening. You can see that in um in the expectant management group and they were a large number of um oh, it's come back, sorry um of antepartum stillbirth and absolutely none in the planned delivery group. Um So, I mean, for me, the that was AAA hugely um important finding that, you know, if we delivered these babies here um a little bit earlier, then you're potentially preventing all of these antenatal stillbirths. The intrapartum stillbirths are obviously harder to prevent. Um And there were more similar numbers of those in both groups. So I think from memory, there were maybe two in the planned delivery group and three in the expectant management group. Um But for the antepartum, the silver, it was really quite a stark difference. And then the other crucial piece of information was obviously looking at the neonatal deaths because again, a lot of um a lot of the kind of initial critiques of the trial when we started was well, ok, as you might be preventing stillbirth. But aren't you just gonna translate that into a higher number of neonatal deaths? Um And actually, that wasn't borne out by the trial, you can see here. Um The numbers were very similar and there was no significant difference in neonatal deaths. Um So that was also, you know, very compelling. And then the other, I think really um really important thing um about preeclampsia, which, you know, I still try and get across in my clinical practice in the UK is that I think that we completely understandably have this tendency to think, well, the longer that the baby stays in utero, the better um in terms of their growth and development. And that may well be true in, in, you know, the majority of situations. But when you have, you know, a toxic placenta that is not doing what it's supposed to be doing, you are actually just exposing that baby to ongoing risk, let alone obviously, the ongoing risk that you're exposing the mother to. Um and you know, if you look at the, the Phoenix trial, which was the same trial as the cradle four, but done in the UK, they found the same thing as we found, which was that actually the babies that were delivered earlier were less growth restricted and had a higher median birth centile. And so again, I think that was a really um important finding some really important when we, it then it comes to kind of counseling women and, and working with our, our pediatric colleagues as well, just waiting for the next slide. Apologies. Hopefully, there we go. Um The other thing that I think um was obviously um something that we worried about was, well, if we're offering all of these women an induction, um are they not gonna end up having um a high Cesarean section rate? And again, you can see there was no difference in um the rate of vaginal delivery between the two groups. And again, I think this is, you know, this is a situation that that is quite specific to preeclampsia. But if we go back to those that basic definition and, and the kind of clinical course of what preeclampsia is, it makes sense because we know that actually the vast majority of women are not going to reach 37 weeks. It, they will progress, they will develop a complication. Um On average, um In the cradle four trial, we found that the women who were managed expectantly gained and on average three additional days of being pregnant before they developed a complication and needed to be delivered. So it then makes sense because actually, you know, if you deliver these women a a few, a few days earlier, when they're a little bit more stable, they're actually more likely to have a vaginal delivery compared to if you wait at that point, they then develop a severe complication, you then don't have time and they end up needing an emergency cesarean section and then coming on to some of the um other more detailed perinatal outcomes. And I can see there's a question in the chat um which um yeah, it's a really a really, really valid question. Um So this might help answer some of it. But if not, I will um I will come to it shortly. Um But in terms of their sort of immediate outcomes, you can see very similar apgar scores, um very similar rates of in terms of needing any, any form of neonatal resuscitation, um and very similar rates in terms of admission to the neonatal unit um marginally better in the, in the planned delivery group. But, but really, you know, not, not significantly different between the two groups. Um And then we looked at um how many babies were admitted to what level of care and how long for? Um So in answer to thank you very much for your question. Um Jason, so acute care was defined as babies that needed invasive respiratory support. So you can see that there were actually only two babies in either group that required that level of care. Um The rest were so subacute care was primarily um CPAP or any other level of um of neonatal care. Um And then actually, the majority of babies required just normal care or kangaroo mother care um was a really big consideration for us because when we were doing that initial piece of feasibility work, um there was a real concern around lack of, of ventilators, but actually, um there wasn't an, there wasn't any difference. And again, I think if anything, the babies that were in the watchful waiting group were ultimately born sicker and so would have been more likely to need um a higher level of of neonatal care. Um So hopefully, I can see I've got about six minutes left Um So I won't spend too much longer just going through the outcomes in detail. Um But again, the kind of take home message from this slide is that the um the other perinatal outcomes were again, very similar between the two groups, which was very, very reassuring, particularly looking at things like respiratory distress syndrome and, and need for respiratory support. And again, that's just a nice visual summary and thanks to thanks to Katie. So we then um came to the end of the trial and it was very exciting and but of course, you then have the challenge of what do you do with these results? Ok. You've published them. That's brilliant. But how do you actually share these findings? Which is again, you know, I'm so, so um happy um to have been asked um to speak today. Um And so we're really now in, in that phase of trying to um share the results, trying to um see if they're replicable in other settings. And I just wanted to share this as a sort of visual infographic summary that we made that really just summarizes the key findings. Um So, you know, the take home messages from the re or four trial is planned delivery from 34 weeks, reduces the risk of stillbirth by 75% reduces the risk of severely high BP um without an increase in neonatal unit admissions or short term neonatal complications or cesarean section. So, our overall conclusion is that it is safe to offer planned delivery to women with late preterm preeclampsia in a low or a low middle income country. And that this is a really important intervention that can reduce preeclampsia associated complications and ultimately save lives. I'm just waiting for the next slide to load. Sorry. Um So these are just some of our site experiences and which was from our final result um meeting where we had the teams from both sites come over and share their key findings. Um So again, some really important successes in terms of the trial finding themselves, but also how that translated into improved knowledge and empowerment of women with preeclampsia, um building the kind of administrative support and research infrastructure that was needed um opportunities to um work in research, develop their own research careers um and overall um improved monitoring and improved care. But of course, many challenges um particularly in enrolling women, um staff training, recruitment, um women's families, um resistance from certain individuals. And, and of course, um you know, making sure that all of the data collected was, was robust and accurate. Um So some really, really useful lessons there which I just wanted to touch upon and then moving, you know, on with the next steps. So we're really thinking about um how can we kind of bridge that gap between these really exciting research findings but then actually um translating them into policy and practice. So this is a paper that was recently published um this year or late last year. Um And this just sort of details our approach to some policy labs that we held where we invited lots of key stakeholders and people working in the space um to try and share the findings. And I think again, this is a really, really useful tool um to just try and um increase the impact of, of your findings. Um And we're now working on developing some shared decision making tools, which again is something that is, you know, increasing a lot within the NHS, but it's still quite a novel concept in many other countries. So just trying to increase the awareness around preeclampsia and this is just the, the first toolkit and then the second one is going to be trying to kind of support and facilitate that decision making process about whether women want to go ahead with a with an earlier delivery. And so that's something that we're working on now and um then just going back to the kind of the wider picture. And so how can we improve detection in the first place? And so the Cradle five trial which has just finished was looking at national implementations and scale up of the cradle devices and training in Sierra Leone. Um And they've managed to train a huge number of health workers across the country um which is a phenomenal achievement. And then I know I'm running out of time. So I'm, I'm kind of rapidly going through this. Um But the other thing that we're looking at is point of care tests. So once we detected again that a woman has preeclampsia, and how do we actually detect those complications earlier? Um And what kind of novel approaches can we use? And so this is a slide summarizing some of Katie's work, um which has been looking at um point of care creatinine testing um to improve detection of AK um uh improved detection of hemorrhage and sepsis using the shock index um which is built into the the cradle device um and then point of care PLGF testing um which I'll also just touch on because I think this is a really important part of the delivery puzzle um because there are still going to be, I think some people that are somewhat resistant to offering women with preeclampsia, um a planned early delivery um and incorporating PLGF testing into that pathway of care, I believe has real potential because we know that L GF is um uh extremely specific in terms of being able to rule in or out a diagnosis of preeclampsia. Um And so, if we are able via a point of care PLGF test to confirm that diagnosis, um then really we that should be clear that, you know, we can then um manage that woman as confirmed preeclampsia, which means inpatient monitoring, close surveillance and delivery from 34 weeks. Those who have a normal PLGF, you know, can be monitored perhaps as an outpatient um or perhaps with slightly higher surveillance. Um again, incorporating some of those point of care tests. Um But it enables um again, particularly people who are working in low resource environments, it enables them to um target their scarce resources to women who are most going to benefit from it. And that includes also um targeting your, your offers of, of planned early delivery. Um And that is a program of work called PAG, which is um also just about to start in Zambia, Sierra, Leone, India and Brazil. Um And one element of that will be looking at um planned early delivery on the basis of a PLGF test. So I think that will hopefully um confirm the findings from cradle four. And then my final slide is also um again, just about thinking about the next piece of the puzzle. So, you know, pregnancy is such a, a an important window into that woman's lifetime health. And so, whilst absolutely, as obstetricians, we need to be detecting those pregnancy complications and acting upon them. We also have somewhat of a responsibility to address the longer term implications. And I've just put here the the associated increased risk um that comes with a, a pregnancy. So um complicated by preeclampsia. Um so, you know, four times more likely to, to end up with end stage kidney disease, for example. Um And so our next program of work is um gonna be called EL B and that is going to be looking at a community led intervention um to reduce longer term cardiovascular risk. Um So I've put aside here for questions, but I can see from the chart, I think we come to questions at the end. Um And I just want to acknowledge the vast teams involved in this work and it's a real privilege to be able to present today on behalf of all of them. And I look forward to your questions. Thank you. Wow, thank you so much, Alice. That was really clear, really um concise but really, really fascinating um to hear about, I've got loads of questions um and read your paper, but the things that you've come up with um and added in has just given us the best insight. So, thank you so much. Um Keep putting your questions in the chat. Um because Alice, hopefully, are you able to stick around Alice for later in the session to answer some? Yeah, absolutely. As long as, as long as my laptop and internet. Um And um yes, we will go on to our next um next powerpoint and that was absolutely to time. So, thank you. Um So I'm just going to give you a bit of an introduction with regards to the emotive trial. Ok. Um So the emotive trial is the early detection of postpartum hemorrhage and treatment using the who emotive first response bundle, which is a cluster randomized controlled trial with health economic analysis and mixed methods evaluation. Um PPH another really important topic, this is defined for the for the non obs and gynae teams and anesthetics is a blood loss of more than 500 mils and it's a leading cause of death worldwide and a major cause of concern particularly in low middle income countries. So Dr Sinu Natarajan is the program manager for the emotive trial in the College of Medicine and Health at the University of Birmingham. Um SDU is a public health physician by training with a previous research background in tropical diseases and vaccines in LM IC settings. And Lean Beeson is the Program Officer for the Emotive Trial in the College of Medicine and Health. University of Birmingham and Lean has worked at Birmingham Clinical Trials Unit for over 12 years and has worked in a trials management role for over nine years. She's worked across several women's health trials including respite mizo and the emotive trial. So welcome team Birmingham and thank you so much for presenting tonight. The floor is yours. Um Thank you Catherine for that very kind introduction. Um So uh last year uh in the same general club, uh we were just so excited to present the groundbreaking results of the fantastic emotive trial. Um But today we are here to uh discuss what's happened uh beyond uh the emotive trial. So myself and Lean are here to walk you across through uh the previous activities that have that have followed post the emotive trial uh next slide, please, right. Um So a quick uh uh a quick uh summary of what we are going to talk about. So we will quickly recap, run a recap on the important uh results of the emotive trial. Then we look at what happened following the emotive uh trial. Uh So we were very fortunate to have some funding to put in place an implementation pivot. Uh We'll tell you why that happened and how that happened. And we were also very fortunate to uh also conduct an implementation study uh in Pakistan which uh went on to represent um the feasibility of implementing emotive in a South Asian setting. And um another very important evaluation that we performed uh parallel to the emotive trial, which was the health economics evaluation. What, what did this uh health economics evaluation find again? Very interest, interesting results. And this went on to be published in Nature medicine. Uh What's beyond uh emotive trial with reference to uh impact and dissemination and a quick um walk through about some other interesting analysis with the emotive trial data and also upcoming publications. Next slide, please. Um So as you all uh might know uh about the emotive trial which was conducted um to address a very, very crucial problem of postpartum hemorrhage, which you all know affects about uh 14 million women across the world with about 70,000 deaths annually. This is heart wrenching. So, uh what was I motive? Really? So, imotil was a multicountry international trial, a cluster randomized trial which aimed to assess a multicompetent clinical intervention bundle uh for uh the treatment of postpartum hemorrhage in uh mothers undergoing vaginal birth. Uh The emotive intervention uh comprised of a calibrated blood collection drip and hence, this represents the E and E motive, which is the early detection of postpartum hemorrhage and further a bundle of first response treatment. The motif bundle where M stands for uterine massage, O stands for Oxytocic drugs or Uterotonics. T stands for Tranexamic Acid IV stands for intravenous fluid. And the final E stands for examination escalation within the motor bundle. This was further supported by an implementation strategy in the intervention group. Um The implementation strategy comp comprised of four important components which included training um the uh implementation of a trolley or a carry case. Um the presence of uh champions. Um uh and um um sorry it, sorry. Uh Am I audible to all of you? Hi. Yes, thank you. Yes, we can hear you. OK. OK. Great, great. Yeah. So uh the implementation strategy, uh the hospitals and the control group were provided with the uh usual care. The primary outcome of the imotil trial was a composite outcome which comprised of severe postpartum hemorrhage, severe postpartum hemorrhage being defined as a blood loss of more than 1000 mils, a laparotomy for bleeding or a maternal death for um from bleeding. Uh We also looked at key secondary implementation outcomes. Uh And there were two key secondary implementation outcomes that we looked at. One being the detection rates of postpartum hemorrhage. And the second being the rates, the rates to the treatment bundle or the motive bundle. Next light, please. Right. So what were the results of the emotive trial? Um As I said, the primary outcome was the composite outcome. Uh So in this table, you can see um there were 39 clusters each in the emotive arm and the usual care arm. The emotive arm comprised about 49,000 women undergoing vaginal birth. And the usual care arm comprised about 50,000 women who underwent a vaginal birth. As you can see to your e um the composite outcome, it fell from 4.3% in the usual care arm to a whooping 1.6% in the emotive intervention arm translating to a risk ratio of 0.4. And if you look at the 95% confidence intervals, you can clearly see how significant this result was. So what does this 0.4 risk ratio translate to it translates to a 60% reduction in the composite primary outcome uh in the emotive arm when compared to the usual care. Um Now something very interesting I would like to mention here is when we were designing the study, we were just looking for a 25% reduction. Well, if the trial was able to bring about a 25% reduction with the help of the emotive intervention, we would call the trial a success. But here we are with a groundbreaking 60% reduction in the composite uh primary outcome. Next slide, please. Now looking at the two key implementation outcomes that I mentioned of uh the postpartum hemorrhage detection rate went in for, went went up by f went up from 51% in the usual care arm to about 93% in the emotive intervention arm. And the compliance of the motor bundle was seen in just about 19% in the usual care arm was whereas this was 91% in the emotive intervention arm. Next slide please. Now, uh we've had a look at the main uh the main results and also the implementation uh outcome results. Now, why does emotive really uh work? Well, here are uh the reason summarized in this slide as to why emotive really works in these settings. This was because the motor bounded compliance was about 92% in the emotive group, which was only about 90% of the usual care group that you saw further. There was improved escalation observed in the emotive group when compared to the usual care group. Now, also if you look at um the um the table towards your right upper corner, what was the time taken to initiate all the bundle confidence in the in both the groups that is the emotive group and the usual care group. It was just about 13 minutes in the emotive group, whereas it was about 23 minutes in the usual care group. This uh table highlights the importance of the fact that every minute your, your chances of losing the mother is quite high. Now, um uh how do we uh dissect this uh difference? How do we understand this difference? What really happened now in the usual care group, what usually is done outside the emotive context is once a PPH diagnosis made now, usually the PPH diagnosis missed or it is made quite late. Now, once a PPH diagnosis made late, uh the treatment is any. Now this treatment, the the components of this treatment is initiated in sequence. So you give one particular drug, you wait for about 1520 minutes and see if the drug is active. Then you go for the next intervention, you give another 20 minutes and you see if the particular intervention is acted. So it is a sequential process of uh treat, treating postpartum hemorrhage. And then when all methods or all interventions have failed, then you go ahead and do the escalation and by then the mother has already passed on into refractor postpartum hemorrhage. Now, what does Imo to really do? So if you look at all the components involved within from the postpartum hemorrhage diagnosis to the treatment and escalation, it, it all looks like it's being compressed with the help of the emotive bundle. So I motif focuses on early and accurate detection of PPH, followed by administration of all components of bundle together. There is no particular order or a sequence. It's just that you go ahead and administer all components of the bundle as fast as you can. And then there is training where uh the healthcare providers taught how to examine and rapidly escalate if the treatment or the motive bundle has not worked. So you can see how compressed or how rapidly emotive is applied when compared to the usual care group. And this is one of the important uh features of the success for the emotive intervention. Next one, please. So that was a story about the emotive trial. Now what happened after the emotive trial where we didn't want to uh just dust our hands and walk away saying the trial is finished. Let's move on uh to the next work. Uh We wanted, we, we spoke with our funders saying that we put in a lot of effort to have the trials, implement emotive. Now, what we want is we want these sites to continue implementing emotive. It was like a good habit, inculcated. We do not want the sites to lose this good habit. And then further, we also wanted to implement e motive in the control sides. So the Gates Foundation was very generous uh to uh help us with uh funding for another one year where we were able to uh support uh the intervention and the control sites. Now, this was the, this the main aim of this uh was to ensure continuity uh and to avoid sites reverting back to the usual care provides a lot of effort has gone into implementation of imotil which has proved to be really, really um successful. So all sites uh in within the imotil trial, about um 80 plus lights uh received a 12 month supply of Dr you know, Dr is one of the most important components uh within the emotive implementation. Uh So all the emotive intervention sites were able to continue implementing emotive. Now, all the control sites in the trial which were following usual care. Uh We were able to uh provide them with calibrated blood collection drips and they also received uh support for training. Uh They were also able to have uh support for other implementation strategies such as champions and also trolleys and carry cases. Uh Another good and an important aspect during this pivot plan or during this pivot implementation for uh phase was that all sites were able to monitor um the implementation of emo to at the sites through an audit and feedback loop system. And they were able to uh send back aggregate level data to us on a monthly basis. So we were also able to monitor uh how imotil was being implemented outside the trial. Uh So technically, um trying to understand how the trial, uh how, how the Imo intervention was being implemented in a real world scenario. Next slide, please. Um So as I mentioned, we were able to collect audit and feedback data from all the sites post emotive trial. Because of this implementation pivot, we tried to compare the results of the emo domain trial with the current pivot plan. Um So on the left, you see um what was present in the New England Journal of Medicine where the imotil trial results were published. And you can see that um sites that implemented emotive, the composite primary outcome drastically fell. This is what I meant by the 60% related risk reduction. Whereas uh if you look at the graph to the right, you can see the post implementation results, both the control sites and the intervention site, all of them showed a massive decrease in the composite primary outcome. Let s like this further, we were able to um do an implementation study now to go back to the background. IO two was done in four African countries, Kenya, Nigeria, Tanzania and South Africa. Uh Pakistan was also bo on board with us during um the emotive trial. But because of certain challenges, Pakistan was able to come only late on board uh in the emotive trial. Now, what happened was the interim analysis revealed that the E motive bundle is has a very, very high efficacy. So we thought that it would be unethical. So uh Pakistan was still in the baseline phase. So, um the data monitoring committee um and the um um uh uh the trial Management Group and everybody felt that it would be unethical to further go on to randomize the Pakistan sites to receive the emotive uh intervention. So, uh Pakistan uh did not go or did not proceed further within the main trial. But this provide us with a wonderful opportunity to assess the implementation of emotive in a South Asian setting. And hence, we went on to uh test whether the emotive intervention was gene generalizability to a South Asian healthcare setting. So the main objectives here were to assess the implementation of emotive in secondary level care hospitals in Pakistan and further to assess the clinical effectiveness outcomes for the emotive intervention. The design adopted was a before and after comparative study. Now this design had to be adopted because it would no more be ethical to um randomize the sites because emotive had now become the standard as wh O updated its guidelines following the publication of the emotive trial results. So the outcomes we looked for were co primary implementation outcomes. That is the detection of PPH and the evidence of the treatment bundle. We also looked at the key key clinical outcomes just like the main trial such as the PPH rates, severe PPH rates, laparotomies for bleeding and also maternal death due to bleeding. Next slide please. So the study was conducted in Pakistan in eight hospitals in the Sindh and the Punjab provinces. Uh all women giving vaginal birth in the study facilities were involved in this before and after study in Pakistan. Next slide, please. So if you look at um this um picture, you can see that there were eight healthcare facilities who first went on to receive the usual care. Now, this was the time when Parkinson was actually a part of the main trial, but we could not proceed because the results already proved to be so good that we could not uh consider a randomization. So further, Pakistan entered a transition phase which allowed for a full embedding of um emotive and then further all these eight healthcare facilities went on to receive emotive intervention. So the baseline phase was for six months, followed by a two-month transition phase and a three-month um intervention phase or the after phase. Uh Almost 99% of vaginal births were captured across all hospitals. We had uh pregnancy outcome data for 99% of the pa participants and the discharge outcome data. The complete was uh was was 100% next slide please. Uh at the moment, the analysis for the Pakistan before and after study has been completed and we are doing some final checks uh before we send off the paper for uh publication. And hence, uh we are unable to present the numbers here, but we can definitely tell you that the emotive implementation in Pakistan resulted in an increased rate of detection of PPH. In fact much higher than what it was seen in the emotive trial. There was a very, very high rate of use of the treatment bundle and significant substantial improvement in the clinical outcomes. So we uh are able to tell you that imotil was highly effective and implementable also in the South Asian setting. Um So manuscript, as I told you, um the publication is uh highly imminent. Uh and um there is a lot of dissemination activities going on um being some uh being planned which will coincide with the upcoming publication. There is also some formative study results and process evaluation work being analyzed and these are due for publication as well. Next slide please further. Um We also did a health economics evaluation of um the emotive uh intervention. Um So the main objective here was to assess the cost effectiveness of the emotive intervention. Now, you all know or you all are aware that within the emotive trial, it is a calibrated blood collection drive for the early detection of PPH uh which is the biggest cost driving factor. Uh So we wanted to assess the cost effectiveness of the emotive intervention which included the blood collection rate and the bundle of first response treatment or the motive bundle. There was multilevel modeling applied to the E motive trial data set to estimate the IC er or the incremental cost effectiveness ratios uh from the perspective of the public healthcare system and it looked for uh two main outcomes. Uh One is um the incremental cost effectiveness ratio with reference to the cost for severe PPH avoided and further the cost per daily or disab adjusted life you're averted. Next slide, please. Uh So what did we find? We found that the average cost per patient of trip and treatment to save a mother's life incurred very minimal additional cost compared with usual care, it would cost just another 30 us cents extra. Um uh compared to the usual care to um achieve the improved uh maternal outcome. Uh Also given that drape was the main cost driver for this whole emotive. Uh We were able to estimate that if the drape price dropped to approximately $1 per unit, this was cost effective. Emotive intervention was cost effective. And if the drape price was pushed down further to less than $1 this could go on to be cost saving. There are huge and immense efforts going around the world to develop drapes and also to lower the prices next. Like this. Uh Leanne will go on to discuss further uh on the impact and dissemination work uh following the emotive trial in the pivot phase. Uh Lean pre yours. Thank you. Thank you, Cindy. Um So looking at um dissemination then, so once we had the um emotive trial results published in a GM that was in May 2023. Um We then quite soon had the WH O update their recommendations within record time in the space of about five or six months. Um And I'll talk on the next side of what the T key recommendations that were included were. Um And also to mention currently the WH O in collaboration with the ICM, the International Confederation of Midwives and Vigo, the International Federation of Gynecology and Obstetrics. They are also um releasing their own designated guidelines and these are due for publication by the end of the first quarter of this year. So by the end of March 2025 um and subsequently the Gates Foundation and also US aid and wh O, they also confirmed that they were pledging over $500 million that they would invest in order to roll out a motive across the 20 highest burden countries with PBH, which is fantastic. Um So looking at the two key recommendations then um that were put out by the wh O. So first of all, for all women giving birth that includes vaginal and Cesarean section deliveries. They confirmed um that there should be objective measurement of postpartum blood loss. So this could be using the same tool that we used in the emotive studies such as a calibrated blood collection drape. But it could also be using a different tool. For example, we're aware that there's the maternal well tray that was developed by a professor just as Hoffmeyer in South Africa and that's a reusable tray which can be washed and reused. And then the second recommendations, this is just women having a vaginal delivery. So, um this was again ensuring that there's objective measurement um of blood loss and also the use of a treatment bundle supported by an implementation strategy. Um And we've also included the link to these recommendations if you'd like to review them after the talk. Ok. So this slide summarizes some information about the study and also dissemination that's happened. So, quite excitingly after the results came out, Bill Gates personally tweeted about the results and we also had the wh O Director General also tweet about them. Um We had some global media coverage and um emotive was also presented by the Nigeria P I, Professor Hadza Galadi um at the Gates Foundation Goalkeeper event that was held in New York. Um And also the wh O released a roadmap as well which outlines um goals, activities and milestones. They'd like to happen between 2023 and 2030. Um And they also got a lot of stakeholders together at a summit in Dubai to go through the roadmap. Um And the Yeah, so the road map was developed for these stakeholders. Um The next few slides show some maps. So we're trying to currently track all dissemination activities that are aware of that happening globally. So we're trying to visually represent these on global maps. These are in draft form at the moment. So these are likely to change. But the idea is that we'll host these on a website. It may be behind a login. Um And the idea is that this will be interactive. So you'll be able to hover over the different countries and get some information of what's happening. And we've also broken this down across different categories. So this one shows countries that are in the process or have already updated their national guidelines. So we've got Pakistan and Nigeria, they were the first countries to update their guidelines and they actually didn't have any preexisting guidelines for PPH. So it's excellent. They've actually introduced their first ones now and we've also got South Africa and Kenya that have released their guidelines towards the end of last year and then ones that are in progress. So we've got Tanzania and Zanzibar um and also Uganda and potentially in the UK, there may be an update to the intrapartum care guidelines. So there were members of our team that met with a representative from the nice committee. Um and they are interested in updating the recommendations in the UK. Um We are aware that there's the case study that's currently ongoing. So it may be that they wait until the results of this trial are out before they update the guidelines. Um and they may also require some additional health economics, data specific to a UK setting to update these. And then this map shows countries that we're aware of, that have got government or ministerial commitment to implement emotive there. And then this is where we're aware of um when there's at least some um implementation of your motive happening. Um So for example, India Ethiopia D RC Congo, they're all taking part in the PPH I study, which is also to do with postpartum hemorrhage. And as part of that study in the training materials, they've now embedded, the emotive recommendations are the training materials. So by default, all of these hospitals taking part in that study are receiving emotive training, which is great. Um And also to mention that from the US, there were some representatives from an NGO that heard about the emotive results and they came to South Africa and visited a hospital there that took part in the trial. And also they met with a dr manufacturer in Cape Town. Um So they wanted to go back to the US to see how they can incorporate the major recommendations over there. And this map shows where trainers located. So we've broken this down by master trainers and regular trainers. So during the study, we had two levels of training events happen. So there were training of trainer events. So these were run by the master trainers. Um and a lead doctor and midwife was invited from each of the emotive sites that were randomized of the interventions. These were trained at the T OT events and then um the league doctor and midwife would go back to their own hospital and then train the rest of the lay board staff in emotive. So that was done an onsite training. Um And then this shows we're aware of those great manufacturers. So um we sourced the drapet motor from India from a company called Excellent Fixable drapes. But there's some other local manufacturers that have now sprung up following the results, which is great and this makes it more sustainable in those countries that they can source them within their own country and not have to import these which incurs additional cost. Um And there's variations in the drape designs and the drape costs. But most of these are single use drapes. But there has been some innovation around reusable designs and semi reusable ones. So for example, in Kenya, there was a hospital that took part in the trial called Malindi Hospital and they developed their own reusable drape funnel which could be washed and disinfected. Um And then the blood would flow into a calibrated steel basin. Um And in Kenya, they've also developed a semi reusable drape called the O BM drape, which has the portion that goes into the woman's buttocks. So that part's washable, I think it can be reused up to about 100 times. And then the funnel part is single use plastic and that's detachable and that can be disposed of. Um And then, yeah, in South Africa, they've um come up with a slightly different design as well where the drapes come on, a big roll. So like where you'd perhaps tear off a plastic bag in a supermarket, it's that um kind of design where you can just tear off a drape one by one. Um And also in Bangladesh, I think the design there was based on using plastic bags that they could source from a local market and making that into a drape shape. Um And I'll go on to talk about um a dr manufacturer in the UK on the next slide. Um So our team were approached by a company called Kimel, they're actually based in the West Midlands. They're local to us and they already supplied hospitals with standard delivery packs and they had a non calibrated drug that was included in this, but it wasn't um trying to be used for PPH detection at all. It was just to try and keep, you know, the delivery area clean and any blood soak swabs, et cetera could just be put into the drape. Um But since they knew about the emotive results, they wanted to develop their own calibrated drape version. So as you can see here, they've applied a sticker. So the drape is now see three rather than blue and they've got this calibration sticker on. So, and they've put the 300 mil yellow line like we had in the study and a red line at 500 mil. And then there's purple lines that start from 1000 mil to indicate a severe PPH. Um So we're aware that they're trying to patent this drape at the moment, we're not actually aware of the unit cost of this and we can't make any guarantees. But if anyone is interested in trying to get some samples of these DRS to try out in your facility, then we can let you know contacts in the company to see if they can get some free samples to you. And this graph supports the fact that, you know, PPH isn't just an issue in low and middle income settings. It can also be a problem in higher income countries like the UK. And this graph contains data that was collected from the WH O Champion trial. So this compared heat stable carbot versus Oxytocin for prevention of PPH. And you can see that. So when women had a PPH, the 500 mils or more of blood loss, only about half of those were getting a tonic administered. And again, when a woman had a severe PPH, so 1000 M or more of blood loss, about 75 to 80% of the women would get to. Um So there are definitely um cases that are missed in the UK. So it, it would be important, I think to roll out a calibrated rape or a similar tool here as well to ensure that there is early detection of PPH and ensure that cases aren't going missed. And finally then said, look at um what other upcoming publications we've got from our team. So um the process evaluation that was conducted during the main trial. So the results of this, they've been accepted for publication in Lancet Global Health and they're due to be published by the end of this month, the end of January. And this includes data that was collected from observations um conducted on healthcare workers where they were caring for women having a vaginal birth. Um So it only includes data captured from the intervention sites for that. And then we've also got survey data and data collected from qualitative interviews with healthcare workers at both the intervention and the control sites. And the implementation outcomes included looking at the fidelity to the intervention, its adoption, any adaptations that were required to ensure its success, the acceptability of the intervention and the feasibility. And also looking at any contamination issues between intervention and control sites and other secondary analogies that we've got coming up include looking at consequences and complications for women that had a PPH during the emotive study versus those that didn't have a PPH. Um And then also looking at the intercountry variation in the effectiveness of your motives. So obviously, the main trial results that have been published at N JM, they only looked at the data set as a whole and it wasn't broken down by country. So this paper look at the results specifically by individually by the four countries. And then finally looking at the um looking at a diagnostic test accuracy study. So looking at um visual estimation versus um measurement of blood loss using a calibrated blood collection drape to see how good each of these approaches are for diagnosis of PPH. Um And also just to mention there will be a Lancet series coming out specifically on the topic of postpartum hemorrhage later this year. And some members of our team have also been involved in working on systematic reviews that will feed into the Lancet series. And also wh o they're currently doing some work around the definition of PPH and the threshold that's used. So it could be that the definition of 500 mils or more blood loss ends up changing. Um So thank you very much everyone for listening and we're happy to take any questions and just in case you haven't read the publication yet, um If you scan this QR code, then that will take you to the, the publication. Thank you. Oh, thank you so much to both presenters. That was absolutely phenomenal. It's really amazing to hear to um really important examples of action research that are gonna be widely implemented. Um And really, really interesting to see your maps and to see um the progress since we last spoke, the last Journal Club where emotive presented. I'm very excited to look at the interactive maps and see um how this research is impacting on the countries and things like that. So, thank you ever so much. I'm going to now hand over to my colleague, Doctor DAO. Um He's going to go through some questions for the speakers and um we'll have a bit more discussion. So um DAO over to you. All right. Um Amazing talks. Um This was really, really great, like we really enjoyed it. Thank you all so much. I think um the first question was already answered. Um That was a question from Jason. So, um I think Jason is happy enough with the answer. So we'll go on to the next question. So the question is for grade four, how accurate gestation was added two sides? Was this based on the L MP or the single ultrasound? Yeah. Thank you. Um So it was, I think on that first slide I showed where you've got the baseline characteristics that roughly about 40% of women had their gestational age determined based on their last menstrual period. Um And we had a huge number of discussions when we were designing the trial about um whether we were, you know, whether that was an accurate enough method um and eventually kind of in, you know, decided to, to go with it in favor of um this being a kind of pragmatic trial and wanting it to be transferrable and applicable to real world settings. And then I think that's definitely one of the challenges is you have you do have to sort of make a decision about, do we, you know, do we try and get everyone the gold standard? But, but know that then after the trial is finished and that might not be feasible or do we try and um implement it in a real world setting? So we went with the, the real world option, which I think does make the results more, um transferrable. Um The other thing that we tried to do was, you know, when possible. So often the ultimately, the clinical team looking after the woman were the ones that decided um if she was eligible for the trial. Um And so if they had access to an ultrasound, they would often perform, you know, a late growth scan, which again, as we all know, is not necessarily as accurate as the first trimester one. but would give us a bit of an idea. The other really key point um to remember is that because our biggest fear was, well, what if um we, you know, obviously these are women who have preeclampsia, so they're likely to have growth restricted babies. Um And so clearly, then you could do a growth scan and think that on the basis of that growth scan, actually, the woman is, you know, 32 weeks and therefore not eligible, but actually, she's 35 weeks and she's got a really growth restricted baby who really needs to be delivered. So that was the other thing that we um, tried to take into consideration. Um But yeah, it's definitely a challenge. Wow. Amazing. Um The next question was, um, induction of labor. Do you think this was relatively uncommon in the center? You did a trial or were they using induction with confidence? Yeah, it was pretty. And again, because these were, um, you know, women, women with preeclampsia, most of them were, were um captured and referred at a tertiary referral hospital. Um So, induction was used um fairly um fairly widely across all of the sites. Um What I would say is again, because of this population, you know, overall in both groups, um the cesarean section rate was high. Um So I think it was for about 40% of women in both groups had a vaginal birth. So, you know, it was, it was um it was high across the board. Um And I think one of the reasons why is because the real challenge with induction. So most of the time it was done with either oral or vaginal mi arosol. So, obviously, different methods to what we would be using in the UK. And the real challenge was the monitoring. Um because again, we don't have um well that there's there was not continuous electronic fetal heart monitoring and even with intermittent auscultation, the midwife to patient ratio meant that that wasn't always able to be done in the way that it should be. So I think that was the biggest challenge with induction was um the monitoring throughout the induction process, which of course, again, was balanced between both groups. Because again, I think what you have to remember is the women in the, it's not that the women in the expectant management group are going to get to term and go into spontaneous labor. They're gonna need an induction at some point. It's just the, the, the question is when should that induction be done? Um So, yeah, the monitoring was definitely a challenge. Um But, and I think that's part of the reason why in these settings, because actually Cesarean section was an intervention that they had available to them. If there was any um concern, then often there'd be quite an early recourse to Cesarean section. OK. All right. So, um the next question, thank you so much for that is from doctor. It was quite a long one, but I think I'll just break it down. It's more like, was there any challenges which you could see in preeclamptic women without severe features, considering some features were detected through investigation that may not be available? Yes. So there were um and um again, because as you've correctly identified, obviously, our child population was women without severe preeclampsia. Um And there was a big challenge because often by the time they arrived at the tertiary referral hospitals, they'd already developed severe features. So we had to sort of adapt our recruitment strategy and go wider and go and try and, um, you know, again, it comes back to that whole piece around earlier detection and so trying to um increase participation by going out more to the primary health center at clinics. Um And then as you say, you know, and I think the person asking the question was also, you know, talking about the point of care testing and I'm very happy to, to put mine and Katie's email addresses in the chat. Um If you want to, to talk more about point of care, because I think that's exactly where, you know, where they come in is, is helping to identify those women. And I think ultimately, that's why we didn't see that really significant drop. Um in terms of the difference in maternal outcomes was because actually in both groups, the women had quite severe complications and even in the expectant management group, they were, they were then delivered. Um you know, quite soon after randomization. Perfect. Thank you so much. If I can just briefly come back and see Jason's, there was one other final point about Jason question if I may. Um because I think this is a really, really important point and it's, it's, it's a very common question about the level of the neonatal support. Hi, Alice, how is today? I think we may have lost Alice. Um Cathy, can you hear her? Oh, yeah, because I can't hear her rarely, maybe some CPAP, but I think the really important thing is that these are babies that are going to need that regardless. So, although the planned delivery group had an earlier delivery, the babies in the watchful waiting group are still at risk of, of becoming sick and needing support if not more at risk because of that risk of the preeclampsia progressing. So even if you're in a very rural remote area without that level of nicu backup, if anything, there's even more of a reason to deliver these babies earlier because actually if you wait three or four or five days and the woman has an abruption, you then have a baby with severe birth, asphyxia, that's gonna need a higher. Hi Ali. So I think your internet was cutting in and out. We kind of got cut off, but thank you so much for that. Um We will appreciate it. We can drop your email in the chart. So I think we will just move on to the next question. Um And this is to the emotive trial. Um The question is, is the emotive trial applicable in Somaliland? Yes, it would definitely be applicable there. It's applicable where any where pph is a problem which is likely in all countries. It's not just, you know, lower income setting, it's high income settings as well. Um And the wh recommendations that were published, they apply globally. So it would be to all countries. Amazing. And um just to follow up the next question is that um it's quite a long question, but I read it out. It's so brilliant to see the sustainability impact of the intervention and that I implantation is now being studied. Have you been able to engage high level stockholders uh in Ministry of Health who are willing to incorporate the bundle into the national guideline and to facilitate um support, procurement and supply chain management? Yeah, so I mentioned that during my slides that um I showed some countries where we're aware that they've got ministerial support. Um So particularly the countries that participated in emotive, they've all been engaging with the ministries of health. Um And also I mentioned about the guideline changes that are happening and um yeah, there is a push to try and get drapes into sort of the regular supply chains. Um So it, you know, it comes through their usual channels, how they would normally get equipment, et cetera from like the state level rather than it being um given by another group from outside. Amazing. Thank you so much. And I think we just have one more question for Alex. Um early preeclampsia onset, prior to 34 weeks. Is it perhaps part of the future re work that may be looked at so tricky, but those women who need delivery before 34 weeks. Are you still there? I'm still here. Yes, sorry. I'm just um there was breaking up a little bit. So I was just trying to read the question um early on to preeclampsia prior to 34 weeks. Yeah, absolutely. And I think that this is um so we also have another project called um Papaya, which is happening at the moment um which is looking at um the, you know, improving antenatal screening. And I think this is also then where all of these point of care tests. Um So PLGF um and then, you know, the adjunct so point of care creatinine um as well um will be really helpful and of course, there will be women that need delivering before 34 weeks. I'm not sure we'll ever get, you know, I do, II think 34 weeks is probably going to be the limit in terms of when people would routinely offer um delivery without severe complications. But absolutely, um looking at, looking at those women too and that's where I'm hoping my um my empowered study, looking at um the women with severe preeclampsia and ak I um I imagine will probably be capturing um a fair few of them. Um So watch, watch the space. Amazing. Thank you so much. And I think this is our last question. Um and this is for the emotive, how long is the training in the country in terms of time? Like how, how long was the training for? Um So during the study, so we allowed a two month transition phase. So that was to try and get him motive embedded during that period and ensure that all of the healthcare workers were trained at the site. So it was a maximum of two months. But I think realistically all the healthcare workers were trained within about a month period. Oh, wow. Amazing. That's good. So just just a month that that's really good to get this amazing work done. So, thank you so much. Um I think that will be our last question just based on time. I'm gonna hand over back to Catie. Thanks Dave. Um Just, just a final sort of query and comment for Alice. Alice. I was just thinking um there's been so much focus from the World Health Organization, importantly on the risks of prematurity and birth outcomes, uh sorry, uh morbidity and mortality in later life. And I wondered how much is this, is this gonna be um a culture change? Do you feel now that cradles gaining momentum um towards showing? Yes, it is OK to deliver these babies late preterm in countries where there are less resources available for um for the neonate and, and whether you've had any of those sort of initial sort of discussions with the World Health Organization about implementation uh worldwide. So, yeah, yeah, I mean, really good question. Um And I think it, it is a really, really difficult culture change. It's a difficult culture change in the UK. Um And I think as you say quite rightly, you know, we obviously want to avoid preterm birth in most situations. Um So I think it's trying to kind of facilitate people getting their head around preeclampsia being this very unique situation that actually, you know, really the benefits do outweigh the risks. Um And, you know, there are a number of, of um sort of population studies that, that I looked at when I was um writing up cradle for that kind of compare, you know, I think the issues that we have with a lot of the sort of um data when you look at outcomes for Children that are born preterm is that they're compared to healthy term controls. Um Whereas again, you know, with these babies born to women with preeclampsia, the alternative is not a healthy term pregnancy. Um And so we really need, I guess better um better studies and that can more clearly delineate the outcomes. And there are, there are a few, in fact, I can put a link to one in the chat, um which I thought was really, really helpful. Um and reassured me um that, you know, we were, we were doing the right thing. Um The other thing I think is um more, more data. Um And so, you know, we're at the moment I'm trying to do um a review. So putting the cradle four trial um into a meta analysis with other trials that have looked at timing of delivery. And I'm really hoping that if we can kind of show conclusively that it's not just um a one off but that actually, um you know, this, this finding is replicated across trials that, that will perhaps give a bit more um uh yeah, a bit more weight to the findings and, and catch the eyes of um the wh O so we haven't had any of those initial conversations. I would love to. Um So, yeah, I need to learn from the emotive dream on that front. That's wonderful. I think if you told the wh o it's only a matter of three days Alice difference, then that's certainly important. And you know, I can, I can definitely see a lot of a lot of very useful streams between cradle and emotive working together um and impacting on global health. So, yeah, fantastic. Um brilliant, brilliant, brilliant examples of real real world action research tonight. Um If, if there are any more questions, we'll wrap up just because I know that everybody might need to go and, you know, get some food, have a bit of a relaxer, read a book or watch some television and switch off for the night. So, um just a final point um on tonight from us. Um So just to say that uh tonight has been hosted by Gas Global Anesthesia Surgery and obstetric Collaboration. Um We are a big group um representing trainees uh globally to try and improve outcomes um from anesthesia, surgery and obstetrics and gynecology. Um We're interested in getting trainees involved in projects we're interested in um frugal innovation and we're interested in action research and um bringing together people to talk at conferences every year. And Gasso this year is 10 years old. So we're having an anniversary and we're going to celebrate big. So just to all of our um members and to be members watch this space over the next few months, we really want to invite you to our um big 10 year celebration um of Gas and that will be in the form of a conference later on this year. And we really hope that emotive team and cradle will be able to come back and join us again. And we really thank all the speakers tonight for all the updates that we've received um because we are really really interested in supporting your work in any way in which we can. Um So VNA is kindly just put in the group there. Um Please sign up to our mailing list to find out more. Um We are a collaborative group. So we really are interested in working together as a multidisciplinary team um to bring together exciting research like this because your work tonight um definitely gives ideas to the surgeons that gives ideas to the anesthetists. So we're really grateful for that. Um Follow us on uh X and O on Instagram. That's Gas O underscore 2015 for X or on Instagram, Gas O UK. Yes. Happy birthday to Gas O. Thank you. Um Tonight. Uh if you have uh um because you've intended, we'll send you a feedback form from medal to uh and uh to complete and then upon completion, you will receive a certificate for attending tonight uh that you can add uh to your CPD or your portfolios. Um So thank you once again. Good evening and we'll see you soon. Take care.