Hi, everyone, I'm Nancy Akande, and I'm going to be covering some papers that were published in the area of clinical research, but I'll also cover a couple of papers that overlap clinical research and public health. I have no disclosures. So the first article was published in the PCCM Journal in February of last year. And the background of this study is premised on the fact that although RBC red blood transfusions can be life-saving in quickly ill children, there are significant risks that are associated, like, for example, increased mechanical ventilation days, as well as mods and even death. And there have been multiple studies, such as the Tri-PICU study, that have demonstrated that restrictive transfusion strategies can reduce transfusion rates without compromising the outcomes of quickly ill children. In 2018, the TAC-C guidelines were published, and they recommended that for children that were hemodynamically stable, non-cardiac, and also had hemoglobin level of 7 or more, that it's recommended for them to not be transfused. But despite these guidelines, as well as studies showing that there are non-inferior outcomes with restrictive transfusion strategies, there are a lot of practices whereby there's liberal transfusion practices going on in our ICUs. It was on this premise that this current study was a secondary analysis of the Age of Blood in Children study, also known as the ABC-PICU study. The objective of this current study was to assess the clinical and economic impact of compliance with the threshold-based TAC-C recommendation for transfusion for non-cardiac, hemodynamically stable, critically ill children. The primary outcome was neuroprogressive mods, and they had a host of secondary outcomes that included the cost of ICU stay, amongst others. From the original ABC-PICU study, they excluded patients, such as those with cardiac disease and those with unknown or unstable hemodynamic status. And this resulted in a sample of about 700 critically ill children, for which they further divided them into two groups based on the initial hemoglobin level prior to their first transfusion. And they divided them into the complying group for those patients that received transfusion for hemoglobin less than seven, and then the non-complying group for those that received a transfusion for seven or more in their hemoglobin level. To balance or to reduce the confounding from pre-transfusion characteristics, a balanced cohort was created using the method, which I'm not going to go into the details of, a stabilized inverse propensity for treatment weighting. And they also carried out weighted regression analysis to fit and evaluate the outcomes based on the guidance compliance. With respect to the baseline variables, not a lot of differences between the two groups, except that they did observe that the pLOD scores were higher in the non-compliant group. With respect to the study outcomes, patients in the complying group who had more ICU free days and more ventilator free days, they didn't observe any significant association between compliance and the other study outcomes, such as their primary outcome mortality. They also noted that there was no significant difference in the maximum degree of organ dysfunction between the groups, as indicated by the worst pLOD2 score. And this is very important to note, because we might think that the patients in the non-compliant group received more non-compliant transfusions because they had a sicker course in the ICU. And then based on the reduction in the ICU days, they estimated a cost savings of about $38,000 per patient in the complying group. So based on this, the authors concluded that non-compliance with the threshold-based transfusion guidelines for hemodynamically stable, critically ill children, but not without cardiac disease, may worsen outcome. And that deferring transfusion in this population apparently could be safe and could also have some clinical and economic benefits. But they also did highlight that, just by the fact that we have these guidelines, and we also have evidence from studies, like the Tri-PQ study, that provider compliance with transfusion, restrictive transfusion strategies, is actually low. But there have been some studies whereby they put interventions, such as peer-to-peer feedback, and as a result of those interventions saw a reduction in the transfusion rates. So their suggestion was that a formal, structured implementation approach is needed to ensure integration of transfusion guidelines into clinical practice. The next paper was also published in the Journal of Pediatric Critical Medicine in March of last year. And as we heard this morning, pediatric sepsis remains a very significant global health challenge and accounts for a significant proportion of kids that we manage in the ICU and is frequently associated with high rates of mortality and morbidity. And despite the fact that there's been a lot of rigorous research in regards to pediatric sepsis, we still don't have targeted treatments for pediatric sepsis. And the use of an adjunctive therapy, such as corticosteroids, remains controversial. Studies on corticosteroid use in pediatric sepsis in both children and adults have conflicting results, with some studies suggesting that early use may shorten the time of shock reversal without increasing morbidity and super-infection, and other studies showing that steroid use is associated with increased risk of adverse outcomes. But alongside this timeline of studies, there have been various transgenomic studies in pediatric sepsis that has led to the identification of sepsis endotypes, as well as the development of a biomarker-based risk stratification tool known as Persevere. Persevere in itself has been shown to reliably identify children at risk of death, and those with greater illness severity from septic shock in pediatrics. So this current study was performed as a secondary analysis of a prospective multi-center court study of about 461 children with septic shock to assess the association of corticosteroid administration within the Persevere 2 risk score categories and 28-day mortality. They also looked at other secondary outcomes, such as ICU free days, complicated course, and maximum filled organs. In this study, corticosteroid administration was defined as the receipt of any formulation of systemic steroids for at least 48 hours within the initial seven days of septic shock, excluding steroids that were given for periextubation purposes. And they used the Persevere 2 score to classify patients into their baseline mortality risk group as to whether it was high or low risk. With regards to their primary outcome, the 28-day mortality, in their regression analysis, they identified that it was an interaction between corticosteroids and the Persevere 2 variable. So on that basis, they performed a stratified analysis. Oops. I went, OK, great. They performed a stratified analysis and identified that children that had a baseline low mortality risk, corticosteroid exposure was not associated with increased mortality. However, for those patients that had a high Persevere 2 score, they had increased odds of mortality with corticosteroid exposure. In addition, for those patients in the high Persevere 2 score risk category who also had exposure to steroids, they had fewer ICU free days. And they were also noted to have a higher odds of complicated course and more likely to have a higher number of organ that were in a dysfunctional state. So the authors have shown us from this study that consistently across multiple outcomes that corticosteroid exposure in the high Persevere group was associated with increased mortality, suggesting that there might be a potential differential response to corticosteroid administration in subgroups of children with septic shock. And thankfully, these findings are being prospectively validated in an ongoing study, SHIP study. I bet most of our centers represented here are fully aware of that study. The third article was published in Kidney International Reports in September of last year. And another concept that's pretty common in our ICUs, AKI. And we know that severe AKI is associated with increased risk of mortality and morbidity. And over the last decade, investigators have conducted a series of studies on the prediction of AKI through risk stratification and the use of biomarkers of AKI in the ICU. The Renal Angina Index, which I'm going to just abbreviate as RI for the purpose of this presentation, calculated at 12 hours after ICU admission plus a unibiomarker NGAR concentration and has been shown to predict severe AKI at 72 hours of ICU admission. In addition, there have been multiple studies highlighting the negative consequences of fluid accumulation in critically ill children and the need for early initiation of CRRT to reduce the mortality risk that is often associated with fluid overload. However, the question remains, can a fluid accumulation prevention strategy be tested prospectively to validate these findings? So to answer this question, a clinician decision pathway, Taking Focus 2, also known as TF2, was developed and implemented as an observational study to personalize fluid management and CRRT initiation based on the validated AKI prediction using RI and the unibiomarker NGAR and the patient's fluid status. In this pathway, patients admitted from July of 2017 received an automated RI result at 12 hours of admission, a urinary NGAR order if the RI was 8 or higher, and CRRT initiation if at the fluid balance or fluid accumulation, weight-based fluid accumulation goal of 10% to 15%. For the analysis, they looked at two cohorts of CRRT patients before and after the TF2 implementation over the span of 7 1⁄2 years to assess the differences in patient outcomes and healthcare costs. Over the course of the entire observation period, they had 178 patients that received CRRT, 71 in pre-TF2 and 107 in TF2. And they observed that patient weight and age and PRISM score will not differ between the two errors. And for their outcomes, they examined ICU admission to CRRT initiation, CRRT cost, and ICU discharge outcomes. They were able to identify that ICU admission to CRRT initiation as well as median CRRT duration, ICU length of stay after CRRT discontinuation, and total ICU length of stay was shorter in the TF2 period. Total waits to ICU discharge after CRRT discontinuation was also higher in the TF2 era. And based on this, they were able to estimate that it was a conservative healthcare savings of about $12,500 due to the reduction in the length of stay in the ICU as well as the decrease in the duration of CRRT. And over the course of the four years of TF2, these observed associations persisted. So this study exemplifies how a clinical decision support system or algorithm or standardized practice change can improve outcomes. However, it's also important to note that for widespread dissemination, that it will require the design of more cost and time efficient solutions because the authors did state that although this intervention was significantly important and led to improved outcomes, that it was very, very cost and time intensive. And for me, as I was reviewing this paper, I think it's also an excellent example of translational research continuum because when I first came across the Rai and the NGAR papers during my fellowship training, I wondered how and when these discoveries will make to translate to the bedside. And now here we are, leaps and bounds, years after, very close or more close to personalized management for AKI and RPQs. And last but not least, an area of very much, I'm very much interested in, I'm going to do a very quick review, very, very quick review of papers published in 2023 that examined the impact of neighborhood childhood opportunity on outcomes of pediatric critical illness. COI, Neighborhood Childhood Opportunity, is a composite index of 29 indicators that impact child health and development. And these cuts across the domains of education, health and environment, as well as social and economic conditions. And we've had a couple of papers published. And from these papers, I'm just going to summarize the salient findings. We were able to identify the proportion, a high proportion of PICU admissions in the U.S. were often for children who resided in very low COI neighborhoods. And that COI was inversely related to mortality and length of stay in critically ill children. And that also children that had severe TBI living in low COI zip codes often had higher injury severity and longer hospital length of stay. And that lastly, children living in neighborhoods with lower COI had an increased risk of PICU readmissions within the first year of ICU discharge. Suggesting that children who are discharged to a disadvantaged neighborhood after critical illness are likely to return to stressful living conditions with under-recognized barriers to recovery. Now, although more research is required in this area, the authors of this paper do suggest that incorporating social risk factors into patient level assessments within our PICUs will help us to early identify those patients that are at risk for adverse long-term outcomes. Will provide opportunities for us to tailor post-ICU interventions to address unmet social needs of children recovering from critical illness. And thus, impact their outcomes at a more personal level. Now, central to all these papers that I selected to review is the fact that as a field, I think we all observe this, that we are moving more from the one-size-fit approach of conventional medicine to more precise and personalized patient care. By which medical decisions and our practices and interventions are more tailored to the individual patient based on their risk of disease and as well as their predicted response. And ultimately, this will lead to improvement in the outcomes of our patients with regards to their health as well as their life. And because care is personalized, I think this will also, as a result, increasingly see a reduction in health disparities related to critical illness. And on that note, thank you very much. And thank you to all the investigators that contributed to these papers.

pediatric critical care

restrictive transfusion strategies

corticosteroid use

fluid management

personalized medicine