Timing of intubation of pediatric hematopoietic cell transplant patients: an international survey.

Introduction: Retrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician's decisions surrounding timing of intubation of pediatric HCT patients. Methods: We validated and distributed a brief survey exploring potential factors that may influence clinician's decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI). Results: One hundred and four of the 869 PALISI Network's members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation. Discussion: Our survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient's poor prognosis as a common reason for delayed intubation.

Retrospective analysis of veno-occlusive disease/sinusoidal obstruction syndrome in paediatric patients undergoing hematopoietic cell transplantation -a multicentre study.

Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. Methods: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients. Findings: The incidence of sinusoidal obstruction syndrome in this cohort (n = 488) was higher by pEBMT (21.5%) vs historic modified Seattle (15.6%) and Baltimore (7.0%) criteria (p < 0.001). Application of pEBMT criteria identified 44 patients who were not previously diagnosed with sinusoidal obstruction syndrome. Overall, 70.5% of all patients diagnosed with sinusoidal obstruction syndrome ultimately developed very severe disease and almost half of diagnosed patients required critical care support. Overall survival was significantly lower in patients who were diagnosed with sinusoidal obstruction syndrome vs those who were not. Interpretation: Taken together, pEBMT criteria may be a sensitive method for prompter diagnosis of patients who subsequently develop severe/very severe sinusoidal obstruction syndrome. To our knowledge, this is the first multi-centre study in the United States (US) to demonstrate that pEBMT guidelines are associated with earlier detection of sinusoidal obstruction syndrome. Since early initiation of definitive treatment for sinusoidal obstruction syndrome has been associated with improved survival in paediatric patients and implementation of pEBMT criteria appears feasible in the US, universal adoption should facilitate prompter diagnosis and lead to improved outcomes of children with sinusoidal obstruction syndrome. Funding: None.

Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications. Methods: We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa. Results: We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa. Conclusions: Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients.

Digital Dating Abuse: An Application of the Theory of Planned Behavior.

Social media and other technologies are being increasingly adopted as mechanisms to perpetrate abuse against dating partners. Using Ajzen's theory of planned behavior as a framework, a sample of 352 emerging adults completed a questionnaire that assessed the core constructs of the theory of planned behavior (i.e., attitudes, subjective norms, perceived behavioral control), as well as intentions to commit three types of digital dating abuse in the near future: digital monitoring and control, digital direct aggression, and digital sexual coercion. The models explained 44%, 34%, and 44% of the variance in intentions to commit digitally facilitated monitoring and control, direct aggression, and sexual coercion, respectively. Attitudes and subjective norms significantly predicted intentions, whereas perceived behavioral control did not. Given the increasing prevalence of digital dating abuse, prevention efforts should target attitudes toward digital dating abuse-related behaviors and perceptions of social acceptability and engagement.

Mortality Risk Factors in Pediatric Onco-Critical Care Patients and Machine Learning Derived Early Onco-Critical Care Phenotypes in a Retrospective Cohort.

OBJECTIVES: To use supervised and unsupervised statistical methodology to determine risk factors associated with mortality in critically ill pediatric oncology patients to identify patient phenotypes of interest for future prospective study. DESIGN: This retrospective cohort study included nonsurgical pediatric critical care admissions from January 2017 to December 2018. We determined the prevalence of multiple organ failure (MOF), ICU mortality, and associated factors. Consensus k-means clustering analysis was performed using 35 bedside admission variables for early, onco-critical care phenotype development. SETTING: Single critical care unit in a subspeciality pediatric hospital. INTERVENTION: None. PATIENTS: There were 364 critical care admissions in 324 patients with underlying malignancy, hematopoietic cell transplant, or immunodeficiency reviewed. MEASUREMENTS: Prevalence of multiple organ failure, ICU mortality, determination of early onco-critical care phenotypes. MAIN RESULTS: ICU mortality was 5.2% and was increased in those with MOF (18.4% MOF, 1.7% single organ failure [SOF], 0.6% no organ failure; p ≤ 0.0001). Prevalence of MOF was 23.9%. Significantly increased ICU mortality risk was associated with day 1 MOF (hazards ratio [HR] 2.27; 95% CI, 1.10-6.82; p = 0.03), MOF during ICU admission (HR 4.16; 95% CI, 1.09-15.86; p = 0.037), and with invasive mechanical ventilation requirement (IMV; HR 5.12; 95% CI, 1.31-19.94; p = 0.018). Four phenotypes were derived (PedOnc1-4). PedOnc1 and 2 represented patient groups with low mortality and SOF. PedOnc3 was enriched in patients with sepsis and MOF with mortality associated with liver and renal dysfunction. PedOnc4 had the highest frequency of ICU mortality and MOF characterized by acute respiratory failure requiring invasive mechanical ventilation at admission with neurologic dysfunction and/or severe sepsis. Notably, most of the mortality in PedOnc4 was early (i.e., within 72 hr of ICU admission). CONCLUSIONS: Mortality was lower than previously reported in critically ill pediatric oncology patients and was associated with MOF and IMV. These findings were further validated and expanded by the four derived nonsynonymous computable phenotypes. Of particular interest for future prospective validation and correlative biological study was the PedOnc4 phenotype, which was composed of patients with hypoxic respiratory failure requiring IMV with sepsis and/or neurologic dysfunction at ICU admission.

CritCom: assessment of quality of interdisciplinary communication around deterioration in pediatric oncologic patients.

Background: High-quality clinical care requires excellent interdisciplinary communication, especially during emergencies, and no tools exist to evaluate communication in critical care. We describe the development of a pragmatic tool focusing on interdisciplinary communication during patient deterioration (CritCom). Methods: The preliminary CritCom tool was developed after a literature review and consultation with a multidisciplinary panel of global experts in communication, pediatric oncology, and critical care to review the domains and establish content validity iteratively. Face and linguistic validity were established through cognitive interviews, translation, and linguistic synthesis. We conducted a pilot study among an international group of clinicians to establish reliability and usability. Results: After reviewing 105 potential survey items, we identified 52 items across seven domains. These were refined through cognitive interviews with 36 clinicians from 15 countries. CritCom was piloted with 433 clinicians (58% nurses, 36% physicians, and 6% other) from 42 hospitals in 22 countries. Psychometric testing guided the refinement of the items for the final tool. CritCom comprised six domains with five items each (30 total). The final tool has excellent reliability (Cronbach's alpha 0.81-0.86), usability (93% agree or strongly agree that the tool is easy to use), and similar performance between English and Spanish tools. Confirmatory factor analysis was used to establish the final 6-domain structure. Conclusions: CritCom is a reliable and pragmatic bilingual tool to assess the quality of interdisciplinary communication around patient deterioration for children in diverse resource levels globally. Critcom results can be used to design and evaluate interventions to improve team communication.

A new measure for multi-professional medical team communication: design and methodology for multilingual measurement development.

Background: As implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts. Methods: The development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in English and Spanish, however, this approach is not language specific. Participants are engaged throughout the process: first, an interprofessional panel of experts and second, through cognitive interviewing for measure refinement. The steps of measure development included: (1) literature review to identify previous measures of team communication; (2) development of an initial measure by the expert panel; (3) cognitive interviewing in a phased approach with the first language (English); (4): formal, forward-backward translation process with attention to colloquialisms and regional differences in languages; (5) cognitive interviewing repeated in the second language (Spanish); (6) language synthesis to refine both instruments and unify feedback; and (7) final review of the refined measure by the expert panel. Results: A draft measure to assess quality of multi-professional team communication was developed in Spanish and English, consisting of 52 questions in 7 domains. This measure is now ready for psychometric testing. Conclusions: This seven-step, rigorous process of multilingual measure development can be used in a variety of linguistic and resource settings. This method ensures development of valid and reliable tools to collect data from a wide range of participants, including those who have historically been excluded due to language barriers. Use of this method will increase both rigor and accessibility of measurement in implementation science and advance equity in research and practice.

Development and pilot testing of PROACTIVE: A pediatric onco-critical care capacity and quality assessment tool for resource-limited settings.

BACKGROUND: Nearly 90% children with cancer reside in low- and middle-income countries, which face multiple challenges delivering high-quality pediatric onco-critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center-specific reports, and identification of common POCC challenges. METHODS: The original 119 consensus-derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha-testing was conducted to confirm face-validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta-testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges. RESULTS: Alpha-testing ensured face-validity and beta-testing demonstrated feasibility and usability of PROACTIVE (October 2020-June 2021). Twenty-two surveys (response rate 99.4%) were used to develop center-specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses. CONCLUSIONS: PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource-levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally.

Outcomes for critical illness in children with cancer: Analysis of risk factors for adverse outcome and resource utilization from a specialized center in Mexico.

Introduction: Children with cancer have a higher risk of adverse outcomes during critical illness than general pediatric populations. In Low- and middle-income countries, lack of resources can further negatively impact outcomes in critically ill children with cancer. Methods: In this study, we describe the outcomes of a large cohort of children with cancer including mortality and resource utilization. We performed a retrospective review of all patients admitted to our PICU between December 12th, 2013 and December 31st, 2019. Outcomes were defined as recovery or death and resource utilization was described via use of critical care interventions, Length of stay as well as PICU- and Mechanical Ventilation- free days. Results: Overall mortality was 6.9% while mortality in the unplanned admissions was 9.1%. This remained lower than expected mortality based on PIM2 scoring. Type of PICU admission, Neurological Deterioration as a cause of PICU admission, and PIM2 were significant as risk factors in univariate analysis, but only PIM2 remained significant in the multivariate analysis. Discussion: Our Study shows that high survival rates are achievable for children with cancer with critical illness in resource-limited settings with provision of high-quality critical care. Organizational and clinical practice facilitating quality improvement and early identification and management of critical illness may attenuate the impact of known risk factors for mortality in this population.

Noninvasive Ventilation Exposure Prior to Intubation in Pediatric Hematopoietic Cell Transplant Recipients.

BACKGROUND: Noninvasive ventilation (NIV) has become more studied in immunocompromised patients. However, it has not been studied in hematopoietic cell transplantation (HCT) recipients, who have higher mortality and higher pulmonary complication rates than other immunocompromised patients. This population may be prone to negative effects from this treatment modality. The aim of this study was to determine whether NIV use is associated with worse outcomes in this vulnerable patient population. METHODS: A secondary analysis of a retrospective multi-center database was performed. Twelve pediatric ICUs across the United States enrolled HCT subjects from 2009-2014 that were admitted to the pediatric ICU (PICU) with the diagnosis of acute respiratory failure. Subjects exposed to NIV prior to intubation were compared against those not exposed to NIV. Our primary outcome was all-cause mortality at 90 d; secondary outcomes included ventilator-free days (VFD) at 28 d and development of pediatric ARDS. Multivariable logistic and linear regression models were constructed using variables significant on univariable analysis. RESULTS: Two-hundred eleven subjects were included. Of these, 82 (39%) received NIV prior to intubation. Those that received NIV prior to intubation were older (13 vs 6 y, P < .001) and more commonly diagnosed with respiratory distress (90% vs 74%, P = .004). On multivariable analysis, NIV use prior to intubation was associated with a higher PICU mortality (hazard ratio 1.51 [95% CI 1.18-2.28], P = .02) and fewer VFD at 28 d (ß -3.50 [95% CI -6.09 to 0.91], P = .008). Those with NIV exposure prior to intubation also had higher rates of development of pediatric ARDS (95% vs 78%, P = .001). CONCLUSIONS: In this cohort of children post-HCT, NIV use prior to intubation was associated with worse outcomes. The benefits and risks of NIV in this patient population should be carefully evaluated prior to its use, and careful patient selection is crucial for its optimal utilization.

Clinical Decision Support in the PICU: Implications for Design and Evaluation.

OBJECTIVES: To assess the current landscape of clinical decision support (CDS) tools in PICUs in order to identify priority areas of focus in this field. DESIGN: International, quantitative, cross-sectional survey. SETTING: Role-specific, web-based survey administered in November and December 2020. SUBJECTS: Medical directors, bedside nurses, attending physicians, and residents/advanced practice providers at Pediatric Acute Lung Injury and Sepsis Network-affiliated PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 109 respondents from 45 institutions, primarily attending physicians from university-affiliated PICUs in the United States. The most commonly used CDS tools were people-based resources (93% used always or most of the time) and laboratory result highlighting (86%), with order sets, order-based alerts, and other electronic CDS tools also used frequently. The most important goal providers endorsed for CDS tools were a proven impact on patient safety and an evidence base for their use. Negative perceptions of CDS included concerns about diminished critical thinking and the burden of intrusive processes on providers. Routine assessment of existing CDS was rare, with infrequent reported use of observation to assess CDS impact on workflows or measures of individual alert burden. CONCLUSIONS: Although providers share some consensus over CDS utility, we identified specific priority areas of research focus. Consensus across practitioners exists around the importance of evidence-based CDS tools having a proven impact on patient safety. Despite broad presence of CDS tools in PICUs, practitioners continue to view them as intrusive and with concern for diminished critical thinking. Deimplementing ineffective CDS may mitigate this burden, though postimplementation evaluation of CDS is rare.

Candidacy for Extracorporeal Life Support in Children After Hematopoietic Cell Transplantation: A Position Paper From the Pediatric Acute Lung Injury and Sepsis Investigators Network's Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup.

OBJECTIVES: The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients. DATA SOURCES: All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation. STUDY SELECTION: All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems). DATA EXTRACTION: All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions. DATA SYNTHESIS: Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process. CONCLUSIONS: Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT). METHODS: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight](kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk). RESULTS: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74). CONCLUSIONS: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.

Delirium in Children Undergoing Hematopoietic Cell Transplantation: A Multi-Institutional Point Prevalence Study.

Introduction: Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant. Methods: This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record. Results: Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children <5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus). Conclusion: Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period.

Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer.

Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.

Extracorporeal Membrane Oxygenation Candidacy in Pediatric Patients Treated With Hematopoietic Stem Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy: An International Survey.

INTRODUCTION: Pediatric patients who undergo hematopoietic cell transplant (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at high risk for complications leading to organ failure and the need for critical care resources. Extracorporeal membrane oxygenation (ECMO) is a supportive modality that is used for cardiac and respiratory failure refractory to conventional therapies. While the use of ECMO is increasing for patients who receive HCT, candidacy for these patients remains controversial. We therefore surveyed pediatric critical care and HCT providers across North America and Europe to evaluate current provider opinions and decision-making and institutional practices regarding ECMO use for patients treated with HCT or CAR-T. METHODS: An electronic twenty-eight question survey was distributed to pediatric critical care and HCT providers practicing in North America (United States and Canada) and Europe through the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and individual emails. Responses to the survey were recorded in a REDCap® database. RESULTS: Two-hundred and ten participants completed the survey. Of these, 159 (76%) identified themselves as pediatric critical care physicians and 47 (22%) as pediatric HCT physicians or oncologists. The majority (99.5%) of survey respondents stated that they would consider patients treated with HCT or CAR-T therapy as candidates for ECMO support. However, pediatric critical care physicians identified more absolute and relative contraindications for ECMO than non-pediatric critical care physicians. While only 0.5% of respondents reported that they consider HCT as an absolute contraindication for ECMO, 6% of respondents stated that ECMO is contraindicated in HCT patients within their institution and only 23% have an institutional protocol or policy to guide the evaluation for ECMO candidacy of these patients. Almost half (49.1%) of respondents would accept a survival to hospital discharge of 20-30% for pediatric HCT patients requiring ECMO as adequate. CONCLUSIONS: ECMO use for pediatric patients treated with HCT and CAR-T therapy is generally acceptable amongst physicians. However, there are differences in the evaluation and decision-making regarding ECMO candidacy amongst providers across medical specialties and institutions. Therefore, multidisciplinary collaboration is an essential component in establishing practice guidelines and advancing ECMO outcomes for these patients.

Leveraging the effector independent nature of motor imagery when it is paired with physical practice.

While considered analogous to physical practice, the nature of imagery-based skill acquisition-specifically whether or not both effector independent and dependent encoding occurs through motor imagery-is not well understood. Here, motor imagery-based training was applied prior to or after physical practice-based training to probe the nature of imagery-based skill acquisition. Three groups of participants (N = 38) engaged in 10 days of training of a dart throwing task: 5 days of motor imagery prior to physical practice (MIP-PP), motor imagery following physical practice (PP-MIP), or physical practice only (PP-PP). Performance-related outcomes were assessed throughout. Brain activity was measured at three time points using fMRI (pre/mid/post-training; MIP-PP and PP-MIP groups). In contrast with physical practice, motor imagery led to changes in global versus specific aspects of the movement. Following 10 days of training, performance was greater when motor imagery preceded physical practice, although remained inferior to performance resulting from physical practice alone. Greater activation of regions that support effector dependent encoding was observed mid-, but not post-training for the PP-MIP group. Findings indicate that changes driven by motor imagery reflect effector independent encoding, providing new information regarding how motor imagery may be leveraged for skill acquisition.