Evaluation of an aPTT guided versus a multimodal heparin monitoring approach in patients on extra corporeal membrane oxygenation: A retrospective cohort study.

INTRODUCTION: Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated. METHODS: This is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements. RESULTS: In total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9). DISCUSSION: The incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.

Lifelong development in medicine: a thematic analysis of coaching goals throughout medical careers.

OBJECTIVES: Healthcare grapples with staff shortages and rising burnout rates for medical students, residents and specialists. To prioritise both their well-being and the delivery of high-quality patient care, it becomes imperative to deepen our understanding of physicians' developmental aims and needs. Our first aim is, therefore, to gain comprehensive insights into the specific developmental aims physicians prioritise by examining the coaching goals they set at the beginning of coaching. Since physicians face distinct roles as they advance in their careers, our second aim is to highlight similarities and differences in developmental aims and needs among individuals at various medical career stages. DESIGN: We conducted a qualitative analysis of 2571 coaching goals. We performed an inductive thematic analysis to code one-half of coaching goals and a codebook thematic analysis for the other half. Our interpretation of the findings was grounded in a critical realist approach. SETTING: Sixteen hospitals in the Netherlands. PARTICIPANTS: A total of 341 medical clerkship students, 336 medical residents, 122 early-career specialists, 82 mid-career specialists and 57 late-career specialists provided their coaching goals at the start of coaching. RESULTS: The findings revealed that coachees commonly set goals about their career and future, current job and tasks, interpersonal work relations, self-insight and development, health and well-being, nonwork aspects and the coaching process. Furthermore, the findings illustrate how the diversity of coaching goals increases as physicians advance in their careers. CONCLUSIONS: Our findings underscore the significance of recognising distinct challenges at various career stages and the necessity for tailoring holistic support for physicians. This insight holds great relevance for healthcare organisations, enabling them to better align system interventions with physicians' needs and enhance support. Moreover, our classification of coaching goals serves as a valuable foundation for future research, facilitating a deeper exploration of how these goals influence coaching outcomes.

An 18-year, single centre, retrospective study of long-term neurological outcomes in paediatric submersion-related cardiac arrests.

Aim: Investigate long-term outcome in paediatric submersion-related cardiac arrests (CA). Methods: Children (age one day-17 years) were included if admitted to the Erasmus MC Sophia Children's Hospital, after drowning with CA, between 2002 and 2019. Primary outcome was survival with favourable neurological outcome, defined as a Paediatric Cerebral Performance Category (PCPC) score of 1-3 at longest available follow-up. Secondary outcome were age-appropriate neuropsychological assessments at longest available follow-up. Results: Upon hospital admission, 99 children were included (median age at time of CA 3.2 years [IQR 2.0-5.9] and 65% males). Forty children died in-hospital (no return of circulation (45%) or withdrawal of life sustaining therapies (55%)) and 4 children deceased after hospital discharge due to complications following the drowning-incident. Among survivors, with a median follow-up of 2.3 years [IQR 0.2-5.5], 47 children had favourable neurological outcome (i.e. PCPC 1-3) and 8 children unfavourable (unfavourable outcome group total n = 52, i.e. PCPC 4-5 or deceased). Twenty-six (47%) children participated in a neuropsychological assessment (median follow-up 4.0 years [IQR 2.3-8.7]). Compared with normative test data, participants obtained worse general (p = 0.008) and performance (p = 0.003) intelligence scores, processing speed (p = 0.002) and visual motor integration scores (p = 0.0012). Conclusions: Although overall outcome in survivors was favourable at longest available follow-up, significant deficits in neuropsychological assessments were found. This study underlines the need for a standardized long term follow-up program as standard of care in paediatric drowning with CA.

Nasopharyngeal microbiota in children is associated with severe asthma exacerbations.

BACKGROUND: The respiratory microbiome has been associated with the etiology and disease course of asthma. OBJECTIVE: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection. METHODS: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 6 years (n = 87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n = 182). The nasopharyngeal microbiota was characterized by 16S-rRNA-gene sequencing. RESULTS: Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R2 = 1.9%; P < .001). We observed significantly higher abundance of Staphylococcus and "oral" taxa, including Neisseria, Veillonella, and Streptococcus spp. and a lower abundance of Dolosigranulum pigrum, Corynebacterium, and Moraxella spp. (MaAsLin2; q < 0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2, P = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection. CONCLUSIONS: Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and "oral" microbes and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and require further investigations.

When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?

AIMS: Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. METHODS: We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of GFRbirth (GFR at birth), and an Emax model dependent on PNA (with GFRmax, PNA50 (PNA at which half of GFR max is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. RESULT: In the GFR model, GFRbirth varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for PNA50, and current weight for GFRmax. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. CONCLUSIONS: GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age.

An electroencephalography-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children.

STUDY OBJECTIVES: Although sleep is frequently disrupted in the pediatric intensive care unit, it is currently not possible to perform real-time sleep monitoring at the bedside. In this study, spectral band powers of electroencephalography data are used to derive a simple index for sleep classification. METHODS: Retrospective study at Erasmus MC Sophia Children's Hospital, using hospital-based polysomnography recordings obtained in non-critically ill children between 2017 and 2021. Six age categories were defined: 6-12 months, 1-3 years, 3-5 years, 5-9 years, 9-13 years, and 13-18 years. Candidate index measures were derived by calculating spectral band powers in different frequent frequency bands of smoothed electroencephalography. With the best performing index, sleep classification models were developed for two, three, and four states via decision tree and five-fold nested cross-validation. Model performance was assessed across age categories and electroencephalography channels. RESULTS: In total 90 patients with polysomnography were included, with a mean (standard deviation) recording length of 10.3 (1.1) hours. The best performance was obtained with the gamma to delta spectral power ratio of the F4-A1 and F3-A1 channels with smoothing. Balanced accuracy was 0.88, 0.74, and 0.57 for two-, three-, and four-state classification. Across age categories, balanced accuracy ranged between 0.83 and 0.92 and 0.72 and 0.77 for two- and three-state classification, respectively. CONCLUSIONS: We propose an interpretable and generalizable sleep index derived from single-channel electroencephalography for automated sleep monitoring at the bedside in non-critically ill children ages 6 months to 18 years, with good performance for two- and three-state classification. CITATION: van Twist E, Hiemstra FW, Cramer ABG, et al. An electroencephalography-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children. J Clin Sleep Med. 2024;20(3):389-397.

Career coach preferences of medical students: coaching specialist or specialistic coach?

BACKGROUND: Medical students' demand for career coaching is growing. However, little is known about what type of career coach they prefer. Using the Warmth-Competence Framework, we investigated if and why medical students prefer physician coaches compared to career psychologist coaches. We also examined whether students' coach choice related to coaches' amount of experience with medical students. METHODS: In a two-by-two between participants vignette study (n = 147), we manipulated coach occupational background (physician vs. psychologist) and experience with coaching medical students (limited vs. considerable). Participants read one coach description, rated the likelihood that they would choose the coach, and rated the coach on dimensions of warmth and competence. RESULTS: Students who evaluated a physician career coach were more likely to choose the coach than students who evaluated a psychologist career coach. Students expected that a physician career coach would better understand their situation and be better able to provide career information, while they expected a psychologist career coach to have better conversation skills, all of which were relevant to choosing a coach. Coaches' experience with coaching medical students was unrelated to students' coach choice and their assessment of the coach's warmth and competence. CONCLUSIONS: Our findings highlight the relevance of coaches' occupational background and have implications for the implementation of career coach interventions. Medical schools could help students choose a career coach by providing information about the coach qualities that students value. Future studies could investigate whether career coaches with different occupational backgrounds differ in coach behaviors and coaching effectiveness.

Diversity of Parent Emotions and Physician Responses During End-of-Life Conversations.

BACKGROUND AND OBJECTIVES: To provide support to parents of critically ill children, it is important that physicians adequately respond to parents' emotions. In this study, we investigated emotions expressed by parents, physicians' responses to these expressions, and parents' emotions after the physicians' responses in conversations in which crucial decisions regarding the child's life-sustaining treatment had to be made. METHODS: Forty-nine audio-recorded conversations between parents of 12 critically ill children and physicians working in the neonatal and pediatric intensive care units of 3 Dutch university medical centers were coded and analyzed by using a qualitative inductive approach. RESULTS: Forty-six physicians and 22 parents of 12 children participated. In all 49 conversations, parents expressed a broad range of emotions, often intertwining, including anxiety, anger, devotion, grief, relief, hope, and guilt. Both implicit and explicit expressions of anxiety were prevalent. Physicians predominantly responded to parental emotions with cognition-oriented approaches, thereby limiting opportunities for parents. This appeared to intensify parents' expressions of anger and protectiveness, although their anxiety remained under the surface. In response to more tangible emotional expressions, for instance, grief when the child's death was imminent, physicians provided parents helpful support in both affect- and cognition-oriented ways. CONCLUSIONS: Our findings illustrate the diversity of emotions expressed by parents during end-of-life conversations. Moreover, they offer insight into the more and less helpful ways in which physicians may respond to these emotions. More training is needed to help physicians in recognizing parents' emotions, particularly implicit expressions of anxiety, and to choose helpful combinations of responses.

Acquired von Willebrand disease in children undergoing extracorporeal membrane oxygenation: a prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for children with severe cardiac and/or pulmonary failure. The incidence of bleeding complications during ECMO support is high. Acquired von Willebrand disease (AVWD) might contribute to the development of bleeding complications. OBJECTIVE: To study the incidence and longitudinal profile of AVWD during the first 14 days of ECMO support in children and to investigate the association between AVWD and bleeding complications. METHODS: This prospective observational study included pediatric patients (0-17 years) receiving ECMO. Blood was sampled prior to and after ECMO start, daily and 12 to 24 hours after stopping ECMO. von Willebrand factor (VWF) parameters and multimer patterns were determined. Clinical data were collected for each patient. AVWD was defined as loss of high-molecular weight multimers (ie, decreased compared with baseline) or a VWF:collagen binding/VWF: antigen (Ag) ratio or VWF:activity/VWF:Ag ratio below 0.7. RESULTS: All of 50 (100%) patients developed AVWD during ECMO. The VWF:collagen binding /VWF:Ag ratio, VWF:activity/VWF:Ag ratio, and high-molecular weight multimers decreased during the initial days and recovered to baseline level within 24 hours after stopping ECMO. The incidence and longitudinal profile of AVWD were similar in patients with and without major bleeding complications. CONCLUSION: Children receiving ECMO support commonly develop AVWD. AVWD develops rapidly after ECMO initiation and recovers quickly after ECMO cessation. Importantly, AVWD appears to be independent of major bleeding.

Characteristics of Long-Stay Patients in a PICU and Healthcare Resource Utilization After Discharge.

OBJECTIVES: To examine the characteristics of long-stay patients (LSPs) admitted to a PICU and to investigate discharge characteristics of medical complexity among discharged LSP. DESIGN: We performed a retrospective cohort study where clinical data were collected on all children admitted to our PICU between July 1, 2017, and January 1, 2020. SETTING: A single-center study based at Erasmus MC Sophia Children's Hospital, a level III interdisciplinary PICU in The Netherlands, providing all pediatric and surgical subspecialties. PATIENTS: LSP was defined as those admitted for at least 28 consecutive days. INTERVENTIONS: None. MEASUREMENTS: Length of PICU stay, diagnosis at admission, length of mechanical ventilation, need for extracorporeal membrane oxygenation, mortality, discharge location after PICU and hospital admission, medical technical support, medication use, and involvement of allied healthcare professionals after hospital discharge. MAIN RESULTS: LSP represented a small proportion of total PICU patients (108 patients; 3.2%) but consumed 33% of the total admission days, 47% of all days on extracorporeal membrane oxygenation, and 38% of all days on mechanical ventilation. After discharge, most LSP could be classified as children with medical complexity (CMC) (76%); all patients received discharge medications (median 5.5; range 2-19), most patients suffered from a chronic disease (89%), leaving the hospital with one or more technological devices (82%) and required allied healthcare professional involvement after discharge (93%). CONCLUSIONS: LSP consumes a considerable amount of resources in the PICU and its impact extends beyond the point of PICU discharge since the majority are CMC. This indicates complex care needs at home, high family needs, and a high burden on the healthcare system across hospital borders.

Hospital-to-home transitions for children with medical complexity: part 2-a core outcome set.

Appropriate outcome measures as part of high-quality intervention trials are critical to advancing hospital-to-home transitions for Children with Medical Complexity (CMC). Our aim was to conduct a Delphi study and focus groups to identify a Core Outcome Set (COS) that healthcare professionals and parents consider essential outcomes for future intervention research. The development process consisted of two phases: (1) a three-round Delphi study in which different professionals rated outcomes, previously described in a systematic review, for inclusion in the COS and (2) focus groups with parents of CMC to validate the results of the Delphi study. Forty-five professionals participated in the Delphi study. The response rates were 55%, 57%, and 58% in the three rounds, respectively. In addition to the 24 outcomes from the literature, the participants suggested 12 additional outcomes. The Delphi rounds resulted in the following core outcomes: (1) disease management, (2) child's quality of life, and (3) impact on the life of families. Two focus groups with seven parents highlighted another core outcome: (4) self-efficacy of parents.   Conclusion: An evidence-informed COS has been developed based on consensus among healthcare professionals and parents. These core outcomes could facilitate standard reporting in future CMC hospital to home transition research. This study facilitated the next step of COS development: selecting the appropriate measurement instruments for every outcome. What is Known: • Hospital-to-home transition for Children with Medical Complexity is a challenging process. • The use of core outcome sets could improve the quality and consistency of research reporting, ultimately leading to better outcomes for children and families. What is New: • The Core Outcome Set for transitional care for Children with Medical Complexity includes four outcomes: disease management, children's quality of life, impact on the life of families, and self-efficacy of parents.

Bacteria in Extracorporeal Membrane Oxygenation Circuit Clots of a Patient With Persistent Bacteremia: A Case Report.

A neonate with pulmonary hypertension was supported with extracorporeal membrane oxygenation (ECMO). During ECMO support, the patient developed Enterococcus faecalis bacteremia, treated with targeted antibiotics. Despite the maximum dose of antibiotics, routine blood cultures remained positive throughout the ECMO treatment. A circuit change was performed due to buildup of thrombotic material and disseminated intravascular coagulation (DIC) inside the circuit. Thrombus formation was more extensive in the first than the second circuit. Gram-positive diplococci were present in all initial circuit clots and gram-positive masses surrounded by fibrin were found inside thrombi of the second circuit. Scanning electron microscopy (SEM) revealed a dense fibrin network with embedded red blood cells and bacteria in the first circuit. In the second circuit, SEM analysis revealed scattered micro thrombi. Polymerase chain reaction for identification of bacteria in the thrombus of the first circuit showed the same bacteria as found in blood cultures and did not achieve a sufficient signal in the second circuit. This case report shows that bacteria can nestle in thrombi of an ECMO circuit and that there is a rationale for a circuit change in a patient with persistent positive blood cultures and DIC.

A Population Pharmacokinetic Model of Pentobarbital for Children with Status Epilepticus and Severe Traumatic Brain Injury.

BACKGROUND: Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI). OBJECTIVES: To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations. METHODS: Develop a PopPK model with non-linear mixed-effects modelling (NONMEM®) with retrospective data (n = 36; median age 1.3 years; median weight 10 kg; 178 blood samples) treated with continuous intravenous pentobarbital. An independent dataset was used for external validation (n = 9). Dosing simulations with the validated model evaluated dosing regimens. RESULTS: A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (Vd; 1) captured data well. Typical CL and Vd values were 3.59 L/70 kg/h and 142 L/70 kg, respectively. Elevated creatinine and C-reactive protein (CRP) levels significantly correlated to decreased CL, explaining 84% of inter-patient variability, and were incorporated in the final model. External validation using stratified visual predictive checks showed good results. Simulations demonstrated patients with elevated serum creatinine and CRP failed to achieve steady state yet progressed to toxic levels with current dosing regimens. CONCLUSIONS: The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.

Physician exhaustion and work engagement during the COVID-19 pandemic: A longitudinal survey into the role of resources and support interventions.

BACKGROUND: Physicians increasingly show symptoms of burnout due to the high job demands they face, posing a risk for the quality and safety of care. Job and personal resources as well as support interventions may function as protective factors when demands are high, specifically in times of crisis such as the COVID-19 pandemic. Based on the Job Demands-Resources theory, this longitudinal study investigated how monthly fluctuations in job demands and job and personal resources relate to exhaustion and work engagement and how support interventions are associated with these outcomes over time. METHODS: A longitudinal survey consisting of eight monthly measures in the period 2020-2021, completed by medical specialists and residents in the Netherlands. We used validated questionnaires to assess job demands (i.e., workload), job resources (e.g., job control), personal resources (e.g., psychological capital), emotional exhaustion, and work engagement. Additionally, we measured the use of specific support interventions (e.g., professional support). Multilevel modeling and longitudinal growth curve modeling were used to analyze the data. RESULTS: 378 medical specialists and residents were included in the analysis (response rate: 79.08%). Workload was associated with exhaustion (γ = .383, p < .001). All job resources, as well as the personal resources psychological capital and self-judgement were associated with work engagement (γs ranging from -.093 to .345, all ps < .05). Job control and psychological capital attenuated the workload-exhaustion relationship while positive feedback and peer support strengthened it (all ps < .05). The use of professional support interventions (from a mental health expert or coach) was related to higher work engagement (estimate = .168, p = .032) over time. Participation in organized supportive group meetings was associated with higher exhaustion over time (estimate = .274, p = .006). CONCLUSIONS: Job and personal resources can safeguard work engagement and mitigate the risk of emotional exhaustion. Professional support programs are associated with higher work engagement over time, whereas organized group support meetings are associated with higher exhaustion. Our results stress the importance of professional individual-level interventions to counteract a loss of work engagement in times of crisis.

Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Withdrawal of Life-Sustaining Therapies in Children With Severe Traumatic Brain Injury.

Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life-sustaining therapies (WLST). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary, and dilemmas regarding WLST persist, which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥1 year post-sTBI. This retrospective, single center observational study included patients <18 years admitted to the pediatric intensive care unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging, and electroencephalogram data were reviewed. Multi-disciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level, and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; interquartile range [IQR] 5.0-14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days (IQR 3-8), 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (5/16), WLST due to poor neurological prognosis (WLST_neuro, 11/16). Significant differences (p < 0.001) between survivors and non-survivors: first GCS score, first pupillary reaction and first lactate, Injury Severity Score, pre-hospital cardiopulmonary resuscitation, and Rotterdam CT (computed tomography) score. WLST_neuro decision timing ranged from 0 to 31 days (median 2 days, IQR 0-5). WLST_neuro decision (n = 11) was based on neurologic examination (100%), brain imaging (100%) and refractory intracranial hypertension (5/11; 45%). WLST discussions were multi-disciplinary with 100% agreement. Immediate agreement between medical team and caregivers was 81%. The majority (42/62, 68%) of survivors were poor outcome (PCPC score 3 to 5) at PICU discharge, of which 12 (19%) in a vegetative state. One year post-injury, no patients were in a vegetative state and the median PCPC score had improved to 2 (IQR 2-3). No patients died after PICU discharge. Twenty percent of survivors could not attend school 2 years post-injury. Survivors requiring an adjusted educational level increased to 45% within this timeframe. Chronic complaints were headache, behavioral problems, and sleeping problems. In conclusion, two-thirds of sTBI PICU mortality was secondary to WLST_neuro and occurred early post-injury. Median survivor PCPC score improved from 4 to 2 with no vegetative patients 1 year post-sTBI. Our findings show the WLST decision process was multi-disciplinary and guided by specific clinical features at presentation, clinical course, and (serial) neurological diagnostic modalities, of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.

The Dutch national paediatric heart transplantation programme: outcomes during a 23-year period.

BACKGROUND: Since 1998, there has been a national programme for paediatric heart transplantations (HT) in the Netherlands. In this study, we investigated waiting list mortality, survival post-HT, the incidence of common complications, and the patients' functional status during follow-up. METHODS: All children listed for HT from 1998 until October 2020 were included. Follow-up lasted until 1 January 2021. Data were collected from the patient charts. Survival, post-operative complications as well as the functional status (Karnofsky/Lansky scale) at the end of follow-up were measured. RESULTS: In total, 87 patients were listed for HT, of whom 19 (22%) died while on the waiting list. Four patients were removed from the waiting list and 64 (74%) underwent transplantation. Median recipient age at HT was 12.0 (IQR 7.2-14.4) years old; 55% were female. One-, 5­, and 10-year survival post-HT was 97%, 95%, and 88%, respectively. Common transplant-related complications were rejections (50%), Epstein-Barr virus infections (31%), cytomegalovirus infections (25%), post-transplant lymphoproliferative disease (13%), and cardiac allograft vasculopathy (13%). The median functional score (Karnofsky/Lansky scale) was 100 (IQR 90-100). CONCLUSION: Children who undergo HT have an excellent survival rate up to 10 years post-HT. Even though complications post-HT are common, the functional status of most patients is excellent. Waiting list mortality is high, demonstrating that donor availability for this vulnerable patient group remains a major limitation for further improvement of outcome.

Factors XI and XII in extracorporeal membrane oxygenation: longitudinal profile in children.

Background: Extracorporeal membrane oxygenation (ECMO) is used in children with cardiopulmonary failure. While the majority of ECMO centers use unfractionated heparin, other anticoagulants, including factor XI and factor XII inhibitors are emerging, which may prove suitable for ECMO patients. However, before these anticoagulants can be applied in these patients, baseline data of FXI and FXII changes need to be acquired. Objectives: This study aimed to describe the longitudinal profile of FXI and FXII antigenic levels and function before, during, and after ECMO in children. Methods: This is a prospective observational study in neonatal and pediatric patients with ECMO (<18 years). All patients with venoarterial ECMO and with sufficient plasma volume collected before ECMO, on day 1 and day 3, and 24 hours postdecannulation were included. Antigenic levels and functional activity of FXI and FXII were determined in these samples. Longitudinal profiles of these values were created using a linear mixed model. Results: Sixteen patients were included in this study. Mean FXI and FXII antigenic levels (U/mL) changed from 7.9 and 53.2 before ECMO to 6.0 and 34.5 on day 3 and they recovered to 8.8 and 39.4, respectively, after stopping ECMO. Function (%) of FXI and FXII decreased from 59.1 and 59.0 to 49.0 and 50.7 on day 3 and recovered to 66.0 and 54.4, respectively. Conclusion: This study provides the first insights into changes of the contact pathway in children undergoing ECMO. FXI and FXII antigen and function change during ECMO. Results from this study can be used as starting point for future contact pathway anticoagulant studies in pediatric patients with ECMO.

Medical students' career decision-making stress during clinical clerkships.

OBJECTIVES: Many medical students experience career decision-making stress in the final phase of training. Yet, the factors that induce or reduce career decision-making stress and how progression in their clerkships relates to these factors are unknown. This knowledge gap limits the possibilities for medical schools to develop and implement interventions targeting students' career decision-making stress. This study explores content, process, and context factors that may affect career decision-making stress. METHODS: Using cross-sectional survey data from medical master students (n = 507), we assessed content (future work self), process (choice irreversibility, time pressure, career decision-making self-efficacy), and context (supervisory support, medical school support, study load, competition) factors and their relationships with career decision-making stress. The hypothesized relationships were tested with structural equation modelling. RESULTS: A clearer future work self and higher career decision self-efficacy were associated with lower career decision-making stress, while experienced time pressure, competition, and study load were associated with higher career decision-making stress. Choice-irreversibility beliefs, supervisory support, and medical school support were unrelated to career decision-making stress. As students' clerkships progressed, they gained a clearer future work self, but also experienced more time pressure. DISCUSSION: Clinical clerkships help students to form a clearer future work self, which can diminish career decision-making stress. Yet, students also experience more time pressure as the period of clerkships lengthens, which can increase career decision-making stress. A school climate of high competition and study load seems to foster career decision-making stress, while school support hardly seems effective in diminishing this stress.