For better or worse? Long-term outcome of critical illness in childhood

__Abstract__ The aim of this thesis was to investigate the long-term outcome of critically ill children admitted to the pediatric intensive care unit (PICU) of the Erasmus MC – Sophia Children’s’ Hospital in Rotterdam, the Netherlands. Our main focus was to investigate the long-term health status, health-related quality of life (HR-QoL), emotional and behavioral functioning, and neuropsychological functioning in survivors of cardiac arrest (CA) in childhood. This included a semi-structured interview, physical and neuropsychological examination, and the use of validated, internationally well-known questionnaires with a multi-informant approach. Further, the influence of medical predictor variables, such as the impact of hyperoxia on mortality after CA, and analgesia-sedation on the long-term neuropsychological outcome after a critical illness (specifically meningococcal septic shock) was examined. In the study described in chapter 2 we analyzed the relationship between the partial pressure of arterial oxygen (PaO2) and in-hospital (IH) mortality in children after CA. We compared the conventional cut-off analysis, with the cumulative analysis, a new method in PaO2 analysis. The innovative aspect of this study is that it uses a novel and simple method (area under the curve) to analyze this cumulative PaO2. We found that patients with mild therapeutic hypothermia (MTH) and higher cumulative PaO2 had a lower mortality rate. With the cumulative PaO2 measurement, we could not reproduce the relationship between higher PaO2 and IH-mortality in children after CA as found in various cut-off studies. In chapter 3 we provided a detailed overview of the long-term health status and health-related quality of life (HR-QoL) in survivors of CA in childhood and their parents. After the initial survival another 9% died following PICU discharge. A minority of CA survivors showed long-term neurological impairments, chronic symptoms, and renal impairments. On health status and HR-QoL, parent-reports of CA survivors showed significantly worse outcomes on physical scales and parental impact compared to normative data. On self-reports no significant differences with normative data were found. Surprisingly, parents reported better scores towards their own functioning. Patients’ health status, general health perceptions and physical summary scores were significantly associated with CA-related pre-existing condition. In chapter 4 the results of the long-term emotional and behavioral functioning of CA survivors are presented. Compared to normative data, CA survivors showed significantly more long-term attention problems and somatic complaints, on parents’ and teachers’ reports. On self-reports, significantly less social problems were found. According to parents, children showed more often psychopathological problem behavior. Remarkably, less social problems (self-reports) and no higher levels on anxiety, depression or posttraumatic stress problems were found. Boys, older children, and basic life support were significantly related to worse scores on the scales Internalizing problems, Externalizing problems, Total problems, and subscale Attention problems. In chapter 5 we described the long-term neuropsychological outcomes in children surviving cardiac arrest (CA). CA survivors scored significantly worse on intelligence. On neuropsychological tests, compared with norms, respectively adjusted for IQ, significantly worse scores were found on visual memory, significantly better on verbal memory recognition, and comparable outcomes on visual-motor integration, attention, and executive functioning. On questionnaires, parents reported better executive functioning, but teachers reported more problems in planning/organizing skills. Boys and older age at time of cardiac arrest were significantly related with worse neuropsychological functioning. The study presented in chapter 6 investigates the association between analgesic and sedative drug use during PICU treatment and long-term neuropsychological outcome in children who survived meningococcal septic shock. The use and dose of opioids were significantly associated with poor outcome on full-scale IQ, verbal IQ and verbal IQ subtests (verbal comprehension and vocabulary) and visual attention/executive functioning (Trail Making Test B). After adjusting for patient and disease characteristics (in particular severity of illness), the use of opioids remained a significant predictor on most neuropsychological tests. The use and dose of benzodiazepines were not significantly associated with any neuropsychological test. In chapter 7 we discussed the findings presented in this thesis, put them into perspective and propose recommendations for future studies

Long-term neuropsychological outcomes in children and adolescents after cardiac arrest

Purpose: Research into neuropsychological functioning of survivors of cardiac arrest (CA) in childhood is scarce. We sought to a

Cardiac arrest in infants, children, and adolescents: long-term emotional and behavioral functioning

Very little is known about the psychological consequences of a cardiac arrest (CA) during childhood. Our aim was to assess long-term emotional and behavioral functioning, and its predictors, in survivors of CA in childhood. This long-term follow-up study involved all consecutive infants, children, and adolescents surviving CA in a tertiary-care university children’s hospital between January 2002 and December 2011. Emotional and behavioral functioning was assessed with the Child Behavior Checklist (CBCL), Teacher’s Report Form (TRF), and Youth Self-Report (YSR). Of the eligible 107 CA survivors, 52 patients, parents, and/or teachers filled out online questionnaires. Compared with normative data, parents and teachers reported significantly more attention and somatic problems (age range 6–18 years). Parents also reported more attention problems for age range 1.5–5 years. Twenty-eight percent of the children (n = 14) scored in the psychopathological range (i.e., for age range 1.5–18 years; p < 0.001) according to parent reports. Male gender, older age, and basic life support were significantly related to worse scores on the scales internalizing problems, externalizing problems, and total problems and subscale attention problems. Conclusion: Long-term deficits in attention and somatic complaints were reported. Attention problems after childhood CA can interfere with school performance. Long-term follow-up with neuropsychological assessment should be organized.(Table presented.

The transiting exoplanet community early release science program for JWST

The James Webb Space Telescope (JWST) presents the opportunity to transform our understanding of planets and the origins of life by revealing the atmospheric compositions, structures, and dynamics of transiting exoplanets in unprecedented detail. However, the high-precision, time-series observations required for such investigations have unique technical challenges, and prior experience with other facilities indicates that there will be a steep learning curve when JWST becomes operational. In this paper we describe the science objectives and detailed plans of the Transiting Exoplanet Community Early Release Science (ERS) Program, which is a recently approved program for JWST observations early in Cycle 1. The goal of this project, for which the obtained data will have no exclusive access period, is to accelerate the acquisition and diffusion of technical expertise for transiting exoplanet observations with JWST, while also providing a compelling set of representative datasets that will enable immediate scientific breakthroughs. The Transiting Exoplanet Community ERS Program will exercise the time-series modes of all four JWST instruments that have been identified as the consensus highest priorities, observe the full suite of transiting planet characterization geometries (transits, eclipses, and phase curves), and target planets with host stars that span an illustrative range of brightnesses. The observations in this program were defined through an inclusive and transparent process that had participation from JWST instrument experts and international leaders in transiting exoplanet studies. Community engagement in the project will be centered on a two-phase Data Challenge that culminates with the delivery of planetary spectra, time-series instrument performance reports, and open-source data analysis toolkits in time to inform the agenda for Cycle 2 of the JWST mission

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument.Comment: Full report: 498 pages. Executive Summary: 14 pages. More information about HabEx can be found here: https://www.jpl.nasa.gov/habex

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Association between shockable rhythms and long-term outcome after pediatric out-of-hospital cardiac arrest in Rotterdam, the Netherlands

Introduction: Shockable rhythm following pediatric out-of-hospital cardiac arrest (pOHCA) is consistently associated with hospital and short-term survival. Little is known about the relationship between shockable rhythm and long-term outcomes (&gt;1 year) after pOHCA. The aim was to investigate the association between first documented rhythm and long-term outcomes in a pOHCA cohort over 18 years. Methods: All children aged 1 day–18 years who experienced non-traumatic pOHCA between 2002–2019 and were subsequently admitted to the emergency department (ED) or pediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital were included. Data was abstracted retrospectively from patient files, (ground) ambulance and Helicopter Emergency Medical Service (HEMS) records, and follow-up clinics. Long-term outcome was determined using a Pediatric Cerebral Performance Category (PCPC) score at the longest available follow-up interval through august 2020. The primary outcome measure was survival with favorable neurologic outcome, defined as PCPC 1–2 or no difference between pre- and post-arrest PCPC. The association between first documented rhythm and the primary outcome was calculated in a multivariable regression model. Results: 369 children were admitted, nine children were lost to follow-up. Median age at arrest was age 3.4 (IQR 0.8–9.9) years, 63% were male and 14% had a shockable rhythm (66% non-shockable, 20% unknown or return of spontaneous circulation (ROSC) before emergency medical service (EMS) arrival). In adolescents (aged 12–18 years), 39% had shockable rhythm. 142 (39%) of children survived to hospital discharge. On median follow-up interval of 25 months (IQR 5.1–49.6), 115/142 (81%) of hospital survivors had favorable neurologic outcome. In multivariable analysis, shockable rhythm was associated with survival with favorable long-term neurologic outcome (OR 8.9 [95%CI 3.1–25.9]). Conclusion: In children with pOHCA admitted to ED or PICU shockable rhythm had significantly higher odds of survival with long-term favorable neurologic outcome compared to non-shockable rhythm. Survival to hospital discharge after pOHCA was 39% over the 18-year study period. Of survivors to discharge, 81% had favorable long-term (median 25 months, IQR 5.1–49.6) neurologic outcome. Efforts for improving outcome of pOHCA should focus on early recognition and treatment of shockable pOHCA at scene.</p