Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol

Introduction: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. Methods and analysis: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2–5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. Ethics and dissemination: Ethical approval has been obtained from the Children’s Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners.Trial registration numberThe trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as ‘Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study – A Multicentre Prospective Trial’. Trial registration: ACTRN12621000904875

Development of a Quantitative Bead Capture Assay for Soluble IL-7 Receptor Alpha in Human Plasma

IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Rα (CD127) and common γ (CD132) chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. Previous reports showed the usefulness of CD127 as a prognostic marker in viral infections such as HIV, CMV, EBV and HCV. A soluble CD127 (sCD127) is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. Measuring sCD127 is important to define its role and may complement existing markers used in lymphopenic disease management. We describe a new quantitative assay for the measurement of sCD127 in plasma and report sCD127 concentrations in healthy adults.We developed a quantitative bead-based sCD127 capture assay. Polyclonal CD127-specific antibodies were chosen for capture and a biotinylated monoclonal anti-CD127 antibody was selected for detection. The assay can detect native sCD127 and recombinant sCD127 which served as the calibrator. The analytical performance of the assay was characterized and the concentration and stability of plasma sCD127 in healthy adults was determined. The assay's range was 3.2–1000 ng/mL. The concentration of plasma sCD127 was 164±104 ng/mL with over a log variation between subjects. Individual sCD127 concentrations remained stable when measured serially during a period of up to one year.This is the first report on the quantification of plasma sCD127 in a population of healthy adults. Soluble CD127 plasma concentrations remained stable over time in a given individual and sCD127 immunoreactivity was resistant to repeated freeze-thaw cycles. This quantitative sCD127 assay is a valuable tool for defining the potential role of sCD127 in lymphopenic diseases

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients &lt;18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

PVMaT improvements in the manufacturing of the PVI Powergrid{trademark}: Final technical report, 27 October 1997--31 October 1998

Photovoltaics International, LLC (PVI), is improving the manufacturing of the Powergrid{trademark} under the Photovoltaic Manufacturing Technology (PVMaT) program in five basic areas: development of an advanced, state-of-the-art lens extrusion system; development of an advanced, state-of-the-art module side extrusion system; development of a second generation automated receiver assembly station; development of low-cost roll-formed steel panel frame members; and development of an automated module assembly process with low usage of volatile organic compounds and hazardous materials. The results of the program were as follows: (1) Manufacturing improvements have led to dramatic improvements in performance, quality, durability and cost. (2) The first ever ethylene vinyl acetate encapsulation system for photovoltaic concentrators was developed, thereby eliminating volatile organic compounds and hazardous materials in the encapsulation process. (3) An in-house extrusion system was developed that produces the highest quality cell assemblies at low labor cost. (4) An advanced automated cell assembly station was developed that produces quality cell assemblies at low labor cost. (5) Solvents have been eliminated in the module assembly eliminating volatile organic compounds and hazardous materials. (6) Roll formed steel panel frame members have been introduced to production that have dramatically reduced cost. (7) A snap-together module assembly has been developed that provides low-cost field assembly of components and thereby also greatly reduced shipping cost. The Powergrid has the potential to be very low cost in the short term. The PVI PVMaT program should allow PVI to reach the cost goals set by the company. This, in turn, will allow PVI to become a substantial player in the PV market and will allow the DOE goals of increased application of PV to become a reality

Risk Factors for Mortality in Pediatric Postsurgical versus Medical Severe Sepsis

Item does not contain fulltextBACKGROUND: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies regarding sepsis do not differentiate between patients who have had recent surgery and those without. Few data exist regarding the risk factors for poor outcomes in pediatric postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with severe sepsis have unique risk factors for mortality. METHODS: Data were extracted from a secondary analysis of an international point prevalence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from 26 countries. Pediatric patients with severe sepsis were categorized into those who had recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis onset. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: A total of 556 patients were included: 138 with postsurgical and 418 with medical sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comorbidities were independent risk factors for death. In medical sepsis, resource-limited region, hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition, higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors for death. CONCLUSIONS: Pediatric patients with postsurgical sepsis had different risk factors for mortality compared with medical sepsis. This included a higher mortality risk in postsurgical patients presenting to the intensive care unit from the hospital ward. These data suggest an opportunity to develop and test early warning systems specific to pediatric sepsis in the postsurgical population

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality

OBJECTIVES: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. DESIGN: Secondary analysis of a prospective, cross-sectional, point prevalence study. SETTING: International, multicenter PICUs. PATIENTS: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). CONCLUSIONS: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints