Challenges in institutional ethical review process and approval for international multicenter clinical studies in lower and middle-income countries: the case of PARITY study.

Background: One of the greatest challenges to conducting multicenter research studies in low and middle-income countries (LMICs) is the heterogeneity in regulatory processes across sites. Previous studies have reported variations in requirements with a lack of standardization in the Institutional Review Board (IRB) processes between centers, imposing barriers for approval, participation, and development of multicenter research.

Objectives: To describe the regulatory process, variability and challenges faced by pediatric researchers in LMICs during the IRB process of an international multicenter observational point prevalence study (Global PARITY).

Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients.

Objectives: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

Design: Prospective population pharmacokinetic study of vancomycin.

Setting: Critically ill patients in quaternary care PICUs.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking.

A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

Background: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies.

Remote Didactic Education Effectively Increases Cardiac Critical Care Nursing Staff Knowledge in Low-Resource Settings.

While progress has been made to decrease mortality in children under age five, there continues to be a need for improvement in the treatment of children with congenital heart disease. Many of these patients require surgical correction and live in areas without the expertise of surgical teams. Research has shown that appropriate training is critical to ensure the best clinical outcomes.

Capacity Building in Pediatric Critical Care-Global Health Research and Education: The Blantyre Experience.

Pediatric critical care medicine (PCCM), as it is practiced in high-income countries, is focused on specialized medical care for the most vulnerable pediatric patient populations. However, best practices for provision of that care globally are lacking. Thus, PCCM research and education programming can potentially fill significant knowledge gaps by facilitating the development of evidence-based clinical guidelines that reduce child mortality on a global scale.

Development of a primate model to evaluate the effects of ketamine and surgical stress on the neonatal brain.

With advances in pediatric and obstetric surgery, pediatric patients are subject to complex procedures under general anesthesia. The effects of anesthetic exposure on the developing brain may be confounded by several factors including pre-existing disorders and surgery-induced stress. Ketamine, a noncompetitive -methyl-d-aspartate (NMDA) receptor antagonist, is routinely used as a pediatric general anesthetic.

Evaluation of the Resources and Inequities Among Pediatric Critical Care Facilities in Pakistan.

Objectives: To evaluate nationwide pediatric critical care facilities and resources in Pakistan.

Design: Cross-sectional observational study.

Setting: Accredited pediatric training facilities in Pakistan.

Expanding current guidelines for management of COVID-19 focusing on low- and middle-income countries.

Within a short time, Coronavirus disease 2019 (COVID-19) has evolved into a pandemic spreading at a speed and scale that has been able to overwhelm even the most advanced health care systems quickly. Multiple guidelines published by organizations such as the WHO and US' CDC address the response to COVID-19 at the international, national, and local levels. Although these guidelines are meant to be globally accessible, implementing them is a challenge given the variability in the health care systems worldwide between low- and middleincome countries (LMIC) and high-income countries and even amongst different regions within each LMIC.

The Burden of Critical Illness in Hospitalized Children in Low- and Middle-Income Countries: Protocol for a Systematic Review and Meta-Analysis.

Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.

We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons.

Global PARITY: Study Design for a Multi-Centered, International Point Prevalence Study to Estimate the Burden of Pediatric Acute Critical Illness in Resource-Limited Settings.

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally.

Application of Nonhuman Primate Models in the Studies of Pediatric Anesthesia Neurotoxicity.

Numerous animal models have been used to study developmental neurotoxicity associated with short-term or prolonged exposure of common general anesthetics at clinically relevant concentrations. Pediatric anesthesia models using the nonhuman primate (NHP) may more accurately reflect the human condition because of their phylogenetic similarity to humans with regard to reproduction, development, neuroanatomy, and cognition. Although they are not as widely used as other animal models, the contribution of NHP models in the study of anesthetic-induced developmental neurotoxicity has been essential.

Outcomes of Pediatric Patients With Sepsis Related to and Methicillin-Resistant Infections Requiring Extracorporeal Life Support: An ELSO Database Study.

Extracorporeal membrane oxygenation (ECMO) is increasingly utilized for pediatric sepsis unresponsive to steroids and inotropic support. Outcomes of children with sepsis are influenced by the type of pathogen causing their illness. To determine if the outcomes of children with sepsis receiving ECMO differed according to microbial sensitivity (Methicillin-resistant [MRSA] vs.

Bedside Rounds in Intensive Care Units during the COVID-19 Pandemic and Beyond.

A survey-based pilot study was performed to examine the feasibility of videoconferencing to facilitate multidisciplinary rounds following the initiation of strict isolation and social distancing policies in a pediatric intensive care unit (PICU). The use of a mobile workstation was implemented as the central hub for rounding at the bedside by the attending physicians, while other members of the multidisciplinary and multispecialty team joined rounds from other locations with maintaining appropriate social distance. Fifty-eight staff members who participated in videoconferencing rounds completed the postimplementation survey.

The Impact of Dedicated Cardiac Intensive Care Units on Outcomes in Pediatric Cardiac Surgery: A Virtual Pediatric Systems Database Analysis.

Care of children undergoing cardiac surgery occurs in dedicated cardiac intensive care units (CICU) or mixed intensive care units. In this article, we analyzed data from Virtual Pediatric Systems (VPS, LLC) database (2009-2014) for children < 18 years of age undergoing cardiac surgery, classified according to Society of Thoracic Surgery-European Association of Cardiothoracic Surgery (STS-EACTS) risk category. We had 25,052 (52%) patients in 53 mixed units (mortality rate, 2.

Understanding the Role of Pharmacometrics-Based Clinical Decision Support Systems in Pediatric Patient Management: A Case Study Using Lyv Software.

Pharmacometrics could play a key role in shifting pediatric pharmacotherapy from dosing for an average patient to individualizing dosing. Clinicians can have these quantitative tools at their disposal without requiring significant training through the development of clinical decision support systems with easy-to-use interfaces that have a back-end analysis engine or pharmacometric model that uses extensive electronic health record data to predict an individualized dose for each patient. There has been increased development of these clinical decision support systems recently, and for these tools to make the proper breakthrough into clinical practice, it is of utmost importance to perform rigorous testing to ensure adequate predictive performance.

Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation.

Background: Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO heart solution (XHS) based cardioplegia.

Multisystem inflammatory syndrome (MIS-C) in Pakistani children: A description of the phenotypes and comparison with historical cohorts of children with Kawasaki disease and myocarditis.

Objectives: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts.

Methods: All children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C.

Post-operative course of pulmonary artery pressure after complete atrioventricular canal defect repair.

Unlabelled: Complete atrioventricular canal defect is a CHD associated with intra-cardiac shunting of blood, which can lead to irreversible changes in pulmonary vascular resistance and pulmonary artery hypertension if unrepaired. Patients with Trisomy 21 are at risk for early development of pulmonary artery hypertension if left uncorrected.1,2.

Outcomes of Children With Firearm Injuries Admitted to the PICU in the United States.

Objectives: Firearm-related injury is the second leading cause of injury and death for children 1-18 years old in United States. The objective of our study was to analyze the outcomes of children admitted to the PICU with firearm injuries.

Design: Retrospective study.

Reduction in paediatric intensive care admissions during COVID-19 lockdown in Maryland, USA.

As a public health measure during the COVID-19 pandemic, governments around the world instituted a variety of interventions to 'flatten the curve'. The government of Maryland instituted similar measures. We observed a striking decline in paediatric intensive care unit (PICU) admissions during that period, mostly due to a decease in respiratory infections.

Botulism in the Pediatric Intensive Care Units in the United States: Interrogating a National Database.

Botulism in children can have severe complications necessitating intensive care. The current literature lacks data of children with botulism requiring critical care. We aim to describe the outcomes of pediatric botulism in the pediatric intensive care unit (PICU).

Comparison of Antithrombin III Products in Pediatric Patients Receiving Extracorporeal Membrane Oxygenation.

The study investigated the safety and efficacy of two antithrombin III (ATIII) products in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) by performing a retrospective analysis of patients who received either recombinant ATIII (rATIII) or human-derived ATIII (hATIII). Twenty-two patients were included in the study from January 2014 to September 2015 and all received unfractionated heparin (UFH) as anticoagulation during ECMO. In total, 86 doses of ATIII were included in the analysis in which 37 doses (43%) were rATIII and 49 doses (57%) were hATIII.