Five-Year Survival Analysis and Causes of Late Deaths of Infants Admitted to the Tertiary Newborn Intensive Care in Latvia.

Background and Objectives: Studies on long-term survival following admission to neonatal intensive care units (NICUs) are scarce. The aim of this study was to analyse the epidemiology, five-year survival, and causes of late death of infants admitted to the only tertiary NICU in Latvia. Materials and Methods: The study population included all newborns admitted to the Children's Clinical University Hospital (CCUH) NICU from 1 January 2013 to 31 December 2017. The unique national identity numbers from the infants or their mothers were used to link the CCUH electronic medical records to the Medical Birth Register and the Database of Causes of Death of Inhabitants of Latvia maintained by The Centre for Disease Prevention and Control of Latvia. Results: During the study period, a total of 2022 patients were treated in the tertiary NICU. The average admission rate was 18.9 per 1000 live births per year. One hundred and four patients (5.1%) died in the tertiary NICU before hospital discharge. A total of 131 (6.5%) patients from the study cohort died before 12 months of age and 143 (7.1%) before 5 years of age. Patients with any degree of prematurity had a lower five-year mortality (0.9%, 9 out of 994 discharged alive) than term infants (3.2%, 30 out of 924 discharged alive; p < 0.001). Of the 39 patients who died after discharge from the NICU, the most common causes of death were congenital heart disease 35.9% (n = 14), multiple congenital malformations and chromosomal abnormalities 17.9% (n = 7), cerebral palsy 10.3% (n = 4), and viral infections 7.7% (n = 3). Conclusions: We observed increased mortality up to five years following NICU admission in both premature and term infants. These findings will help to guide the NICU follow-up programme.

Pediatric Readiness in the Emergency Department and Its Association With Patient Outcomes in Critical Care: A Prospective Cohort Study.

OBJECTIVES: Pediatric mortality in Latvia remains one of the highest among Europe. The purpose of this study was to assess the quality of pediatric acute care and pediatric readiness and determine their association with patient outcomes using a patient registry. DESIGN: This was a prospective cohort study. Pediatric readiness was measured using the weighted pediatric readiness score based on a 100-point scale. The processes of care were measured using in situ simulations to generate a composite quality score. Clinical outcome data-including PICU and hospital length of stay as well as 6-month mortality-were collected from the Pediatric Intensive Care Audit Network registry. The associations between composite quality score and weighted pediatric readiness score on patient outcomes were explored with mixed-effects regressions. SETTING: This study was conducted in all Latvian Emergency Departments and in the national PICU. PATIENTS: All patients who were transferred into the national PICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All (16/16) Latvian Emergency Departments participated with a mean composite quality score of 35.3 of 100 and a median weighted pediatric readiness score of 31 of 100. A total of 254 patients were included in the study and followed up for a mean of 436 days, of which nine died (3.5%). Higher weighted pediatric readiness score was associated significantly with lower length of stay in both the PICU and hospital (adjusted ß, -0.06; p = 0.021 and -0.36; p = 0.011, respectively) and lower 6-month mortality (adjusted odds ratio, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: These data provide a national assessment of pediatric emergency care in a European country. Pediatric readiness in the emergency department was associated with patient outcomes in this population of pediatric patients transferred to the national PICU.

Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker.

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as "life-threatening organ dysfunction due to a dysregulated host response to infection". In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.

Enteral Feeding Practices in Infants With Congenital Heart Disease Across European PICUs: A European Society of Pediatric and Neonatal Intensive Care Survey.

OBJECTIVES: To describe enteral feeding practices in pre and postoperative infants with congenital heart disease in European PICUs. DESIGN: Cross-sectional electronic survey. SETTING: European PICUs that admit infants with congenital heart disease pre- and postoperatively. PARTICIPANTS: One senior PICU physician or designated person per unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-nine PICUs from 18 European countries responded to the survey. PICU physicians were involved in the nutritional care of children with congenital heart disease in most (76%) PICUs, but less than 60% of units had a dedicated dietician. Infants with congenital heart disease were routinely fed preoperatively in only 63% of the PICUs, due to ongoing concerns around prostaglandin E1 infusion, the presence of umbilical venous and/or arterial catheters, and the use of vasoactive drugs. In three quarters of the PICUs (76%), infants were routinely fed during the first 24 hours postoperatively. Units cited, the most common feeding method, both pre and postoperatively, was intermittent bolus feeds via the gastric route. Importantly, 69% of European PICUs still did not have written guidelines for feeding, but this varied for pre and postoperative patients. CONCLUSIONS: Wide variations in practices exist in the nutritional care between European PICUs, which reflects the absence of local protocols and scientific society-endorsed guidelines. This is likely to contribute to suboptimal energy delivery in this particularly vulnerable group.

Incidence and Outcomes of Patients with Functionally Univentricular Heart Born in Latvia, 2007 to 2015.

Background and Objectives: A functionally univentricular heart is the term used to describe congenital heart defects where it is impossible to restore two pumping chambers. These lesions are associated with high mortality, morbidity, and medical resource utilization. The aim of this study was to review incidence and outcomes of patients with a functionally univentricular heart at the only pediatric cardiac surgery center in Latvia. Methods: We performed a retrospective review of medical records of (i) all children with a functionally univentricular heart treated at the Clinic of Pediatric Cardiology and Cardiac Surgery, and (ii) all prenatally diagnosed cases of univentricular heart at Children's Clinical University Hospital in Latvia. We reviewed data regarding children born from January 1, 2007, to December 31, 2015. The children's cardiac anatomy and interventions were categorized in accordance with the International Pediatric and Congenital Cardiac Code (v3.3). Results: During the study period, 49 patients with a functionally univentricular heart were admitted to Children's Clinical University Hospital with a corrected incidence of 0.69 per 1000 live births per year. There were 26 patients that had a hypoplastic left ventricle, and 22 patients that had a hypoplastic right ventricle, while one patient had an indeterminate ventricle. Thirty (61.2%) patients had died by the end of data collection. Twenty-one of the 30 deaths occurred before or immediately after stage I surgical palliation. Cumulative neonatal and 5-year survival of patients with a hypoplastic right ventricle was 81.8% and 63.6%, respectively; for patients with hypoplastic left ventricle-46.2% and 17.3%, respectively. Discussion: This is the first mid-term outcome study of patients with a univentricular heart in Latvia. The high mortality reflects the challenges of a small-volume, developing congenital cardiac surgery center. Data from this study will be used as a baseline for quality improvement.

Molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in Latvia.

Lower respiratory tract infections caused by the human respiratory syncytial virus (HRSV) represent an immense burden of the disease, especially in young children. This study aimed to investigate the evolutionary history of HRSV strains isolated in the Children's Clinical University Hospital (Riga, Latvia) over three consecutive HRSV seasons. Of 207 samples from children hospitalized with lower respiratory tract infections, 88 (42.5%) tested positive for HRSV by RT-PCR. The seasonal activity started and peaked later than the average for the Northern hemisphere. Patients with HRSV lower respiratory tract infection were significantly younger than patients not infected with HRSV. HRSV-A viruses predominated for two consecutive seasons and were followed by an HRSV-B dominant season. Phylogenetic analysis based on glycoprotein G gene partial sequences revealed that viruses of both groups belonged to the worldwide dominant genotypes NA1 (HRSV-A) and BA-IV (HRSV-B). High diversity of this gene was driven only partially by selection pressure, as only two positively selected sites were identified in each group. Two of the HRSV-A isolates in this study contained a 72-nt duplication in the C-terminal end of the G gene (genotype ON1) that was first described in Canada in the 2010-2011 season. Initial spatial and temporal dynamics of this novel genotype were reconstructed by discrete phylogeographic analysis. Fifteen years after acquiring comparable 60-nt duplication in the G gene, genotype BA lineages have replaced all other HRSV-B strains. However, the population size of genotype ON1 plateaued soon and even decreased slightly before the beginning of the 2012-2013 season.

Molecular epidemiology of respiratory syncytial virus during the 2009-2010 season in Latvia.

For the first time, we studied molecular epidemiology of respiratory syncytial virus in hospitalized children in Latvia. During the study period, ten unique group A and three group B strains were identified and assigned to a single genotype within each group-GA2 for group A and BA-IV for group B.

Predicting the Risk of Mortality in Children using a Fuzzy-Probabilistic Hybrid Model.

Introduction: The mortality risk in children admitted to Pediatric Intensive Care Units (PICU) is usually estimated by means of validated scales, which only include objective data among their items. Human perceptions may also add relevant information to prognosticate the risk of death, and the tool to use this subjective data is fuzzy logic. The objective of our study was to develop a mathematical model to predict mortality risk based on the subjective perception of PICU staff and to evaluate its accuracy compared to validated scales. Methods: A prospective observational study in two PICUs (one in Spain and another in Latvia) was performed. Children were consecutively included regardless of the cause of admission along a two-year period. A fuzzy set program was developed for the PICU staff to record the subjective assessment of the patients' mortality risk expressed through a short range and a long range, both between 0% and 100%. Pediatric Index of Mortality 2 (PIM2) and Therapeutic Intervention Scoring System 28 (TISS28) were also prospectively calculated for each patient. Subjective and objective predictions were compared using the logistic regression analysis. To assess the prognostication ability of the models a stratified B-random K-fold cross-validation was performed. Results: Five hundred ninety-nine patients were included, 308 in Spain (293 survivors, 15 nonsurvivors) and 291 in Latvia (282 survivors, 9 nonsurvivors). The best logistic classification model for subjective information was the one based on MID (midpoint of the short range), whereas objective information was the one based on PIM2. Mortality estimation performance was 86.3% for PIM2, 92.6% for MID, and the combination of MID and PIM2 reached 96.4%. Conclusions: Subjective assessment was as useful as validated scales to estimate the risk of mortality. A hybrid model including fuzzy information and probabilistic scales (PIM2) seems to increase the accuracy of prognosticating mortality in PICU.

Remote rapid cycle deliberate practice simulation training during the COVID-19 pandemic.

The COVID-19 pandemic is posing new challenges for medical education and simulation practice given local social distancing requirements. This report describes the use of an online platform for rapid cycle deliberate practice simulation training that can be used and tailored to local COVID-19 pandemic restrictions as it allows for participants, facilitators and simulation equipment to be apart.

Telementoring for remote simulation instructor training and faculty development using telesimulation.

Introduction: Simulation-based training is essential for high-quality medical care, but it requires access to equipment and expertise. Technology can facilitate connecting educators to training in simulation. We aimed to explore the use of remote simulation faculty development in Latvia using telesimulation and telementoring with an experienced debriefer located in the USA. Methods: This was a prospective, simulation-based longitudinal study. Over the course of 16 months, a remote simulation instructor (RI) from the USA and a local instructor (LI) in Latvia cofacilitated with teleconferencing. Responsibility gradually transitioned from the RI to the LI. At the end of each session, students completed the Debriefing Assessment for Simulation in Healthcare (DASH) student version form (DASH-SV) and a general feedback form, and the LI completed the instructor version of the DASH form (DASH-IV). Outcome measures were the changes in DASH scores over time. Results: A total of eight simulation sessions were cofacilitated of 16 months. As the role of the LI increased over time, the debrief quality measured with the DASH-IV did not change significantly (from 89 to 87), although the DASH-SV score decreased from a total median score of 89 (IQR 86-98) to 80 (IQR 78-85) (p=0.005). Conclusion: In this study, telementoring with telesimulations resulted in high-quality debriefing. The quality-perceived by the students-was higher with the involvement of the remote instructor and declined during the transition to the LI. This concept requires further investigation and could potentially build local simulation expertise promoting sustainability of high-quality simulation.

A Simulation-Based Failure Mode Analysis of SARS-CoV-2 Infection Control and Prevention in Emergency Departments.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19)] outbreak has been declared a global pandemic by the World Health Organization. The COVID-19 pandemic has highlighted problems of sustainable infection prevention and control measures worldwide, particularly the emerging issues with an insufficient supply of personal protective equipment. The aim of this study was to provide an action plan for mitigation of occupational hazards and nosocomial spread of SARS-CoV-2 through a failure mode analysis based on observations during in situ simulations. METHODS: A multicenter, cross-sectional, observational, simulation-based study was performed in Latvia from March 2 to 26, 2020. This study was conducted at 7 hospitals affiliated with Riga Stradins University. The presentation of a COVID-19 patient was simulated with an in situ simulations, followed by a structured debrief. Healthcare Failure Modes and Effects Analysis is a tool for conducting a systematic, proactive analysis of a process in which harm may occur. We used Healthcare Failure Modes and Effects Analysis to analyze performance gaps and systemic issues. RESULTS: A total of 67 healthcare workers from 7 hospitals participated in the study (range = 4-17). A total of 32 observed failure modes were rated using a risk matrix. Twenty-seven failure modes (84.4%) were classified as either medium or high risk or were single-point weaknesses, hence evaluated for action type and action; 11 (40.7%) were related to organizational, 11 (40.7%) to individual, and 5 (18.5%) to environmental factors. CONCLUSIONS: Simulation-based failure mode analysis helped us identify the risks related to the preparedness of the healthcare workers and emergency departments for the COVID-19 pandemic in Latvia. We believe that this approach can be implemented to assess and maintain readiness for the outbreaks of emerging infectious diseases in the future.

Prospective paediatric intensive care registry in Latvia: one year outcomes.

BACKGROUND: In Latvia, there is a single eight-bed paediatric intensive care unit (PICU) where all critically ill children are admitted. A recent retrospective audit of the outcomes of paediatric critical care in this unit revealed a high number of unplanned extubations and excess crude mortality. In 2017, our centre joined the UK and Ireland based Paediatric Intensive Care Audit Network (PICANet) as a pilot project to investigate the feasibility of developing a paediatric critical care registry in Latvia and in the Baltic states. METHODS: Riga Stradins University Ethics Committee approved the study. Anonymized data on all patients admitted to our unit from 1 June, 2017 to 31 May 2018 were prospectively entered onto the PICANet database. RESULTS: A total of 774 PICU admissions were analysed; 45% of admissions were elective. The median age was 59 months (IQR: 14-149). The highest admission rate was on Wednesdays representing the flow of elective surgical patients. The median length of stay was 0.95 days (IQR: 0.79-1.98). Twenty-five percent required respiratory support. The expected number of deaths estimated using the Paediatric Index of Mortality 3 (PIM 3) 15.16; 15 patients (1.94%) died resulting in Standartized Mortality Ratio (SMR) of 0.99 (95% CI 0.57-1.60). The emergency readmission rate within 48 hours after PICU discharge was 0.9%. There were 1.8 unplanned extubations per 100 invasive ventilation days. Other paediatric intensive care audit networks reported similar adjusted mortality rates but lower rates of unplanned extubations. Thirty days after PICU discharge, 653 (84.36%) patients were alive and outside hospital, 98 (12.66%) were inpatients, six (0.78%) had died, two (0.26%) were lost to the follow-up. We observed a marked peak of infant emergency respiratory admissions in February. CONCLUSIONS: This project explored the possibility of prospective paediatric critical care audit in Latvia by joining an established international network. This allowed direct comparison of outcomes between the countries. Excess mortality was not observed during one-year data collection period, however a high rate of unplanned extubations was revealed. The results allowed a better planning of elective patient flow by spreading elective cases over the week to avoid "rush hours".

Extracorporeal membrane oxygenation cannula malposition in the azygos vein in an infant.

INTRODUCTION: Misplacement of extracorporeal membrane oxygenation (ECMO) venous cannula in the azygos vein has previously been described only in newborns. CASE: For the first time, we report an aberrant ECMO cannula placement in the azygos vein in a child outside neonatal period. History of chronic lung disease and ligation of persistent ductus arteriosus leading to elevated right ventricular pressure was the potential risk factor. CONCLUSIONS: This rare complication should be considered whenever the patient has inadequate venous return on ECMO and it can be easily ruled out with a lateral chest radiograph.

Melanoma vaccine candidates from chimeric hepatitis B core virus-like particles carrying a tumor-associated MAGE-3 epitope.

Vaccination of melanoma patients with tumor-specific antigens recognized by cytotoxic T lymphocytes (CTLs) may produce significant tumor regressions. Here, we suggest a novel type of tumor vaccines, with well-studied CTL epitopes presented on highly immunogenic virus-like particle (VLP) carriers. Cancer-germline gene MAGE-3 encodes for an antigenic nonapeptide (MAGE-3(168-176) peptide) that is recognized by CTLs on human leukocyte antigen (HLA)-A1 and HLA-B35 molecules. A set of recombinant genes encoding hepatitis B virus core protein carrying MAGE-3 epitope was constructed and expressed in Escherichia coli cells. Variants that led to formation of chimeric VLPs in vivo were purified and analyzed for their DNA binding properties in vitro. VLPs exhibiting the most pronounced nucleic acid binding affinity were selected and loaded either with single-stranded DNA oligodeoxynucleotides rich in nonmethylated CG motifs, or with longer double-stranded DNA fragments. Packaged DNA was protected, at least partially, against the action of bacterial DNase. Such highly purified chimeric VLPs with entrapped immunomodulatory sequences could possibly be used as antitumor vaccines.