Recommendations of the Netzwerk Kindersimulation for the Implementation of Simulation-Based Pediatric Team Trainings: A Delphi Process.

BACKGROUND: Serious or life-threatening pediatric emergencies are rare. Patient outcomes largely depend on excellent teamwork and require regular simulation-based team training. Recommendations for pediatric simulation-based education are scarce. We aimed to develop evidence-based guidelines to inform simulation educators and healthcare stakeholders. METHODS: A modified three-round Delphi technique was used. The first guideline draft was formed through expert discussion and based on consensus (n = 10 Netzwerk Kindersimulation panelists). Delphi round 1 consisted of an individual and team revision of this version by the expert panelists. Delphi round 2 comprised an in-depth review by 12 external international expert reviewers and revision by the expert panel. Delphi round 3 involved a revisit of the guidelines by the external experts. Consensus was reached after three rounds. RESULTS: The final 23-page document was translated into English and adopted as international guidelines by the Swiss Society of Pediatrics (SGP/SSP), the German Society for Neonatology and Pediatric Intensive Care (GNPI), and the Austrian Society of Pediatrics. CONCLUSIONS: Our work constitutes comprehensive up-to-date guidelines for simulation-based team trainings and debriefings. High-quality simulation training provides standardized learning conditions for trainees. These guidelines will have a sustainable impact on standardized high-quality simulation-based education.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Impact of personal protective equipment on neonatal resuscitation procedures: a randomised, cross-over, simulation study.

BACKGROUND AND OBJECTIVE: Healthcare providers should use personal protective equipment (PPE) when performing aerosol-generating medical procedures during highly infectious respiratory pandemics. We aimed to compare the timing of neonatal resuscitation procedures in a manikin model with or without PPE for prevention of SARS-COVID-19 transmission. METHODS: A randomised controlled cross-over (AB/BA) trial of resuscitation with or without PPE in a neonatal resuscitation scenario. Forty-eight participants were divided in 12 consultant-nurse teams and 12 resident-nurse teams. The primary outcome measure was the time of positive pressure ventilation (PPV) initiation. The secondary outcome measures were duration of tracheal intubation procedure, time of initiation of chest compressions, correct use of PPE and discomfort/limitations using PPE. RESULTS: There were significant differences in timing of PPV initiation (consultant-nurse teams: mean difference (MD) 6.0 s, 95% CI 1.1 to 10.9 s; resident-nurse teams: MD 11.0 s, 95% CI 1.9 to 20.0 s), duration of tracheal intubation (consultant-nurse teams: MD 22.0 s, 95% CI 7.0 to 36.9 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s) and chest compressions (consultant-nurse teams: MD 32.3 s, 95% CI 14.4 to 50.1 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s). Twelve participants completed the dressing after entering the delivery room. PPE was associated with visual limitations (43/48 participants), discomfort in movements (42/48), limitations in communication (32/48) and thermal discomfort (29/48). CONCLUSIONS: In a manikin model, using PPE delayed neonatal resuscitation procedures with potential clinical impact. Healthcare workers reported limitations and discomfort when wearing PPE. TRIAL REGISTRATION NUMBER: NCT04666233.

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy.

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature.

Intracranial penetration during attempted nasotracheal intubation is a potentially devastating complication, which should be carefully evaluated and the risk should be addressed in neonatal resuscitation trainings.

Thermal management with and without servo-controlled system in preterm infants immediately after birth: a multicentre, randomised controlled study.

BACKGROUND: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed. OBJECTIVE: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth. STUDY DESIGN AND SETTING: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals. PARTICIPANTS: Infants with estimated birth weight <1500 g and/or gestational age <30+6 weeks. INTERVENTION: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room. PRIMARY OUTCOME: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C). RESULTS: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01). CONCLUSIONS: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge. TRIAL REGISTRATION NUMBER: NCT03844204.

Heterozygous SOX9 mutations allowing for residual DNA-binding and transcriptional activation lead to the acampomelic variant of campomelic dysplasia.

Campomelic dysplasia is a malformation syndrome with multiple symptoms including characteristic shortness and bowing of the long bones (campomelia). CD, often lethal due to airway malformations, is caused by heterozygous mutations in SOX9, an SRY-related gene regulating testis and chondrocyte development including expression of many cartilage genes such as type II collagen. Male to female sex reversal occurs in the majority of affected individuals with an XY karyotype. A mild form without campomelia exists, in which sex-reversal may be also absent. We report here two novel SOX9 missense mutations in a male (c.495C>G; p.His165Gln) and a female (c.337A>G; p.Met113Val) within the DNA-binding domain leading to non-lethal acampomelic CD. Functional analyses of mutant proteins demonstrate residual DNA-binding and transactivation of SOX9-regulated genes. Combining our data and reports from the literature we postulate a genotype-phenotype correlation: SOX9 mutations allowing for residual function lead to a mild form of CD in which campomelia and sex reversal may be absent.

Furosemide use in Italian neonatal intensive care units: a national survey.

BACKGROUND: Furosemide is approved in full term neonates to treat edema associated with congestive heart failure, cirrhosis and renal diseases. It is often administered off-label in premature neonates, to treat respiratory conditions and at doses greater-than-recommended. We conducted a national survey on behalf of the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology (SIN), to investigate its use in Italian neonatal intensive care units (NICUs), in conformity with current guidelines. METHODS: Between December 2016 and June 2017, a 14-item multiple-choice online questionnaire was sent to all NICU directors from the SIN directory. Gestational age, route of administration, posology, indications, referenced guidelines, adverse effects monitoring and the presence of Paediatric Cardiology or Cardiosurgery service on site were assessed. A chi-square test was performed 1) to evaluate differences in the distribution of responses between NICUs administering furosemide at doses higher-than-recommended; 2) to compare the proportion of NICUs administering furosemide at high doses in institutions with versus without a Paediatric Cardiology or Cardiosurgery service. RESULTS: The response rate was 50% (57/114). The intravenous and oral routes were chosen primarily; the intravenous administration in single doses predominated over continuous infusion. Its main therapeutic indications were congestive heart failure/overload (94.7%) and oligo-anuria (87.7%) however furosemide was also frequently used for broncopulmonary dysplasia (50.9%) and respiratory distress syndrome and/or transient tachypnea of the newborn (24.6%). In 28/57 NICUs furosemide was administered at doses higher-than-recommended. In most NICUs the same posology was used in term and preterm neonates. Compared to the total sample, a larger proportion of NICUs administering doses greater-than-recommended referenced current literature for reasons to do so (19.3 and 32.1% respectively). The presence of a Paediatric Cardiology or Cardiosurgery service on site did not correlate with the chosen posology. The majority of NICUs performed acoustic test and renal ultrasound for furosemide exposure greater than 2 weeks. CONCLUSIONS: In Italian NICUs, furosemide is commonly prescribed to term and preterm newborns for label and unlabeled indications. Doses greater-than-recommended are frequently administered. Such use is not necessarily inappropriate. More research is required to assess the efficacy and safety of unlabeled use.

Decision making and situational awareness in neonatal resuscitation in low resource settings.

INTRODUCTION: Data on non-technical skills (i.e. task management, team working, situation awareness and decision-making) of healthcare providers during real-life newborn resuscitation in low-resource settings are lacking. We aimed to assess non-technical skills of trained midwives during real-life newborn resuscitation in a low-resource setting before and after participation in a modified NRP course, and after a low-dose/high-frequency training. METHODS: One-hundred and fifty video-recorded resuscitations (50 before and 50 after participation in a modified NRP course, and 50 after a low-dose/high-frequency training) collected at the Beira Central Hospital (Mozambique) were independently viewed and rated by two neonatologists with expertise in high fidelity simulation. Non-technical skills regarding task management, situation awareness and decision-making were evaluated using the modified Anesthetists' Non-Technical Skills tool. RESULTS: Overall, most non-technical skills were scored as poor or marginal. Small improvements were observed in task management (planning and preparing p = 0.02; providing/maintaining standards p = 0.03) after the course. Limited improvements were observed in task management (prioritizing p = 0.03; providing/maintaining standards p = 0.04; identifying and utilizing resources p = 0.02) and decision-making (identifying options p = 0.04; balancing risk/selecting options p = 0.02) after the low-dose/high-frequency training. No differences were observed in situation awareness, apart from a small improvement in recognizing/understanding (p = 0.04) after the low-dose/high-frequency training. CONCLUSION: An educational intervention including a modified NRP course and a low-dose/high-frequency training on neonatal resuscitation had a limited impact on non-technical skills of participants. All items remained significantly under the recommended standards. Behavioral skills should be considered in training programs in order to improve the quality of neonatal resuscitation in low resource settings.

Status Quo in Pediatric and Neonatal Simulation in Four Central European Regions: The DACHS Survey.

INTRODUCTION: Simulation has acquired wide acceptance as an important component of education in health care and as a key tool to increase patient safety. This study aimed at identifying to what extent and how pediatric and neonatal simulation-based training (SBT) was being carried out in four Central European regions. METHODS: We surveyed all pediatric and neonatal health care institutions in Germany, Austria, Switzerland, and South Tyrol on their current state of SBT using an online questionnaire. RESULTS: We dispatched 440 questionnaires with a 45.9% response rate. Sixty-one percent (61.4%) of institutions performed SBT (algorithm training, 87.4%; skill training, 62.2%; high-fidelity SBT, 56.8%). Training was conducted interprofessionally at 88.9% of surveyed institutions. Physicians and nurses most often received SBT once per year. Lack of financial (62.2%) and personnel (54.1%) resources were the most frequent impediments to establish SBT. CONCLUSIONS: Although delivered heterogeneously, widespread use of pediatric simulation and a considerable number of already existing SBT programs are the key findings of this survey. These data are encouraging enough to promote more effective networking in simulation-based research, education, training, and quality improvement, as we aim to ultimately increase patient safety for neonates, infants, and children.

Very low birth weight preterm infants are at risk for hypoglycemia once on total enteral nutrition.

OBJECTIVE: To determine the occurrence of hypoglycemic episodes in very low birth weight preterm infants under total enteral nutrition and identify potential risk factors. METHODS: In this single centre cohort study, we analyzed the patients' charts of preterm infants with a gestational age <32 weeks (n = 98). Infants were analyzed in two groups (group 1: birth weight <1000 g, n = 54; group 2: birth weight 1000-1499 g, n = 44). A total of 3640 pre-feeding blood glucose measurements were screened. Risk factors for the development of hypoglycemia were identified by linear and multiple logistic regression analyses. RESULTS: In group 1, 44% (24 of 54) of infants experienced at least one asymptomatic episode of blood glucose <45 mg/dl (<2.5 mmol/l) as compared with 23% (10 of 44) in group 2. Regression analysis identified low gestational age and high carbohydrate intake as potential risk factors for the development of hypoglycemia. CONCLUSIONS: Our results indicate that numerous preterm infants experience hypoglycemic episodes once on total enteral nutrition, especially those who are <1000 g at birth and those with a higher carbohydrate intake. Further studies evaluating a possible impact of these common although asymptomatic episodes on later development could help to better define thresholds that should be considered as "hypoglycemia" in this population.

A novel mutation in AVPR2 causing congenital nephrogenic diabetes insipidus with complete resistance to antidiuretic hormone.

A 6-month-old male infant presented with failure to thrive. Hypernatraemia and elevated serum osmolality in the presence of low urine sodium and osmolality led to the diagnosis of diabetes insipidus. Administration of 1-deamino-8-D-arginine vasopressin (dDAVP) neither decreased urine volume nor increased urine osmolality indicating congenital nephrogenic diabetes insipidus. Molecular analysis in the arginine-vasopressin receptor-2 gene (AVPR2) located on chromosome Xq28 demonstrated a novel 5-base pair deletion (c.962-966delACCCC; g.1429-1433delACCCC) leading to a shift of the reading frame (p.Asn321fs) and a premature termination codon implying an absent or non-functional protein. Treatment with hydrochlorothiazide, amiloride and indomethacin led to a favourable clinical course.

Effect of intravesical instillation on performance of uCYT+ test.

OBJECTIVES: To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guérin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells. METHODS: A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series. RESULTS: Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity (P = 0.512) and specificity (P = 0.558) for the uCyt+ test in the two groups of patients. CONCLUSIONS: The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.