The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on 'trial and error'. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking. METHODS AND ANALYSIS: In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018-2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses. ETHICS AND DISSEMINATION: Ethics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained. TRIAL REGISTRATION NUMBER: NTR6982; Pre-results

Estudio del perfil glucémico previo al alta en recién nacidos muy prematuros

[spa] Los neonatos pretérmino presentan múltiples factores para padecer una desregulación del metabolismo de la glucosa, sobre todo en los primeros días de vida. Parece que los sistemas hormonales y enzimáticos para la regulación de la glucemia son inmaduros en estos pacientes incluso a la edad de término.Nuestra hipótesis es que en los recién nacidos muy prematuros (RNMP), el riesgo de presentar oscilaciones marcadas de la glucemia persiste en el momento del alta hospitalaria, lo que podría afectar a su desarrollo psicomotor. En nuestro estudio objetivamos la existencia de episodios de hiperglucemia e hipoglucemia asintomáticos en este grupo de pacientes sin poder determinar un perfil hormonal característico mediante monitorización subcutanea continua de glucosa (monitor ciego). No encontramos variables clínicas que puedan ser consideradas como factores de riesgo para presentar hipoglucemias pero parece que el retraso de crecimiento intrauterino (RCIU) y el sexo femenino son factores de riesgo para padecer hiperglucemias. Sobre este aspecto del estudio, decir a modo de conclusión que hemos demostrado que los RNMP al llegar a la edad de término, estando clínicamente estables y con nutrición enteral total, siguen siendo una población vulnerable a presentar anormalidades en la regulación de la glucemia (46.7% de la cohorte global presentan algún episodio de anormalidad de la glucosa), presentando hiper y/o hipoglucemias prolongadas (tiempo en hipoglucemia (media ± DE): 2.9 ± 2.8 horas/paciente afecto/periodo monitorización (PM); tiempo en hiperglucemia (media ± DE): 4.0 ± 4.0 horas/paciente afecto/PM) y repetidas (el 50% de los pacienets que presentan altersciones d elos niveles de glucosa tienen 2 ó más episodios). También construimos una curva de respuesta normal a la ingesta y realizamos diferentes curvas según tipo de alimentación y patrón de crecimiento intrauterino y extrauterino. Mediante estas curvas, objetivamos que aquellos pacientes con RCIU presentaron niveles significativamente inferiores que aquellos pacientes con un crecimiento correcto tanto al inicio como durante la toma, pero no en el momento de finalizar la toma ni en el periodo post-toma. Este hecho llama la atención ya que es en este último periodo cuando tienen lugar la mayoría de los episodios de hiperglucemia y la explicación que encontramos fue que existe una mayor variabilidad en las cifras de glucosa los estos RCIU. También demostramos que los pacientes alimentados mediate lactancia materna presentan cifras medias de glucosa significativamente superiores durante todo el ciclo de alimentación en comparación con los pacientes alimentados mediante leche de fórmula (LF). Este hecho podría ser explicado por el perfil hormonal de estos pacientes, ya que aquellos alimentados con LF presentan una insulinemia mayor con una concentración inferior de cuerpos cetónicos, lo que podría favorecer la entrada de glucosa al interior de la célula y, por consiguiente, daría lugar a unas cifras más bajas de glucosa a nivel del intersticio. Asimismo, vemos que la monitorización continua de glucosa es un método seguro, exacto y que este grupo de pacientes vulnerable tolera bien. Además, tiene un alto porcentage de lecturas congruentes con el método de referencia de este estudios (glucemia capilar), ya que tan sólo el 1 .7% de lecturas aisladas hubieran llevado a tratamiento incorrecto del paciente pero se debe tener en cuenta que, probablemente, al analizar las tendencias de la monitorización continua, los errores de tratamiento hubieran sido menores.[eng] Disturbances in glucose homeostasis are prevalent disorders in Very Preterm (VPT) infants. In spite of evidence of frequent abnormal glucose levels in VPT infants during the first days of life and of delayed maturation of the metabolic pathways involved, there is a lack of data regarding the prevalence of glucose abnormalities in preterm babies at the time they leave hospital. Further knowledge in this area would be clinically relevant, given that both hypo and hyperglycemia have been associated to adverse outcomes. Therefore, we sought to determine if very preterm babies are capable of independently maintaining normal glucose levels at or near term postmenstrual age. To address this problem, we performed subcutaneous continuous glucose monitoring (blind monitoring) in a population of stable VPT babies who were about to be discharged home. In our study, we have shown that VPT infants continue to present abnormal glucose values (46.7% of the cohort), especially hyperglycemia, by the time of hospital discharge, being all of these episodes asymptomatic, persistent (hypoglycemia mean ± SD: 2.9 ± 2.8 hours/affected patient/monitoring period and hyperglycemia mean ± SD: 4.0 ± 4.0 hours/affected patient/monitoring period) and frequent (50% of the babies with abnormal glucose levels presented more than 2 episodes). We couldn’t demonstrate any specific hormonal profile in those patients with glucose abnormalities. No specific factors identify babies at higher risk for hypoglycemia, while intrauterine growth restriction (IUGR) and female gender seemed to predispose to hyperglycemia. Also, we represented with a chart the normal response to enteral nutrition in this population and we also constructed different charts in relation to intrauterine and extrauterine growth pattern and type of enteral feed. We demonstrated that those patients with IUGR had significant lower glucose values at the beginning and during the feed but they had no differences at the end and in the post-feed period; this profile could be explained because of a greater variability in glucose values in IUGR patients. In those patients nourished with mother milk, the glucose values in all the studied period were significantly higher than those of formula feed infants. This find could be related to the hormonal profile of these babies that consist in lower insulin with higher ketone bodies levels if we compare these molecules in relation to formula fed babies

Mobile Communication in Asia: Issues and Imperatives

10.1111/jcc4.12080Journal of Computer-Mediated Communication193663–66

Distinguishing outcomes of neonatal intestinal volvulus: review of our experience over the last 20 years

Aim: There are two types of intestinal volvulus: midgut (MGV) and segmental (SV). Patients with different types of intestinal volvulus are often included in the same case series, which may affect the perception of how severe "intestinal volvuli" are. We aimed to compare both types of intestinal volvulus. Methods: This is a retrospective observational study including all patients with MGV and SV up to 28 days of life admitted to a tertiary hospital in Spain over a 20-year-period (1999-2019). A comparison between groups and a logistic regression model for mortality were done. Results: We identified 32 patients: 23 MGV and 9 SV. Malrotation was exclusive of MGV. Prenatal diagnosis, cystic fibrosis, and intestinal resection were significantly more frequent in SV. Surgery was performed at a significantly lower age in SV. The mortality observed in acute MGV with intestinal compromise (41.7%) is four times higher than the mortality of SV (11.1%). The overall mortality of all MGV patients (21.7%) is almost twice that of SV. Mortality was best predicted by the presence of hemodynamic instability (OR 27.5 95% CI 2.50-302.17; p = 0.007). Conclusion: SV and MGV have a different clinical presentation. Hemodynamic instability is the major risk factor for death