Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Abstract Background Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. Methods The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. Discussion Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. Trial registration ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020

Granulomatous meningo-encephalitis caused by Toxoplasma gondii in three bulls, a possible explanation for unexplained sporadic bovine meningo-encephalitis

peer reviewe

Applications thoraco-abdominales de l'IRM chez le fœtus

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Giant Magnetothermal Conductivity and Giant Magnetothermopower in Granular Co-ag Solids

We report measurements on the thermal conductivity and thermoelectric power of granular Co20Ag80 solids annealed at various temperatures. Thermal conductivity is dominated by its electronic contribution and the Wiedemann-Franz law is found to be satisfied between 2K and 300K, which is mainly ascribed to dominant large-angle elastic scattering processes. The thermoelectric power is negative and is considerably reduced by the annealing process. Giant magnetothermal conductivity and giant magnetothermopower are found to be correlated with the giant magnetoresistance

Thermal and Thermoelectric Properties of Granular Co-ag Solids

We report measurements on the temperature and magnetic field dependences of the thermal conductivity, thermoelectric power, and specific heat of granular Co20Ag80 solids annealed at various temperatures. Giant magnetothermal conductivity and giant magnetothermopower are found to be correlated with the giant magnetoresistance. Thermal conductivity is dominated by its electronic contribution, and the Wiedemann-Franz law is found to be satisfied between 2 and 300 K, indicating that large-angle electron scattering processes dominate. The thermoelectric power is negative and its magnitude is considerably reduced by the annealing process. The contrasting relationship between electrical resistivity and thermoelectric power on annealing and in applied field is curved and discussed. No marked variation of specific heat with magnetic field in relation to the giant magnetoresistance has been observed. At very low temperatures, i.e. below T similar to 1 K, a nuclear contribution to the specific heat appears, whose temperature and magnetic field dependences have been explored

A clinical case of congenital tremors in piglets without evidence of PCV-1 and PCV-2

Congenital tremor (CT) is a disease of newborn pigs characterized by spontaneous clonic contractions of one or more groups of voluntary muscles. Besides suspected or confirmed etiologies of CT such as classical swine fever virus, pseudorabies virus, Japanese encephalomyelitis virus, hereditary disorders in Landrace or Saddleback pigs, organophosphorus poisoning etc., porcine circovirus (PCV) has been described as a potential cause of CT. The type AII seems to be the most common form of CT. Although a potential association between PCV1 or PCV2 and CT-AII has been observed, about 50% CT cases described up till now are caused by unknown reasons. In a PCV-seropositive 108-sow, farrow-to-finish Belgian pig farm breeding hyperprolific Landrace, 42 litters with shaking piglet(s) were reported since June 2006. On March 2012, piglets born from four sows of a 27 sow batch demonstrated CT. After exclusion of main etiologies of CT from these CT-affected piglets, it was hypothesized that PCV1 or PCV2 could be the reason. Necropsies (n=8) and histopathology (n=3) were performed and no evidence of macroscopic or microscopic lesions were seen in cerebrum, cerebellum and spinal cord. Pre-suckled and post-suckled (after 3 days of colostrum uptake) serum samples were also collected from 9 piglets to determine PCV1- and PCV2-specific Ab titres by an immuno-peroxidase monolayer assay (IPMA). No PCV-specific Ab titres were observed in pre-suckled serum samples (≤40), whereas IPMA Ab titres of ≥640 were observed in post-suckled serum samples. Both PCV1 and PCV2 could not be isolated (<101.7 TCID50/g tissue) from 4 tested piglets (in heart, brain and lungs). The present results do not support the hypothesis that PCV1 or PCV2 are linked to CT in newborn piglets

Doxapram versus placebo in preterm newborns : a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Abstract: BackgroundApnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age.MethodsThe DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18-24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle.DiscussionDoxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants.Trial registrationClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020