Neonatal Sepsis

Purpose: Over the last 10 years, recommendations regarding the ideal level of oxygen for resuscitation in preterm infants have changed from 100 percent, down to low levels of oxygen (\<30 percent), up to moderate concentration (30-65 percent). In addition, in 2010, oxygen saturation targeting was recommended as standard of care and this contributed to a change in clinical practice as clinicians were more likely and comfortable to start resuscitation at either 21percent (room air) or titrated levels of oxygen such as 30-40 percent. When the guidelines were again revised in 2015, the International Liaison Committee on Resuscitation (ILCOR) acknowledged that a critical knowledge gap continued to exist for the resuscitation of the preterm infants \<37 weeks, highlighting the need to provide more concrete guidelines. This leaves clinicians in a challenging position. Despite the advances that have been achieved in perinatal and neonatal care, neonates are still vulnerable to the consequences of the oxidative effects from hyperoxia as well as the deleterious effects from hypoxia. A large, multi-centre international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidenced to guide clinical practice with confidence. Hypothesis: the null hypothesis for this study is that the incidence of mortality or abnormal neurodevelopmental outcomes at 24+/- 6 months corrected age will be no different by using either higher initial oxygen concentration of 60 percent compared to using lower initial oxygen concentration of 30 percent for resuscitation of preterm infants of 23 0/7- 28 6/7 weeks gestation. Justification: The use of supplementary oxygen may be crucial, but also potentially detrimental to premature infants at birth. High oxygen levels may lead to organ damage through oxidative stress, while low oxygen levels may lead to increased mortality. Excess oxygen exposure during the early post-birth period is associated with many complications and morbidities of preterm birth. Preterm infants have lower levels of anti-oxidant pathways consistent with their expected fetal environment of low oxygen exposure. Excess of oxygen free-radicals in infants intrinsically deficient in enzymatic antioxidants and non-enzymatic antioxidants may contribute to these morbidities. Pulmonary oxygen toxicity, through the generation of reactive oxygen and nitrogen species in excess of antioxidant defenses, is believed to be a major contributor to the development of bronchopulmonary dysplasia (BPD). Using lower oxygen concentrations at birth results in decreased oxidative stress markers and a decrease risk of developing BPD compared to higher oxygen concentrations. Other organs that may be damaged by such oxidative stress include kidneys, myocardium and the retina. There is equally growing evidence that using lower oxygen concentrations will lead to lower oxygen saturation levels and bradycardia, which may lead to increased rates of mortality in this vulnerable group of infants. An individual patient analysis of clinical trials reported that 46% of preterm infants resuscitated with initial low oxygen concentration did not reach SpO2 of 80% at 5 min. This was associated with increased risk of major intraventricular hemorrhage (IVH), and an almost five times higher risk of death in this vulnerable group of infants. These data provide a warning note for the use of higher vs. lower initial oxygen concentration during delivery room resuscitation. As the investigator proceed in determining a safe range for resuscitation of ELBW/ELGA infants, it is highly likely that the optimum level of oxygen concentration is between the two extremes of 21 percent and 100 percent. Objectives: To determine whether initial resuscitation of preterm neonates with 60 percent versus 30 percent oxygen results in better neurodevelopmental outcomes at 24+/- 6 months. Research Method/Procedures: This will be a cluster crossover design, unmasked randomized controlled trial (RCT) comparing two oxygen concentrations at initiation of resuscitation. Infants will be placed on the resuscitation table with the initial steps of resuscitation carried out as per standard of care at each centre which usually follows current resuscitation guidelines. All centres will make every effort to establish adequate lung expansion using CPAP or positive pressure ventilation as needed. Enrolled infants will have a pulse oximeter sensor placed on the right arm in the first minute of life. Their resuscitation will be initiated with an oxygen concentration of 30 or 60 percent depending on the randomization sequence at the centre at the given time. Infants in the 30 percent group will remain in 30 percent oxygen until 5 min of age unless the infant's heart rate (HR) remains 100/min or less and does not show a tendency towards progressive increase before reaching 5 min of age or infant needs chest compression and/or epinephrine. No alteration in oxygen concentration will be made for an infant who is responding to resuscitation efforts with HR progressively increasing as minutes go by. At 5 min of age, the clinical team will assess oxygen saturation. If the saturation is less than 85 percent, oxygen should be increased by 10-20 percent every 60 sec to achieve saturations of 85 percent or greater or a saturation of 90-95 percent at 10 min of age. If saturations are greater than 95 percent at or before 5 min of age, oxygen should be decreased stepwise (every 60 sec) with an aim to maintain saturations of 85 percent or greater during 5-10 min of age or 90-95 percent at and beyond 10 min of age. The procedure for infants in the 60 percent group will be identical. The intervention duration for the trial will be the first 5 min after birth followed by initial monitoring/action for the next 5 min where titration in oxygen concentration will be made to achieve stability making a total of 10 min for study intervention. Titration of oxygen before 5 min after birth will only be made if the infant remains bradycardic (HR less than 100) and does not show a tendency towards a sustained increase in HR or if the oxygen saturation exceeds 95 percent. If the infant does not respond to ventilation with increasing HR in the first 5 min after birth, steps to ensure effective ventilation should be done before oxygen is titrated. Plan for Data Analysis: Generalized linear mixed model with binary outcome and maximum likelihood estimate will be used to evaluate the effect of an oxygen concentration on the primary outcome (as a composite at 24+/- 6 months corrected age of all-cause mortality or the presence of a major neurodevelopmental outcome). To account for cluster crossover design of the study, effects of centers (clusters) and a period (oxygen concentration) within center will be considered random, and effects of a period (oxygen concentration) will be entered as a fixed effect. This hierarchical model allows for the correlation of patients within periods and within clusters. The model will be adjusted for gestational age and whether or not infant required mask ventilation as potential confounding variables. Similar generalized linear mixed models will be performed to evaluate the effect of group on secondary outcomes. In addition, three subgroup analysis will be performed: i) Gestational age will be categorized into 2 categories: 23+0- 25+6 vs. 26+0-28+6 weeks; ii) Breathing support will be categorized by infants supported only with CPAP vs. received mask ventilation; iii) Sex/Gender will be categorized into 2 categories: female vs. male. For subgroup analysis baseline characteristics will be compared using linear and generalized linear mixed models. Sensitivity analysis will be performed to analyze the missing data; however, a very low number of missing values are expected due to the design of the study.

Background: Liberation from mechanical ventilation (MV) involves a three-step process; weaning, readiness testing, and extubation. Readiness testing uses objective clinical criteria to determine whether a patient is ready to begin weaning from MV. These criteria include improvement of the underlying indication for MV, hemodynamic stability, and the ability to initiate and sustain both adequate inspiration and expiration. Successfully extubation from invasive MV is a critical milestone in the recovery from severe respiratory failure and and is a clinical challenge for clinicians. Spontaneous breathing trials (SBT) are conducted to evaluate a patient's readiness for ventilator liberation in the intensive care unit (ICU). Extubation is considered successful if invasive mechanical support is not required within 48 hours after the removal of the endotracheal tube. As the final step of the weaning process, the decision to extubate is typically guided by objective criteria demonstrating the patient's ability to sustain respiratory function without mechanical assistance. Considering the complex pathologies of intensive care patients, besides SBT many clinical parameters have been used as predictors of weaning and extubation. For this reason, different multi-component scales and scores have been developed. The study protocol is designed and will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. The aim of this study is to develop a multi-component Readiness for EXtubation score (REXs) that can predict extubation readiness and to analyze this score that can be applied to patients under invasive MV in the ICU. Sample Size: The sample size was calculated as 427 using the Area Under ROC Curve in the ExPreS study. The total targeted sample size was accepted 470 patients with estimating that there would be a 10% dropout. Screening and Admission: The daily screen will be performed between 8:00 and 10:00 a.m. by the clinician assigned to the unit each morning that the patient was on invasive mechanical ventilation. Patients meeting the criteria will be included in the study. Data Collection and Anonymization: The data collected are part of routine clinical care, and the data will be anonymized. Clinicians will add anonymously the data they obtain to a created electronic case report form (e-CRF). Clinicians will be allowed to assign numbers to patients so that they can be distinguished by the clinicians who add them. The dataset that constitute the e-CRF for each patient are; demographics (country, age, sex, BMI), ICU type, cause of ICU admission, number of comorbidities, weaning/extubation type, SBT duration, arterial blood gases (ABG: pH, PaCO2, PaO2), ventilation parameters (brand/model, FiO2, PEEP, ventilation index, RSBI, MVspont/MVtotal, PCF, P0.1, vital capacity, NIF, Cdyn), secretion type, agitation and sedation score (RASS), heart rate, hemoglobin, nutrition target percentage, ventilatory support after extubation, extubation failure (24,48 and 72 hrs), duration of invasive MV, ICU and hospital length of stay and mortality. pH: It measures the acidity or alkalinity of blood and is crucial for assessing acid-base balance. Normal arterial pH is 7.35-7.45. A pH lower than 7.35 indicates acidosis, while a pH higher than 7.45 indicates alkalosis. Abnormal pH can indicate metabolic or respiratory disorders. The pH of the blood is crucial when assessing the success of weaning. The pH outside the normal range can indicate an imbalance in acid-base homeostasis, which may suggest inadequate respiratory function or metabolic disturbances that would make weaning unsafe. Maintaining a normal pH ensures that the patient's respiratory and metabolic systems can function without requiring excessive ventilatory support. PaCO2: PaCO2 is a direct measure of ventilation. During weaning, a PaCO2 level within normal limits is needed for extubation success. Persistent hypercapnia during weaning suggests that the patient may be unable to sustain adequate ventilation on their own, leading to potential failure. PaO2/FiO2: This ratio is a measure of the severity of hypoxemia. During weaning, a higher PaO2/FiO2 ratio suggests that the lungs are functioning well enough to support breathing without mechanical assistance. A low ratio suggests the need for continued mechanical ventilation. PEEP: PEEP is used to prevent alveolar collapse and improve oxygenation. When weaning, reducing PEEP gradually helps assess whether the patient can maintain oxygenation without it. High levels of PEEP might be detrimental when reducing ventilatory support, as it can affect weaning success. Ventilation Index (VI): The ventilation index (VI) combines respiratory rate and tidal volume, giving an overall assessment of ventilation efficiency. A low VI is favorable during weaning because it indicates that the patient is able to achieve adequate ventilation with minimal support. VI is calculated as VI="(PIP\* PaCO2\*RR)/1000". Rapid Shallow Breathing Index (RSBI): The rapid shallow breathing index (RSBI), also known as the ratio of respiratory rate to tidal volume (RR/VT), is the most commonly used predictor of weaning success due to its simplicity and ease of interpretation. The clinical utility of the RSBI is emphasized in the 2007 international consensus guidelines for weaning from mechanical ventilation, the 2007 Brazilian consensus guidelines, and the 2013 Brazilian guidelines for mechanical ventilation, all of which recommend its use. MVspont/MVtotal: This ratio reflects the proportion of ventilation that is spontaneous versus mechanical in one minute. A higher spontaneous ventilation (MVspont) relative to total ventilation (MVtotal) indicates that the patient is relying less on mechanical support, which may be reflect favorable for weaning. Peak Cough Flow (PCF): PCF is an indicator of a patient's ability to clear secretions. Secretion retention is a key factor in weaning failure, as it increases respiratory load and is often linked to an ineffective cough. Evaluating cough strength in ICU patients can help predict weaning outcomes, as insufficient cough strength appears to be associated with higher in-hospital mortality. Consequently, assessing cough strength in intubated patients is increasingly being integrated into ICU extubation protocols. The subject is instructed to take a deep breath and cough as forcefully as possible. The clinician then freezes the ventilator screen and measures the maximal expiratory flow (L/min) from the flow curve. Clinicians can use the mechanical ventilator's algorithm if available. The average of three successful measurements will be taken. P0.1: In a study on healthy subjects, Whitelaw et al. conducted random, brief end-expiratory occlusions using a specialized circuit during both resting and CO2 rebreathing. They observed that the decrease in airway pressure (Paw) within the first 100 milliseconds (0.1 s) of an occluded breath remained relatively constant, was consistent for each subject under different conditions, and correlated more strongly with end-tidal CO2 than with minute ventilation. They introduced this parameter as airway occlusion pressure Pocc, or P0.1. P0.1 reflects the inspiratory effort of the patient. It is used to assess the respiratory drive. Normal P0.1 suggests that the patient has adequate respiratory drive to maintain spontaneous breathing. Clinicians can use the mechanical ventilator's algorithm if available. The average of three successful measurements will be taken. Vital Capacity (VC): Vital capacity (VC) reflects the total volume of air a person can exhale after a maximal inhalation. During weaning, a VC of at least 10-15 mL/kg is generally considered adequate for successful extubation. Vital capacity is measured by instructing patients to inhale deeply to their maximum capacity, followed by a forceful exhalation. The clinician then freezes the ventilator screen and measures maximal volume (mL) from the volume curve. Clinicians can use the mechanical ventilator's algorithm if available. The maximum of three successful measurements will be taken. Negative Inspiratory Force (NIF): Negative inspiratory force (NIF), also referred to as maximum inspiratory pressure, reflects the maximal effort of the inspiratory muscles during inhalation against an obstructed airway. This index is used to evaluate respiratory muscle strength, with a value greater than - 30 cm H2O serving as a criterion for initiating the mechanical ventilator weaning process. After exhaling, the patient is given the command to take a deep breath. The clinician freezes the screen when the patient perform the fastest inhalation during expiratory hold maneuver. The clinician measures the minimum pressure from the pressure curve. Clinicians can use the mechanical ventilator's algorithm if available. The minimum of three successful measurements will be taken. Cdyn: Dynamic compliance is a measure of lung and chest wall compliance during mechanical ventilation. High compliance typically indicates less stiff lungs, which is favorable during weaning. It is obtained by dividing the VT by the difference between PIP and PEEP. Secretion: In mechanically ventilated patients, the primary mechanisms of secretion clearance-mucociliary transport and cough-are impaired. Major contributing factors to pulmonary secretion retention include the presence of an artificial airway, insufficient humidification of inspired gases, and limited mobility. Ineffective secretion clearance increases the risk of ventilator dependency and reintubation due to airway obstruction, aspiration, or infection. Agitation/Sedation: Effective management of agitation and sedation is essential for successful weaning in mechanically ventilated patients, as both excessive sedation and agitation can impede the process. Over-sedation reduces respiratory drive, weakens respiratory muscles, prolongs ventilation, and increases the risk of ventilator-associated pneumonia. In contrast, agitation can heighten the work of breathing, increase the risk of self-extubation, and cause cardiovascular strain. The Richmond Agitation-Sedation Scale (RASS) is a 10-point tool that categorizes patient states, ranging from severe agitation (+4, combative) to deep sedation and unresponsiveness (-5), with 0 indicating a calm and alert state. Heart rate: Heart rate is an important indicator of cardiovascular stability during weaning. A significant increase in heart rate during mechanical ventilation or SBTs can signal distress, leading to the suspension of the weaning attempt. Hemoglobin: The impact of hemoglobin levels on weaning outcomes in mechanically ventilated patients remains controversial, with limited data, particularly for those experiencing difficult weaning. Patients with weaning difficulties may benefit more from higher hemoglobin levels than those in the early stages of respiratory failure, as sufficient hemoglobin is essential for adequate oxygen delivery during the weaning process. Lower hemoglobin levels reduce arterial oxygen content, impair oxygen delivery, and increase respiratory muscle workload, potentially hindering successful weaning. %Nutrition Target: Adequate nutrition is essential for survival and reducing hospital stay in critically ill patients, as it supports muscle strength, including respiratory muscles, which is crucial for successful weaning from mechanical ventilation. Malnutrition can impair weaning by weakening respiratory function. To guide evidence-based nutritional therapy, several global guidelines have been published. The American Society for Parenteral and Enteral Nutrition (ASPEN) and the Society of Critical Care Medicine (SCCM) recommend energy intake of 25-30 kcal/kg/day and protein intake of 1.2-2.0 g/kg/day, while the European Society for Parenteral and Enteral Nutrition (ESPEN) suggests 20-25 kcal/kg/day with 1.3 g/kg of protein equivalents per day. Statistical Analysis: Statistical analysis will be performed using IBM SPSS Statistics 26 (IBM Corp., Armonk, NY, USA). Categorical variables will be summarized as numbers (n) and frequencies (%). The Fisher's exact test will be applied for 2×2 contingency tables, and the Chi-square test will be used for all other contingencies to evaluate associations between clinical/demographic characteristics and extubation success or failure. For continuous variables, the Shapiro-Wilk test will be used to assess normality of distribution. Normally distributed variables will be summarized as means (± standard deviation), while non-normally distributed variables will be expressed as medians (with interquartile range). The independent samples Student's t-test will be employed to compare groups for normally distributed variables, and the Mann-Whitney U test will be used for non-normally distributed variables. All parameters with a p-value \< 0.4 in group comparisons (extubation success vs. failure) will be further investigated using univariable logistic regression analysis to assess their association with extubation outcome; odds ratios (OR) and 95% confidence intervals (CI) will be calculated. Receiver operating characteristic (ROC) analysis will be performed to evaluate the predictive value of each parameter. The cutoff values optimizing sensitivity and specificity will be determined using the Youden Index. The REXs cutoffs used in comparisons will be established based on the Youden Index. Finally, REXs cutoff values indicating low, moderate, and high probability of extubation risk will be determined.

The purpose of this study is to evaluate prospectively the safety and performance of the MOBYBOX System in the veno-arterial configuration in patients with cardiorespiratory failure or in the veno-venous configuration in patients with severe respiratory failure.

INTRODUCTION Many newborn infants have difficulty breathing after birth. Some of these babies have a tube inserted into their "windpipe" (trachea) - an endotracheal tube (ETT) - through which they are given breathing support (ventilation). When clinicians attempt to intubate (insert an ETT), they use an instrument called a laryngoscope to view the airway in order to identify the entrance to the trachea (larynx). Standard laryngoscopes have a "blade" (which, despite its name, is not sharp) with a light at the tip. Doctors insert the blade into the baby's mouth to view the larynx. Traditionally, clinicians used a standard laryngoscope to look directly into the baby's mouth to view the larynx (direct laryngoscopy, DL). When clinicians attempt to intubate newborns with DL, less than half of first attempts are successful. Also adverse effects - such as falls in the blood oxygen levels (fall in oxygen saturation (SpO2), or "desaturation"), slowing down of the heart rate (bradycardia), oral trauma - are relatively common. In recent years, video laryngoscopes (VL) have been developed. In addition to a light, VL have a video camera at the tip of the blade. This camera acquires a view of the larynx and displays it on a screen that the clinician views when attempting intubation (indirect laryngoscopy). In a randomised study performed at the National Maternity Hospital, Dublin, Ireland, more infants were successfully intubated at the first attempt when clinicians used VL compared to DL \[79/107 (74%) versus 48/107 (45%), P\<0.001\]. While this study was large enough to show that VL resulted infants being successfully intubated at the first attempt in one hospital, it couldn't give information about how it might work in a range of hospitals, and it wasn't large enough to see what effect VL had on adverse events. There is a large difference in cost between a standard laryngoscope (approx. €300) and a video laryngoscope (approx. €21,000). This is a matter of concern for all hospitals, particularly in settings where resources are more limited. The investigators aim to assess whether VL compared to DL results in more infants being intubated at the first attempt without physiological instability. STUDY DESIGN A recent single centre study reported that that more newborn infants were successfully intubated at the first attempt when VL was used to indirectly view the airway compared to DL. This study was not large enough to determine the effect of VL on adverse effects that are seen commonly (e.g. desaturation) or more rarely (e.g. bradycardia, receipt of chest compressions or adrenaline, oral trauma) during intubation attempts. For the current study, the investigators chose a stepped-wedge cluster randomised controlled design, where the participating centre, rather than the individual infant, will be the unit of randomisation. This design has been found appropriate to test the effects of an intervention that encompasses a behavioural aspect and to implement interventions while studying them at the same time. In this study, all centres will begin in the "control group"; where clinicians will routinely attempt intubation with DL, as is their usual practice. At specified intervals, centres will be randomly assigned to cross over to the "intervention group", where clinicians will routinely attempt intubation with VL. All participating centers will have included patients in both arms by the end of the study. SAMPLE SIZE ESTIMATION To determine the intra-cluster correlation (that means the correlation between two observations from the same centre), the investigators used the dataset of the MONITOR trial that included infants from 7 delivery rooms worldwide. In this trial, the intra-cluster correlation for intubation in the delivery room was reported as 0.1. This complete stepped-wedge cluster-randomized design includes 21 time periods (including the baseline) and 20 centres that will be including patients, with each randomised to a unique sequence. Each time period lasts a fortnight. Each time period, 1 centre will switch their treatment from DL to VL. With all centres including 2 patients each time period, 42 patients will be included per centre which will provide a total sample size of 840 patients. Assuming a control proportion of 0.4, this sample will achieve 90% power (0.9091) to detect a treatment proportion of 0.55, assuming a conservative ICC of 0.05. The power is not very sensitive to ICC values up to 0.1 (power of \>90% to detect difference 40% versus 56%). The test statistic used is the two-sided Wald Z-Test. TREATMENT OF SUBJECTS DIRECT LARYNGOSCOPY (DL, control period) At the start of the study, clinicians at participating centres will attempt intubation using a standard laryngoscope to perform DL as is their normal practice. VIDEO LARYNGOSCOPY (VL, intervention period) For each centre, a lot will be drawn which indicates the month in which endotracheal intubation will be routinely attempted with VL rather than DL. In the month before the switch, centres will be provided with a C-MAC VL by the manufacturers, Karl Storz-Endoskop (Tuttlingen, Germany). The system will be provided on loan for the duration of the study and will consist of an 8" high-definition monitor with connecting cable and reusable straight Miller type blades size 0 and size 1. The equipment will be demonstrated by representatives from Karl Storz, and clinicians who intubate babies at participating hospitals will be encouraged to practice with the equipment on mannequins. We will have an virtual meeting with each centre in the week before they are due to switch to review the protocol, data collection and to answer any queries that they may have. All other procedures in the delivery room and NICU will be performed according to international and local guidelines. All other aspects of the approach to intubation at the participating centre are at the discretion of the local clinicians and should remain the same for the duration of the study; e.g.: * The drugs used before intubation attempts (e.g. opiate, atropine, curare-like drug) * The route by which intubation is usually attempted (i.e. oral or nasal) * Whether they use a stylet is routinely used * Whether supplemental oxygen is given during attempts

Improvements in treatments for people with CF have meant that more are becoming pregnant. CFTR modulators (CFTRm) are one of these treatments. They work by tackling the underlying cause of CF. These changes have created a need and an opportunity for research into the health and experiences of people with CF and their children in the CFTRm era. The study is called 'MATRIARCH\_CF' and includes 3 related sub-studies: 'Mama' is enrolling participants aged 16 years or older with CF under the care of the Royal Brompton Hospital (RBH) adult CF Unit who are planning a pregnancy or pregnant. The aim is to describe the impact of pregnancy and the first 12-24 months of parenthood in females with CF on their physical and psychological health. Investigations in eight visits include blood tests, lung function, imaging, and interviews. 'Mini' is enrolling biological offspring of people with CF (mothers and fathers) cared for by the RBH Adult CF Service, from birth to age two. The aim is to collect information that will allow for assessment of health outcomes in offspring of parents with CF in the short term. There will be up to four visits over two years with investigations including blood tests, sweat tests, and brain ultrasound. 'Midi' explores the same question as 'Mini' but in the longer term for those aged three-to-six. There will be up to two visits, and they include lung function testing and a lung MRI. This study is described as 'observational' as investigators will not provide or change any treatment. Participant's health will be monitored with a range of investigations, many of which are optional. Knowledge gained from this study will be used to create guidelines to help families with CF and their medical teams make decisions around pregnancy and their offspring.

This is an observational study to collect data from Japanese babies with retinopathy of prematurity (ROP) who will be treated with Eylea. In observational studies, only observations are made without specified advice or interventions. ROP is a condition that affects the eye and occurs only in babies who are born too early. Most cases of ROP are mild and get better without treatment, but more serious cases need to be treated in time. ROP happens when the blood vessels in the "retina" grow abnormally. The retina is the layer of tissue at the back of the eye that picks up light and sends messages to the brain. In babies with ROP, these abnormal blood vessels can leak. This causes damage to the retina and can sometimes move it out of place causing medical problems such as blindness. Eylea is received as an injection into the eye. It works by blocking a certain protein (VEGF) that can cause blood vessels in the retina to grow abnormally. Eylea is already available in Japan and is approved for doctors to prescribe to babies with ROP. The participants in this study are Japanese babies with ROP that their doctors decided to treat with Eylea before the start of this study. Babies with ROP that were already prescribed Eylea by their doctors may also be included. The main purpose of this study is to collect more data on how safe the treatment with Eylea is in babies with ROP under a real-world setting. Another purpose of this study is to collect more data on how well Eylea works in these participants. To see how safe Eylea is, the study doctors will collect all medical problems that the participants treated with Eylea have. These medical problems are called adverse events. Doctors keep track of all the adverse events that happen, even if they do not think that they might be related to the treatment. To see how well Eylea works, the study doctors will check the number of participants: * with no active ROP after starting treatment * where ROP came back up to 6 months after start of treatment In this study, the study doctor will: * collect past data of the participants from medical records * interview the participants * collect treatment-related data during routine visits. The study duration is 6 months with 3 planned visits. One visit will be at start of treatment, one at one month and one at 6 months after start of treatment. All data required for this study will be collected during routine visits. Besides this data collection, no further tests or examinations are planned in this study.

The primary objective is to compare the rates of reintubation and post-extubation respiratory failure for high-risk patients with systolic heart failure extubated to HFNC or NIV. Reintubation will be at the discretion of the attending physician. In doing so, this pilot study will provide the framework for an appropriately powered randomized controlled trial.

Acutelines is a prospective biobank including patients with a broad spectrum of acute conditions. Its aim is to facilitate interdisciplinary research on the etiology and development of acute diseases with the aid of systematically collected biomaterials and medical data over various timepoints, both during the course of the patient's disease and after recovery. Clinical data, imaging data and biomaterial (i.e. blood, urine, feces, hair) are collected for patients presenting to the Emergency Department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy), is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure in place and the software used ensures automated capturing of all bed-side monitoring data (i.e. electrophysiological waveforms, vital parameters), and the secure importation of data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration, health insurance companies and pharmacy. Follow up data are collected for all included patients during the first 72-hours of their hospitalization and 3-months, 1-year, 2-years and 5 years after their ED visit. Data and materials to be collected includes: * Demographic and health data (i.e. \[experiences\] health, quality of life, functional status) * Medical history (i.e. co-morbidity, intoxications, medication use) * Admission reason to emergency department * Physical examination and vital parameters * Clinical diagnostic data (i.e. \[point-of-care\] ultrasound, X-ray, CT-scan, laboratory results) * Electrophysiological waveforms (i.e. electrocardiogram \[ECG\], plethysmography) * Biomaterials * Treatment (i.e. medication use, non-pharmacological treatment, treatment decisions, length-of-stay in hospital, admission to intensive care unit \[ICU\])

When the transition from intrauterine to extrauterine life necessitates Neonatal Resuscitation, specialized monitoring of vital signs is required. Sudden Unexpected Postnatal Collapse (SUPC) is an apnea or cardiorespiratory failure occurring in otherwise healthy near-term or term neonates, usually in the first 48 hours of age, during the initial Kangaroo Mother Care (KMC) in the obstetrical center. SUPC carries a high morbidity and mortality rate. Approximately 10 million babies do not breathe immediately after birth, and 60% require basic resuscitation interventions. Sudden Unexpected Postnatal Collapse has been estimated to occur in 2.6-133 cases per 100.000 newborns and over 50% of the cases occur following accidental suffocation, which frequently goes unrecognised by parents in the obstetrical center during unsupervised KMC. Current guidelines recommend monitoring of heart rate (HR), oxygen saturation (SpO2), and skin temperature (Tskin) during neonatal resuscitation. This is usually achieved by using wired electrodes and sensors that require expensive and large base units attached to a power supply. SUPC is a rare but largely preventable cause of neonatal mortality that deserves particular attention. Better resuscitation and prevention of SUPC might be achieved by continuous non-intrusive monitoring of vital signs immediately after delivery and while in the obstetrical center. This research will address a very important gap in care; the need for safe and accurate advanced, non-invasive, and non-intrusive wireless technologies for monitoring of vital signs immediately after birth and during the immediate postnatal care, potentially preventing cases of SUPC while in the obstetrical center. Reliable and low-cost wireless monitoring that could be used immediately after delivery would promote widespread adoption of neonatal resuscitation recommendations in low and middle income countries, improve detection of vital signs quickly after delivery and during early unsupervised KMC, and optimize neonatal care in the obstetrical centers or during hospital stay, to prevent cases of SUPC and its associated high mortality.

The goal of a pilot study is to test a study plan to see if it is appropriate for a larger study. This study plan is looking at whether the use of inhaled sedatives (medications that help people be calm and sleep) can reduce delirium (extreme confusion) in children who need a ventilator (breathing machine) compared to IV or oral sedatives. The main question\[s\] it aims to answer are: * Will people join the study? (recruitment) * Will participants finish the study? * Will healthcare teams accept the study procedures? Participants will be randomized to receive study treatment (inhaled sedation) or standard of care (IV sedation). They will be monitored daily for up to 28 days. They will complete memory, thinking and behaviour tasks after 9-12 months.