High incidence of acute lung injury in children with Down syndrome

OBJECTIVE: Acute respiratory tract infection is a common reason for hospitalization in children with Down syndrome (CDS) and is characterized by a high morbidity. The severe course of disease in CDS may be related to a higher incidence of acute lung injury (ALI). This study evaluated the incidence of ALI and acute respiratory distress syndrome (ARDS) in mechanically ventilated CDS. DESIGN AND SETTING: Retrospective cohort study in a pediatric ICU. PATIENTS AND PARTICIPANTS: Cases were all mechanically ventilated CDS admitted to our unit between January 1998 and July 2005. All mechanically ventilated patients without Down syndrome from January 1998 to January 2001 served as controls. Postoperative patients (cases and controls) and those with a cardiac left to right shunt were excluded. MEASUREMENTS AND RESULTS: The main outcome measure was the incidence of ALI and ARDS. The criteria for ALI were met in 14 of 24 CDS (58.3%) in 41 of 317 of controls (12.9%; OR 9.4, 95% CI 3.9-22.6). The criteria for ARDS were met in 11 of 24 CDS (46%) and in 21 of 317 of controls (7%; OR 11.9, 95% CI 4.8-29.8). None of the CDS with ALI died; in the control group ten patients with ALI died. CONCLUSIONS: CDS had a significantly higher incidence of ALI and ARDS than children without Down syndrome. The explanation for this remains to be elucidated; further study is necessary before clinical implications become clea

Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study):a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40–50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU). METHODS: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H(2)O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS. TRIAL REGISTRATION: ClinicalTrials.govNCT02902055. Registered on September 15, 2016

Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU:a randomized controlled trial

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups. Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences

How doctors actually (do not) involve families in decisions to continue or discontinue life-sustaining treatment in neonatal, pediatric, and adult intensive care: a qualitative study

Background: Intensive care doctors have to find the right balance between sharing crucial decisions with families of patients on the one hand and not overburdening them on the other hand. This requires a tailored approach instead of a model based approach. Aim: To explore how doctors involve families in the decision-making process regarding life-sustaining treatment on the neonatal, pediatric, and adult intensive care. Design: Exploratory inductive thematic analysis of 101 audio-recorded conversations. Setting/participants: One hundred four family members (61% female, 39% male) and 71 doctors (60% female, 40% male) of 36 patients (53% female, 47% male) from the neonatal, pediatric, and adult intensive care of a large university medical center participated. Results: We identified eight relevant and distinct communicative behaviors. Doctors' sequential communicative behaviors either reflected consistent approaches-a shared approach or a physician-driven approach-or reflected vacillating between both approaches. Doctors more often displayed a physician-driven or a vacillating approach than a shared approach, especially in the adult intensive care. Doctors did not verify whether their chosen approach matched the families' decision-making preferences. Conclusions: Even though tailoring doctors' communication to families' preferences is advocated, it does not seem to be integrated into actual practice. To allow for true tailoring, doctors' awareness regarding the impact of their communicative behaviors is key. Educational initiatives should focus especially on improving doctors' skills in tactfully exploring families' decision-making preferences and in mutually sharing knowledge, values, and treatment preferences.Analysis and support of clinical decision makin

Daily interruption of sedation in critically ill children: Study protocol for a randomized controlled trial

Background: In adult patients who are critically ill and mechanically ventilated, daily interruption of sedation (DSI) is an effective method of improving sedation management, resulting in a decrease of the duration of mechanical ventilation, the length of stay in the intensive care unit (ICU) and the length of stay in the hospital. It is a safe and effective approach and is common practice in adult ICUs. For critically ill children it is unknown if DSI is effective and feasible. The aim of this multicenter randomized controlled trial is to evaluate the safety and

The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial

Objective To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections

Epidemiology and Outcome of Critically Ill Pediatric Cancer and Hematopoietic Stem Cell Transplant Patients Requiring Continuous Renal Replacement Therapy: A Retrospective Nationwide Cohort Study

Objective: Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU. Design: A nationwide, multicenter, retrospective, observational study. Setting: Eight PICUs of a tertiary care hospitals in the Netherlands. Patients: Pediatric cancer and hematopoietic stem cell transplan

Relational Algebra Processor

Import 22/07/2015Cílem této práce je navrhnout a implementovat procesor relační algebry, který bude vykonávat příkazy nad daty a~zároveň vytvoří plán spouštění. S~tím souvisí návrh jazyka a~implementace jeho operátorů. Také je třeba představit relační algebru, čímž se bude zabývat úvod práce a porovnáním programu s~existujícími procesory v závěru práce.Main goal of this thesis is design and implementation of relational algebra processor capable of executing queries over actual data and creating execution plan, which will be stored in tree structure. Another thing associated with processor is design of language and implementation of its operators. Another very important topic is relation algebra itself, which will be described at the first part of the thesis. Last part of thesis is to compare my processor with already existing programs.460 - Katedra informatikyvýborn

Argumentation in end-of-life conversations with families in Dutch intensive care units: a qualitative observational study

PurposeIn intensive care units (ICUs), decisions about the continuation or discontinuation of life-sustaining treatment (LST) are made on a daily basis. Professional guidelines recommend an open exchange of standpoints and underlying arguments between doctors and families to arrive at the most appropriate decision. Yet, it is still largely unknown how doctors and families argue in real-life conversations. This study aimed to (1) identify which arguments doctors and families use in support of standpoints to continue or discontinue LST, (2) investigate how doctors and families structure their arguments, and (3) explore how their argumentative practices unfold during conversations.MethodA qualitative inductive thematic analysis of 101 audio-recorded conversations between doctors and families.ResultsSeventy-one doctors and the families of 36 patients from the neonatal, pediatric, and adult ICU (respectively, N-ICU, P-ICU, and A-ICU) of a large university-based hospital participated. In almost all conversations, doctors were the first to argue and families followed, thereby either countering the doctor's line of argumentation or substantiating it. Arguments put forward by doctors and families fell under one of ten main types. The types of arguments presented by families largely overlapped with those presented by doctors. A real exchange of arguments occurred in a minority of conversations and was generally quite brief in the sense that not all possible arguments were presented and then discussed together.ConclusionThis study offers a detailed insight in the argumentation practices of doctors and families, which can help doctors to have a sharper eye for the arguments put forward by doctors and families and to offer room for true deliberation.Analysis and support of clinical decision makin