Enhance quality care performance: Determination of the variables for establishing a common database in French paediatric critical care units

Abstract Selected variables for the French Paediatric Intensive Care registry. Rationale, aims, and objectives Providing quality care requires follow-up in regard to clinical and economic activities. Over the past decade, medical databases and patient registries have expanded considerably, particularly in paediatric critical care medicine (eg, the Paediatric Intensive Care Audit Network (PICANet) in the UK, the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry in Australia and New Zealand, and the Virtual Paediatric Intensive Care Unit Performance System (VPS) in the USA). Such a registry is not yet available in France. The aim of this study was to determine variables that ought to be included in a French paediatric critical care registry. Methods Variables, items, and subitems from 3 foreign registries and 2 French local databases were used. Items described each variable, and subitems described items. The Delphi method was used to evaluate and rate 65 variables, 90 items, and 17 subitems taking into account importance or relevance based on input from 28 French physicians affiliated with the French Paediatric Critical Care Group. Two ratings were used between January and May 2013. Results Fifteen files from 10 paediatric intensive care units were included. Out of 65 potential variables, 48 (74%) were considered to be indispensable, 16 (25%) were considered to be optional, and 1 (2%) was considered to be irrelevant. Out of 90 potential items, 62 (69%) were considered to be relevant, 23 (26%) were considered to be of little relevance, and 5 (6%) were considered to be irrelevant. Out of 17 potential subitems, 9 (53%) were considered to be relevant, 6 (35%) were considered to be of little relevance, and 2 (12%) were considered to be irrelevant. Conclusions The necessary variables that ought to be included in a French paediatric critical care registry were identified. The challenge now is to develop the French registry for paediatric intensive care units

SMAD6 overexpression leads to accelerated myogenic differentiation of LMNA mutated cells

Abstract LMNA gene encodes lamins A and C, two major components of the nuclear lamina, a network of intermediate filaments underlying the inner nuclear membrane. Most of LMNA mutations are associated with cardiac and/or skeletal muscles defects. Muscle laminopathies include Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy 1B, LMNA-related Congenital Muscular Dystrophy and Dilated Cardiomyopathy with conduction defects. To identify potential alterations in signaling pathways regulating muscle differentiation in LMNA-mutated myoblasts, we used a previously described model of conditionally immortalized murine myoblasts: H-2K cell lines. Comparing gene expression profiles in wild-type and Lmna ∆8–11 H-2K myoblasts, we identified two major alterations in the BMP (Bone Morphogenetic Protein) pathway: Bmp4 downregulation and Smad6 overexpression. We demonstrated that these impairments lead to Lmna ∆8–11 myoblasts premature differentiation and can be rescued by downregulating Smad6 expression. Finally, we showed that BMP4 pathway defects are also present in myoblasts from human patients carrying different heterozygous LMNA mutations

Deciphering DSC2 arrhythmogenic cardiomyopathy electrical instability: From ion channels to ECG and tailored drug therapy

International audienceBackground: Severe ventricular rhythm disturbances are the hallmark of arrhythmogenic cardiomyopathy (ACM), and are often explained by structural conduction abnormalities. However, comprehensive investigations of ACM cell electrical instability are lacking. This study aimed to elucidate early electrical myogenic signature of ACM.Methods: We investigated a 41‐year‐old ACM patient with a missense mutation (c.394C>T) in the DSC2 gene, which encodes desmocollin 2. Pathogenicity of this variant was confirmed using a zebrafish DSC2 model system. Control and DSC2 patient‐derived pluripotent stem cells were reprogrammed and differentiated into cardiomyocytes (hiPSC‐CM) to examine the specific electromechanical phenotype and its modulation by antiarrhythmic drugs (AADs). Samples of the patient's heart and hiPSC‐CM were examined to identify molecular and cellular alterations.Results: A shortened action potential duration was associated with reduced Ca2+ current density and increased K+ current density. This finding led to the elucidation of previously unknown abnormal repolarization dynamics in ACM patients. Moreover, the Ca2+ mobilised during transients was decreased, and the Ca2+ sparks frequency was increased. AAD testing revealed the following: (1) flecainide normalised Ca2+ transients and significantly decreased Ca2+ spark occurrence and (2) sotalol significantly lengthened the action potential and normalised the cells’ contractile properties.Conclusions: Thorough analysis of hiPSC‐CM derived from the DSC2 patient revealed abnormal repolarization dynamics, prompting the discovery of a short QT interval in some ACM patients. Overall, these results confirm a myogenic origin of ACM electrical instability and provide a rationale for prescribing class 1 and 3 AADs in ACM patients with increased ventricular repolarization reserve

Accurate height and length estimation in hospitalized children not fulfilling WHO criteria for standard measurement: a multicenter prospective study

Purpose: In hospitalized children, height should be measured. When world health organization (WHO) height measurement gold standards is impossible, the ideal height estimation technique is still unclear.Methods: We conducted an international prospective study in 8 different pediatric intensive care units to assess the accuracy, precision, practicability, safety, and inter-rater reliability of 12 different height estimation techniques, based on body segment measurement extrapolation, or other calculations using previous or projected heights. All extrapolation techniques were performed on each child, and later compared to their WHO gold standard heights.Results: 476 patients were enrolled. In the &lt;2-year subgroup, board length use and growth chart extrapolation performed best. In the ≥2-year subgroup, growth chart extrapolation and parents’ report were the most accurate, followed by height measurement alongside the body with a tape measure. In both groups, body segment extrapolations were poorly predictive and showed mean bias and limits of agreement that varied a lot with age. Most body segment-based techniques presented with frequent measurement difficulties, but children’s safety was rarely compromised. The inter-rater reliability of body segment measurement was low in the &lt;2-year subgroup. Conclusions: To accurately estimate height in hospitalized children, health care professionals should integrate the accuracy, precision, practicability, and reliability of each measurement technique to select the most appropriate one. Body segment-based techniques were the least accurate and should probably not be used. Simple techniques like growth chart extrapolation, or measurement alongside the body (and length board measurement in the youngest) should be implemented in daily practice. <br/

Clinical practice guidelines: management of severe bronchiolitis in infants under 12&nbsp;months old admitted to a pediatric critical care unit.

International audiencePurposeWe present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines.MethodsTwenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French‐speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies. The questions were written in the Patient-Intervention-Comparison-Outcome (PICO) format. An extensive Anglophone and Francophone literature search indexed in the MEDLINE database via PubMed, Web of Science, Cochrane and Embase was performed using pre-established keywords. The texts were analyzed and classified according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. When this method did not apply, an expert opinion was given. Each of these recommendations was voted on by all the experts according to the Delphi methodology.ResultsThis group proposes 40 recommendations. The GRADE methodology could be applied for 17 of them (3 strong, 14 conditional) and an expert opinion was given for the remaining 23. All received strong approval during the first round of voting.ConclusionThese guidelines cover the different aspects in the management of severe bronchiolitis in infants admitted to pediatric critical care units. Compared to the different ways to manage patients with severe bronchiolitis described in the literature, our original work proposes an overall less invasive approach in terms of monitoring and treatment

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes