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ObjectivesLevofloxacin is widely used because of its broad-spectrum antimicrobial activity and convenient dosing schedule. However, the relevance of its use in children remains to be investigated. The purpose of this study is to investigate the efficacy and safety of levofloxacin use in children with severe infections.MethodsWe conducted a retrospective observational study of patients

Aims: Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics. Methods: Ultra‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann–Whitney U test corrected by Benjamini‐Hochberg and partial least squares discriminant analysis (PLS‐DA). Results: The PLS‐DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS‐DA with R2Y = 0.992 and Q2 = 0.798). A total of 49 prognosis‐related metabolites were identified. Of these metabolites, 20 including glutamyl‐glutamine, 3‐iodothyronamine, and L‐fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl‐glutamine and 3‐iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis. Conclusions: This study highlighted the prognosis‐related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl‐glutamine and 3‐iodothyronamine with high predictive value was established. [ABSTRACT FROM AUTHOR]

Objectives: To develop a population pharmacokinetic model of meropenem in children with sepsis receiving extracorporeal life support (ECLS) and optimize the dosage regimen based on investigating the probability of target attainment (PTA). Methods: The children with sepsis were prospectively enrolled in a pediatric intensive care unit from January 2018 to December 2019. The concentration-time data were fitted using nonlinear mixed effect model approach by NONMEM program. The stochastic simulation considering various scenarios based on proposed population pharmacokinetics model were conducted, and the PTAs were calculated to optimize the dosage regimens. Results: A total of 25 children with sepsis were enrolled, of whom13 received ECMO, 9 received CRRT, and 4 received ECMO combined with CRRT. 12 children received a two-step 3-h infusion and 13 children received 1-h infusion. Bodyweight and creatinine clearance had significant impacts on the PK parameters. ECMO intervention was not related to the PK properties. If 100%T > MIC was chosen as target, children receiving 40 mg/kg q8h over a 3 h-infusion only reached the PTA up to 77.4%. If bacteria with MIC 2 mg/L were to be treated with meropenem and the PTA target was 50%T > MIC, a dose of 40 mg/kg q8h for 1 h infusion would be necessary. Conclusions: The PK properties of meropenem in septic children receiving extracorporeal life support were best described. We recommended the opitimized dosing regimens for septic children receiving ECLS depending on the PTA of PK target 50%T > MIC and 100%T > MIC, for children with sepsis during ECLS with different body weight, estimated creatinine clearance (eCRCL) and MIC of bacteria. [ABSTRACT FROM AUTHOR]

The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. We conducted a retrospective case–control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality. [ABSTRACT FROM AUTHOR]

Summary: What is known and Objective: Meropenem, a broad‐spectrum carbapenem, is frequently used to treat severe bacterial infections in critically ill children. Recommendations for meropenem doses in adult infections are available; however, few studies have been published regarding the use of meropenem in children with sepsis, especially in those receiving continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). We aimed to investigate the pharmacokinetic (PK) parameters of meropenem in children with sepsis receiving extracorporeal life support (ECLS). Methods: This was a prospective observational clinical study of children with sepsis receiving ECMO or CRRT in the paediatric intensive care unit (PICU) of a children's hospital. The enrolled children received 20 mg/kg meropenem infusion over 1 hour, every 8 hours, and were grouped into children receiving ECMO, children receiving CRRT and children receiving neither ECMO nor CRRT. Plasma meropenem concentrations were determined using a validated high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS). The key PK parameters were determined using the non‐compartmental approach. Results and discussion: Twenty‐seven patients were finally enrolled. The eCLCR of the CRRT group was lower than that of the ECMO group. The values of elimination half‐life (t1/2), area under the plasma concentration‐time curve (AUCtau), area under the plasma concentration‐time curve from time zero to infinity (AUC0‐∞), and total clearance (CL) in the ECMO group were not different from those of the other groups (all p > 0.05). However, the AUCtau (p = 0.0137) and AUC0‐∞ (p = 0.0234) significantly decreased after filtration through a hemofiltration membrane in patients receiving CRRT. What is new and Conclusion: No significant alterations in the PK parameters of meropenem occurred in children with sepsis administered ECMO and/or CRRT. Further investigations including PK modelling could provide evidence for appropriate meropenem dosing regimens during ECLS administration. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE).Methods: Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed.Results: Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI]: 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI: 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants.Conclusion: This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology. [ABSTRACT FROM AUTHOR]

Purpose: To describe the aetiology, clinical features, and short-term outcomes of children with status epilepticus (SE), in particular super-refractory SE (SRSE), by a nationwide multicentre study in China.Methods: In this retrospective study, inpatient children with SE were identified from neurology departments and paediatric intensive care units from 44 hospitals in 27 provinces of China between 2013 and 2015. Clinical data were exported from the Hospital Information System.Results: Clinical records from children with SE (n = 4255) aged 1 month to 18 years were enrolled; 13.1 % were diagnosed with SRSE. The most common known SE aetiology was acute symptomatic aetiology (42.8 %) and 50.2 % of SE was caused by epilepsy of unknown aetiology. Acute central nervous system (CNS) infections (38.8 %) were associated with SRSE (P < 0.001). The overall SE in-hospital mortality rate was 3.0 %, which was significantly higher in the children with SRSE than in those with non-SRSE (15.2 % versus 1.4 %, respectively; P < 0.001). Fourteen percent of the children with SE had various levels of neurological dysfunction at discharge. SRSE was a risk factor for in-hospital mortality (hazard ratio = 4.14; 95 % confidence interval [CI]: 2.34-7.32; P < 0.001) and neurological dysfunction at discharge (odds ratio = 2.85; 95 % CI: 1.90-4.27; P < 0.001).Conclusion: Acute symptomatic aetiology was the most common known cause of paediatric SE. Aetiology was associated with progression to SRSE and short-term neurological dysfunction at discharge. Furthermore, SRSE was considered a risk factor for in-hospital mortality and short-term neurological dysfunction. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Nursing-sensitive indicators are considered effective tools for improving the quality of care in hospitals. However, these have not been used in paediatric intensive care units ( PICUs) in China. Aim To develop nursing-sensitive indicators for PICUs and to assess the quality of nursing in PICUs in China based on the nursing-sensitive indicators. Design Multi-centre, cross-sectional study. Methods Structure, process and outcome indicators were developed and measured from 1 January to 31 March 2014 in seven PICUs in China. Results The structure indicators showed that one nurse cared for an average of 2·8 patients in a PICU, and 44% of nurses had a bachelor's degree. The process indicators revealed that hand-washing compliance varied across PICUs, whereas pain management and physical restraint have not been adequately addressed in China. The outcome indicators revealed that the incidence rates of ventilator-associated pneumonia and central-line-associated blood stream infections were 2·96 and 0·7, respectively, per 1000 device days. Patients were intubated for a total of 4392 mechanical ventilator days, and 32 patients (7·29‰) had an unplanned extubation. Nurses were moderately satisfied in their jobs (3·1 ± 0·3), and parents reported that nurses provide high quality of care. Conclusions This study developed and used nursing-sensitive indicators to assess the quality of nursing in PICUs in China, which provided a reference for national and international comparisons of nursing quality in PICUs. Nursing staffing levels and education should be improved. Pain management and physical restraints should be regulated in China's PICUs. Nurse managers need to explore staff attitudes towards implementation of family-centred care. The development of a national database of nursing quality indicators can contribute to quality and safety improvement. Relevance to clinical practice This study developed a set of nursing-sensitive indicators, and these indicators were used to assess and improve the quality of nursing in PICUs. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Definitions for pediatric sepsis were established in 2005 without data-driven criteria. It is unknown whether the more recent adult Sepsis-3 definitions meet the needs of providers caring for children. We aimed to explore the use and applicability of criteria to diagnose sepsis and septic shock in children across the world. METHODS: This is an international electronic survey of clinicians distributed across international and national societies representing pediatric intensive care, emergency medicine, pediatrics, and pediatric infectious diseases. Respondents stated their preferences on a 5-point Likert scale. RESULTS: There were 2835 survey responses analyzed, of which 48% originated from upper-middle income countries, followed by high income countries (38%) and low or lower-middle income countries (14%). Abnormal vital signs, laboratory evidence of inflammation, and microbiologic diagnoses were the criteria most used for the diagnosis of "sepsis." The 2005 consensus definitions were perceived to be the most useful for sepsis recognition, while Sepsis-3 definitions were stated as more useful for benchmarking, disease classification, enrollment into trials, and prognostication. The World Health Organization definitions were perceived as least useful across all domains. Seventy one percent of respondents agreed that the term sepsis should be restricted to children with infection-associated organ dysfunction. CONCLUSIONS: Clinicians around the world apply a myriad of signs, symptoms, laboratory studies, and treatment factors when diagnosing sepsis. The concept of sepsis as infection with associated organ dysfunction is broadly supported. Currently available sepsis definitions fall short of the perceived needs. Future diagnostic algorithms should be pragmatic and sensitive to the clinical settings. [ABSTRACT FROM AUTHOR]

• SE in children was a cost intensive disease in China. • The median inpatient medical cost of children with SE was $1175.5 (665.1–2320.6). • Cost-driving factors including LOS, etiology and examinations, and treatments. • PFS and idiopathic/cryptogenic epilepsy were associated with a lower cost. To describe the inpatient medical cost during hospitalization in children with status epilepticus (SE) and identify factors associated with the cost by a nationwide, multicenter study in China. We retrospectively identified pediatric inpatients with SE form Hospital Information System (HIS) of 44 hospitals in 27 provinces in China between 2013 and 2015. Inpatient medical cost and factors associated with the cost were analyzed. A total of 4041 children diagnosed with SE with inpatient medical cost were enrolled in the present study. The median age at admission was 2.9 (range 0.1–18) years, and 2271 patients were male (56.2%). The median inpatient medical cost of children with SE was $1175.5 (665.1–2320.6). The median inpatient medical cost was $3865.6 (1837.4–8210.4) in children with SRSE and $1048.6 (619.8–1865.4) in those with N-SRSE (p < 0.0001). Children with length of hospital stay (LOS) > 7 showed a much higher inpatient medical cost than those with LOS ≤ 7 day ($2300.7 vs. $767.2, p < 0.0001). Regarding different etiologies, children with acute symptomatic etiology showed the highest median inpatient medical cost of $1681.1 (901.0–3699.6), in which children with central nervous system (CNS) infection reported $2606.0 (1380.0–5016.1) and prolonged febrile seizures (PFS) reported $909.8 (649.3–1322.0). Additionally, children with idiopathic/cryptogenic etiology reported a medical cost of $923.2 (548.9–1534.5). Multiple linear regression analysis of cost-driving factors revealed LOS > 7, examinations, treatment equipment and procedures, and treatment medicines were independently associated with a higher inpatient medical cost (R 2 = 60.91). In addition, PFS and idiopathic/cryptogenic epilepsy etiology were independently associated with a lower cost. SE in children was a cost intensive disease in China with a median inpatient medical cost of $1175.5. LOS, etiology and examinations, treatment equipment and procedures, and treatment medicines were significantly associated with inpatient medical cost. [ABSTRACT FROM AUTHOR]