Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands: a nationwide prospective observational study (the BRICK study).

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity. Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25-89). The median length of PICU admission was 5 days (IQR 3-8). The total RSV-related PICU costs are € 3,826,386 in 2021-2022, and € 3,183,888 in 2022-2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. Funding: None.

Treatment of Post-Coarctectomy Hypertension With Labetalol-A 9-Year Single-Center Experience.

BACKGROUND: Although considering the pathophysiology of post-coarctectomy hypertension, ß-blockers should be effective, experience with labetalol for treatment is limited in the literature. METHODS: Retrospective collection and analysis of data in children aged ≤6 years following coarctectomy in our tertiary care university medical center between January 2009 and June 2018. RESULTS: 96 patients were included, 45 were treated with intravenous labetalol and 51 received no treatment. Median time to maximum dose received (median 1.1 mg/kg/h) was 2.7 h, and median time to the reduction of labetalol dose was 8.3 h. No antihypertensives had to be added. In one child, labetalol was switched to nitroprusside due to bronchoconstriction. Of patients receiving intravenous labetalol, 48% had been switched to oral labetalol at discharge. CONCLUSIONS: Intravenous labetalol is a fast, effective, and safe drug to treat hypertension following aortic coarctation repair. Labetalol is easily converted to oral therapy when the continuation of treatment is considered necessary.

Risk factors for intensive care admission in children with severe acute asthma in the Netherlands: a prospective multicentre study.

RATIONALE: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). OBJECTIVES: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. METHODS: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. MEASUREMENTS AND MAIN RESULTS: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. CONCLUSIONS: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors.

Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit.

BACKGROUND: S-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AIMS: The aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18 years during long-term sedation. Twenty-five children (median age: 0.42 years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6 mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4 hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the ¾ power model. RESULTS: A total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS-KETAMINE =112 L/h/70 kg, V1S-KETAMINE =7.7 L/70 kg, V2S-KETAMINE =545L/70 kg, QS-kETAMINE =196 L/h/70 kg, and CLS-NORKETAMINE =53 L/h/70 kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. CONCLUSION: Substantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation.

Reliability and validity of functional health status and health-related quality of life questionnaires in children with recurrent acute otitis media.

In this study the reliability and validity of generic and disease-specific questionnaires has been assessed focusing on responsiveness. This is part of a study on the effects of recurrent acute otitis media (rAOM) on functional health status (FHS) and health-related quality of life (HRQoL) in 383 children with rAOM participating in a randomized clinical trial. The following generic questionnaires were studied: 1. RAND general health rating index, 2. Functional Status Questionnaire (FSQ Generic and FSQ Specific), 3. TNO-AZL Infant Quality of Life (TAIQOL), and the following disease-specific questionnaires: 1. Otitis Media-6 (OM-6), 2. Numerical rating scales (NRS) for child and caregiver (NRS Child and NRS Caregiver), and 3. a new Family Functioning Questionnaire (FFQ). Reliability was good to excellent (Cronbach's alpha range 0.80-0.90, intraclass correlation coefficient range 0.76-0.93). Moderate to strong correlations were found between the questionnaires as well as between questionnaires and relevant clinical indicators (r = 0.29-0.49), demonstrating construct validity. Discriminant validity for children with few versus frequent episodes of acute otitis media per year was good for most questionnaires (P < 0.004) but poor for the otitis media-related subscales of the TAIQOL (P = 0.10-0.97) and both NRS (P = 0.22 and 0.48). Except for the TAIQOL subscales, change scores were significant (P < 0.003) for generic and disease-specific questionnaires. Effect sizes were somewhat higher for disease-specific compared to generic questionnaires (0.55-0.95 versus 0.32-0.60) except for the TAIQOL subscales, which showed very poor sensitivity to change. Anchor-based methods resulted in a somewhat larger range of estimates of MCID than distribution-based methods. Combining distribution-based and anchor-based methods resulted in similar ranges for the minimally clinical important differences for generic and disease-specific questionnaires: 2-15 points on a 0-100 scale. Apart from the generic TAIQOL subscales, both generic and disease-specific questionnaires used in this study showed good psychometric qualities and responsiveness for use in clinical studies on children with rAOM.

Health-related quality of life in children with otitis media.

BACKGROUND: Growing interest in health-related quality of life (HRQoL) in children with otitis media has brought the need to study the currently available HRQoL instruments with respect to their results and their applicability in clinical practice and research of otitis media. OBJECTIVE: To review existing literature on health-related quality of life research in children with otitis media with respect to: (1) the measured impact of otitis media on HRQoL; and (2) the applicability of HRQoL instruments used in research and clinical practice based on their characteristics and contents. METHODS: A search was performed in EMBASE (1988-November 2004) and on NLM Gateway (1966-November 2004) for studies assessing health-related quality of life or functional health status by means of disease-specific or generic questionnaires in children aged 0-18 years with chronic or recurrent otitis media with effusion or acute otitis media. The bibliographies of the selected articles were searched manually. RESULTS: Only 13 of the 141 retrieved articles retrieved fulfilled the criteria for inclusion. In these studies, physical suffering (pain, high fever, etc.), difficulties with hearing or speech, behavioural problems, or emotional distress were reported to be the most important problems experienced by children with otitis media. Almost all instruments applied in these studies measure functional health status instead of health-related quality of life. Data on validity and reliability of these instruments are incomplete. CONCLUSIONS: Recurrent or chronic otitis media is reported to have a substantial and negative effect on various domains of functional health status and health-related quality of life of children. The OM-6 appears to be the best available instrument to assess functional health status in children with OM in a research setting. However, the lack of true HRQoL instruments as well as incomplete data on their reliability and validity, limit both our current knowledge of HRQoL in OM and the application of current instruments in both research and clinical practice.

Effect of pneumococcal vaccination on quality of life in children with recurrent acute otitis media: a randomized, controlled trial.

BACKGROUND: Limited effectiveness of current treatment strategies for recurrent acute otitis media (RAOM) and increasing antibiotic resistance have diverted attention to prevention of AOM by vaccination. Pneumococcal vaccination for AOM seems to have only modest clinical efficacy. Thus far, the effects on health-related quality of life (HRQoL) or functional health status (FHS) have not been studied. OBJECTIVE: To assess the effect of vaccination on HRQoL or FHS. METHODS: In a double-blind, randomized, controlled trial, 383 children 1 to 7 years old with RAOM were vaccinated with either heptavalent pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine (pneumococcal group: n = 190) or with hepatitis A or B vaccines (control group: n = 193). Parents completed validated Dutch versions of 8 HRQoL and FHS instruments assessing generic FHS (Rand, Functional Status Questionnaire specific, and Functional Status Questionnaire generic), otitis media-specific FHS (OM-6), otitis media-specific child HRQoL (Numerical Rating Scale for Child), family functioning (Family Functioning Questionnaire), and otitis media-specific caregiver HRQoL (Numerical Rating Scale for Caregiver). Scores were compared at baseline and at 14 and 26 months' follow-up. RESULTS: At baseline, the average AOM incidence in the pneumococcal and control group was 5.0 (SD: 2.8) and 4.9 (SD: 2.6) episodes per year, respectively, with 38.4% and 36.8% having suffered from > or =6 episodes per year. AOM frequency decreased 4.4 episodes per year in both groups, with a considerable and comparable improvement in HRQoL and FHS. No substantial differences in HRQoL or FHS were found between the pneumococcal and the control group at baseline or at 14 or 26 months' follow-up. CONCLUSION: Pneumococcal vaccination has no beneficial effect compared with control vaccination on either HRQoL or FHS in children 1 to 7 years old with RAOM.