Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

New Resident Training Strategy Based on Gamification Techniques: An Escape Room on Sepsis in Children.

AIM: Adapting "escape rooms" for educational purposes is an innovative teaching method. The aim of this study was to ascertain the degree of learning of the residents. A secondary objective was to determine their degree of satisfaction. METHODS: A prospective, observational study took place in October 2019. A sepsis-based escape room was designed and carried out. A mix of paediatric medical residents and paediatric nursing residents were enrolled. A prior knowledge test was carried out, which was repeated right at the end of the escape room and then again three months later. Furthermore, all participants completed an anonymous post-study survey. RESULTS: We enrolled 48 residents, 79.2% of whom were women. The mean score for the pre-escape room exam was 7.85/9 (SD 1.65), that for the post-escape room exam was 8.75/9 (SD 0.53), and for the exam three months later, it was 8.30/9 (SD 0.94). Among the participants, 18.8% did not manage to leave before the established 60 min time limit. The results of the satisfaction survey showed high participant satisfaction. CONCLUSIONS: The escape room proved to be a valuable educational game that increased students' knowledge of sepsis management and showed a positive overall perceived value among the participants.

Ventilator-associated events in children: A multicentre prospective cohort study.

BACKGROUND: The Centres for Disease Control and Prevention (CDC) broadened the focus of surveillance from ventilator-associated pneumonia to ventilator-associated event (VAE) for quality purposes. No paediatric definition of VAE (PaedVAE) has been accurately validated. We aimed to analyse the incidence and impact on patient outcomes resulting from the application of the adult and two paediatric VAE (PaedVAE) criteria. SECONDARY OBJECTIVE: to evaluate VAE/PaedVAE as factors associated with increased duration of mechanical ventilation (MV) and Paediatric Intensive Care Unit (PICU) stay. METHODS: Multicentre observational prospective cohort study in 15 PICUs in Spain. VAEs were assessed using the 2013/2015 CDC classification. PaedVAE were assessed using the CDC definition based on mean airway pressure (MAP-PaedVAE) versus a paediatric definition based on positive end-expiratory pressure (PEEP-PaedVAE). Children who underwent MV ≥ 48 h were included. RESULTS: A total of 3626 ventilator-days in 391 patients were analysed. The incidence of VAE, MAP-PaedVAE and PEEP-PaedVAE was 8.55, 5.24 and 20.96 per 1000 ventilator-days, respectively. The median time [IQR] for VAE, MAP-PaedVAE and PEEP-PaedVAE development from the MV onset was 4 [3-12.5], 4 [3-14], and 5 [3-7.75] days, respectively. Among survivors, all three were associated with increased MV duration (> 7 days) and PICU stay (> 10 days) at univariate analysis. Multivariate analysis showed that PEEP-PaedVAE was the only definition independently associated with MV above 7 days [OR = 4.86, 95% CI (2.41-10.11)] and PICU stay [OR = 3.49, 95% CI (1.68-7.80)] above ten days, respectively. CONCLUSIONS: A VAE definition based on slight PEEP increases should be preferred for VAE surveillance in children.

Risk factors and incidence of invasive bacterial infection in severe bronchiolitis: the RICOIB prospective study.

BACKGROUND: Bacterial infection (BI), both community-acquired (CA-BI) and hospital-acquired (HAI), might present as a severe complication in patients with bronchiolitis. This study aimed to describe BI in children with severe bronchiolitis, and to define risk factors for BI. METHODS: This was a prospective, descriptive study that included infants admitted to the pediatric intensive care unit (PICU) due to bronchiolitis between 2011 and 2017. The BROSJOD score was calculated to rate the severity of bronchiolitis. RESULTS: Inclusion of 675 patients, with a median age of 47 days (IQR 25-99). 175 (25.9%) patients developed BI, considered HAI in 36 (20.6%). Patients with BI had higher BROSJOD score, PRISM III, and required invasive mechanical ventilation and inotropic support more frequently (p < 0.001). BI was independently associated with BROSJOD higher than 12 (OR 2.092, 95%CI 1.168-3.748) CA-BI was associated to BROSJOD > 12 (OR 2.435, 95%CI 1.379-4.297) and bacterial co-infection (OR 2.294 95%CI 1.051-5.008). Concerning HAI, an independent association was shown with mechanical ventilation longer than 7 days (OR 5.139 95%CI 1.802-14.652). Infants with BI had longer PICU and hospital stay (p < 0.001), Mortality was higher in patients with HAI. CONCLUSIONS: A quarter of infants with severe bronchiolitis developed BI. A BROSJOD > 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality.

Bronchiolitis, epidemiological changes during the SARS-CoV-2 pandemic.

BACKGROUND: Bronchiolitis is the most common viral infection of the lower respiratory tract in infants under 2 years of age. The aim of this study was to analyze and compare the seasonal bronchiolitis peaks before and during the SARS-CoV-2 pandemic. METHODS: Descriptive, prospective, and observational study. Patients with severe bronchiolitis admitted to the Pediatric Intensive Care Unit (PICU) of a referral tertiary hospital between September 2010 and June 2021 were included. Demographic data were collected. Viral laboratory-confirmation was carried out. Each season was analyzed and compared. The daily average temperature was collected. RESULTS: 1116 patients were recruited, 58.2% of them males. The median age was 49 days. Respiratory syncytial virus (RSV) was isolated in 782 cases (70.1%). In April 2021, the first and only case of bronchiolitis caused by SARS-CoV-2 was identified. The pre- and post-pandemic periods were compared. There were statistically significant differences regarding: age, 47 vs. 73 days (p = 0.006), PICU and hospital length of stay (p = 0.024 and p = 0.001, respectively), and etiology (p = 0.031). The peak for bronchiolitis in 2020 was non-existent before week 52. A delayed peak was seen around week 26/2021. The mean temperature during the epidemic peak was 10ºC for the years of the last decade and is 23ºC for the present season. CONCLUSION: The COVID-19 pandemic outbreak has led to a clearly observable epidemiological change regarding acute bronchiolitis, which should be studied in detail. The influence of the environmental temperature does not seem to determine the viral circulation.

Use of procalcitonin and C-reactive protein in the diagnosis of bacterial infection in infants with severe bronchiolitis.

The objective was to evaluate the use of procalcitonin (PCT) and C-reactive protein (CRP) for the diagnosis of bacterial infection in bronchiolitis patients. A prospective, single-centre, descriptive, and comparative observational study was carried out on patients with severe bronchiolitis admitted to the paediatric intensive care unit (PICU), from January 2011 to July 2017. Two cohorts were compared: patients with invasive bacterial infection (IBI) and patients with no bacterial infection (NBI). We included 675 patients, 399 of whom were males (59.1%), with median age of 47 days (IQR 25-100.3). Of them, 181 patients were diagnosed with IBI (26.8%). Seventy-two had sepsis (10.7%), 106 had pneumonia (15.7%), and 41 had a urinary tract infection (6.1%). PCT and CRP values were significantly higher in patients with IBI. ROC curves compared the ability of PCT and CRP to diagnose IBI at admission, 24 h, and 48 h. PCT showed a better AUC for diagnosing IBI, with statistically significant differences at all time points (p < 0.001). The best PCT cut-off for IBI diagnosis at admission was 1.4 ng/mL, with a sensitivity of 69% (95% CI 58.4-74.9) and a specificity of 91% (95% CI 88.1-92.5). Procalcitonin showed a better AUC for diagnosing both sepsis and pneumonia, which makes it an excellent predictor.Conclusion: We present PCT as a novel test in comparison with the traditional CRP screening test to discern which bronchiolitis patients have IBI. We highlight the importance of PCT for the diagnosis of pneumonia and sepsis, as it proved to be more sensitive and specific than CRP, with statistically significant differences. What is Known: • Bronchiolitis should be treated with antibiotics only when a bacterial infection is present. • The rate of antibiotic prescription in severe bronchiolitis is extremely high, so diagnostic tools are needed. What is New: • PCT is a good biomarker to discern which bronchiolitis patients have IBI, specially for pneumonia and sepsis diagnoses. It is more sensitive and specific than CRP, with statistically significant differences. • Implementation of PCT cut-off values may prevent unnecessary antibiotic use.

Procalcitonin-guided protocol decreased the antibiotic use in paediatric patients with severe bronchiolitis.

AIM: Our aim was to determine the effectiveness and safety of a procalcitonin-guided protocol to decrease antibiotic use in infants with severe bronchiolitis. METHODS: This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin-guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010-2014 and 366 in 2015-2017. RESULTS: We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0-100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol. CONCLUSION: The implementation of a procalcitonin-guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.

Noninvasive Respiratory Support During Pediatric Ground Transport: Implementation of a Safe and Feasible Procedure.

BACKGROUND: The purpose of this work was to determine the safety and feasibility of noninvasive support in children with acute respiratory failure (ARF) during interhospital ground transport. METHODS: This was a prospective, single-center observational clinical study in the pediatric transport unit of a tertiary-care pediatric hospital. We included all subjects with ARF transported from November 2010 to March 2013. A specific noninvasive support protocol was used for all cases. Transport ventilators used were the Crossvent 2+ and Oxylog 3000; interfaces were an oronasal mask, nasopharyngeal tube, or nasal prongs. RESULTS: A total of 288 children diagnosed with ARF were transported. Fifty-four subjects (19%) were transported with invasive ventilation, 50 with CPAP, 58 with NIV, and 126 (44%) with oxygen cannula or nebulization. The median age was 3.4 months (interquartile range 1.2-17 months). ARF was mainly due to bronchiolitis (58%), asthma (15%), and pneumonia (15%). Stabilization time, which is defined as the time between the arrival in the parking lot of the referring hospital and departure, was lower with noninvasive support than with invasive ventilation (median 48 min vs 83 min, P < .001). Median transport time was 35 min (interquartile range 20-65). Noninvasive ventilation and oronasal interface use rose progressively during the study period (P < .001 for the NIV and P < .036 for the interface). One complication was observed: One subject required intubation during transport. Evolution of subjects transferred while receiving noninvasive support was recorded in the receptor hospitals: 21% of subjects were intubated, and 55% continued with NIV. CONCLUSIONS: NIV seems to be a safe and feasible technique during pediatric ground transport. Careful patient selection, adequate material, and a well-trained transport team are crucial to minimize risks to the patient.

Bronchiolitis Score of Sant Joan de Déu: BROSJOD Score, validation and usefulness.

OBJECTIVE: To validate the bronchiolitis score of Sant Joan de Déu (BROSJOD) and to examine the previously defined scoring cutoff. PATIENTS AND METHODS: Prospective, observational study. BROSJOD scoring was done by two independent physicians (at admission, 24 and 48 hr). Internal consistency of the score was assessed using Cronbach's α. To determine inter-rater reliability, the concordance correlation coefficient estimated as an intraclass correlation coefficient (CCC) and limits of agreement estimated as the 90% total deviation index (TDI) were estimated. An expert opinion was used to classify patients according to clinical severity. A validity analysis was conducted comparing the 3-level classification score to that expert opinion. Volume under the surface (VUS), predictive values, and probability of correct classification (PCC) were measured to assess discriminant validity. RESULTS: About 112 patients were recruited, 62 of them (55.4%) males. Median age: 52.5 days (IQR: 32.75-115.25). The admission Cronbach's α was 0.77 (CI95%: 0.71; 0.82) and at 24 hr it was 0.65 (CI95%: 0.48; 0.7). The inter-rater reliability analysis was: CCC at admission 0.96 (95%CI 0.94-0.97), at 24 h 0.77 (95%CI 0.65-0.86), and at 48 hr 0.94 (95%CI 0.94-0.97); TDI 90%: 1.6, 2.9, and 1.57, respectively. The discriminant validity at admission: VUS of 0.8 (95%CI 0.70-0.90), at 24 h 0.92 (95%CI 0.85-0.99), and at 48 hr 0.93 (95%CI 0.87-0.99). The predictive values and PCC values were within 38-100% depending on the level of clinical severity. CONCLUSION: There is a high inter-rater reliability, showing the BROSJOD score to be reliable and valid, even when different observers apply it. Pediatr Pulmonol. 2017;52:533-539. © 2016 Wiley Periodicals, Inc.