Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

BACKGROUND: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. METHODS: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. RESULTS: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. CONCLUSIONS: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

Serum cotinine cut-points for secondhand smoke exposure assessment in children under 5 years: A systemic review.

BACKGROUND: Serum cotinine has become the most widely used biomarker of secondhand smoke exposure (SHS) over time in all ages. The aim of this study was to review the serum cotinine cut-points used to classify children under 5 years as exposed to SHS. METHODS: A systematic review performed in the Pubmed (MEDLINE) and EMBASE databases up to April 2021 was conducted using as key words "serum cotinine", "tobacco smoke pollution" (MeSH), "secondhand smoke", "environmental tobacco smoke" and "tobacco smoke exposure". Papers which assessed SHS exposure among children younger than 5 years old were included. The PRISMA 2020 guidelines were followed. Analysis was pre-registered in PROSPERO (registration number: CRD42021251263). RESULTS: 247 articles were identified and 51 fulfilled inclusion criteria. The selected studies were published between 1985-2020. Most of them included adolescents and adults. Only three assessed postnatal exposure exclusively among children under 5 years. None of the selected studies proposed age-specific cut-points for children < 5 years old. Cut-point values to assess SHS exposure ranged from 0.015 to 100 ng/ml. The most commonly used cut-point was 0.05 ng/ml, derived from the assay limit of detection used by the National Health and Nutrition Examination Survey (NHANES). CONCLUSIONS: No studies have calculated serum cotinine age-specific cut-points to ascertained SHS exposure among children under 5 years old. Children's age-specific cut-points are warranted for health research and public health purposes aimed at accurately estimating the prevalence of SHS exposure and attributable burden of disease to such exposure, and at reinforcing 100% smoke-free policies worldwide, both in homes, private vehicles and public places.

[Tobacco use in pregnancy: prevalence and factors associated with maintenance of consumption]. / Consumo de tabaco en el embarazo: prevalencia y factores asociados al mantenimiento del consumo.

OBJECTIVE: Tobacco use during pregnancy is detrimental to pregnant women and to the fetus. In Galicia, the data regarding prevalence of tobacco use during pregnancy is outdated and the characteristics of women who continue to smoke during pregnancy are not known. The objectives of this work were to estimate, before and during pregnancy, the prevalence of tobacco use and characterize its consumption, and to identify factors associated with the maintenance of tobacco use during pregnancy. METHODS: A cross-sectional study was conducted in 2016 targeting women who had given birth within the previous 12 months (n=6.436) in Galicia. Information was collected regarding the mother's status before and during pregnancy, at the time of delivery and survey. Smoking prevalence was estimated both globally and by women related characteristics. Regression models were performed to identify variables associated with smoking maintenance. Prevalence and odds ratio are presented accompanied with 95% confidence interval. RESULTS: Smoking prevalence during pregnancy was 11.9% (11.1-12.8). Among women who maintain tobacco consumption during pregnancy, the percentage of cigarette smokers decreased, but prevalence of rolled tobacco remain stable. The maintenance of smoking during pregnancy was related to being Spanish, education or having been a daily smoker before pregnancy. CONCLUSIONS: Despite the fact that more than half of Galician women stop smoking during pregnancy, smoking prevalence remains at 12%. The different demographic factors identified in this study as predictors of smoking maintenance, should be kept in mind when intervention programs focused on pregnant women will be design.

OBJETIVO: El consumo de tabaco durante el embarazo es perjudicial para las mujeres embarazadas y el feto. En Galicia la prevalencia del consumo durante el embarazo no está actualizada y se desconocen las características de las mujeres que continúan fumando durante el embarazo. Los objetivos de este trabajo fueron estimar, antes y durante el embarazo, la prevalencia del uso del tabaco, caracterizar su consumo e identificar factores asociados al mantenimiento durante el embarazo. METODOS: Estudio transversal realizado en 2016 en mujeres que habían dado a luz en los 12 meses previos (n =6436) en Galicia. Se recogió información sobre la madre en diferentes momentos temporales. La prevalencia del consumo de tabaco se estimó a nivel global y en función de diferentes características. Se ajustaron modelos de regresión para identificar las variables asociadas al mantenimiento del consumo. Se presentan prevalencia y razones de odds acompañadas de intervalos de confianza al 95%. RESULTADOS: La prevalencia del consumo de tabaco durante el embarazo fue del 11,9% (11,1-12,8). Entre las mujeres que mantuvieron el consumo durante el embarazo, el porcentaje de fumadoras de cigarrillos disminuyó, el de tabaco de liar permaneció estable. Seguir fumando durante el embarazo estuvo relacionado con la nacionalidad, el nivel educativo, o con el consumo previo. CONCLUSIONES: A pesar de que más de la mitad de las mujeres dejan de fumar durante el embarazo, la prevalencia es del 12%. Los diferentes predictores de mantenimiento deben tenerse en cuenta cuando se diseñan programas de intervención orientados a mujeres embarazadas.