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.

Randomized clinical trial to assess the impact of oral intervention with cetylpyridinium chloride to reduce salivary SARS-CoV-2 viral load.

AIM: Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus. The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride (CPC) to reduce the viral load in the saliva of Coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: In this multi-centre, single-blind, randomized, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomized to two groups, namely test (n = 40) and placebo (n = 40). Saliva samples were collected at baseline and 2 h after rinsing. The samples were analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay test specific for the nucleocapsid (N) protein of SARS-CoV-2. RESULTS: With RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 h after a single rinse, N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus. CONCLUSIONS: The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.

Genomic Prediction of Resistance to Tan Spot, Spot Blotch and Septoria Nodorum Blotch in Synthetic Hexaploid Wheat.

Genomic prediction combines molecular and phenotypic data in a training population to predict the breeding values of individuals that have only been genotyped. The use of genomic information in breeding programs helps to increase the frequency of favorable alleles in the populations of interest. This study evaluated the performance of BLUP (Best Linear Unbiased Prediction) in predicting resistance to tan spot, spot blotch and Septoria nodorum blotch in synthetic hexaploid wheat. BLUP was implemented in single-trait and multi-trait models with three variations: (1) the pedigree relationship matrix (A-BLUP), (2) the genomic relationship matrix (G-BLUP), and (3) a combination of the two matrices (A+G BLUP). In all three diseases, the A-BLUP model had a lower performance, and the G-BLUP and A+G BLUP were statistically similar (p ≥ 0.05). The prediction accuracy with the single trait was statistically similar (p ≥ 0.05) to the multi-trait accuracy, possibly due to the low correlation of severity between the diseases.

Results of the Galician registry in the treatment of complex aortoiliac aneurysms with GORE® EXCLUDER® Iliac Branch Endoprosthesis (GALIBER).

OBJECTIVE: The objective of this study is to report the medium-term results of GORE® EXCLUDER® Iliac Branch Endoprosthesis (IBE, W. L. Gore & Associates, Flagstaff, Ariz) for the treatment of aortoiliac aneurysms by using the GALIBER registry. METHODS: Patients with aortoiliac or isolated common iliac/hypogastric aneurysms treated with Iliac Branch Endoprosthesis device between January 2014 and May 2019 were prospectively collected from 5 centers. Demographic, clinical, and radiologic data were extracted from electronic databases. Technical success was defined as successful implantation of the Iliac Branch Endoprosthesis device with exclusion of aortoiliac aneurysm, as well as patency of Iliac Branch Endoprosthesis in the follow-up. Iliac Branch Endoprosthesis patency was evaluated by Doppler ultrasound and/or computed tomography based on the protocol of each participant center. Follow-up was 731 days +/- 499. RESULTS: Between January 2014 and May 2019, 105 iliac arteries were treated with GORE® IBE device, in 81 patients (79 men, two women; mean age 71, range 52-91). Only seven patients (8.6%) were symptomatic. 60 patients (74%) had aortic and iliac enlargement. Thirty-three patients presented bilateral iliac aneurysms (40.7%): In twenty-four (29.6%) patients, an Iliac Branch Endoprosthesis device was implanted in both sides, and in nine patients (11.1%), one Iliac Branch Endoprosthesis was used with the embolization of the contralateral hypogastric artery. Technical success was achieved in the 99% (104/105 iliac branch device implanted). There were no procedural deaths or type I or III intraoperative endoleaks observed. During the follow-up (range 55-1789 days), 28 (34.5%) type II endoleaks were observed and one (1.2%) type Ia was observed. The patency of the hypogastric arteries treated with the iliac branch device was 98.1% during the follow-up (range 55-1789 days). In 30% of the patients with contralateral hypogastric embolization, some kind of complications was observed in the embolizated side: one developed ischemic colitis and two buttock claudication. CONCLUSIONS: Preservation of internal iliac artery with the Iliac Branch Endoprosthesis device can be performed safely with excellent technical success and good medium-term patency rates. These results support hypogastric preservation whenever possible to prevent ischemic complications.

Use of Nanocellulose to Produce Water-Based Conductive Inks with Ag NPs for Printed Electronics.

The need for more sustainable printed electronics has emerged in the past years. Due to this, the use of nanocellulose (NC) extracted from cellulose has recently been demonstrated to provide interesting materials such as functional inks and transparent flexible films due to its properties. Its high specific surface area together with the high content of reactive hydroxyl groups provide a highly tailorable surface chemistry with applications in ink formulations as a stabilizing, capping, binding and templating agent. Moreover, NC mechanical, physical and thermal properties (high strength, low porosity and high thermal stability, respectively) provide an excellent alternative for the currently used plastic films. In this work, we present a process for the production of water-based conductive inks that uses NC both as a template for silver nanoparticles (Ag NPs) formation and as an ink additive for ink formulation. The new inks present an electrical conductivity up to 2 × 106 S/m, which is in the range of current commercially available conductive inks. Finally, the new Ag NP/NC-based conductive inks have been tested to fabricate NFC antennas by screen-printing onto NC-coated paper, demonstrating to be operative.

Characterization of an osteomyelitis case caused by dalbavancin, ceftaroline, and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus.

We report a case of osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) that is also non-susceptible to vancomycin, dalbavancin, ceftaroline, and ceftobiprole, in the absence of exposure to the latter three antibiotics. It was isolated from a patient with a 26-year history of cranial surgeries and episodes of osteomyelitis. Whole-genome sequencing was performed. It was found to belong to ST247 and the mecA gene was detected within the SSCmec type I (1B) gene cassette that lacked the E447K mutation known to produce resistance to ceftobiprole and ceftaroline. However, mutations in other genes related to resistance to these antibiotics were found.

Risk factors for gentamicin-resistant E. coli in children with community-acquired urinary tract infection.

According to many guidelines, gentamicin is the empirical parenteral treatment for children with community-acquired urinary tract infection (CA-UTI). However, increasing resistance rates are reported. The purpose of this study is to analyze risk factors for presenting with a UTI caused by a community-acquired gentamicin-resistant Escherichia coli in children in our hospital and to describe their clinical outcome. A retrospective case-control local study was performed in a tertiary care hospital from January 2014 to December 2016. Cases and controls were children below 14 years old diagnosed in the Emergency Department with febrile CA-UTI caused by gentamicin-resistant and gentamicin-susceptible febrile E. coli strains, respectively. During the study period, 54 cases were included and compared with 98 controls. Patients with chronic conditions were more likely to present with a UTI due to gentamicin-resistant E. coli (OR 3.27; 95% CI 1.37-7.8, p < 0.05), as well as children receiving antibiotic prophylaxis (OR 3.5; 95% CI 1.2-10.1, p < 0.05). Cases had longer hospital stays than controls (5.8 ± 5 days vs. 4.4 ± 4 days, p = 0.017). Gentamicin-resistant strains associated higher rates of cefuroxime (29% vs. 3%), cefotaxime (27% vs. 0%), and quinolone resistance (40.7% vs. 6%) (p < 0.01) and produced more frequently extended-spectrum beta-lactamases (ESBL) (20% vs. 0%, p < 0.01) and carbapenemases (7.4% vs. 0%; p = 0.015). All gentamicin-resistant strains were amikacin-sensitive. The presence of chronic conditions and antibiotic prophylaxis could be potential risk factors for gentamicin-resistant E. coli CA-UTI in children. Simultaneous resistance to cephalosporins, quinolones, and ESBL/carbapenemase production is frequent in these strains.

A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation.

Exposure to ultraviolet (UV) radiation from sunlight accounts for 90% of the symptoms of premature skin aging and skin cancer. The tumor suppressor serine-threonine kinase LKB1 is mutated in Peutz-Jeghers syndrome and in a spectrum of epithelial cancers whose etiology suggests a cooperation with environmental insults. Here we analyzed the role of LKB1 in a UV-dependent mouse skin cancer model and show that LKB1 haploinsufficiency is enough to impede UVB-induced DNA damage repair, contributing to tumor development driven by aberrant growth factor signaling. We demonstrate that LKB1 and its downstream kinase NUAK1 bind to CDKN1A. In response to UVB irradiation, LKB1 together with NUAK1 phosphorylates CDKN1A regulating the DNA damage response. Upon UVB treatment, LKB1 or NUAK1 deficiency results in CDKN1A accumulation, impaired DNA repair and resistance to apoptosis. Importantly, analysis of human tumor samples suggests that LKB1 mutational status could be a prognostic risk factor for UV-induced skin cancer. Altogether, our results identify LKB1 as a DNA damage sensor protein regulating skin UV-induced DNA damage response.

Risk factors for colonization by carbapenemase-producing enterobacteria at admission to a Surgical ICU: A retrospective study.

INTRODUCTION: In 2011, a hospital-wide outbreak of OXA-48 producing Klebsiella pneumoniae occurred in our hospital, an epidemiological setting of high ESBL-producing K. pneumoniae rates. This study identifies risk factors for colonization with carbapenemase-producing enterobacteria (CPE) at Surgical Intensive Care Unit (SICU) admission. METHODS: A 2-year retrospective study was performed in all patients admitted to the SICU that following routine had a rectal swab collected upon admission. RESULTS: Of 254 patients admitted, 41 (16.1%) harbored CPE (five showing two carbapenemase-producing isolates). Most frequent carbapenemase-producing isolates and carbapenemases were K. pneumoniae (39/46, 84.8%) and OXA-48 (31/46; 76.1%), respectively. Carriers significantly had higher rates of chronic renal disease, previous digestive/biliary endoscopy, hospitalization, ICU/SICU admission, intraabdominal surgery, and antibiotic intake, as well as higher median values of clinical scores (SOFA, SAPS II and APACHE II). In the multivariate analysis (R2=0.309, p<0.001), CPE carriage was associated with prior administration of 3rd-4th generation cephalosporins (OR=27.96, 95%CI=6.88, 113.58, p<0.001), ß-lactam/ß-lactamase inhibitor (OR=11.71, 95%CI=4.51, 30.43, p<0.001), abdominal surgery (OR=6.33, 95%CI=2.12, 18.89, p=0.001), and prior digestive/biliary endoscopy (OR=3.88, 95%CI=1.56, 9.67, p=0.004). CONCLUSIONS: A strong association between production of ESBLs and carriage of CPE (mainly OXA-48 producing K. pneumoniae) was found. According to the model, the co-selection of ß-lactamases by previous exposure to broad-spectrum cephalosporins and ß-lactam/ß-lactamase inhibitors (with lower relative risk), abdominal surgery and prior digestive/biliary endoscopy were factors associated with CPE carriage.

Life Is Precious: Views of Adolescents and Their Mothers on Methods to Reduce Suicidal Behavior in Latinas.

Life is Precious (LIP) was developed to help reduce suicidal behavior in Latina adolescents. As part of an external evaluation of the LIP program, we conducted focus groups with adolescent participants and mothers to learn whether participants and families believe that the activities of LIP address risks for suicidal behavior. Four focus groups were conducted: three with Latina adolescent LIP participants ( n = 31) and one with mothers ( n = 8). Transcripts were analyzed using ATLAS.ti. A grounded theory approach was used to identify themes and subthemes. The following themes emerged: (1) challenges contributing to suicidal behavior and self-harm among Latina adolescents, (2) how respondents believe that LIP is helping to reduce suicidal behavior, and 3) ongoing challenges. Participants say that the LIP program helps adolescents feel better and improve social relationships, academic performance, and relationships with their family. School nurses may wish to identify community-based programs offering similar services.

The influence of a biopsychosocial educational internet-based intervention on pain, dysfunction, quality of life, and pain cognition in chronic low back pain patients in primary care: a mixed methods approach.

BACKGROUND: Low back pain is the highest reported musculoskeletal problem worldwide. Up to 90 % of patients with low back pain have no clear explanation for the source and origin of their pain. These individuals commonly receive a diagnosis of non-specific low back pain. Patient education is a way to provide information and advice aimed at changing patients' cognition and knowledge about their chronic state through the reduction of fear of anticipatory outcomes and the resumption of normal activities. Information technology and the expedited communication processes associated with this technology can be used to deliver health care information to patients. Hence, this technology and its ability to deliver life-changing information has grown as a powerful and alternative health promotion tool. Several studies have demonstrated that websites can change and improve chronic patients' knowledge and have a positive impact on patients' attitudes and behaviors. The aim of this project is to identify chronic low back pain patients' beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques. METHODS/DESIGN: This study has a mixed-method sequential exploratory design. The participants are chronic low back pain patients between 18-65 years of age who are attending a primary care setting. For the qualitative phase, subjects will be contacted by their family physician and invited to participate in a personal semi-structured interview. The quantitative phase will be a randomized controlled trial. Subjects will be randomly allocated using a simple random sample technique. The intervention group will be provided access to the web site where they will find information related to their chronic low back pain. This information will be provided in different formats. All of this material will be based on the information obtained in the qualitative phase. The control group will follow conventional treatment provided by their family physician. DISCUSSION: The main outcome of this project is to identify chronic low back pain patients' beliefs about the origin and meaning of pain to develop a web-based educational tool using different educational formats and gamification techniques. TRIAL REGISTRATION: ClinicalTrials.gov NCT02369120 Date: 02/20/2015.

Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistance.

OBJECTIVES: To characterize at the genomic level the evolution of multiresistance during an outbreak of Klebsiella pneumoniae in a burns intensive care unit. The outbreak involved a DHA-1 ß-lactamase-producing strain that later acquired carbapenem and fosfomycin resistance, and in one case colistin resistance. METHODS: The genomes of two isolates were sequenced and compared with a previously sequenced genome. The role of hypermutability was investigated by measuring the mutation frequencies of the isolates and comparison with a collection of control strains. RESULTS: Sequence comparison identified four single-nucleotide variants and two transposon insertions. Analysis of the variants in the whole collection related carbapenem and fosfomycin resistance to a nonsense mutation in the ompK36 porin gene and colistin resistance to an IS1 insertion in the mgrB gene. The plasmid carrying the blaDHA-1 gene was unstable in the absence of antibiotics, and analysis of isolates that had lost the plasmid showed that the porin mutation alone was not sufficient to generate carbapenem resistance. The mutation frequencies were similar among all the strains analysed. CONCLUSIONS: Carbapenem resistance required production of the DHA-1 ß-lactamase and decreased permeability, but fosfomycin resistance depended only on permeability. Resistance to colistin might be related to an alteration in the regulation of the phoPQ system. Hypermutation is not related to the selection of porin mutants. Plasmid instability might be due to the high number of mobile elements and suggests a major role for antibiotic selection pressure in the emergence and evolution of this outbreak.

Dinuclear ruthenium complexes containing the Hpbl ligand: synthesis, characterization, linkage isomerism, and epoxidation catalysis.

Three dinucleating Ru-Cl complexes containing the hexadentate dinucleating ligand [1,1'-(4-methyl-1H-pyrazole-3,5-diyl)bis(1-(pyridin-2-yl)ethanol)] (Hpbl) and the meridional 2,2':6',2″-terpyridine ligand (trpy) have been prepared and isolated. These complexes include {[RuCl(trpy)]2(µ-pbl-κ-N(3)O)}(+) (1a(+)), {[RuCl(trpy)]2(µ-Hpbl-κ-N(3)O)}(2+) (1b(2+)), and {[RuCl(trpy)]2(µ-Hpbl-κ-N(2)O(2))}(2+) (1c(2+)) and were characterized by analytic and spectroscopic techniques. In addition, complexes 1b(2+) and 1c(2+) were characterized in the solid state by monocrystal X-ray diffraction analysis. The coordination versatility of the Hpbl ligand allows the presence of multiple isomers that can be obtained depending on the Ru oxidation state and were thoroughly characterized by electrochemical techniques, namely, cyclic voltammetry and coulometry. Finally, 1a(+) and its recently reported mononuclear analogue, in-[RuCl(Hpbl)(trpy)](+), have been tested as catalysts for epoxidation of cis-ß-methylstyrene.

Synthesis, characterization, and linkage isomerism in mononuclear ruthenium complexes containing the new pyrazolate-based ligand Hpbl.

A new tetradentate dinucleating ligand [1,1'-(4-methyl-1H-pyrazole-3,5-diyl)bis(1-(pyridin-2-yl)ethanol)] (Hpbl) containing an O/N mixed donor set of atoms has been synthesized and characterized by analytical and spectroscopic techniques. The Ru-Cl and Ru-aqua complexes containing this ligand of general formula [Ru(II)X(Hpbl)(trpy)](y+) (trpy = 2,2':6',2″-terpyridine; X = Cl, y = 1; X = H2O, y = 2) have been prepared and thoroughly characterized by spectroscopic and electrochemical techniques. The Ru-aqua complex 2 undergoes N → O linkage isomerization as observed electrochemically, and the related thermodynamic and kinetic parameters are extracted from cyclic voltammetry experiments together with DIGISIM, a CV simulation package. Under basic conditions an additional isomer is observed where the pyrazolyl group in the Hpbl ligand is replaced by the geminal pyridyl group. Further structural and electronic characterization of all the isomers has been carried out by means of DFT calculations.

Hybrid Materials: A Metareview.

The field of hybrid materials has grown so wildly in the last 30 years that writing a comprehensive review has turned into an impossible mission. Yet, the need for a general view of the field remains, and it would be certainly useful to draw a scientific and technological map connecting the dots of the very different subfields of hybrid materials, a map which could relate the essential common characteristics of these fascinating materials while providing an overview of the very different combinations, synthetic approaches, and final applications formulated in this field, which has become a whole world. That is why we decided to write this metareview, that is, a review of reviews that could provide an eagle's eye view of a complex and varied landscape of materials which nevertheless share a common driving force: the power of hybridization.

Genomic Prediction from Multi-Environment Trials of Wheat Breeding.

Genomic prediction relates a set of markers to variability in observed phenotypes of cultivars and allows for the prediction of phenotypes or breeding values of genotypes on unobserved individuals. Most genomic prediction approaches predict breeding values based solely on additive effects. However, the economic value of wheat lines is not only influenced by their additive component but also encompasses a non-additive part (e.g., additive × additive epistasis interaction). In this study, genomic prediction models were implemented in three target populations of environments (TPE) in South Asia. Four models that incorporate genotype × environment interaction (G × E) and genotype × genotype (GG) were tested: Factor Analytic (FA), FA with genomic relationship matrix (FA + G), FA with epistatic relationship matrix (FA + GG), and FA with both genomic and epistatic relationship matrices (FA + G + GG). Results show that the FA + G and FA + G + GG models displayed the best and a similar performance across all tests, leading us to infer that the FA + G model effectively captures certain epistatic effects. The wheat lines tested in sites in different TPE were predicted with different precisions depending on the cross-validation employed. In general, the best prediction accuracy was obtained when some lines were observed in some sites of particular TPEs and the worse genomic prediction was observed when wheat lines were never observed in any site of one TPE.

Fiberbots: Robotic fibers for high-precision minimally invasive surgery.

Precise manipulation of flexible surgical tools is crucial in minimally invasive surgical procedures, necessitating a miniature and flexible robotic probe that can precisely direct the surgical instruments. In this work, we developed a polymer-based robotic fiber with a thermal actuation mechanism by local heating along the sides of a single fiber. The fiber robot was fabricated by highly scalable fiber drawing technology using common low-cost materials. This low-profile (below 2 millimeters in diameter) robotic fiber exhibits remarkable motion precision (below 50 micrometers) and repeatability. We developed control algorithms coupling the robot with endoscopic instruments, demonstrating high-resolution in situ molecular and morphological tissue mapping. We assess its practicality and safety during in vivo laparoscopic surgery on a porcine model. High-precision motion of the fiber robot delivered endoscopically facilitates the effective use of cellular-level intraoperative tissue identification and ablation technologies, potentially enabling precise removal of cancer in challenging surgical sites.

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.

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study.

BACKGROUND: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). METHODS: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. FINDINGS: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the seasonal group and 3188 (95·4%) of 3340 in the catch-up group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. INTERPRETATION: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. FUNDING: Sanofi and AstraZeneca. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.