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.

The role of traditional NSAIDs and selective COX-2 inhibitors on COVID-19 outcomes: a real-world data study.

The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections.

COVID-19 vaccine effectiveness in children by age groups. A population-based study in Galicia, Spain.

BACKGROUND: Studies on vaccine effectiveness (VE) against COVID-19 in the pediatric population are outgoing. We aimed to quantify VE against SARS-CoV-2 in two pediatric age groups, 5-11 and 12-17-year-old, while considering vaccine type, SARS-CoV-2 variant, and duration of protection. METHODS: A population-based test-negative control study was undertaken in Galicia, Spain. Children 5-11-year-old received the Comirnaty® (Pfizer, US) vaccine, while those aged 12-17-year-old received the Comirnaty® (Pfizer, US) or SpikeVax® (ModernaTX, Inc) vaccine. Participants were categorized into unvaccinated (0 doses or one dose with <14 days since vaccination), partially vaccinated (only one dose with ≥14 days, or two doses with <14 days after the second dose administration), and fully vaccinated (two doses with ≥14 days after the second injection). Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated using multiple logistic regression models. VE was calculated as (1-OR) * 100. Stratified and sensitivity analyses were performed. RESULTS: In the fully vaccinated 5-11-year-old children, VE against the Omicron variant was 44.1% (95% CI: 38.2%-49.4%). In the fully vaccinated 12-17-year-old individuals, VE was 83.4% (95% CI: 81.2%-85.3%) against Delta and 74.8% (95% CI: 58.5%-84.9%) against Omicron. Comirnaty® and SpikeVax® vaccines showed a similar magnitude of VE against Delta [Comirnaty® VE: 81.9% (95% CI: 79.3%-84.1%) and SpikeVax® VE: 85.3% (95% CI: 81.9%-88.1%)]. Comirnaty® (Pfizer, US; VE: 79.7%; 95% CI: 50.7%-92.4%) showed a slightly higher magnitude of protection against Omicron than SpikeVax® (ModernaTX, Inc), yet with an overlapping CI (VE: 74.3%; 95% CI: 56.6%-84.9%). VE was maintained in all age subgroups in both pediatric populations, but it declined over time. CONCLUSIONS: In Galicia, mRNA VE was moderate against SARS-CoV-2 infections in the 5-11-year-old populations, but high in older children. VE declined over time, suggesting a potential need for booster dose schedules.

Sleep quality as a mediator of the relation between depression and chronic pain: a systematic review and meta-analysis.

BACKGROUND: Chronic pain and depression represent two global health problems with considerable economic consequences. Although existing literature reports on the relation between depression and pain conditions, meta-analytic evidence backing the mediating role of sleep disturbance as one of the main symptoms of depression is scarce. To examine the extent to which sleep disturbance mediates the depression-chronic pain association, we conducted a systematic review and meta-analysis of the associations of chronic pain, depression, and sleep quality. METHODS: We systematically searched for literature in MEDLINE and other relevant databases and identified cohort and case-control studies on depression, sleep disturbance, and chronic pain. Forty-nine studies were eligible, with a total population of 120 489 individuals. We obtained direct and indirect path coefficients via two-stage meta-analytic structural equation modelling, examined heterogeneity via subgroup analyses, and evaluated primary studies quality. RESULTS: We found a significant, partial mediation effect of sleep disturbance on the relation between depression and chronic pain. The pooled path coefficient (coef.) of the indirect effect was 0.03 (95% confidence interval [CI]: 0.01-0.05) and accounted for 12.5% of the total effect of depression on chronic pain. This indirect effect also existed for cohort studies (coef. 0.02; 95% CI: 0.002-0.04), European studies (coef. 0.03; 95% CI: 0.004-0.05), and studies that adjusted for confounders (coef. 0.04; 95% CI: 0.01-0.09). CONCLUSIONS: Sleep disturbance partially mediates the association between depression and pain. Although plausible mechanisms could explain this mediation effect, other explanations, including reverse causation, must be further explored. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022338201.

Gastroesophageal reflux disease and asthma exacerbation: A systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GORD) is highly prevalent and often coexists with asthma exacerbation. Divergent findings about the association between the two diseases were reported. We conducted a systematic review and meta-analysis to determine whether there exists an association between GORD and asthma. METHODS: We searched MEDLINE, EMBASE, and other databases and then performed a manual search, to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. We evaluated the quality of included studies, explored heterogeneity between studies, undertook subgroup analyses, assessed publication bias, and performed sensitivity analyses. RESULTS: We identified 32 eligible studies, conducted in 14 countries and including a total of 1,612,361 patients of all ages. Overall, GORD shows a weak association with asthma exacerbation (OR = 1.27; 95% CI 1.18-1.35). This association was observed in cohort, case-control, and cross-sectional designs and in European as well as non-European populations. Subgroup analyses show that GORD is associated with frequent asthma exacerbations (≥3 exacerbations, OR = 1.59; 95% CI 1.13-2.24) and with exacerbations needing oral corticosteroid therapy (OR = 1.24; 95% CI 1.09-1.41). GORD pediatric patients are at higher odds of asthma exacerbation than adults. We did not detect any evidence of publication bias and the association between GORD and asthma exacerbation held in all undertaken sensitivity analyses. CONCLUSIONS: Gastroesophageal reflux disease and asthma exacerbation are weakly associated.

Association between alcohol consumption and chronic pain: a systematic review and meta-analysis.

INTRODUCTION: Chronic pain represents a global health problem with a considerable economic burden. The relation of alcohol intake and chronic pain conditions was assessed in several studies with conflicting results. We used dose-response meta-analysis techniques to answer the question of whether alcohol intake is related to chronic pain occurrence. METHODS: We searched MEDLINE, Embase, and other databases to identify cohort and case-control studies on alcohol consumption and chronic pain. Sixteen studies were eligible with a total population of 642 587 individuals. Fixed-effects and random-effects pooled estimates were obtained by weighting log odds ratios (ORs) in case-control studies and log incidence rate ratios in cohort studies by the inverse of their variance. A heterogeneity assessment and a dose-response analysis were carried out. Quality scoring was also performed. RESULTS: Our results show that any alcohol consumption was related to lower odds of chronic pain (pooled OR=0.76; 95% confidence interval [CI], 0.61-0.95). The association was non-linear. The ORs by quartile of alcohol doses were as follows: OR2nd quartile=0.74; 95% CI, 0.64-0.87; OR3rd quartile=0.67; 95% CI, 0.53-0.86; and OR4th quartile=0.75; 95% CI, 0.50-1.14. This association was observed for cohort studies (OR=0.77; 95% CI, 0.61-0.98) and European studies (OR=0.65; 95% CI, 0.48-0.87) only. Studies with complete adjustment for confounding factors showed a stronger relation than those with incomplete adjustment (OR=0.69; 95% CI, 0.48-0.99 and OR=0.85; 95% CI, 0.65-1.11, respectively). CONCLUSION: Alcohol consumption presents a non-linear inverse association with the occurrence of chronic pain. Although plausible mechanisms could explain this protective effect, other explanations, including reverse causation, are probable.

Effectiveness of COVID-19 vaccine booster in the general population and in subjects with comorbidities. A population-based study in Spain.

BACKGROUND: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients. METHOD: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020-November 2021). VE and 95% confidence interval (CI) were estimated using multivariate logistic regression models. RESULTS: 1,512,415 (94.13%) negative and 94,334 (5.87%) positive SARS-CoV-2 test results were included. A booster dose of COVID-19 vaccine is associated with substantially higher protection against SARS-CoV-2 infection than vaccination without a booster [VEboosted = 87% (95%CI: 83%; 89%); VEnon-boosted = 66% (95%CI: 65%; 67%)]. The high VE was observed in all ages, but was more pronounced in subjects older than 65 years. VE against COVID-19 severity was analyzed in a mixed population of boosted and non-boosted individuals and considerable protection was obtained [VE: hospitalization = 72% (95%CI: 68%; 75%); intensive care unit administration = 83% (95%CI: 78%; 88%), in-hospital mortality = 66% (95%CI: 53%; 75%)]. Boosted comorbid patients are more protected against SARS-CoV-2 infection than those who were non-boosted. This was observed in a wide range of major diseases including cancer (81% versus 54%), chronic obstructive pulmonary disease (84% versus 61%), diabetes (84% versus 65%), hypertension (82% versus 65%) and obesity (91% versus 67%), among others. CONCLUSIONS: A booster dose of COVID-19 vaccine increases the protection against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients.

Diabetes mellitus and oral lichen planus: A systematic review and meta-analysis.

OBJECTIVE: To undertake a meta-analysis of the association of Oral Lichen Planus (OLP) with diabetes, two diseases with an important impact on public health and the economy, but the evidence of which about their association is inconsistent. METHODS: Relevant studies were localized by searching MEDLINE, EMBASE, Conference Proceedings, and other databases from inception to October 2020, without restrictions. The reference lists of included studies and of related reviews were also inspected. Global pooled odds ratios were calculated, and predefined subgroup analyses were performed. The heterogeneity between studies and publication bias was assessed and sensitivity analysis was carried out. RESULTS: Thirty-two studies were included in the meta-analysis. Pooled ORs showed a moderate association between diabetes and OLP [OR: 1.87 (95%CI: 1.57, 2.34)]. The association is limited to studies carried out on adults only [OR: 2.12 (95%CI: 1.75, 2.57)] and is observed in all study designs. Globally, the heterogeneity was low to moderate. Studies carried out in European populations show a stronger association of diabetes and OLP than Asiatic studies [OR: 2.49 (95%CI: 1.87, 3.32) and 1.60 (95%CI: 1.25, 2.03), respectively]. CONCLUSIONS: Diabetes and OLP are moderately associated. Systematic diagnosis of diabetes in OLP patients could prove useful.

Socioeconomic status and occurrence of chronic pain: a meta-analysis.

OBJECTIVE: To examine the association between socioeconomic status (SES) and the occurrence of chronic pain, defined as pain that persists or recurs for >3 months. METHODS: We performed a structured search in Medline, Embase, WHO Global Index Medicus and Conference Proceedings Citation Index-Science databases to identify cohort and case-control studies on chronic pain and SES and its subgroups (SES combined index, educational level, income and occupational status). We extracted study characteristics, outcome measures and measures of association and their 95% CIs. Literature search, data extraction and risk of bias assessment were conducted by two independent researchers. We performed main and subgroup meta-analyses using random-effects model, and formally assessed heterogeneity and publication bias. RESULTS: A total of 45 studies, covering a population of ∼175 000 individuals, were meta-analysed, yielding a pooled Odds Ratio (OR) of 1.32 (95% CI: 1.21, 1.44) and 1.16 (95% CI: 1.09, 1.23) for low and medium SES levels, respectively, compared with high level. We obtained similar results in all the subgroup analyses. Heterogeneity was generally moderate to high across strata, and some evidence of publication bias for low socioeconomic status was found. CONCLUSION: Our results support a moderate increase in the risk of chronic pain for low and medium SES when compared with high SES, a feature that remained constant in all measures of exposure or outcome used. Further prospective research on populations from developing countries are needed to confirm our findings as the studies available for this meta-analysis were carried out exclusively in developed countries.

Blood eosinophil count as predictor of asthma exacerbation. A meta-analysis.

BACKGROUND: Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta-analysis was to determine whether elevated blood eosinophil count predicts asthma exacerbation. METHODS: We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle-Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses. RESULTS: Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation [OR: 1.31 (95% CI: 1.16, 1.49)], specifically with asthma-related outpatient visits [OR: 1.46 (95% CI: 1.25, 1.70)] and emergency department visits [OR: 1.63 (95% CI: 1.29, 2.07)]. A significant association was observed starting from an eosinophils' cutoff value of 200 cells/µl. The association was observed for cohort studies [OR: 1.30 (95%CI: 1.13, 1.49)], North American studies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian populations [OR: 1.67 (95%CI: 1.34, 2.08)], children [OR: 1.38 (95%CI: 1.22, 1.56)], and studies that adjusted for inhaled corticosteroids therapy [OR: 1.42 (95%CI: 1.28, 1.56)]. CONCLUSIONS: Blood eosinophil counts ≥ 200 cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies.

Nomophobia and Alcohol, Tobacco, and Cannabis Consumption in Adolescents in Galicia.

This study aimed at exploring the association of nomophobia with alcohol, tobacco, and/or cannabis consumption among high school students. We carried out a cross-sectional study among high school and vocational training students in Galicia, Northwest Spain (N = 3,100). Collected data included nomophobia, sociodemographic variables, and alcohol, tobacco, and cannabis consumption. Nomophobia was measured using the validated Nomophobia Questionnaire. Adjusted odds ratios (ORs) and their 95 percent confidence intervals (CIs) were estimated using generalized linear mixed models. More than a quarter of the adolescents (27.7 percent) had nomophobia. We found an association between nomophobia and a high level of tobacco smoking in the last month in boys (OR = 2.16; 95 percent CI: 1.55-3.03). Nomophobia was also associated with higher odds of binge drinking in both genders (girls: OR = 1.86; 95 percent CI: 1.61-3.52; boys: OR = 2.29; 95 percent CI: 1.68-3.13) and with cannabis consumption in boys (OR = 1.74; 95 percent CI: 1.07-2.81). Our findings highlight the importance of a comprehensive investigation of the factors underlying alcohol, tobacco, and cannabis consumption in the adolescent population.

New Vaccines for Chronic Respiratory Patients.

Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients.

COVID-19 InfoVaccines: A WHO-supported educational project to promote COVID-19 vaccination information among professionals and the general population.

COVID-19 vaccine uptake varied across countries, in part due to vaccine hesitancy fueled by a lack of trustworthy information. To help health workers provide evidence-based answers to common questions about COVID-19 vaccines and vaccination, and thereby, assist individuals´ decisions on vaccine acceptance, COVID-19 InfoVaccines, a joint WHO-EU project, was launched in February 2021 to support COVID-19 vaccine rollout in 6 Eastern European countries. COVID-19 InfoVaccines was made available in seven languages and shared on social media networks. A total of 262,592 users accessed COVID-19 InfoVaccines.com between February 11, 2021, and January 31st, 2023. The users were most interested in: general questions; vaccine efficacy and duration of protection; vaccine safety; vaccine co-administration, and dose-interval and interchangeability; though the interest in a specific theme varied in function of the epidemiological situation. A total of 118,510 (45.1%) and 46,644 (17.7%) users scrolled up to 35% and 75% of the COVID-19 InfoVaccines webpage, respectively. The average engagement rate was 71.61%. The users accessed COVID-19 InfoVaccines from 231 countries and territories, but the majority were in Ukraine (N = 38,404; 14.6%), Spain (N = 23,327; 8.9%), and Argentina (N = 21,167; 8.1%). Older Facebook users were more interested in COVID-19 information than younger individuals (X2 p-value < .0001). Two hundred twenty-eight videos were shared on YouTube. The average Click-Through-Rate on Facebook was 7.82%, and that on YouTube was 4.4%, with 60 videos having a Click-Through-Rate >5%, falling in the range of average YouTube video Click-Through-Rate (2% - 10%). As misinformation about vaccines and vaccination spreads easily and can negatively impact health-related decisions, initiatives like COVID-19 InfoVaccines are crucial to facilitate access to reliable information.

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 catch-up group and 3188 (95·4%) of 3340 in the seasonal 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.

Music compensates for altered gene expression in age-related cognitive disorders.

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.

Education level and misuse of antibiotics in the general population: a systematic review and dose-response meta-analysis.

BACKGROUND: Numerous studies evaluated the association of education level with misuse of antibiotics by the general population, yet divergent findings were reported. Therefore, a meta-analysis was conducted to summarize this association. METHODS: A categorical and continuous dose-response meta-analysis of the association of education level with antibiotic misuse was undertaken. Summary odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using random-effect model. RESULTS: The meta-analysis included 85 studies from 42 countries of different socioeconomic status. Compared to low education (≤ 9 years), medium education (> 9-12 years) is associated with 20% lower odds of antibiotic misuse in high-income countries (OR = 0.80; 95% CI 0.66, 0.97), while high education (> 12 years) is associated with 14% lower odds of any aspect of antibiotic misuse (OR = 0.86; 95% CI 0.72, 1.03). The association is more pronounced in Middle East (OR = 0.64; 95% CI 0.42, 1.00) and countries of lower-middle economies (OR = 0.67, 95% CI 0.41, 1.11). Inversely, in Europe, high education is associated with 25% higher odds of antibiotic misuse (OR = 1.25, 95% CI 1.00, 1.58). Each additional year of education was associated with 4% lower odds of any aspect of antibiotic misuse in lower-middle economies (OR = 0.96; 95% CI 0.92, 1.00) and in Middle East (OR = 0.96; 95% CI 0.93, 1.00). Conversely, it was associated with 3% higher odds of antibiotic storage, a specific type of misuse (OR = 1.03, 95% CI 1.01, 1.06). CONCLUSION: Individuals misuse antibiotics irrespective of their education level. Intervention programs to enhance the proper use of antibiotics should target all communities independent of their education level.

Income level and antibiotic misuse: a systematic review and dose-response meta-analysis.

OBJECTIVES: To quantify the association between income and antibiotic misuse including unprescribed use, storage of antibiotics and non-adherence. METHODS: We identified pertinent studies through database search, and manual examination of reference lists of selected articles and review reports. We performed a dose-response meta-analysis of income, both continuous and categorical, in relation to antibiotic misuse. Summary odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated under a random-effects random effects model. RESULTS: Fifty-seven studies from 22 countries of different economic class were included. Overall, the data are in agreement with a flat linear association between income standardized to socio-economic indicators and antibiotic misuse (OR per 1 unit increment = 1.00, p-value = 0.954, p-value non-linearity = 0.429). Data were compatible with no association between medium and high income with general antibiotic misuse (OR 1.04; 95% CI 0.89, 1.20 and OR 1.03; 95% CI 0.82, 1.29). Medium income was associated with 19% higher odds of antibiotic storage (OR 1.19; 95% CI 1.07, 1.32) and 18% higher odds of any aspect of antibiotic misuse in African studies (OR 1.18; 95% CI 1.00, 1.39). High income was associated with 51% lower odds of non-adherence to antibiotic treatment (OR 0.49; 95% CI 0.34, 0.60). High income was also associated with 11% higher odds of any antibiotic misuse in upper-middle wealth countries (OR 1.11; 95% CI 1.00, 1.22). CONCLUSIONS: The association between income and antibiotic misuse varies by type of misuse and country wellness. Understanding the socioeconomic properties of antibiotic misuse should prove useful in developing related intervention programs and health policies.

Association of knowledge and attitudes with the misuse of tranquilizers in parents: a study in Beirut (Lebanon).

OBJECTIVE: To measure the association between knowledge, attitudes and practices of personal misuse of tranquilizers among parents of schoolchildren in Beirut (Lebanon). DESIGN: We carried out a cross-sectional study in 1396 adults recruited from parents of students of eleven public and private schools, from primary schools to high schools, using a Knowledge, Attitude and Practices (KAP) questionnaire of personal use of tranquilizers. MAIN OUTCOME MEASURES: We assessed five patterns of tranquilizers' misuse: unprescribed use, shortened treatment, stored leftovers, doubled forgotten doses or taken when remembered, changed dose without medical recommendation, and a sixth composite outcome: 'any misuse'. RESULTS: Sixty-three (62.2%) of 91 parents who used tranquilizers reported at least one misuse pattern. Higher odds of 'any misuse' were observed among parents who reported taking tranquilizers to sleep better, to enjoy themselves with their families or to work better [2.35 ≤ adjusted interquartile odds ratio (aIqOR) ≤ 1.99]. Storing tranquilizers for future need was strongly associated with misuse [aIqOR: 5.00 (95% CI: 3.30, 7.59)]. Greater awareness about hazards of tranquilizers and the importance of therapeutic compliance was associated with lower odds of specific misuse patterns (0.50 ≤ aIqOR ≤ 0.72). CONCLUSIONS: Poor knowledge and medically disapproved attitudes increase the likelihood of practices of tranquilizer misuse.

Development and Validation of a Knowledge, Attitude and Practice Questionnaire on Antibiotic Use in Arabic and French Languages in Lebanon.

OBJECTIVES: Validated knowledge-attitude-practice (KAP) questionnaires are essential to design and evaluate intervention programs on antibiotic use. Recently, we validated the first KAP questionnaire on antibiotics in Spain. Cross-cultural adaptation and validation of research tools increase their universal usefulness. Here, we aimed to validate the questionnaire in a developing country with different socioeconomic characteristics from that of Spain. METHODS: We translated the previously developed KAP-questionnaire into Arabic and French, tailored it and then validated it in adult population in Lebanon. The item content validity index (I-CVI), scale content validity index (S-CVI/Ave) and modified Kappa (k*) were calculated. The construct validity of the questionnaire was evaluated using confirmatory factorial analysis (CFA, N = 1460) and its reliability was assessed using intraclass correlation coefficients (ICC, N = 100) and Cronbach's alpha statistic. RESULTS: ICV-I (>0.78), k* (equal to ICV-I for all items) and S-CVI/Ave (≥0.95) confirmed the questionnaire content validity. Pilot testing (N = 40) and face validity showed the understandability of the questionnaire by the population. Test-retest reliability analysis (N = 100) yielded ICC ≥ 0.59 for all knowledge and attitude items, showing the capacity of the questionnaire to generate reproducible results. CFA evidenced adequate fit of the chosen model, thus establishing the construct validity of the questionnaire (root mean squared error approximation = 0.053, standardized root mean square residual = 0.045, comparative fit index = 0.92 and Tucker-Lewis index = 0.90). The questionnaire showed an acceptable internal reliability (Cronbach's alpha = 0.62) and was highly accepted in Lebanon (response rate = 96% and item response rates ≥ 94%). CONCLUSIONS: The validity of the KAP-questionnaire on antibiotics in Arabic and French was demonstrated in Lebanon.