ImportanceRespiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.ObjectiveTo compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.Data SourcesIn this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.Study SelectionRandomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.Main Outcomes and MeasuresThe main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.ResultsFifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: −123 [95% CI, −138 to −100]; palivizumab: −108 [95% CI, −127 to −82]; motavizumab: −136 [95% CI, −146 to −125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: −54 [95% CI, −64 to −38; palivizumab: −39 [95% CI, −48 to −28]; motavizumab: −48 [95% CI, −58 to −33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (−8 [95% CI, −9 to −4] and −5 [95% CI, −7 to 0], respectively) and supplemental oxygen use per 1000 participants (−59 [95% CI, −63 to −54] and −55 [95% CI, −61 to −41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (−59 [95% CI, −65 to −40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.Conclusions and RelevanceIn this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.

Human asthma is caused by interactions between a range of genetic and environmental factors. However, the specific pathogenesis of asthma remains controversial. This study explored the contribution of DNA methylation to asthma using computer learning methods. Relevant datasets and information related to patients with asthma were collected from the Gene Expression Omnibus (GEO) database. A multivariate linear regression model was established. Differentially expressed genes and DNA methylation sites were identified. The results showed that the expression of 169 genes was significantly different between the two groups. Through differential analysis of methylation and differential analysis of gene expression, 44 differentially expressed genes that may be affected by DNA methylation modification were identified. The results of the multiple linear regression model showed that DNA methylation could explain 9.81% of the variation in gene expression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes, HLA-DMB, IL4, HLA-DPB1 , and CD40LG , were related to the occurrence of asthma, and HLA-DMB expression was significantly reduced in allergic asthma. There was a positive correlation between cg04933135 and HLA-DMB expression, and cg04933135 was a differential site for DNA methylation. Using blood samples from asthma patients, we confirmed that HLA-DMB expression is down-regulated, which may be affected by abnormal DNA methylation. DNA methylation plays an important role in the development of asthma, and HLA-DMB which modified by abnormal DNA methylation can be regarded as a new biomarker of asthma.

Background Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid adenosine deaminase (ADA) in the detection of paediatric pleural TB. Methods PubMed, Web of Science Core Collection, Embase and Cochrane Library databases were searched up to 20 December 2021. We used the bivariate and hierarchical summary receiver operating characteristic models to compute pooled estimates for the overall diagnostic accuracy parameters of ADA for diagnosing paediatric pleural TB. Results Eight studies, including 290 pleural fluid samples, met the inclusion criteria. The pooled sensitivity of ADA was 0.85 (95% CI: 0.78–0.90, I 2 : 55.63% < 75%) for detecting patients with paediatric pleural TB. A total of 262 pleural fluid samples from four studies were included to differentiate patients with paediatric pleural TB from controls. At a unified cut-off value of 40 U/L, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve of ADA were 0.89, 0.58, 2.09, 0.20, 10.48 and 0.89, respectively. Conclusions At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity. Key message Accurate identification of paediatric pleural TB will help eliminate TB in children. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity.

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