Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 244 appraisals
Journal of medical Internet research
Advancing Human-Centered AI in Clinical Decision Support: Sociocognitive Human-in-the-Loop Study in HIV Care
BACKGROUND: AI-powered clinical decision support systems (CDSS) have shown promise in improving prediction, monitoring, and treatment optimization across clinical domains, including HIV care. However, translating AI outputs derived from electronic health records into clinically meaningful, trustworthy, and actionable decision support remains challenging, underscoring the need for more human-centered and socioecologically grounded CDSS design. OBJECTIVE: This study aimed to explore how we can effectively translate the outputs of machine learning models based on HIV electronic health records into a real AI-powered CDSS for HIV care. Using the human-in-the-loop method, we engaged a set of stakeholders, including HIV physicians, nurse practitioners, infectious disease pharmacists, social workers, and case managers. Stakeholders interacted with an AI-powered CDSS prototype to identify barriers and challenges to adoption, as well as to inform a more holistic and context-aware AI-powered CDSS design. METHODS: We conducted a field study at Prisma Health in South Carolina that included pre- and postsurveys, interactive usability testing sessions, think-alouds, and in-depth interviews with 16 clinicians providing HIV care between March and September 2025. We analyzed survey responses using descriptive statistics, and then transcribed and analyzed think-aloud and interview data using an etic and emic approach. RESULTS: Clinicians identified multiple challenges and design considerations for AI-powered HIV CDSS, demonstrating that clinician-AI interaction is inherently sociotechnical and embedded across multiple socioecological levels. While clinicians relied on familiar clinical indicators as cognitive anchors for interpreting AI predictions, they emphasized that social determinants of health were central to their own risk assessment and clinical decision-making. Additionally, clinicians' trust in AI is conditional and develops over time, with explainability and actionability emerging as critical factors for translating predictions into meaningful clinical interventions. CONCLUSIONS: Findings highlight the need to move beyond technically accurate predictions toward AI-powered CDSS designs that align with clinicians' cognitive practices and socioecological realities of HIV care. By extending a sociocognitive framework through empirical grounding in HIV clinical practice, this study offers design insights for developing AI-powered CDSS that are trustworthy, context-aware, and capable of supporting actionable decision-making in HIV care settings and beyond.
2 Aug 2026
Read appraisal →JBJS reviews
One-Stage or Two-Stage Revision for Infected Shoulder Arthroplasty: A Head-to-Head Meta-Analysis of Comparative Studies
BACKGROUND: Periprosthetic joint infection (PJI) following shoulder arthroplasty is a devastating complication associated with substantial morbidity and revision burden. While 2-stage revision has traditionally been regarded as the gold standard for chronic shoulder PJI, single-stage revision has emerged as a potential alternative. The aim of this systematic review was to directly compare infection-related outcomes and complications between single-stage and 2-stage revision arthroplasties for shoulder PJI. METHODS: This systematic review was prospectively registered with PROSPERO (CRD420251159566) and conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE, EMBASE, and Web of Science were searched up to September 22, 2025. Comparative observational studies and randomized controlled trials (RCTs) evaluating single-stage vs. 2-stage revision for shoulder PJI in adults were eligible; no RCTs were identified. Primary outcomes were reinfection and infection control success; overall complications were secondary. Odds ratios (ORs) were calculated within each study and pooled using a random-effects model. Risk of bias was assessed with the Risk of Bias in Non-randomized Studies of Interventions tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Thirteen retrospective comparative studies involving 260 patients (127 single-stage and 133 two-stage) were included. Compared with 2-stage revision, single-stage revision showed a lower, but not statistically significant, odds of reinfection (OR 0.46, 95% confidence interval [CI] 0.21-1.04; p = 0.06; I2 = 0%) and overall complications (OR 0.52, 95% CI 0.18-1.53; p = 0.24; I2 = 0%) and a higher, but nonsignificant, odds of infection control success (OR 1.57, 95% CI 0.45-5.40; p = 0.48; I2 = 17%). CONCLUSION: Single-stage revision demonstrated infection control and complication rates comparable with 2-stage revision for shoulder PJI. Although no statistically significant differences were observed, trends favored single-stage revision. Given that the certainty of the evidence was graded as low, these findings should be interpreted with caution, and high-quality RCTs are required to define optimal patient selection and surgical strategy. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
30 July 2026
Read appraisal →Signal transduction and targeted therapy
Mucosal immunity and vaccine development
The mucosal system, which includes the respiratory, gastrointestinal, and urogenital tracts, serves as a primary entry point for pathogens, with a unique immune microenvironment and specialized defense mechanisms. In recent years, especially following the onset of the COVID-19 pandemic, there has been increasing recognition of the importance of mucosal immunity, motivated by an enhanced comprehension of its fundamental mechanisms. Currently, strategies based on mucosal delivery systems to administer antigens and induce strong mucosal protective immunity have become a key focus in the development of mucosal vaccines. Compared with conventional intramuscular delivery, mucosal vaccination can simultaneously elicit a robust local mucosal response, effectively block pathogen entry into the local mucosa, and generate systemic immune responses to prevent symptomatic infections and severe disease. In addition, mucosal delivery offers advantages such as ease of administration and low invasiveness, making it a more widely acceptable approach to vaccination. In the present study, we conducted a systematic review of the mechanisms of mucosal immunity, the technological platforms for mucosal vaccines, and proposed a perspective on the challenges and future directions for the development of next-generation mucosal vaccines, with the goal of enhancing public knowledge and awareness regarding mucosal immunity and its possible effects on global health.
27 July 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Utility of Repeating Blood Cultures in Candidemia: Insights From 2 Large Clinical Data Repositories
We evaluated utility of repeating blood culture for candidemia using 2 electronic health record datasets. Among 1386 candidemia episodes, repeated blood culture detected 23% of episodes at Houston Methodist Hospital and 45% in Medical Information Mart for Intensive Care IV after the initial negative cultures. These findings support repeating blood cultures when candidemia is highly suspected.
24 July 2026
Read appraisal →Emergency medicine journal : EMJ
Are rapid diagnostic tests reliable for the detection of malaria in the emergency department?
A short systematic review assessed the diagnostic accuracy of malaria rapid diagnostic tests in febrile adults from malaria-endemic regions. A database search of MEDLINE, EMBASE, Cochrane and Google Scholar returned 138 papers. Six papers met the inclusion criteria and were included in our analysis.
23 July 2026
Read appraisal →Human vaccines & immunotherapeutics
Factors influencing vaccine uptake during pregnancy: A systematic literature review.
A systematic literature review was conducted to build a comprehensive evidence base of qualitative/quantitative studies to identify barriers and enablers influencing maternal immunization (MI). Searches of seven databases on 20/10/2023 and 26/10/2023 yielded 87,367 records. Two reviewers performed full-text screening of 484 records. English-language articles from countries that had national recommendations for pertussis-containing maternal vaccines and reported on maternal vaccine acceptance, trust, and hesitancy were eligible. Overall, 184 studies were included. Barriers involving individual and group influences like lack of knowledge and reduced awareness of MI, pre-existing anti-vaccination beliefs and attitudes, and perceived concerns about vaccine safety and efficacy were the most prominent. Proactive communication and recommendations from healthcare professionals and public health authorities were major enablers, alongside trusting the information provided by healthcare professionals. Our results show that vaccine hesitancy is a complex phenomenon. Addressing both practical and perceptual barriers to MI might increase vaccination coverage among pregnant individuals. What is the context? Vaccines administered during pregnancy help protect both mother and newborn from serious infections. Yet, some expectant mothers hesitate to receive such vaccines.What is new? We systematically searched the available scientific literature to identify the factors that positively and negatively influence vaccine acceptance among expectant mothers.We analyzed data from 184 studies from countries across Europe, North America, Oceania, Asia, and South America that have national recommendations for vaccines against whooping cough.We found that vaccine refusal was mainly driven by personal perceptions of the vaccine or influences of the social environment.Convincing recommendations from healthcare professionals, fair access to prenatal care, increased trust in healthcare authorities and vaccines, and clear communication with the expectant mother were identified as promoters of vaccine acceptance.What is the impact? Addressing the identified issues might increase vaccine uptake among expectant mothers, which might have a serious impact on reducing infectious disease severity in newborns.
23 July 2026
Read appraisal →mSystems
MeLSI: Metric Learning for Statistical Inference in microbiome community composition analysis
Microbiome beta diversity analysis relies on distance-based methods, including permutational multivariate analysis of variance (PERMANOVA) combined with fixed ecological distance metrics (Bray-Curtis, Euclidean, Jaccard, and UniFrac), which treat all microbial taxa uniformly, regardless of their biological relevance to community differences. This "one-size-fits-all" approach may miss subtle but biologically meaningful patterns in complex microbiome data. We present Metric Learning for Statistical Inference (MeLSI), a novel machine learning framework that learns data-adaptive distance metrics optimized for detecting community composition differences in multivariate microbiome analyses. MeLSI employs an ensemble of weak learners using bootstrap sampling, feature subsampling, and gradient-based optimization to learn optimal feature weights, combined with rigorous permutation testing for statistical inference. The learned metrics can be used with PERMANOVA for hypothesis testing and with principal coordinates analysis for ordination visualization. Comprehensive validation on synthetic benchmarks and real data sets shows that MeLSI maintains proper type I error control while delivering competitive or superior statistical power for detecting subtle community shifts and, crucially, supplies interpretable feature-weight profiles that clarify which taxa drive group separation. On the DietSwap data set, MeLSI was the only method to achieve significance at α = 0.05, demonstrating that adaptive weighting can detect diet-induced community shifts that fixed metrics miss. Across all data sets, the learned feature weights identified biologically relevant taxa while providing actionable insight that no fixed distance metric can supply. MeLSI therefore offers a statistically rigorous tool that augments beta diversity analysis with transparent, data-driven interpretability.IMPORTANCEUnderstanding which microbes differ between groups of interest could reveal therapeutic targets and diagnostic biomarkers. However, current analysis methods treat all microbes equally (similar to using the same ruler to measure everything, regardless of what matters most). This means subtle but biologically important differences may go undetected, especially when only a few key species drive disease states while hundreds of "bystander" species add noise. Metric Learning for Statistical Inference (MeLSI) solves this by learning which microbes matter most for each specific comparison. In comparing male and female gut microbiomes, MeLSI identified specific bacterial families driving the differences, providing actionable biological insights that standard methods miss. This capability is particularly crucial for detecting early disease biomarkers, where differences are subtle and masked by biological variability. By telling researchers not just whether groups differ, but which specific microbes drive those differences, MeLSI accelerates the path from microbiome data to testable biological hypotheses and clinical applications.
22 July 2026
Read appraisal →Scientific reports
The role of AI in combating misinformation: leveraging text mining and social networking analysis
Misinformation on social media can be a severe threat to social trust, safety, and health of the population, especially in times of an epidemic like the Monkeypox outbreak. This study specifically focuses on a hybrid RoBERTa-GRU architecture designed to capture both contextual semantics and temporal dependencies in social media discourse. This research presents how the combination of text mining and social network analysis enables Artificial Intelligence (AI) to support misinformation detection. The proposal of a hybrid architecture that integrates RoBERTa and GRU-based embeddings in a contextual fashion and GRU-based modelling of sequential patterns helps identify and substantiate misinformation in social media posts. Based on a curated X (formerly Twitter) dataset consisting of Monkeypox posts (5787 posts), the model provided state-of-the-art results, with ROC-AUC 0.9979 and Cohen's kappa 0.9887; standalone baselines were also surpassed. Results reveal that the proposed transformer-RNN hybrid effectively captures both semantic depth and temporal relationships in misinformation detection tasks. In addition to performance, the paper addresses the limitations of dataset bias, multilingual constraint issues, and scalability as related to cross-linguistic applicability, multimodal study, and performance in real-time and resource-limited systems. The study adds value in this emerging body of knowledge on AI-driven social media analytics by offering practical guidance for mitigating health-related misinformation online.
22 July 2026
Read appraisal →ACS synthetic biology
LysePred: A Multiscale Convolutional Neural Network for Predicting Hemolytic Activity of Antimicrobial Peptides
Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics, yet hemolytic toxicity remains a critical barrier to clinical translation, with approximately 70% of known AMPs exhibiting high or moderate hemolytic activity. Existing computational prediction methods are often constrained by deficiencies, including high computational complexities, the inability to capture multiscale sequence patterns, and insufficient generalization across diverse datasets. We present LysePred, a multiscale convolutional neural network to address these deficiencies concurrently by employing parallel branches with exponentially spaced kernel sizes to simultaneously capture local amino acid motifs (bigrams, 4-g) and longer-range amphipathic patterns (8- to 32-g). LysePred achieves top-tier performance on six benchmark datasets, exceeding the performance of the second-best method by 9.13% in MCC and 3.65% in ACC on average, while maintaining exceptional stability (MCC CV < 6.92%, ACC CV < 2.73%). Furthermore, independent validation on the HemoPI2 dataset demonstrates that LysePred delivers highly competitive results with a computationally parsimonious design (∼0.55 M parameters). This represents a reduction in parameter density of 1 to 2 orders of magnitude compared to Transformer-based approaches, such as the 8M-parameter ESM-2 or the 110M-parameter BERT Base while maintaining linear complexity for high-throughput screening. Ablation studies validate that the multiscale architecture contributes meaningfully to performance, with single-scale variants showing up to 13.35% MCC degradation. Interpretability analyses via t-SNE visualization and SHAP feature importance reveal that LysePred learns biologically meaningful representations integrating both local sequence motifs and global structural patterns. LysePred offers a practical, efficient, and interpretable tool for rapid hemolytic toxicity prediction in antimicrobial peptide development. Code and data are available at https://github.com/lincubator/LysePred.
20 July 2026
Read appraisal →International journal of technology assessment in health care
Consideration of intersectoral costs and benefits in health economic evaluations of pneumococcal conjugate vaccines: a systematic review.
OBJECTIVES: This systematic review explores which intersectoral costs and benefits (ICBs) are considered in the economic evaluation of pneumococcal conjugate vaccines (PCVs) across different age groups and the related impacts on the results of economic evaluations. METHODS: Seven databases were searched from 2009 to 2024 for full economic evaluations (Ees) of PCVs from a societal perspective. ICBs were presented narratively and in tabular form. Studies were appraised on quality, and PRISMA guidelines were followed. RESULTS: In all, 57 studies were included. ICBs were captured in the following sectors: patient and family, paid labor (productivity), nonpaid productivity, other sectors (education, leisure, consumption), unspecified sectors for ecological effects (herd immunity, serotype replacement, cross-protection), and equity. In cases where the comparator was no vaccination, 10 studies reported that PCVs were dominant when ICBs were included. After excluding dominant analyses, the median QALY-based incremental cost-effectiveness ratio (ICER) reduction ranged from -3.25 percent (for patient/family costs and productivity loss) to -46.02 percent (in children with ecological effects). Among DALY-based studies, the inclusion of ecological effects reduced the median ICER by -22.97 percent. In head-to-head comparisons, 16 studies reported that PCVs were dominant when ICBs were included. CONCLUSION: Inclusion of ICBs, except for serotype replacement, showed favorable cost-effectiveness results. This study provides a framework for identifying the intersectoral costs and benefits for the health economic evaluation of PCVs in children and adults.
19 July 2026
Read appraisal →Renal failure
Effects on mortality of different blood purification techniques in sepsis patients: an umbrella review of systematic reviews and meta-analyses
Sepsis remains a leading cause of mortality worldwide, and extracorporeal blood purification has been widely implemented despite ongoing uncertainty regarding its survival benefit. We conducted an umbrella review of 42 systematic reviews and meta-analyses evaluating mortality across major extracorporeal blood purification modalities. Mortality estimates generally favored extracorporeal blood purification over conventional care, but effect sizes and consistency varied substantially by modality, and the overall certainty of evidence for mortality was low. At the review level, polymyxin B hemoperfusion showed a relatively consistent direction toward lower mortality, whereas renal replacement therapy-based strategies were typically closer to the null. However, most included reviews were of low or critically low methodological quality, with downgrading driven by risk of bias, inconsistency, and potential publication bias. Therefore, these findings should be interpreted cautiously and should not be considered definitive evidence of survival benefit. They highlight persistent evidentiary fragility and underscore the need for rigorously designed, phenotype-informed trials to clarify modality-specific effects in sepsis. What is known: Extracorporeal blood purification has been widely used as an adjunctive therapy for sepsis, but its mortality benefit remains uncertain across different modalities.What this study adds: This umbrella review synthesizes evidence from 42 systematic reviews and meta-analyses and shows that mortality estimates generally favor extracorporeal blood purification, although effects vary substantially by modality and the overall certainty of evidence remains low.Potential impact: These findings support cautious, modality- and phenotype-informed interpretation of extracorporeal blood purification in sepsis and highlight the need for rigorously designed trials with standardized protocols.
19 July 2026
Read appraisal →Antonie van Leeuwenhoek
Advancements in the study of gut microbiome in disease diagnosis
This review summarizes disease-associated changes in gut microbial composition and evaluates the diagnostic performance of models constructed with different machine-learning algorithms. The review seeks to answer questions related to the relationship between the human gut microbiome and disease progression, how different machine learning algorithms affect disease diagnosis using gut microbiome data, and how disease-specific microbial communities impact diagnostic models. Multiple studies report that gut microbiome dysbiosis is commonly observed in many diseases, though patterns vary between conditions and cohorts. Large-scale computational analyses are increasingly applied to identify microbial signatures and to build diagnostic models; however, model performance often depends on data source, preprocessing and choice of algorithm. Overall, evidence indicates disease-associated shifts in gut microbial composition, and that diagnostic model accuracy is sensitive to cohort, sequencing and modeling choices. While certain taxa recur across studies for some diseases, heterogeneity between cohorts limits immediate clinical translation; thus, harmonized study designs and external validation are required. Future work should prioritize reproducible multi-cohort analyses, transparent reporting (e.g., PRISMA for reviews) and prospective validation before clinical deployment.
18 July 2026
Read appraisal →Inflammation research : official journal of the European Histamine Research Society ... [et al.]
Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review.
OBJECTIVE AND DESIGN: This systematic review synthesized evidence for a conserved lipopolysaccharide (LPS)-mediated pathogenic mechanism across diverse tissues and evaluated its potential relevance to peripheral neuropathy. METHODS: Studies were identified in which LPS was the independent exposure and pro-inflammatory, M1-like macrophage activation/polarization was an outcome. Structured evidence mapping was used to code in-vivo studies for direct measurement of prespecified steps along a proposed pathway: gut perturbation→barrier disruption→circulating LPS→systemic inflammation→tissue interface disruption→innate immune activation→M1-like macrophage skew→tissue dysfunction. Conditional concordance and downstream chain completeness scores were calculated. RESULTS: Mechanistic patterns were conserved between pulmonary, cardiac, renal, lymphatic, gastrointestinal, central nervous, adipose, osseous, urologic, dental, hepatic, uterine, and pancreatic tissues. Conditional concordance with the proposed pathway was high (mean 0.984 ± 0.053). Eleven studies assessed all downstream steps from LPS exposure to tissue dysfunction, each demonstrating full chain completeness. M1 macrophage skew (87%), innate immune activation (87%), and circulating LPS (82.6%) were the most frequently reported steps. CONCLUSIONS: These findings demonstrate conservation of LPS-driven M1-like macrophage polarization and tissue injury across systems, supporting the need to further investigate the biological plausibility of a gut-immune-nerve axis contributing to peripheral neuropathy.
18 July 2026
Read appraisal →ACS applied materials & interfaces
The Evolving Landscape of Terahertz Biosensing: From Sensitivity to Precision
Terahertz (THz) spectroscopy has recently gained significant attention as a powerful tool for biomacromolecule detection due to its exceptional sensitivity in capturing molecular fingerprints, attributed to its unique wavelength range. THz biosensing platforms offer distinct advantages in identifying molecular rotational and vibrational states, making them effective for high-sensitivity, high-precision biomacromolecule analysis. This review highlights recent advancements in THz biosensing platforms, focusing on their spectroscopy interpretation and practical applications. We begin by introducing commonly used THz equipment and various metamaterials, followed by an overview of the key spectroscopy interpretation strategies for THz spectral analysis, including refractive index sensing and molecular fingerprint recognition. We also summarize the machine learning (ML) methods applied to enhance spectral analysis in THz biosensing platforms. Lastly, we provide an integrated perspective on the spectroscopy interpretation, clinical applications, and recent technological advancements in THz biosensing platforms, with an emphasis on how to construct a standardized THz-based biosensing workflow. We believe THz biosensing platforms hold immense potential to revolutionize molecular detection by enabling precise, label-free, and highly sensitive analysis of biomacromolecule interactions, paving the way for breakthroughs in medical diagnostics, environmental monitoring, and biochemical research.
17 July 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Magnetically actuated microrobotic system for sequential treatment of biofilm
Biofilm-associated infections present a critical therapeutic challenge due to antibiotic resistance and impaired tissue healing. Here, we present a microrobotic system (MZ-8) that integrates real-time human-steered navigation with autonomous, microenvironment-responsive therapy to actively eradicate biofilms and promote tissue regeneration. This microrobotic system features a spine-inspired structure for mechanical biofilm disruption, a pH-responsive ZIF-8 coating for immunomodulatory Zn2+ release, and closed-loop actuation under second near-infrared fluorescence guidance. In a rat model of periprosthetic joint infection, MZ-8 achieved effective biofilm removal, induced a pro-regenerative immune response by polarizing macrophages toward the M2 phenotype, and significantly enhanced tissue regeneration. Transcriptomic analysis further revealed the activation of immunomodulatory pathways and upregulation of M2-associated genes, confirming the system's sequential shift from eradication to repair. Moreover, validation in a rabbit model and human knee joint confirmed its operational feasibility under clinical imaging guidance and excellent biosafety. This work establishes that integrating physical eradication, biochemical immunomodulation, and interactive control within a single system is essential for advancing from infection clearance to functional tissue restoration. Thus, it provides a therapeutic paradigm for biofilm-associated diseases and lays a foundation for future intelligent, clinically adaptive anti-infective systems.
15 July 2026
Read appraisal →Archives of microbiology
SigMine and OPathDb: a literature-mining pipeline and database of potential opportunistic pathogens
Conversion of unstructured biomedical literature into structured knowledge for identifying cross-domain associations between biological entities remains a challenging task. SigMine is an automated pipeline constructed to mine biomedical literature to identify significantly associated biological entities. SigMine performs biomedical entity recognition from PMC articles using the EuropePMC Annotation API. Advanced entity recognition was performed using Python scripting, NCBI E-Utilities, and an n-gram algorithm followed by extensive data cleaning and mapping against standard databases. Statistical evaluation identified significantly co-occurring entities. The entire workflow was automated through a modular framework developed in Python v3.13 with a Tkinter-based Graphical User Interface. SigMine enhances usability while retaining the flexibility to use new dictionaries for annotation. SigMine was used to construct a literature-derived potential human Opportunistic Pathogens Database (OPathDb), housing 5,626 potential opportunistic pathogens significantly co-occurring with 1440 diseases and 7121 genes mined from 25,000 PMC articles. Additional annotation of 598 significantly co-occurring metabolites and 30 affected tissues is available for 3204 and 227 pathogens, respectively. OpathDb has a user-friendly query interface searchable by organism, disease, tissue, gene, protein and metabolite available at https://www.opathdb.cbsblab-nsut.in . Organism-entity associations can be visualized as weighted networks, with color-coded nodes and significance-scaled edges. Significant associations of opportunistic pathogens like Akkermansia mucinifila with colorectal cancer and Segatella copri with glucose intolerance can be identified through OpathDb. Through this database, the SigMine framework demonstrates conversion of unstructured text in vast and heterogenous corpora into standardized and well-organized information. Statistically inferred associations in OPathDb are potential candidates for clinical and experimental validation.
13 July 2026
Read appraisal →Vaccine
Interventions to improve pre-school vaccination timeliness: a systematic review.
BACKGROUND: Improving the timeliness of pre-school vaccinations (children aged 0 to 5 years) is an important public health goal to prevent outbreaks and maximise protection during early childhood. Multiple studies have highlighted the need for effective public health interventions to improve timely vaccination, and consequently the overall effectiveness of vaccination programmes. We aim to synthesise evidence on vaccination timeliness interventions and subsequently provide recommendations to improve pre-school vaccination timeliness in England. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) and non-randomised studies. Studies were eligible if they were conducted in high-income countries and evaluated an intervention to improve timeliness of any pre-school vaccination on the United Kingdom (UK) national childhood vaccination schedule. Five databases and grey literature were searched to February 2025. Risk of bias was assessed using Cochrane risk of bias tools. Data were analysed using random-effects meta-analyses and synthesis without meta-analysis (using effect direction plots). RESULTS: Of the 10,385 records from database searches and 1490 records from citation searches, 33 studies were eligible (15 RCTs, 18 non-randomised studies). Most studies were conducted in the USA (n = 24) and reported on the timeliness of multiple pre-school vaccines (n = 23). Twelve studies (36%) were judged as serious or critical risk of bias, eleven at moderate and ten at low risk. Various intervention groups were identified: call-recall (n = 10), quality improvement (n = 9), education (n = 5), multicomponent (n = 5), combination vaccines (n = 2), communication (n = 1) and vaccination schedule change (n = 1). We found limited evidence from a small number of studies of a potential beneficial effect of combination vaccines, communication, quality improvement, education and schedule change interventions. CONCLUSION: We identified several possible interventions to improve pre-school vaccination timeliness. However, we found limited quantity and quality of evidence on this topic. We recommend further high-quality studies evaluating interventions to improve vaccination timeliness in England, and application of consistent vaccination timeliness definitions.
12 July 2026
Read appraisal →PloS one
Machine learning-based analysis of drug resistance mutations in Mycobacterium tuberculosis
Tuberculosis is a deadly airborne disease caused by Mycobacterium tuberculosis. Drug-resistant tuberculosis presents significant challenges for treatment and control of the disease. Resistant strains of Mycobacterium tuberculosis arise from specific mutations in the bacterium. Identification and characterization of resistance-associated mutations are crucial for effective treatment strategies because the first- and second-line drugs for the disease target distinct genes in the bacterium and serve different purposes. Our study developed a machine learning prediction model to analyze mutations across multiple drug-resistance types. The proposed framework predicts drug-resistance mutations across four drug-resistance types, including Rifampicin Resistance, Isoniazid Resistance, Multidrug Resistance, and Pre-extensively Drug-Resistant tuberculosis. The NIAID-NIH TB portal is a publicly available dataset of tuberculosis patients, including drug-resistance information. Our study analyzed 3,065 cases of drug-resistant TB. Eight supervised ML algorithms were implemented for the study. A Random Forest classifier with 10-fold cross-validation shows higher predictive performance than the other seven algorithms considered for further analysis. Significant drug resistance mutations were identified using SHapley Additive exPlanations feature importance. The World Health Organisation mutation catalogues, considered the gold standard for drug-resistant mutations, were used to evaluate prediction results. Mutations not reported in the WHO catalogues were identified during the post-prediction comparative analysis stage, as they may represent potential resistance-conferring markers warranting further investigation, including structural and functional validation or experimental validation. The mutations are rpoB-I480T, rpoC-G332R, L527V, gyrA-D94V, KatG-G99E, A106V, W191R, W328C, T380I, and M420T. The study further checks the stability and pathogenicity of the mutations using computational tools, including I-Mutant 2.0 and PredictSNP. The findings added more clarity and further evidence for the significance of the mutation, based on its contribution to drug resistance.
11 July 2026
Read appraisal →ACS infectious diseases
Machine Learning Approaches Using High-Throughput Profiling Data for Antibiotic Discovery
Antibiotic-resistant bacterial infections continue to increase globally, creating an urgent need for new antibacterials with novel mechanisms of action. Early stages of antibiotic discovery are often limited by the difficulty of identifying compounds that act through previously unrecognized pathways and by challenges in determining their mechanisms. Machine learning (ML) integrated with high-throughput profiling now provides systematic approaches to overcome these barriers. Beyond initial hit discovery, multilayer profiling using morphological phenotyping, transposon sequencing, transcriptomics, proteomics, and metabolomics captures cellular responses that reflect the mechanisms of action. Because profiling data sets are typically high-dimensional and contain defined features and variables, ML can extract complex patterns associated with pathway-level responses and predict mechanisms for unknown compounds. In this review, we summarize current progress in high-throughput profiling and describe how ML applied to each data set can accelerate the identification of antibacterials with new mechanisms. These approaches accelerate the transition from large-scale compound screening to mechanistic validation and enable effective prioritization of lead compounds in early-stage antibiotic discovery.
11 July 2026
Read appraisal →Cell host & microbe
Mining the code of life for new antibiotics.
Antimicrobial resistance (AMR) is outpacing antibiotic development, creating an urgent need for discovery strategies that are faster, broader, and more systematic. Here, we review the transition from classical "dirt mining" and phenotypic screening toward digital discovery approaches that treat chemical structures and biological sequences as searchable, engineerable substrates for antibiotic innovation. Modern extensions of conventional screening, including in situ cultivation, co-culture, and microfluidics, have broadened access to previously uncultured microbes. Computer-aided approaches spanning virtual screening, molecular networking, and deep learning have enabled identification of unconventional antibacterial scaffolds from ultra-large chemical libraries. Mining genomes, proteomes, and metagenomes has uncovered antimicrobial peptides, encrypted peptides, and biosynthetic gene clusters encoding novel small-molecule antibiotics. Generative AI now enables design of peptides and small molecules under multiobjective constraints, including potency, toxicity, stability, and resistance risk. Together, these advances point toward discovery platforms that improve novelty, hit rates, and long-term durability in the face of AMR.
10 July 2026
Read appraisal →Cell host & microbe
Predicting antimicrobial resistance for precision medicine
Antibiotics are among medicine's greatest successes, but resistance evolution threatens their continued efficacy. Decades of research have deepened our understanding of the mechanisms and evolutionary dynamics of antimicrobial resistance. More recently, advances in machine learning (ML) and artificial intelligence (AI) show promise in predicting antimicrobial resistance in pathogens based on rapid whole-genome sequencing and other accessible data. In this perspective, we highlight advances in understanding the mechanisms and spread of antimicrobial resistance. We discuss how this knowledge, coupled with ML- and AI-based approaches, can inform the prediction of resistance and a precision-medicine strategy that targets pathogenic bacteria specifically, thereby limiting resistance evolution and collateral damage to the microbiome. These accurate predictions of bacterial vulnerabilities will enable the adaptation of classical antimicrobial treatments with adjuvants, as well as the use of novel, narrow-spectrum therapeutics. Implementing these strategies, while also identifying key challenges, will help bring this strategy into clinical practice.
10 July 2026
Read appraisal →Cell host & microbe
Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial
Gut microbiota may influence antidepressant treatment outcomes, yet whether targeted modulation can enhance efficacy remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in patients with major depressive disorder, administering a 2-week course of fecal microbiota transplantation (FMT) capsules or placebo as an adjunct to escitalopram (ChiCTR2300071421). Remission rates at week 8 did not differ significantly between groups, but FMT produced greater reductions in Hamilton Depression Rating Scale, 17-item version (HAMD-17) scores at weeks 2 and 8. FMT was well-tolerated with a safety profile comparable to placebo. Multi-omics analyses show durable donor microbial engraftment and enrichment of beneficial Lachnospiraceae and Oscillospiraceae taxa. Microbial remodeling is accompanied by an increase in serum bile acids that correlate with the alleviation of depressive symptoms. Mediation analysis supports a bile-acid-mediated suppression of inflammatory pathways linking microbial changes to antidepressant effects. Overall, FMT may provide a safe avenue to enhance escitalopram efficacy through microbiota-directed regulation of bile-acid metabolism and inflammation.
10 July 2026
Read appraisal →Metabolomics : Official journal of the Metabolomic Society
Clinical lipidomics in bacterial sepsis: a systematic review of serum and plasma evaluations
BACKGROUND: Lipid metabolism plays a central role in host-pathogen interactions and immune regulation during bacterial sepsis, with its dysregulation contributing to organ failure and mortality. Blood-based lipidomics has emerged as a promising approach for identifying diagnostic and prognostic biomarkers in sepsis. However, discrepancies in lipid profiles between serum and plasma remain a major challenge for clinical translation. This systematic review synthesizes lipidomic evidence from serum and plasma in bacterial sepsis patients to identify reproducible lipid biomarkers, evaluate methodological heterogeneity and assess associations with clinical outcomes. METHODS: A systematic search of five databases (Scopus, Pubmed, Ovid MEDLINE, Web of Science and Google Scholar) identified nine eligible studies published between 2016 and 2025 that applied untargeted or targeted lipidomics on human serum and plasma samples from adult bacterial sepsis patients (PROSPERO: CRD420251086177). RESULTS: Across both matrices, reproducible candidate lipid biomarkers included triacylglycerols (TAG), phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM) and ceramides. Synthesized findings revealed characteristically distinct directional trajectories: consistent elevation of TAG, bidirectional shifts of PC, depletion of LPC, bidirectional shifts of SM and elevation of SM. Preliminary trend within the literature indicates that serum-based studies more frequently captured prognostic alterations, whereas plasma-based studies often focused on diagnostic discrimination. Substantial heterogeneity was observed in sample handling, lipid extraction protocols and analytical platforms. CONCLUSIONS: Overall, both matrices offer valuable clinical insights, though these apparent differences in diagnostic or prognostic utility may reflect primary study designs rather than intrinsic matrix superiorities. Methodological heterogeneity limits reproducibility, highlighting the need for standardized workflows to enable translation of sepsis lipid biomarkers.
9 July 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
More Than a Message: Death by a 1000 'Chats'.
Secure electronic messaging within the electronic health record (EHR), such as Epic Chat, has transformed communication in hospitals by enabling rapid, asynchronous communication. Yet for Infectious Diseases (ID) consultants, the constant barrage of messages comes at a cost: fragmented attention, disrupted clinical reasoning, and potential patient harm. Messages that are repetitive, trivial, or casually worded can also fuel miscommunication and even medicolegal risk. As this type of messaging becomes increasingly prevalent in clinical practice, we must establish clearer boundaries and a cultural shift that values purposeful communication. Practical strategies include defining what requires chat versus direct phone or in-person conversation, batching responses, protecting focus time, and teaching messaging etiquette. To optimize patient care and protect clinician well-being, we must be intentional about when and how we communicate.
9 July 2026
Read appraisal →Transactions of the Royal Society of Tropical Medicine and Hygiene
Atomic clarity: how structural biology is shaping blood-stage malaria vaccines
Developing an effective malaria vaccine is challenging because Plasmodium parasites use complex strategies to invade host cells. The blood stage, where parasites replicate inside red blood cells, causes disease symptoms and relies on large multiprotein surface complexes that are difficult to target. Understanding their structure is essential for rational vaccine design. Cryogenic electron microscopy (cryoEM) enables atomic-level analysis of dynamic and membrane-associated complexes without crystallization, revealing key processes such as protein trafficking, nutrient uptake, and host cell remodeling. Recent advances in artificial intelligence and deep learning have improved cryoEM data analysis and structural modeling. Together with genomic data, this integrated approach is accelerating progress toward broadly protective malaria vaccines.
9 July 2026
Read appraisal →Journal of computer-aided molecular design
Two faces of drug repurposing data in machine learning-driven structure-based virtual screening supported by interaction fingerprints
Ensemble docking is a prominent source of protein-ligand complex structures, which could be conveniently analyzed with interaction fingerprints approach in a machine learning framework. Nevertheless, the chemical nature and provenance of the source data libraries used for model development may influence the predictive ability. We assessed the performance of SARS-CoV-2 main protease (Mpro) inhibitors classification by random forest models trained on different fingerprint implementations using three inhibitor libraries, comprising drug repurposing data or compounds rationally designed as Mpro inhibitors. Models trained on drug repurposing data showed a low prediction performance on their own, while infusion of these data into libraries with specific inhibitors greatly improved applicability domains of the models. Our results highlight the importance of balanced dataset preparation for machine learning applications in medicinal chemistry, especially when relied on drug repurposing experiments.
8 July 2026
Read appraisal →Journal of medical economics
Evaluation of nirmatrelvir/ritonavir treatment for COVID-19 on health-related outcomes: a global economic value systematic literature review.
AIMS: Nirmatrelvir/ritonavir (NMV/r)i is an antiviral drug indicated for the treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe disease. We performed an updated economic systematic literature review (eSLR) of NMV/r to build upon evidence reported in our previous eSLR and additionally examine the health-related outcomes associated with NMV/r and any potential effect of long COVID. METHODS: A systematic search of Embase, PubMed, Cochrane, and EconLit and of conference and health technology assessment agency websites was performed to identify economic analyses published between January 2022 and October 2025. RESULTS: Of the 33 included economic evaluations, most were cost-utility analyses (n = 16) and used an analysis of a short-term decision tree with a long-term Markov model (n = 11). Several types of health-related endpoints were reported by studies, with most including hospital-related endpoints (n = 20), quality-adjusted life-years (QALYs) (n = 18), and death-related endpoints (n = 18). Positive health-related outcomes were associated with NMV/r treatment, including reductions in hospitalizations and deaths and an increase in QALYs. NMV/r treatment was also associated with a reduced number of patients with long COVID complications. LIMITATIONS: Most studies were conducted in high-income countries, were based on different COVID-19 variants, and were limited in data on the long COVID population. CONCLUSION: In addition to monetary benefits, NMV/r provides short-term and long-term health-related benefits to patients with mild to moderate COVID-19. This study provides further support for NMV/r as a cost-effective treatment option.
7 July 2026
Read appraisal →Journal of epidemiology
Comparison of Influenza Epidemic Trends Based on a Large-scale Claims Database and National Infectious Disease Surveillance in Japan
BACKGROUND: Seasonal influenza is a recurrent respiratory infection, and timely detection is essential for public health. In Japan, surveillance is conducted through sentinel medical institutions under the National Epidemiological Surveillance of Infectious Diseases (NESID). Recently, access to large claims databases, such as the JMDC claims database (JMDCdb), has increased. While both are sample-based systems, JMDCdb covers a much larger population. We aimed to assess consistency between these sources in estimating influenza cases and the effective reproduction number (Rt) and to explore their utility in epidemic analysis. METHODS: We analyzed data from week 36 of 2016 to week 35 of 2019. Influenza cases were estimated from NESID (reported cases and cases per sentinel) and JMDCdb (cases with influenza-related diagnoses and antiviral prescriptions). Daily infection counts were derived to estimate Rt. RESULTS: Although minor differences appeared at epidemic peaks, estimates from NESID reports aligned well with JMDCdb. Estimates based on cases per sentinel were lower. Rt values were consistent across data sources. Rt exceeded 1.0 when cases per sentinel surpassed 0.2-0.3. Using a threshold of 0.25 cases per sentinel enabled detection of epidemic onset 4-5 weeks earlier than current standards. CONCLUSION: Claims data, such as those from JMDCdb, may be useful for retrospective examination of influenza trends. Moreover, a detailed analysis of the number of cases reported per sentinel suggested the potential to propose threshold values that enable earlier prediction of epidemics than conventional criteria.
7 July 2026
Read appraisal →International health
Antimicrobial stewardship interventions currently implemented at primary healthcare settings across low- and lower-middle-income countries (LLMICs)
BACKGROUND: Antimicrobial resistance (AMR) is a top global public health and development threat. Antimicrobial stewardship programs (AMSPs) are one of the most cost-effective interventions to optimize the use of antimicrobials. This study reviews AMSPs that have been implemented in low- and lower middle-income countries. METHODS: A systematic search was conducted on electronic databases including MEDLINE, PubMed, Embase, OVID, Web of Science and Cochrane Library on 18 July 2024 for published papers from 2014 to 2024 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Relevant published literature was then selected based on the established inclusion/exclusion criteria. Each article was screened by two independent reviewers. Data were extracted and synthesized in the review. RESULTS: Of the 425 articles screened, only 13 were eligible for review and included in this study. Two studies were multinationals. Five studies were randomized controlled trials. Among the three key focuses of AMSPs, most of the interventions focused on optimizing antibiotic use (n=8), followed by improving diagnostics and monitoring (n=3) and education and training (n=2). The most commonly reported barriers to implementing AMSPs was a lack of resources (n=9). Facilitators reported included knowledge of AMS (n=8), availability of educational and training resources (n=8), adequate funding (n=6), accountable and transparent procedures (n=5) and positive communication within healthcare facilities (n=4). CONCLUSIONS: All included studies show improvement in AMS through innovative programs. However, only a few have been adopted nationwide and influence policy formulation in the country. We recommend adoption of effective AMSPs into the national strategic planning and implementation across primary health settings.
5 July 2026
Read appraisal →BMJ open
Impact of climatic variables on postoperative outcomes in various surgical disciplines: a systematic review.
OBJECTIVES: The impact of climate change on health is well recognised, yet its influence on postoperative complications remains underexplored. This systematic review examines how climatic factors-particularly temperature, humidity and seasonal variations-affect surgical outcomes. DESIGN: Systematic review with narrative synthesis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. DATA SOURCES: A comprehensive search of PubMed, Web of Science and the Cochrane Library from June 2015 to June 2025 was conducted. An additional supplementary PubMed search was performed to identify further relevant studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included were studies published in English or German that examined associations between climatic factors, including temperature, humidity, precipitation or seasonality and postoperative outcomes in surgical patients. Studies without a surgical or climatic focus, animal studies, reviews and commentaries were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies and extracted data using predefined criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to methodological heterogeneity, findings were synthesised narratively. RESULTS: Fifteen studies were included. High ambient temperatures were frequently associated with increased risks of surgical site infections (SSIs). Some large studies reported that even a one-degree rise significantly elevated infection rates. Humidity was also linked to higher infection rates, with evidence suggesting an independent effect in some cases. Seasonal changes influenced complication rates across regions and surgical disciplines, with infection and pneumonia peaks in summer or winter months. A few studies reported increased risks during heavy rainfall or institutional transitions such as the 'July effect'. CONCLUSION: Overall, elevated temperature and humidity appear to be associated with increased postoperative risks, especially SSIs. Seasonal patterns may further influence outcomes depending on geography and procedure type. While the available evidence supports a link between climate and surgical complications, methodological differences and limited adjustment for confounders highlight the need for more rigorous studies.
5 July 2026
Read appraisal →Infectious diseases of poverty
Broadly neutralizing antibodies for HIV therapy in clinical trials: a systematic review
BACKGROUND: Lifelong daily antiretroviral therapy (ART) effectively suppresses human immunodeficiency virus type 1 (HIV-1) replication but does not eradicate the virus, underscoring the urgent need for long-acting antivirals and functional cure strategies. Broadly neutralizing antibodies (bNAbs) have emerged as a promising approach for achieving durable HIV-1 remission. In this systematic review, we summarize recent advances in the development of bNAbs for HIV-1 treatment. METHODS: We searched PubMed, Embase, and Web of Science for clinical trials published up to March 22, 2026. We included data evaluating intravenously administered bNAbs, with or without concomitant conventional ART, and comparing them with placebo, ART or no intervention. These data were used to evaluate the pharmacokinetics, antiviral efficacy, resistance profiles, immunologic effects, and safety of intravenously administered bNAbs. RESULTS: LS-modified bNAbs extended half-life by 2- to 5-fold relative to their parental counterparts (e.g., VRC01LS: 71 vs 15 days), although viremia reduced half-life by 20-40%. In viremic participants harboring bNAb-sensitive virus, monotherapy achieved viral load (VL) reductions of 0.93-1.8 log₁₀ copies/ml, with rebound occurring within approximately 4-8 weeks, whereas combinations regimens achieved declines of up to 2.04 log₁₀ copies/ml and delayed rebound to 15-33 weeks. No consistent reduction in total reservoir size was observed, although early intervention and baseline viral sensitivity appeared to limit reservoir expansion. Resistance emerged through epitope-proximal mutations, with cross-resistance observed mainly among antibodies targeting shared epitope classes. Overall, bNAbs were well tolerated, with rare discontinuations (0.4%) and low immunogenicity. CONCLUSIONS: LS-engineered bNAbs exhibit a longer half-life than their parental antibodies. Combination regimens achieve greater VL reductions and a longer delayed rebound compared with monotherapy, indicating that LS-modified multi-epitope bNAb cocktails are promising for long-acting HIV-1 remission. To become clinically competitive, larger resistance-guided trials are needed to extend dosing intervals, improve resistance mitigation, and define optimal integration with other long-acting therapies.
4 July 2026
Read appraisal →The Kurume medical journal
Development of Machine Learning Models to Predict Candidemia in Hospitalized Adult Patients
PURPOSE: We aimed to develop a generalizable machine learning model that leverages electronic medical record (EMR) data to predict candidemia using information available on or before the date of blood culture collection. METHODS: This study included adult patients admitted to Shin Koga Hospital (April 2014-March 2022) who underwent blood cultures at least 14 days after admission. We prepared two datasets: a "Complete case dataset" (13 variables, no missing values) and a "Imputed full-variable dataset" (36 variables, single imputation). We evaluated the discriminative performance of four machine learning models, including extreme gradient boosting, random forest, least absolute shrinkage and selection operator (LASSO) logistic regression, and logistic regression using stratified 5-fold cross-validation by comparing their area under the receiver operating characteristic curve (AUROC). The model with the highest mean AUROC was selected, assessed on the entire dataset, and internally validated using 1,000 bootstrap replicates. RESULTS: A total of 919 patients were included, of whom 47 (5.1%) had candidemia. The LASSO logistic regression demonstrated the best performance and was selected as the final model. The AUROC (95% CI) was 0.880 (0.836-0.924) for the Complete case dataset and 0.913 (0.878-0.948) for the Imputed full-variable dataset. The optimism-corrected AUROCs were 0.851 and 0.876, respectively. CONCLUSION: We developed two versions of the LASSO logistic regression model using only information automatically extracted from EMR, considering real-world data availability. These models have the potential to serve as practical tools to support early diagnosis and therapeutic intervention for candidemia.
3 July 2026
Read appraisal →Advanced drug delivery reviews
Artificial intelligence and machine learning in smart vaginal formulation development
Vaginal drug delivery in women's health remains underutilized and insufficiently studied, largely due to the complexity and dynamic nature of the vaginal microenvironment. Variations in vaginal pH, hormonal levels, and microbiota composition introduce significant biological variability, complicating formulation design and contributing to inconsistent therapeutic outcomes and poor patient adherence. Conventional vaginal formulations often fail to account for these individual differences, highlighting the need for more adaptive and predictive approaches. Emerging advances in artificial intelligence (AI) and machine learning (ML) offer promising strategies to address these challenges by enabling multi-parameter, data-driven formulation development that explicitly considers biological variability. Despite their transformative potential, the application of AI and ML in vaginal drug delivery remains limited. This review addresses this gap by examining the emerging role of AI/ML in the design, optimization, and development of next-generation vaginal formulations, including mucoadhesive, mucus-penetrating, bio-responsive, and controlled-release systems. Key factors influencing formulation performance, such as vaginal microbiota composition, are discussed, and ethical, regulatory, and technical challenges relevant to integrating AI/ML into vaginal drug delivery are also considered. Although research is in its early stages, existing studies indicate that AI and ML integration can enhance predictability, efficiency, and reproducibility in vaginal formulation development. Finally, we highlight the potential of developing personalized medicines through the integration of AI/ML and digital health monitoring devices to create patient-centered vaginal drug delivery systems, thereby advancing therapeutic outcomes and transforming women's health.
1 July 2026
Read appraisal →CPT: pharmacometrics & systems pharmacology
A Narrative Review of Artificial Intelligence for Drug Repurposing: Lessons From COVID-19 and Oncology (2020-2025)
Drug repurposing presents a cost-effective and time-efficient strategy to identify new therapeutic applications for existing drugs. Recent advances in artificial intelligence, including machine learning, deep learning, knowledge graphs, and natural language processing, have revolutionized this field by enabling automated discovery of drug-disease associations. This review examines the role of artificial intelligence in drug repurposing, drawing insights from two critical case areas: Coronavirus disease 2019 and oncology. We explore current trends, methodological frameworks, and technological innovations in artificial intelligence-driven drug repurposing, as well as challenges and emerging future directions. The findings of this paper underscore the transformative potential of artificial intelligence in biomedical research and justify its continued integration in pharmaceutical pipelines.
1 July 2026
Read appraisal →PloS one
Forecasting COVID-19 new cases using NBEATS deep learning and mobility data
COVID-19 is a highly contagious disease transmitted primarily through human contact. Therefore, understanding population mobility is essential for predicting COVID-19 case trends. In this paper, we propose a novel deep learning approach for forecasting new COVID-19 cases using a neural architecture called Neural Basis Expansion Analysis for Interpretable Time Series (N-BEATS). The N-BEATS model effectively handles long input sequences and large output horizons without information loss or increased computational complexity. We compare the performance of N-BEATS with a state-of-the-art benchmark model, LSTM-Markov, across four major countries: the United States, the United Kingdom, Russia, and Brazil. Three distinct COVID-19 datasets from Google, Apple, and Our World in Data (OWID) were used in this study. Incorporating Google and Apple mobility data as covariates enhances both the accuracy and interpretability of the N-BEATS model. Our results show that N-BEATS consistently outperforms LSTM-Markov across all datasets and countries, consistently yielding lower Root Mean Squared Error (RMSE) and Mean Absolute Percentage Error (MAPE). Furthermore, the N-BEATS model with covariates outperforms its counterpart without covariates, indicating that mobility data provide substantial value for forecasting new COVID-19 cases. Overall, this study demonstrates the effectiveness of the N-BEATS architecture in capturing pandemic dynamics and offers valuable insights for policymakers and public health officials in managing future outbreaks.
30 June 2026
Read appraisal →European journal of hospital pharmacy : science and practice
A bibliometric analysis of the application trends of information technology in antimicrobial stewardship within hospitals
OBJECTIVES: This study uses bibliometric analysis to systematically map research trends, knowledge structure and evolution of information technology (IT) in hospital antimicrobial stewardship (AMS) over the last 20 years. METHODS: A Web of Science Core Collection search (2000-2025) yielded 258 English-language publications on IT applications in hospital AMS. A bibliometric analysis, utilising CiteSpace and Bibliometrix, quantitatively evaluated domain evolution through temporal analysis, network mapping, keyword clustering, burst detection and examination of highly cited publications. RESULTS: The bibliometric analysis reveals a fluctuating yet overall increasing trend in annual publications, peaking at 49 articles in 2024. The US (131 publications) and European nations demonstrate significant research output (centrality >0.2), with major collaborative networks coalescing around institutions including Harvard University and Imperial College London. Keyword analysis identifies 'AMS' as a core theme, closely associated with technological keywords such as 'machine learning (ML)', 'clinical decision support systems (CDSS)', 'electronic health records (EHR)' and 'artificial intelligence (AI)'. Emerging trends suggest a shift in research focus from foundational strategies to data-driven prediction of antimicrobial resistance (AMR) and precision interventions. Highly cited literature emphasises the integration of EHR and ML technologies for optimising prescriptions and predicting resistance patterns. CONCLUSIONS: IT-driven AMS research has shifted from empirical management to data science. Despite EHR integration, and ML and CDSS support, challenges remain in data standardisation, technical deployment and ethics. Future work must emphasise global collaboration, standardisation, design refinement and ethical guidelines, and provide clear algorithm explanations to enhance AMR mitigation.
26 June 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Cough biomarkers for diagnosis and monitoring of respiratory disease: a systematic review
Cough is a common and physiologically informative component of respiratory morbidity, but its potential for diagnosing and monitoring disease is not thoroughly investigated. This systematic review synthesised the literature on algorithmic and statistical models analysing cough acoustics for diagnosing or monitoring respiratory conditions. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, five databases (PubMed, Embase, Scopus, Web of Science and CENTRAL) were systematically searched for studies published from January 2010 to June 2025. Eligible studies performed quantitative acoustic feature analysis of human coughs using statistical, machine learning or deep learning models and reported diagnostic or prognostic performance. 89 studies from 34 countries were assessed, covering cough detection (n=31), disease classification (n=55) and disease severity prediction (n=3), reflecting potential applications in disease monitoring. Deep learning approaches, especially convolutional and recurrent networks, were predominant (n=56) and tended to achieve the higher accuracies, although machine learning ensemble methods and logistic regression also demonstrated strong performance, particularly with well-engineered features. Across different diseases, sensitivities and specificities were often reported to be ≥90%, notably for tuberculosis, asthma and COVID-19. However, methodological weaknesses were common, with only 11.2% of studies introducing external validation, 71.1-87.6% demonstrating high risk of bias (according to PROBAST-AI) and most based on small, homogeneous or crowdsourced cohorts with limited generalisability. These limitations contribute to inflated internal performance and uncertainty about real-world applicability. Cough acoustic biomarkers hold promise as an adjunctive tool for screening and longitudinal monitoring in low-resource environments. Nevertheless, widespread implementation will require large, multicentre validation, standardised calibration, bias control and incorporation into privacy-preserving workflows.
25 June 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Mucoactive agents in bronchiectasis: a systematic review and meta-analysis
BACKGROUND: Mucoactive agents aim to improve mucociliary clearance in bronchiectasis, disrupting the cycle of impaired clearance, infection and inflammation. Registry data show 28% of patients use these agents, but prescribing varies due to limited evidence. We aimed to update evidence on mucoactive agents' effects in adults with bronchiectasis. METHODS: We conducted a systematic review and meta-analysis, searching Medline, Embase, CENTRAL and trial registries to 1 October 2025. Eligible studies included adults with bronchiectasis, evaluating any mucoactive agent versus placebo or control. Cystic fibrosis and paediatric studies were excluded. The primary outcome was exacerbation frequency; secondary outcomes included lung function, quality of life and adverse events. FINDINGS: From 1512 records, 24 studies (20 randomised, four observational: n=7051) evaluated eight mucoactive agents (ambroxol, bromhexine, carbocisteine, erdosteine, hypertonic saline, mannitol, N-acetylcysteine, rhDNase). Most trials had high or some risk of bias. Seven randomised studies (n=1259) reported exacerbations; pooled analysis did not demonstrate a statistically significant difference in annualised exacerbation incidence (mean difference -0.40 per patient per year, 95% CI -1.04-0.24; p=0.22; I2=91%; very low certainty). Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV1 % pred), showing a small mean increase of 3.23% (95% CI 0.31-6.15; p=0.03; I2=69.9%; very low certainty). Pooled analyses did not demonstrate significant differences for other spirometry measures, quality of life or adverse events. INTERPRETATION: Pooled evidence did not show a reduction in exacerbations and FEV1 % pred improvements were small. Evidence certainty was low/very low, meaning overall clinical benefit remains uncertain, highlighting the need for targeted trials of specific agents and subgroups.
25 June 2026
Read appraisal →Rheumatology international
Mortality and survival in patients with systemic lupus erythematosus in the Middle East and North Africa: a systematic review and meta-analysis
Systemic lupus erythematosus (SLE) is associated with increased mortality compared with the general population, with outcomes influenced by ethnicity and organ involvement. Data from the Middle East and North Africa (MENA) remain limited, particularly regarding long-term survival and mortality predictors. To estimate and compare all-cause mortality and survival rates among adult patients with SLE in the MENA region and identify predictors of mortality. A systematic review and meta-analysis of cohort studies reporting survival and mortality in patients with SLE in the MENA region was conducted. Eligible studies were identified through a comprehensive database search and screened according to PRISMA guidelines. Data on treatment exposures and clinical predictors of mortality were extracted. Twelve cohort studies, including 3,478 adults with SLE from five MENA countries (Türkiye, Iran, Egypt, Israel, and Tunisia), were analyzed. The pooled all-cause mortality rate was 9.9% (95% CI: 7.2%-14.0%; I² = 89.7%). Survival remained high at 5 years (93.9%) and 10 years (90.0%), but declined at 15 years (85.5%) and 20 years (71.7%), with long-term estimates highly sensitive to single-study exclusion. Leave-one-out analysis slightly increased survival estimates and reduced heterogeneity. Major mortality predictors included renal involvement, cardiovascular disease, infections, hypertension, diabetes, hematologic abnormalities, and male sex. Higher cumulative corticosteroid and cyclophosphamide exposure was linked to increased mortality, whereas hydroxychloroquine and azathioprine appeared protective. Infection was the leading cause of death, followed by active disease, renal failure, and cardiovascular complications. Patients with SLE in the MENA region show high short-term survival, but long-term outcomes remain variable. Mortality is mainly driven by renal, cardiovascular, and infectious complications, with treatment exposure contributing to risk. These findings highlight the need for multicenter registries, standardized reporting, and strategies to reduce infection burden and optimize nephritis care.
23 June 2026
Read appraisal →Vaccine
Impact of standing orders on vaccine uptake: A systematic review.
OBJECTIVE: We sought to evaluate the impact of standing orders on vaccine coverage in clinical settings. METHODS: Two reviewers independently screened and included studies that evaluated use of standing orders either alone or in combination with other interventions and collected data on vaccine coverage. We extracted effect sizes for studies that used only standing orders as an intervention and had a comparison group. RESULTS: The search yielded 56 eligible studies, 22 of which evaluated standing orders-only interventions. Standing orders increased vaccine uptake by a median of 13 percentage points (IQR 2-20 percentage points). Eight of these studies had a comparison group including 1 randomized trial; 5 were at low risk of bias. The overall findings were similar those for seasonal influenza vaccine (median increase of 12 percentage points; IQR, 6-24; 7 studies) and pneumococcal vaccines (14 percentage points; 2-20; 5 studies), the two most studied outcomes. Multi-component studies paired standing orders with interventions for providers frequently (34%-63% of studies), patients often (20%-49%), and systems least often (3%-14%). CONCLUSIONS: Standing orders show one of the largest effects among vaccine uptake interventions. Future research should focus on randomized trials, childhood vaccination, and behavioral aspects of implementation in healthcare systems.
21 June 2026
Read appraisal →Sexual health
Digital versus clinic-based sexual health services: patterns of use and equity implications from a UK-based evaluation
BACKGROUND: Digital sexual health services have expanded rapidly in England; yet, concerns remain regarding equitable access among different population groups. We compared demographic characteristics and outcomes between online and clinic-based sexual health service users in Leicester, Leicestershire, and Rutland. METHODS: A retrospective analysis of data (April 2019-June 2023) compared online contacts, via SH:24, a UK online sexual health service providing postal sexually transmitted infection (STI) testing and remote contraception, with in-clinic attendances. Demographic variables included age, gender, ethnicity and Index of Multiple Deprivation (IMD 2019) decile, where Deciles 1-2 represent the most deprived areas. Ethnicity was recoded into Office for National Statistics categories. Reasons for attendance, contraception methods, and STI test outcomes were analysed. Risk ratios with 95% confidence intervals compared proportions between modalities. RESULTS: Online users were younger than clinic attendees (mean age, 25.1 vs 31.4 years). A slightly higher proportion of women accessed online services although gender was unrecorded in 59.1% of online attendances. White and mixed ethnicity groups were more likely to use online services than Black, Asian and 'Other' ethnic groups. Individuals living in the most deprived areas were less likely to access online services. STI testing was more frequent online (56.8% vs 43.3%), while positivity rates for infections were lower. CONCLUSIONS: Complementary to clinic-based sexual health services, online pathways provide accessible STI testing and contraception. Differences in uptake by age, ethnicity and deprivation highlight the importance of monitoring equitable access as digital provision expands. Maintaining both online and face-to-face provision is likely to remain important for equitable sexual health care.
16 June 2026
Read appraisal →International immunopharmacology
Antimicrobial peptides in malaria and tuberculosis management: a systematic review of emerging evidence
AMPs (Antimicrobial peptides) are small molecules that are crucial components of biological activities, viz wound healing, angiogenesis, antimicrobial activity, immune regulation, and exhibit anticancer properties. This systematic review summarizes the origin, sequence, efficacy, and structure-activity mechanisms of AMPs against tuberculosis and malaria, the world's leading killer infectious diseases, employing the AMP database (APD3) (till June 2025) and PubMed search (January 1965 to June 2025). The comprehension is well addressed by covering the inhibitory activity, SAR (structure-activity relationships), and action mechanisms of AMPs (natural and synthetic) against Mycobacterium tuberculosis and Plasmodium spp., as both pathogens exhibit multidrug resistance. The review also illustrates how these specific motifs, along with their properties such as hydrophobicity, charge, or amphipathicity, influence the AMPs activity against the pathogens. Moreover, challenges in the AMPs use and the way forward, including the recent breakthroughs employing nanocarriers, inhalable formulations for TB, and targeted erythrocyte delivery for malaria, are also highlighted. AMPs have illustrated promising anti-TB and antimalarial efficacy owing to their unique structure and novel mode of action, despite exhibiting varying extents of toxicity. Anti-malarial AMPs are grouped in defensins and cecropins, while the majority of natural anti-TB AMPs are classified as bacteriocins, defensins, and cathelicidins. Synthetic AMPs, in contrast, are designed to enhance activity and selectivity while reducing toxicity and the development of resistance. AMPs have α-helical, β-sheet, or random-coil structures and are cationic, amphipathic, and highly hydrophobic, attributes that contribute to observed anti-TB and anti-malarial potential. A comprehensive understanding of AMP's structure and function, along with the use of artificial intelligence (AI) and machine learning, can provide impetus for AMP therapy as an alternative to tackle tuberculosis and malaria.
15 June 2026
Read appraisal →BMC cardiovascular disorders
Trends in cardiac implantable electronic device infections: 2015 to 2019
BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) improve survival in patients with cardiac rhythm disorders but carry risks of complications, most notably major infections. Reported infection rates vary internationally, and contemporary large-scale data from Germany are scarce. We aimed to determine nationwide rates of CIED infection-related hospitalizations and associated mortality over a five-year period. METHODS: We analyzed administrative claims from Germany's largest statutory health insurer covering more than 27 million beneficiaries. All CIED procedures performed between January 2015 and December 2019 were identified, including initial implantations, upgrades or downgrades, generator replacements, early revisions, and device extractions. Major infections were detected using International Classification of Diseases (ICD-10-GM) and procedural codes, and stratified as generator pocket infections or lead-associated endocarditis. In-hospital mortality was determined from discharge records. RESULTS: Among 282,205 patients (57.7% male) undergoing CIED procedures, 6,577 individuals (2.33%) experienced 7,704 major infections within three months. Generator pocket infections occurred in 5,396 cases (1.91%), lead-associated endocarditis in 2,308 (0.82%), and combined infections in 1,127 patients (0.39%) within the acute 90-day observation period. CIED infections substantially increased healthcare utilization: Infected patients required substantially more procedures than non-infected patients, despite correct treatment. In-hospital mortality reached 8.36% for pocket infections and 15.0% for endocarditis. Extended follow-up in the 2015 cohort revealed a 4.33% infection-related procedure rate over five years. CONCLUSIONS: Nationwide German data reveal higher acute CIED infection rates than previously reported, with considerable mortality and procedural burden. These findings highlight an urgent need for improved prevention and management strategies.
14 June 2026
Read appraisal →Human vaccines & immunotherapeutics
Immunogenicity and safety of AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8)-like influenza vaccine in adults: Phase 1/2, observer-blinded, randomized trial
Influenza pandemics arise from novel influenza A viruses. Recent emergence of a new clade (2.3.4.4.b) of the highly pathogenic H5N1 in animals and humans highlighted its pandemic potential. We evaluated the immunogenicity and safety of GSK's AS03-adjuvanted H5N8 vaccine in adults. In this phase 1/2, observer-blinded, age-stratified, randomized trial, healthy US adults (age, ≥18 y) received two intramuscular doses of hemagglutinin antigen (3.75 or 7.50 μg) with AS03A or AS03B, administered 21 d apart. Immunogenicity - seroprotection rates (SPRs), seropositivity, geometric mean titers (GMTs), geometric mean fold rise (GMFR), and seroconversion rates (SCRs) - was evaluated on day 43 using hemagglutination inhibition (HI) and microneutralization (MN) assays. Safety was monitored throughout the study. Of 520 enrolled participants, 518 were vaccinated. On day 43, the US Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research criteria for influenza vaccines were met. HI SPRs, seropositivity rates, SCRs, GMTs, and GMFR appeared to be higher in the AS03A vs AS03B group. Immune responses were generally higher in younger (aged 18-64 y) vs older (aged ≥65 y) adults. Immune responses were also detected in MN assays, with a correlation between HI and MN responses on day 43 across age groups and vaccine formulations. Safety was acceptable, with no increase in adverse events post-dose 2. Reactogenicity appeared more common in younger adults. The antigen-sparing potential of AS03 was demonstrated, with an acceptable safety profile. The benefit/risk profile was favorable for all formulations tested, including 3.75 µg AS03A (licensed in the US).ClinicalTrials.gov registration: NCT05975840. Influenza pandemics occur when new influenza viruses emerge, causing widespread illness. A recent study investigated a new vaccine, GSK’s AS03-adjuvanted H5N8 influenza vaccine, for its ability to trigger an immune response and its safety in adults aged 18–64 y and older adults aged ≥65 y. Overall, 518 participants received at least one dose of the vaccine, with different amounts of hemagglutinin antigen (3.75 or 7.50 µg) combined with different concentrations of AS03 adjuvant. Immune responses were assessed at multiple time points, with the primary endpoint measured on day 43 post-vaccination. The vaccine produced a strong immune response in both age groups, with younger adults showing slightly better responses than older adults. The vaccine met the required standards for an immune response set by the US Food and Drug Administration (FDA). AS03A typically induced greater immune response than AS03B. Safety monitoring showed that the vaccine was generally well tolerated, with the most common side effects being mild, such as injection-site pain and muscle ache. This study confirmed that the AS03-adjuvanted H5N8 vaccine has the potential to provide protection against influenza with an acceptable safety profile, making it a valuable candidate for pandemic preparedness.
14 June 2026
Read appraisal →JMIR public health and surveillance
Digital Health Center App for Community and National Malaria Surveillance in Cambodia: Implementation Case Study
BACKGROUND: By 2015, the emergence and dissemination of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion threatened regional and global malaria control efforts. In response, Greater Mekong Subregion countries committed to malaria elimination by 2030, with strengthened surveillance as a strategic pillar. In 2017, Cambodia introduced an elimination-oriented digital Malaria Information System (MIS). Its health center app enables real-time, geo-located, case-based malaria reporting across primary health centers, and is fully integrated with the MIS. OBJECTIVE: This study aimed to evaluate the real-world national implementation of Cambodia's Android-based health center app, considering coverage, fidelity, timeliness, and data use, and their effects on malaria surveillance performance, case management, programmatic response, and public health outcomes. METHODS: System performance and public health use were assessed using system-generated metadata, national surveillance data, and user surveys. Operational indicators included technical performance, data completeness, and reporting timeliness, alongside surveillance outcomes such as case notification, classification, reactive case detection, and foci investigation. Nationwide user experience was measured via a survey of 761 health centers across 21 provinces, with in-depth structured surveys at 9 health centers in 3 provinces. Descriptive analyses evaluated system functionality, contribution to malaria surveillance and response, and usability among frontline health workers. RESULTS: The health center app demonstrated strong technical performance, with rapid loading and resilient data transmission under low-bandwidth conditions, supporting reliable reporting in resource-constrained settings. Integrated real-time dashboards provided analytics for case management, surveillance monitoring, risk stratification, and targeted public health interventions. Data completeness remained high (99%, 89/90 fields in 2024), demonstrating consistent routine use even as case incidence declined. Between January 1, 2025, and July 31, 2025, 69 malaria cases were reported nationally (23 locally acquired, 7 domestically imported, and 39 internationally imported). Of these, 95.7% (66/69) were notified and classified within 1 day. Reactive case detection was completed within 3 days for all 21 eligible cases, and 16 of 19 eligible foci received a response within 7 days, indicating strong operational responsiveness. User surveys showed 96.3% (733/761) of health centers were satisfied or very satisfied, 90.1% (686/761) reported rare or no technical issues, and 91.7% (698/761) found the app easy to navigate. Operational challenges included limited internet connectivity, transport to remote areas, and electricity interruptions. In-depth surveys confirmed high uptake, confidence in reporting, and routine use of surveillance data, although gaps in local analytical capacity were identified. CONCLUSIONS: Developed and managed locally to enhance sustainability, the MIS drove significant reductions in malaria case incidence, with the health center app contributing timely, complete, structured reporting at the point of care. Public health responses were facilitated by real-time analysis, targeted interventions, and decentralized decision-making. User engagement was sustained as malaria cases declined, and further enhancements are planned to ensure seamless transition to postelimination surveillance, reducing the risk of malaria reestablishment in Cambodia.
13 June 2026
Read appraisal →Human vaccines & immunotherapeutics
Safety and immunogenicity of a booster dose of COVAC-2, a Sepivac SWE™ adjuvanted SARS-CoV-2 recombinant protein vaccine in previously vaccinated healthy adults; a randomized controlled multicentre trial.
This Phase 1 clinical trial evaluated the safety and immunogenicity of COVAC-2, a recombinant protein subunit vaccine as a heterologous booster in adults previously immunized with authorized COVID-19 vaccines (NCT05226702). COVAC-2 contains the SARS-CoV-2 S1 spike protein subunit adjuvanted with Sepivac SWE™, an open-access oil-in-water adjuvant. Sixty participants were randomized to receive a single intramuscular dose of COVAC-2 (10 µg or 25 µg) or placebo, with follow-up through Day 180. The vaccine was well tolerated, with most adverse events being mild or moderate; no serious adverse events were attributed to vaccination. Immunogenicity assessments included spike-binding antibody ELISA, pseudovirus neutralization assays (PNA), ELISpot, and flow cytometry. The 25 µg dose elicited the strongest humoral and cellular responses, with peak antibody titers observed 14 d after COVAC-2 vaccination. While titers waned, they were sustained above baseline through Day 180. ELISpot and flow cytometry revealed elevated IFN-γ and IL-2 responses indicating antigen-specific T-cell activation. Minimal IL-4 and IL-13 responses were demonstrated by flow cytometry. These findings support the safety and immunogenicity of COVAC-2 as a heterologous booster, particularly at the 25 µg dose level. The favorable safety profile, induction of immune responses, and thermal stability of the vaccine formulation suggest its potential utility in global vaccination strategies, especially in low- and middle-income countries. COVAC-2 may offer a scalable and accessible platform for enhancing protection against COVID-19.Clinicaltrials.gov: NCT05226702 - Registered 22 Jul 2022.
13 June 2026
Read appraisal →BMJ open
Prediction of ICU length of stay, hospital discharge outcomes and discharge location among ICU-admitted patients diagnosed with viral hepatitis using machine learning: a retrospective cohort study of the MIMIC-IV database
BACKGROUND: Hepatitis, a disease characterised by inflammation of the liver, is a leading global health challenge that contributes to over 1.3 million deaths annually, with hepatitis B and C accounting for many of these fatalities. Intensive care unit (ICU) management of patients is particularly challenging due to the complex clinical care and resource demands. Despite advancements in ICU predictive analytics, limited research has specifically addressed hepatitis patients, creating a gap in optimising care for this population. METHODS: This study focuses on predicting ICU length of stay (LoS), hospital discharge outcomes and discharge location for ICU-admitted viral hepatitis patients using a comparative assessment of machine learning (ML) models. Leveraging data from the Medical Information Mart for Intensive Care-IV database, which includes around 94 500 ICU patient records, this study uses sociodemographic details, clinical characteristics and resource utilisation metrics to develop predictive models such as Random Forest, Logistic Regression, Gradient Boosting Machines and Generalised Additive Model with Negative Binomial Regression. RESULTS: Among 3875 ICU-admitted hepatitis patients, Random Forest classification outperformed Logistic Regression in predicting discharge outcomes, achieving higher accuracy (0.87 vs 0.82) and greater discriminative ability (area under the receiver operating characteristic curve 0.95 vs 0.89). For ICU LoS prediction, Random Forest regression applied to log-transformed LoS demonstrated strong performance (R² up to 0.82), while the generalised additive model with negative binomial distribution explained approximately 76% of LoS variance. Prediction of discharge location yielded moderate performance across Gradient Boosting and multinomial logistic regression models (accuracy 0.55 and 0.56), reflecting challenges associated with multi-class imbalance. Variable importance analyses across ML models consistently identified medication counts, procedure counts, comorbidity burden, age, race and total LoS as the most influential predictors of discharge outcomes and discharge location. CONCLUSIONS: This study demonstrates the value of ML models for predicting clinical outcomes for hepatitis patients, including ICU LOS and hospital discharge status. The results underscore the influence of factors like race and age, revealing disparities that must be addressed in predictive care strategies. While the models show promise, challenges such as variability in prolonged stays and limited multiclass prediction accuracy point to the need for ongoing refinement and research.
11 June 2026
Read appraisal →Vaccine
Can a DNA vaccine protect against Chagas disease? A systematic review of preclinical studies.
Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited treatment options. DNA-based vaccination has been explored as a preventive strategy, but its overall efficacy and translational value remain uncertain. Despite encouraging preclinical findings, the evidence on DNA-based vaccines against T. cruzi remains heterogeneous and has not been systematically integrated across outcomes. A comprehensive review is therefore needed to contextualize the current knowledge and define the translational relevance of this platform. To systematically review preclinical in vivo evidence on the efficacy of DNA-based vaccination against T. cruzi, focusing on parasitological, immunological, histopathological, and cardiac outcomes. PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched without date restrictions. Eligible studies were controlled in vivo experiments evaluating DNA vaccines against T. cruzi in animal models. Two reviewers performed study selection, data extraction, risk-of-bias (SYRCLE) and certainty of evidence (GRADE) assessment independently. Thirty preclinical studies were included. Murine models predominated, especially BALB/c, C57BL/6, and C3H/He mice, although canine studies added translational relevance. Naked plasmid DNA, Salmonella-delivered constructs, and adjuvanted DNA vaccines were the most common platforms. The principal antigens belonged to the trans-sialidase family and amastigote surface proteins. Overall, vaccination was associated with reduced parasitemia, improved survival in several murine models, Th1 immune responses characterized by increased IFN-γ, IgG2a, and CD8+ T-cell activation, as well as attenuation of inflammatory, histopathological, and cardiac damage. In canine models, vaccination also reduced parasite burden and myocardial inflammation, although protection remained incomplete. Confidence in the evidence was limited by substantial heterogeneity in animal background, antigen selection, parasite strain, inoculation route, dosing regimens, and follow-up duration. Frequent unclear risk of bias and incomplete reporting prevented meta-analysis and constrain causal inference. DNA-based vaccination against T. cruzi can induce Th1 immunity and reduce parasitological and tissue injury outcomes, but protection is often partial and rarely sterilizing.
11 June 2026
Read appraisal →Vaccine
Immunogenicity and safety of Sabin-strain inactivated poliovirus vaccine in infants: a systematic review and meta-analysis
BACKGROUND: Poliomyelitis remains a threat to children under five despite global vaccination efforts. The Sabin-strain inactivated poliovirus vaccine (sIPV) has emerged as a safer alternative to conventional Salk-strain IPV (cIPV) due to lower biosafety requirements. This systematic review and meta-analysis evaluated the immunogenicity and safety of sIPV compared with cIPV in healthy infants completing the primary IPV series. METHODS: PubMed, Embase, Scopus, and Cochrane Library were searched for RCTs. Outcomes included seroconversion rates, seroprotection rates, geometric mean titers (GMTs), and adverse events. Data were pooled using random-effects models, and evidence certainty was assessed using RoB 2.0 and GRADE. RESULTS: Seven RCTs with 4646 infants were included. Seroconversion rates were comparable: PV1 100% (RR 1.00, 95% CI 1.00-1.01), PV2 102% (RR 1.02, 95% CI 0.98-1.07), PV3 100% (RR 1.00, 95% CI 0.99-1.01). GMTs were higher for sIPV after PV1 (MD 1.50, 95% CI 0.98-2.02) and PV2 (MD 0.52, 95% CI 0.06-0.98). Local adverse events were similar (OR 1.27, 95% CI 0.95-1.71), while systemic adverse events were higher with cIPV (OR 1.36, 95% CI 1.15-1.60). Fever (OR 1.50, 95% CI 1.20-1.87) and allergic reactions (OR 2.19, 95% CI 1.02-4.69) were slightly more frequent with sIPV. CONCLUSIONS: sIPV provides immunogenicity comparable to cIPV with an acceptable safety profile in infants. Its lower biosafety requirements support its use in global polio eradication programs.
11 June 2026
Read appraisal →Human vaccines & immunotherapeutics
Safety and immunogenicity of 4CMenB and MenACWY-CRM meningococcal vaccines when administered concomitantly in healthy adolescents: A phase 3b, randomized, observer-blind study.
Meningococcal vaccination of adolescents/young adults is recommended in various countries, including the United States (US). This phase 3b, observer-blind study (NCT04318548) evaluated the safety, reactogenicity, and immunogenicity of serogroup B vaccine, 4CMenB, and quadrivalent conjugate vaccine, MenACWY-CRM, when co-administered to healthy individuals aged 16-18 y, as per US Advisory Committee on Immunization Practices recommendations. Adolescents, who had received MenACWY vaccination ≥4 y previously, were randomized (N = 940; 1:1:1) to one of three groups to assess co-administration versus 4CMenB and MenACWY-CRM administered alone. Co-primary objectives were to demonstrate the non-inferiority of antibody responses after concomitant administration to antibody responses after 4CMenB (two doses administered 2 months apart) and MenACWY-CRM (single dose), as measured by human serum bactericidal assay (hSBA). Vaccine safety and reactogenicity were assessed as another primary objective. The co-primary endpoints were met: the lower limit of 2-sided 95% confidence intervals for all between-group ratios of hSBA geometric mean titers was >0.5 for the concomitant administration group versus 4CMenB group and MenACWY-CRM group. hSBA data after two 4CMenB doses and one MenACWY-CRM dose showed comparable between-group geometric mean ratios versus baseline, and percentages of participants with 4-fold rises in titers and titers ≥lower limit of quantitation. The safety profile of 4CMenB co-administered with MenACWY-CRM was comparable with that of 4CMenB administered alone. In conclusion, 4CMenB and MenACWY-CRM co-administration was well tolerated in adolescents aged 16-18 y and immune responses were comparable versus administration of each vaccine alone, which is consistent with a previous study of co-administration in infants. Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, poses a life-threatening risk but can be prevented through vaccination. Effective vaccines are available against the most common disease-causing meningococcal serogroups, A, B, C, W, and Y. Evidence from clinical studies and immunization programs over the last decade with the 4-component meningococcal serogroup B vaccine, 4CMenB, and serogroups A, C, W, and Y vaccine, MenACWY-CRM, confirms the effectiveness of both vaccines in population age groups at higher risk of meningococcal disease, including infants and adolescents. It was previously shown that the administration of 4CMenB and MenACWY-CRM to healthy infants at the same visit induced good immune responses and was well tolerated by young children. Adolescent vaccination with 4CMenB and MenACWY-CRM is recommended in various countries, including in the United States. We conducted a study to test the safety of concomitant administration and its ability to induce immune responses in 945 healthy adolescents aged 16–18 y; 834 from the United States and 111 from Italy. We found that most reactions to the 4CMenB and MenACWY-CRM injections were mild or moderate, and were similar whether the vaccines were given together or separately, with no unexpected side effects. Co-administration to adolescents induced robust immune responses against serogroup B and serogroups A, C, W, and Y. These results support the use of concomitant meningococcal vaccinations in adolescent immunization programs.
11 June 2026
Read appraisal →Global health action
mHealth-supported tuberculosis contact investigation by community health workers in high-burden countries: a scoping review
Mobile health (mHealth) implementation strategies in tuberculosis (TB) contact investigations are intended to increase community health workers' (CHWs) engagement in TB contact investigations and case detection. This scoping review aimed to map and synthesize existing evidence on the design and development of acceptable and feasible mHealth implementation strategies for CHW-led TB contact investigations. We conducted a scoping review following the Arksey and O'Malley framework and PRISMA-ScR guidelines. We searched PubMed, Scopus, Cochrane Library, Web of Science, and Google Scholar for English-language studies published through October 2024 on mHealth interventions for TB contact investigation by CHWs. Eligible studies included empirical studies conducted in high-burden countries (HBCs) for TB, HIV-associated TB, and MDR/RR-TB. Studies were screened, and data were extracted using Rayyan AI-assisted software. We mapped implementation strategies, barriers, facilitators, acceptability, and feasibility of mHealth interventions. Quantitative findings were described, and qualitative data were synthesized thematically. Nine studies were included. Most interventions used hybrid mHealth technologies for communication, case registration, health records, and decision support. Implementation strategies specified actors, actions, targets, temporality, dose, and justifications. Barriers were related to CHWs, digital systems, service implementation, and TB-affected persons. Facilitators included stakeholder support, CHW training, mHealth design, community engagement, and patient-centered approaches. Overall, CHWs perceived mHealth interventions as acceptable and feasible. Successful implementation in HBCs requires strengthened CHW capacity, reliable technology, optimizing interaction between CHWs and digital tools, and continuous monitoring and evaluation throughout implementation. Main findings: Health interventions for tuberculosis contact investigation by community health workers in three global lists of high-burden countries for tuberculosis, human immunodeficiency virus-associated tuberculosis, and multidrug-resistant/rifampicin-resistant tuberculosis are generally acceptable and feasible, but their effectiveness depends heavily on a clear implementation strategy and the ability to address multilevel barriers at the individual, technology, and service system levels.Added knowledge: Given the ongoing development of digital health interventions for TB contact investigation by community health workers, this review provides a novel contribution by systematically mapping seven dimensions of implementation strategies, classifying barriers and facilitators at multiple levels, and highlighting the importance of synergies between human actors and digital systems in determining implementation success.Global health impact for policy and action: These findings confirm that strategic integration of mHealth into national tuberculosis policies and programs – with sustained funding, community health worker capacity building, digital system interoperability, and implementation-based monitoring – is crucial for closing the contact investigation gap and accelerating the achievement of the global tuberculosis elimination target.
11 June 2026
Read appraisal →International journal of biometeorology
Integrating google trends and hybrid statistical-machine learning models for dengue surveillance in an inland vietnamese province: a 94-month evaluation (2013-2021) with search-signal anomaly screening
Dengue transmission in inland Southeast Asia shows strong seasonality and short-term surges that challenge timely public-health response. We assessed whether province-level Google search activity can support short-horizon dengue monitoring in Dong Nai, Vietnam. Monthly reported dengue cases from July 2013 to April 2021 were aligned with the Google Trends index (GTI) for "Sốt xuất huyết". Models were evaluated using leakage-free rolling-origin expanding-window cross-validation with 3-month validation blocks. We compared a negative binomial (NB) autoregressive baseline, NB models incorporating GTI, tree-based machine-learning models using the same covariates, and a simple NB-random-forest ensemble. Predictive performance was assessed using root mean squared error (RMSE), mean absolute error (MAE), R2, and discrimination for 95th-percentile outbreak exceedance. Cross-correlation peaked at lag 0, indicating that GTI functioned primarily as a contemporaneous nowcasting signal rather than a long-lead predictor. NB models incorporating GTI showed competitive calibration, while boosted tree models achieved the lowest point-estimate errors; XGBoost achieved RMSE ≈ 40.95 and R2 ≈ 0.861 compared with RMSE ≈ 45.23 and R2 ≈ 0.823 for NB with GTI. Adding GTI to the autoregressive NB baseline reduced RMSE by 11.77%, but the 95% confidence interval crossed zero, indicating modest and statistically non-significant incremental gain. Search-signal anomaly screening suggested that GTI spikes largely coincided with epidemic peaks and did not clearly inflate out-of-sample errors. Overall, GTI provides operational value for dengue nowcasting and alert triage in inland provinces, while future systems should integrate climate, vector, mobility, and media-monitoring data.
9 June 2026
Read appraisal →PloS one
Reinforcement learning for policymaking in epidemic control: A scoping review
BACKGROUND: Managing an epidemic demands policies that respond at the pace of the outbreak. Conventional rule‑based interventions struggle to keep up, prompting interest in reinforcement learning (RL) for designing non‑pharmaceutical interventions (NPIs). However, current evidence is fragmented across diverse models and reporting styles. OBJECTIVES: To systematically map how RL is applied for epidemic NPI design, describe modeling choices, algorithm architectures, evaluation practices, and identify trends and research gaps. METHODS: Peer-reviewed studies (2014-2025, English) that applied deep RL to select NPIs were retrieved from IEEE Xplore, ACM Digital Library, ScienceDirect, and Scopus, searched on December 23, 2025. Reference list scanning supplemented database results. Predefined data items (bibliographic details, epidemic and RL model characteristics, experiments, validation methods, outcomes) were charted and summarized descriptively. RESULTS: Of 512 retrieved records, 10 met the inclusion criteria, and three additional studies were identified via reference-list scanning, yielding 13. Five employed value‑based methods, four policy‑gradient, and four hybrid; one study additionally incorporated model-based planning. Six simulations relied on compartmental models, six on agent‑based models, and one on a hybrid model. Action spaces were predominantly discrete restriction levels. Five studies incorporated sequence-modeling techniques to include temporal context into a state space. Eleven studies designed reward functions as a trade-off between pandemic severity and socio-economic cost. According to the reviewed studies, RL policies across various settings outperform heuristic, rule-based, and historical baselines in reducing infections, deaths, or lockdown duration while limiting economic loss. CONCLUSIONS: RL shows promise for adaptive epidemic control. Comparison is hampered by simplified economic costs, inconsistent calibration rigor, varied evaluation metrics, and limited uncertainty or policy robustness analysis. Future work should establish common benchmark environments and reporting standards, incorporate empirically grounded economic and behavioral models, adopt uncertainty-aware and probabilistic RL, develop more sophisticated control spaces, investigate more advanced algorithms, and validate learned policies prospectively to enable real-world deployment.
9 June 2026
Read appraisal →Acta microbiologica et immunologica Hungarica
Characteristics of fungaemia caused by Trichosporon species in South-Eastern Europe
The incidence of fungaemia caused by rare yeasts, particularly Trichosporon species, is rising globally, posing diagnostic and therapeutic challenges-especially in immunocompromised patients. This systematic review aims to analyse the epidemiology, diagnostic approaches, antifungal susceptibility, and clinical outcomes of Trichosporon fungaemia (TF) in South-Eastern Europe, including Turkey. A comprehensive search was conducted in PubMed and Scopus in August 2025. A total of 59 cases from 12 studies were identified, with Trichosporon asahii being the most prevalent species (86.4%). Cases originated from Turkey (79.7%), Greece (18.6%), and Croatia (1.7%). Diagnostic techniques varied, with phenotypic methods still widely used. MALDI-TOF MS and DNA sequencing were mainly applied as confirmatory methods. Haematologic disorders were the most frequently reported underlying conditions among the patients. Sixteen breakthrough fungaemia cases-occurring despite empirical or prophylactic antifungal therapy-were identified. Although rare, TF represents a severe infection with significant mortality in South-Eastern Europe. Early and accurate species identification-facilitated by advanced diagnostic tools-is crucial for effective management. In addition to diagnostic difficulties, treatment is also challenging. Voriconazole appears to be the preferred antifungal agent, even in breakthrough fungaemia cases. Enhanced awareness, routine use of molecular diagnostics, and ongoing epidemiological monitoring are essential to improve patient outcomes.
1 June 2026
Read appraisal →Archives of microbiology
AI-driven big data analysis and predictive modeling of infectious disease immunity: from correlates to causal, multiscale understanding
The ability to reliably predict protective immunity against infectious diseases remains a central challenge in immunology, vaccine development, and public health. Despite major advances in immunological measurement, immunity prediction has historically relied on simplified correlates most notably antibody titers that often fail to generalize across pathogens, populations, and time. The emergence of large-scale, high-dimensional immune datasets spanning multi-omics, longitudinal cohort studies, electronic health records, and pathogen genomics has created new opportunities for artificial intelligence (AI)-driven modeling. However, early applications reveal that predictive accuracy alone is insufficient and is frequently undermined by spurious correlations, limited generalizability, and a lack of biological interpretability. This review synthesizes current advances and limitations in AI-based immunity prediction, arguing that meaningful progress requires embedding machine learning within immune biology, causal reasoning, and rigorous validation frameworks. We examine the biological foundations of immunity relevant to modeling including innate immune programming, trained immunity, adaptive immune dynamics, and immune memory and map these processes to appropriate data modalities and model classes. We critically evaluate predictive tasks across individual and population scales, from early infection outcomes and vaccine responsiveness to immunity waning and herd-level protection. Emphasis is placed on validation beyond internal cross-validation, on interpretability grounded in immune mechanisms, and on robustness under demographic diversity and pathogen evolution. We conclude that immunity is best understood and predicted as a dynamic, probabilistic, and multiscale system rather than as a static trait. AI has substantial potential to improve infectious disease preparedness and clinical decision-making.
1 June 2026
Read appraisal →Human vaccines & immunotherapeutics
Safety and durability of influenza and SARS-CoV-2 antibody responses through 6 months after a single dose of mRNA-1083, a multicomponent influenza and COVID-19 vaccine, in adults ≥50 years.
Seasonal influenza and SARS-CoV-2 continue to contribute substantially to global morbidity and mortality. mRNA-1083 is an investigational multicomponent mRNA vaccine targeting seasonal influenza and SARS-CoV-2. In this phase 3, observer-blind, active-controlled trial (NCT06097273), adults (aged ≥50 y) were randomly assigned (1:1) to receive mRNA-1083 (40 µg; plus placebo) or age-appropriate licensed comparator vaccines for influenza and COVID-19. Two substudies were included: Cohort A (≥65 y) and Cohort B (50-64 y). Primary objectives were to demonstrate noninferiority of mRNA-1083 versus comparators for influenza hemagglutination inhibition (HAI) responses and SARS-CoV-2 neutralizing antibody (nAb; PsVNA) responses at Day 29 after vaccination and to evaluate safety and reactogenicity of study vaccines. Here, we report safety, reactogenicity, and immunogenicity of mRNA-1083 through Day 181 in adults aged ≥50 y. mRNA-1083 induced HAI titers against all vaccine-matched influenza strains that were maintained through 6 months and were generally comparable to, or higher than, comparator responses. SARS-CoV-2 nAb responses remained higher for mRNA-1083 than comparators through 6 months. Reactogenicity was predominantly grade 1-2 in severity, and vaccination-related unsolicited adverse events were similar between groups. No serious adverse events or deaths related to vaccination were reported through 6 months. In adults aged ≥50 y, mRNA-1083 elicited durable influenza and SARS-CoV-2 humoral immune responses with an acceptable safety profile through 6 months. These findings support the use of mRNA-1083 as a multicomponent vaccine.ClinicalTrials.gov identifier: NCT06097273 (https://clinicaltrials.gov/study/NCT06097273).
1 June 2026
Read appraisal →PLoS medicine
Characterization of the VHH-Fc construct rimteravimab in healthy adults and patients hospitalized for mild-to-moderate COVID-19: Two Phase 1 randomized clinical trials
BACKGROUND: Variable Heavy domain of Heavy chains (VHH) are innovative tools to target unique epitopes, yet few have been developed as heavy chain-only antibodies for clinical use. Rimteravimab (referred to here as XVR011) is a humanized antibody developed for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19), consisting of two identical VHHs targeting the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike, with a human immunoglobulin (Ig) G1 fragment constant of antibody (Fc), silenced for Fc effector functions. We conducted two Phase 1 studies in healthy volunteers or hospitalized COVID-19 patients to evaluate its safety, tolerability, pharmacokinetics and immunogenicity. METHODS AND FINDINGS: A randomized, double-blinded, single-center, placebo-controlled, single ascending dose study was performed in healthy volunteers (Phase 1a, EXEVIR0102, EudraCT 2021-003707-17), in parallel to an open-label, multi-center, single ascending dose study in patients hospitalized for mild to moderate COVID-19 (Phase 1b, EXEVIR0101, EudraCT 2020-005299-36, NCT04884295). Participants received a single intravenous infusion of 250, 500 or 1,000 mg of XVR011. The primary objective for both trials was the safety and tolerability of XVR011. Pharmacokinetics were evaluated as a secondary objective in Phase 1a and as an exploratory objective in Phase 1b. Efficacy (evaluated as respiratory parameters and COVID-19 clinical status) and antiviral activity in patients were evaluated as a secondary objective in Phase 1b. Immunogenicity was evaluated as an exploratory objective. Part 2 of the EXEVIR0101 study (initially a phase 1b/2 study) was not conducted due to the loss of XVR011 potency against SARS-CoV-2 Omicron BA.2. Demographics, safety, efficacy, and immunogenicity were analyzed using descriptive statistics, while pharmacokinetics were analyzed with noncompartmental pharmacokinetics (PK) modeling. In the Phase 1a study, there were no infusion-related reactions, serious treatment-emergent adverse events (TEAEs) or TEAEs grade ≥3. 22/30 volunteers (73.3%) reported 53 TEAEs (49 Grade 1, 4 Grade 2) with none being related to XVR011. The most common TEAE was headache (n = 8, 26.7%) in various treatment groups. In the Phase 1b study, 27 hospitalized patients were enrolled, and followed up to 30 days. Seven patients (25.9%) reported a total of 15 TEAEs, the majority (80%) being mild to moderate (Grade 1-2). There were no treatment-related serious TEAEs. All TEAEs resolved by the end of the study. Peak exposure (maximal concentration, Cmax) and systemic exposure (area under the curve, AUC0-t, and AUC0-inf) for XVR011 increased dose-proportionally. Geomean half-life ranged from 15.4 to 17.0 days in Phase 1a, while individual half-life ranged from 11.4 to 15.6 days in Phase 1b. SARS-CoV-2 viral load, as detected in nasopharyngeal samples by reverse transcription and quantitative polymerase chain reaction (RT-qPCR), decreased similarly in all cohorts compared to baseline. No treatment-induced anti-drug antibodies (ADA) were detected in Phase 1a. In Phase 1b, higher XVR011 concentrations increased the likelihood of ADA formation, without impacting pharmacokinetics and pharmacodynamics. No obvious dose-response in COVID-19 clinical status or respiratory parameters was observed. Technological limitations included study size, absence of placebo for the Phase 1b, absence of repeated dosing, evolving SARS-CoV-2 variants and standard-of-care. CONCLUSIONS: XVR011 displayed a favourable safety, tolerability, pharmacokinetics, and immunogenicity profile, both in healthy volunteers and in patients hospitalized for mild to moderate COVID-19. These data pave the way for the design and clinical development of VHH-Fc constructs.
31 May 2026
Read appraisal →Human vaccines & immunotherapeutics
Strategies implemented to increase HPV vaccine uptake and confidence among men who have sex with men and transgender people: A systematic review
Men who have sex with men (MSM) and transgender persons are disproportionately affected by HPV-related disease. The HPV vaccine effectively prevents infection, but vaccine uptake remains suboptimal in this group. Thus, this systematic review aimed to synthesize the literature on interventions and strategies implemented to increase HPV vaccine confidence and uptake among MSM and transgender persons. Six databases were searched in May 2025. We assessed risk of bias and extracted and descriptively summarized key data through narrative synthesis and content analysis. Sixteen articles reporting on eight interventions were identified, all implemented in high-income settings. The interventions can be broadly categorized into two types: strategies to integrate HPV vaccination into existing health services and digital interventions aimed at generating vaccine demand. Overall, evidence remains limited on interventions to increase HPV vaccine uptake in these groups, particularly studies focusing on the needs of transgender persons.
31 May 2026
Read appraisal →Medicine
Burden of Helicobacter pylori infection in children and adults in Vietnam: A systematic review and meta-analysis of prevalence
BACKGROUND: Although Helicobacter pylori (H. pylori) prevalence has declined in many high-income countries, data from Vietnam remain limited and fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of H. pylori infection in Vietnamese adults and children. METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for observational studies published between January 2000 and September 2025. Eligible studies reported H. pylori prevalence in Vietnamese populations using validated diagnostic methods. Random-effects meta-analyses were used to calculate pooled prevalence estimates with 95% confidence intervals (CIs). Subgroup analyses were conducted by age group, geographic area, and study setting. RESULTS: Twenty-five studies met inclusion criteria, comprising 8204 adults and 4641 children. The pooled prevalence of H. pylori infection was 58.7% (95% CI: 49.9%-67.2%) in adults and 77.2% (95% CI: 67.1%-86.0%) in children, with high heterogeneity across studies (I2 > 98%, P < .001). Among adults, prevalence was 56.4% in those aged <50 years and 65.8% in those ≥50 years (P = .455). Prevalence was lower in rural areas (46.8%) compared to urban areas (60.7%) (P = .045), with no significant difference between community- and hospital-based settings (P = .723). Funnel plot assessment did not indicate evident publication bias. CONCLUSION: H. pylori infection remains common in the populations represented in this study, particularly among urban and healthcare-seeking groups in Vietnam. These findings underscore the need for expanded surveillance and monitoring to better characterize H. pylori infection patterns and inform appropriate response strategies.
31 May 2026
Read appraisal →Medicine
Prevalence and long-term outcomes of brain fog and cognitive impairment in individuals with long COVID: A systematic review
BACKGROUND: Long COVID is increasingly recognized as a complex multisystem condition, with brain fog and cognitive impairment emerging as some of its manifestations. Despite growing literature, the pooled prevalence, subgroup differences, and underlying mechanisms remain incompletely understood. METHODS: We systematically reviewed 47 studies (2000-2025) encompassing over 25,000 patients to evaluate the prevalence of brain fog and cognitive impairment among long COVID populations. Data were extracted on study design, patient demographics, follow-up duration, and subgroup variables including gender, hospitalization, vaccination, and geographic region. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS v9.0) and JBI checklists. Quantitative synthesis was performed with subgroup and temporal analyses, presented in forest plots and summary figures. RESULTS: The pooled prevalence of brain fog was 30% (95% CI: 28-32), while cognitive impairment was 25% (95% CI: 23-27). Female patients consistently showed higher rates compared to males (34% vs 23% for brain fog; 29% vs 21% for cognitive impairment). Community-managed patients demonstrated higher prevalence compared to hospitalized cohorts, and unvaccinated individuals had a greater burden than vaccinated ones. Temporal analyses indicated that prevalence increased with longer follow-up, suggesting symptom persistence or late manifestation. Pathophysiological explanations include neuroinflammation, microvascular injury, immune dysregulation, and psychosocial stressors. CONCLUSION: Brain fog and cognitive impairment are common, persistent, and clinically significant features of long COVID. Gender differences, vaccination status, and follow-up duration influence prevalence. Future studies should focus on mechanisms, preventive strategies, and targeted interventions to mitigate long-term cognitive sequelae.
31 May 2026
Read appraisal →Scientific reports
Prevalence and Risk Factors for Cytomegalovirus Retinitis Among People Living with HIV in Sub-Saharan Africa in the Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis
Cytomegalovirus retinitis has remained an alarming and potentially vision-threatening opportunistic disease in the population living with HIV, especially in cases of extreme immunosuppression. Although the introduction of antiretroviral therapy has led to a drastic decline in the number of cytomegalovirus retinitis cases reported in most parts of the world, the current epidemiology of cytomegalovirus retinitis in sub-Saharan Africa has seemed unusual in early reports, unexpectedly portraying low disease prevalence rates despite the high number of HIV cases in the concerned region. This systematic review and meta-analysis aimed to estimate the pooled prevalence of cytomegalovirus retinitis among people living with HIV in sub-Saharan Africa in the antiretroviral therapy era, and to identify associated risk factors. The search of databases included Medline using the search engine PubMed, Google Scholar, and the African Journals Online database named AJOL. For inclusion, studies must have included an eye examination to verify the presence of cytomegalovirus retinitis. The data was combined using the logit transformation model. Heterogeneity was tested using the I-squared test and the Cochran Q test. A total of ten studies involving 1,931 participants from nine sub-Saharan Africa countries were found eligible. The proportion of cytomegalovirus retinitis varied from 0.34% to 15.8%. Pooled prevalence was found to be 3% (95% CI: 1.6-5.4%) with low to moderate inter-study variation (I² = 17.8%). Substantial variation in the proportion was found in different sub-Saharan Africa regions; it was found to be less than 1% in West Africa, 3-4% in Southern Africa, 7% in East Africa and 6% in Central Africa. Across all studies, the strongest and most consistent risk factors for cytomegalovirus retinitis were profound immunosuppression, particularly CD4 < 50 cells/µL. Antiretroviral therapy-naïve status, poor adherence, and presence of advanced AIDS-defining illnesses were additional contextual risk markers. Cytomegalovirus retinitis is an under-recognized but important source of preventable blindness among people living with HIV. Prevalence in sub-Saharan Africa differed from that in Asian early antiretroviral therapy era cohorts but is relevant in settings where late HIV presentation occurs. Systematic retinal screening in people living with HIV with low CD4 counts < 50 cells/µL and expanded HIV care and treatment services are important to prevent blindness due to cytomegalovirus retinitis.
31 May 2026
Read appraisal →JMIR formative research
Wearable- and Mobile App-Based Activity Pacing and Fatigue Management in Post-COVID-19 Condition: Exploratory Observational Study
BACKGROUND: Post-COVID-19 fatigue affects millions worldwide; yet, evidence-based management strategies remain limited. Activity pacing, regulating activity to match available energy and minimize symptom exacerbation, may support symptom management, although optimal pacing approaches remain unclear. OBJECTIVE: This study aimed to explore associations between activity pacing strategies delivered through a mobile app and daily fatigue levels in individuals with post-COVID-19 fatigue. METHODS: In this exploratory observational study, 19 adults with post-COVID-19 fatigue used wearable devices (Fitbit Inspire 3) for objective activity monitoring and a mobile app (FatigueSense) to self-report daily symptoms (fatigue and energy levels) and optionally select activity pacing goals (light, balanced, or active) over a period of 3 months. We examined associations between pacing strategies and symptom outcomes by using mixed-effects linear models with random intercepts. Same-day outcomes (fatigue and energy reported on the day of goal selection) were analyzed controlling for age and sex. Next-day outcomes (fatigue and energy reported the day following goal selection) were analyzed controlling for age, sex, and prior-day symptoms. RESULTS: Across 2182 observation days, participants self-selected pacing goals on 816 (37.4%) days, demonstrating symptom-responsive behavior with higher baseline fatigue on pacing days (mean score 1.74, SD 0.59 vs 1.58, SD 0.54 on nonpacing days on a 0-3 scale where 0="none" and 3="severe"; P=.004). On pacing days (584/816, 71.6% with complete data from 18 participants), active pacing was associated with reduced same-day fatigue (β=-0.34, 95% CI -0.49 to -0.19; P<.001) and increased same-day energy (β=8.8, 95% CI 4.7-12.9; P<.001) compared to light pacing. Balanced pacing also showed significant reductions in fatigue (β=-0.15; P=.008) and increases in energy (β=5.8; P<.001) compared to light pacing. Next-day effects were attenuated and nonsignificant (fatigue: β=-0.05, P=.53; energy: β=1.1, P=.61). Individual heterogeneity was substantial, with an intraclass correlation coefficient of 0.32, indicating that 32% of the variance was attributable to between-person differences. Among participants trying multiple strategies, 58.3% (7/12) showed meaningful responses (≥0.3-point fatigue reduction) to structured pacing strategies. CONCLUSIONS: Structured activity pacing strategies (active and balanced) were associated with improved same-day symptom management in individuals with post-COVID-19 fatigue. However, substantial confounding by indication (self-selection of pacing based on symptom state) and individual heterogeneity limit causal interpretation. These exploratory findings warrant testing in randomized controlled trials to establish efficacy and identify responder characteristics.
30 May 2026
Read appraisal →PLoS neglected tropical diseases
Feasibility study of an AI-powered mobile app to support cutaneous leishmaniasis diagnosis in the Brazilian Amazon
BACKGROUND: Cutaneous leishmaniasis (CL) remains a major public health challenge, especially in Brazil's Amazon, where environmental and economic pressures sustain transmission. Delayed diagnosis drives morbidity, stigma, and costs. Community health workers are pivotal yet under-equipped for early triage. Artificial intelligence, effective in dermatologic imaging, is underused for CL; feasible, offline clinical tools could accelerate referral and timely care. This study aimed to evaluate the feasibility of an AI-assisted tool for early CL triage in the Brazilian Amazon by: (i) developing an AI model for CL identification from clinical skin lesion images; (ii) integrating the model into an offline-optimized mobile application for resource-limited settings; and (iii) conducting initial, real-world clinical validation. METHODS: Exploratory, IRB-approved feasibility study. Retrospective images from Brazilian Amazon sites informed a two-stage AI pipeline (lesion segmentation+classification) integrated into an offline mobile app. Multicenter validation in ideal- and real-world scenarios. Primary metric AUC-ROC; secondary sensitivity/specificity. One-sided tests: AUC-ROC [Formula: see text]0.70; ideal-world sensitivity [Formula: see text]0.75. RESULTS: For the Classification Model, 64 images were assigned to the test set while 1,160 were used for training and validation (80:20 split), with DenseNet121 yielding the highest accuracy of 0.88. The full AI pipeline (Segmentation and Classification models) achieved an accuracy of 0.81, an F1-score of 0.80, an AUC-ROC of 0.90, and a sensitivity of 0.76. In the ideal-world analysis, sensitivity reached 0.92, the F1-score was 0.84, and specificity was 0.42. CONCLUSIONS: We demonstrate the feasibility of an offline, AI-assisted mobile tool to support triage and referral for cutaneous leishmaniasis in the Brazilian Amazon. Performance reflects preliminary, descriptive point estimates from an initial diagnostic accuracy assessment and should be interpreted with caution; the tool is not intended for standalone diagnosis. Next steps include prospectively powered clinical validation, usability refinements, and regulatory evaluation, including alignment with ANVISA requirements in Brazil. Overall, this work represents an initial step toward closing the gap in clinically supported diagnostic tools for neglected tropical diseases in resource-constrained settings.
30 May 2026
Read appraisal →Human vaccines & immunotherapeutics
Comparison of safety and immunogenicity between high-dose and low-dose quadrivalent influenza vaccines in children aged 6-35 months in China: A randomized, double-blind clinical study
Influenza vaccines for children aged 6-35 months are typically low-dose (0.25 mL, 7.5 μg hemagglutinin per strain). However, studies have shown that high-dose influenza vaccines (0.5 mL, 15 μg hemagglutinin per strain) can enhance protective efficacy without increasing the risk of adverse reactions. We conducted a randomized, double-blind clinical study in children aged 6-35 months in China. A total of 3,000 participants were randomized (1:1:1) to receive two doses of either an investigational high-dose quadrivalent influenza vaccine (H-QIV), an investigational low-dose quadrivalent influenza vaccine (LQIV-01) or a commercially available low-dose quadrivalent influenza vaccine (LQIV-02). Hemagglutination inhibition (HI) antibody titers 30 d post-vaccination were measured and vaccine safety and tolerability within 6 months post-vaccination were evaluated in these participants. The primary objectives were to demonstrate the non-inferiority of investigational vaccines to the commercially available vaccine in immunogenicity and to compare the H-QIV to L-QIVs. Both investigational vaccines demonstrated non-inferiority, with their seroprotection rates (SPRs), seroconversion rates (SCRs) and geometric mean titers (GMTs) meeting immunogenicity criteria. The H-QIV exhibited >11-fold increases in GMTs against H1N1, H3N2, B/Yamagata and B/Victoria strains compared to pre-vaccination levels, with SPRs exceeding 95% and SCRs exceeding 89%. The H-QIV was superior to both L-QIVs as it induced a stronger immune response to influenza viruses. All vaccines showed comparable safety profiles. The H-QIV can provide greater protection and benefits to this high-risk population.
29 May 2026
Read appraisal →European journal of pediatrics
Pentoxifylline in children with acute encephalitis syndrome: a randomized control trial
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The primary objective was to assess the efficacy of pentoxifylline in terms of time taken for improvement in Glasgow coma scale (GCS) from baseline, in children with AES. The secondary objectives were adverse effects of pentoxifylline and frequency of sequelae among the survivors. This open-label randomized controlled trial (RCT) was conducted in a tertiary care teaching institution for 2 years (January 2022 to December 2023). Children aged 1 month to 14 years with a clinical diagnosis of AES were randomized to receive either standard treatment along with pentoxifylline or standard treatment alone. The data were recorded in case record forms. Forty-four children were randomized (median age, 77 months; male 72.7%). There was no significant difference in the time (median, IQR) taken for improvement of Glasgow coma scale (GCS) by 3 points or normalization between the pentoxifylline group [26 (19-50) hours] and control group [28 (16-52) hours] (p = 0.92). Other outcomes like requirement of mechanical ventilation, mortality, and sequalae were not significantly different between the two groups. The adverse event rate was also not different. Conclusion: Adjunctive pentoxifylline did not provide significant clinical benefit in children with AES, although it was safe and well tolerated. Larger, adequately powered multicenter trials with etiological stratification and biomarker integration are needed to identify potential subgroup benefits. What is Known: • Acute encephalitis syndrome (AES) is associated with high mortality and significant neurological sequelae, largely driven by host-mediated inflammatory responses. • No immunomodulatory adjunct therapy has yet shown proven benefit in pediatric AES. What is New: • Adjunctive pentoxifylline did not significantly improve neurological recovery or clinical outcomes in children with AES. • Pentoxifylline was safe and well tolerated, supporting further evaluation in larger, etiology-stratified trials.
29 May 2026
Read appraisal →JAMA
Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia: The FAST Randomized Clinical Trial
IMPORTANCE: Novel blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs) but have unclear clinical impact. OBJECTIVE: To evaluate clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli in regions with high prevalence of antimicrobial resistance. DESIGN, SETTING, AND PARTICIPANTS: Open-label randomized clinical trial that enrolled participants from December 2023 to May 2025 (final follow-up, June 18, 2025) at 7 medical centers in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1). Hospitalized patients (adults and children) with BSIs caused by gram-negative bacilli were eligible. Statistical analysis was conducted from August 2025 to January 2026. INTERVENTION: Patients were randomized to undergo blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413) vs standard susceptibility testing alone (n = 437). Local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations. MAIN OUTCOMES AND MEASURES: The primary outcome was a desirability of outcome ranking (DOOR) at day 30, with 3 categories (alive without deleterious events, alive with deleterious events, and death). The difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. Superiority was concluded if the lower limit of the 95% CI exceeded 50%. Secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days. RESULTS: Of the 899 patients randomized, 850 were included in the primary outcome analysis (median [IQR] age, 72 [21] years; 43% female). The probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Median time to effective antibiotic therapy was not different between the groups in the as-randomized population. Median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6-22) in the as-randomized population. There were no differences between the groups in other secondary outcomes. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group (difference, -18 hours [95% CI, -42 to 6]). CONCLUSIONS AND RELEVANCE: Among patients with gram-negative bacilli BSIs, rapid blood culture AST was not superior to standard testing by DOOR. When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06174649.
29 May 2026
Read appraisal →mSphere
Novel machine learning-based approach to identify viral biomarkers of human respiratory emissions from oral and nasal metagenomes
Humans spend approximately 90% of their lives in built environments, making virus transmission indoors a key determinant of health. Environmental sampling of respiratory viral pathogens is often challenging because of frequent non-detect measurements. Non-detect measurements do not differentiate between samples containing low or no pathogens from samples that simply lack respiratory expulsions altogether. This ambiguity can be resolved by scanning samples for a biomarker of human respiratory emissions. To do so, reliable biomarkers for environmental monitoring need to be identified. Ideal biomarkers are prevalent across individuals, abundant, and unique to the human respiratory tract. Here, we present a new machine learning-based approach to query for suitable biomarker candidates from publicly available metagenomes and apply it to identify viral biomarkers of healthy oral and nasal microbiomes. Twelve viral biomarker candidates were selected from 1,232 curated viral operational taxonomic units. The viral biomarker candidates had as much as 63% prevalence across respiratory metagenomes, and prevalence was further increased to 77%-81% by combining two or three biomarkers. Real-time PCR confirmed that these viral biomarkers were prevalent and abundant in nasal swabs and saliva samples. Notably, top candidate biomarkers remained stable and detectable through multiple lab purification steps, increasing confidence in their viral origins and demonstrating their suitability for environmental monitoring. These findings demonstrate that existing metagenomes can be used to identify effective biomarker candidates for environmental sampling.IMPORTANCEDeveloping non-pharmaceutical interventions to reduce virus transmission indoors relies on robust environmental monitoring methods. Monitoring viral pathogens is challenging because of frequent non-detect measurements that introduce uncertainty. For instance, a non-detect measurement could indicate either the absence of the pathogen or simply the lack of human respiratory activity and, thus, exposure. To aid in distinguishing these scenarios, this study identifies viruses from the human respiratory tract using publicly available sequencing data that can be incorporated into environmental monitoring as biomarkers of human respiratory activity. These viral biomarkers will improve indoor monitoring to help enact interventions to mitigate virus transmission. Furthermore, our approach to identify biomarkers from existing metagenomes can be adapted for future biomarker identification in any system.
28 May 2026
Read appraisal →Cell reports
Artificial intelligence-driven donor-recipient gut microbiome matching for optimized fecal microbiota transplantation
Fecal microbiota transplantation (FMT) has emerged as a promising therapy for gastrointestinal diseases, yet its clinical efficacy remains individually variable. Here, we analyze multi-kingdom and functional profiles in pre- and post-FMT metagenomes from 515 FMTs across 30 cohorts and 12 diseases, in which 94 metagenomes from 44 FMTs are newly collected. We reveal a robust association between clinical efficacy and post-FMT microbiome convergence of recipients toward donors, across diseases. To predict post-FMT microbial convergence, we develop MOZAIC (Microbiome Matching Optimization via Artificial Intelligence), a framework that integrates multi-dimensional donor-recipient microbiota features. MOZAIC achieves an average area under the curve (AUC) of 0.88 and accuracy/recall >0.80 in forecasting microbiome convergence, with 78.7% accuracy in predicting clinical outcomes, and retrospectively simulates a 1.44-fold improvement (from 49.4% to 71.0%) in clinical response rates over baseline. This study establishes microbiome convergence as a key mediator of FMT and provides a scalable tool for precision matching in microbiota-based therapies.
28 May 2026
Read appraisal →Journal of chemical information and modeling
Machine Learning-Driven Simulations of the SARS-CoV-2 Fitness Landscape from Deep Mutational Scanning Experiments
Predicting protein variant effects is a key challenge in preparing for pathogenic viral strains, understanding mutation-linked diseases, and designing new proteins. Protein sequence-structure-function relationships are difficult to model due to complex allosteric and epistatic effects. To investigate efficient modeling strategies, we trained supervised machine learning (ML) models with deep mutational scanning (DMS) libraries of SARS-CoV-2 receptor binding domain (RBD) sequences labeled with angiotensin converting enzyme 2 (ACE2) binding affinity. These models demonstrate superior performance predicting combinatorial mutation effects compared to adding or averaging the effects of point mutations and exhibit strong extrapolative performance ranking omicron variants when training only near wild type (WT) variants. We characterize the RBD fitness landscape by combining ML with Markov Chain Monte Carlo simulations to predict evolutionary patterns from the WT sequence. These generate comparable sequence profiles to high-fitness sequences in DMS data and predict mutations in unseen omicron variants. These models provide insight into the relationship between RBD sequence elements and offer a new perspective on the use of DMS to predict emerging viral strains, which we anticipate will be applicable to other evolutionary prediction tasks. To facilitate application and future development of this strategy, we introduce Mavenets: https://github.com/SztainLab/mavenets.
27 May 2026
Read appraisal →NEJM evidence
Outcomes of Pneumonia in ICUs in Low- and Middle-Income Countries - A Systematic Review
BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of intensive care unit (ICU) admission and death in low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to estimate mortality among patients with CAP admitted to ICUs in LMICs. METHODS: We searched multiple databases using terms related to CAP admitted to the ICU and LMIC. We included both observational studies and clinical trials. The primary outcome was all-cause ICU, 28-day or 30-day mortality. Demographics, comorbidities, clinical characteristics, mechanical ventilation, and length of ICU stay were described. We registered the study in PROSPERO (CRD42022363048). RESULTS: A total of 52 studies from 18 countries met inclusion criteria, encompassing 48,707 patients. Most studies originated in upper-middle-income countries and no studies from low-income countries were identified. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, and diabetes. Mechanical ventilation was reported in 36 studies, with median use in 59% (interquartile range, 41.4-77.4) of patients. Pooled mortality was 37% (95% confidence interval [CI], 31-42), rising to 61 (44-75) among patients requiring mechanical ventilation. In a meta-regression, age and mechanical ventilation were the strongest moderators of mortality, explaining 55.2% of heterogeneity in short-term mortality. CONCLUSIONS: Mortality among patients with CAP admitted to ICUs in middle-income countries remains high, especially in older and mechanically ventilated patients. The lack of data from low-income countries is notable.
27 May 2026
Read appraisal →Renal failure
Prognostic factors in malaria patients with acute kidney injury: a systematic review and meta analysis
This systematic review and meta-analysis aims to evaluate the predictors of mortality in malaria patients with AKI. Studies were searched in PubMed, Scopus, Ebsco, and ScienceDirect. We included observational studies that showed the association between clinical or laboratory abnormalities and mortality, reported in odds ratio. The quality of each study was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R. Sixteen studies with 1,104 patients were analyzed. Factors significantly associated with mortality were respiratory distress syndrome (OR: 18.50, p < 0.001), neurological involvement (OR: 12.83, p < 0.001), disseminated intravascular coagulation (OR: 12.00, p < 0.001), hypotension (OR: 18.23, p < 0.001), oliguria (OR: 3.41, p = 0.002), ventilator requirement (OR: 30.35, p < 0.001), leukocytosis (OR: 4.87, p = 0.003), hyponatremia (OR: 3.67, p = 0.048), acidosis (OR: 4.88, p < 0.001), hyperkalemia (OR: 3.99, p < 0.001), and jaundice (OR: 5.03, p = 0.001). ARDS, neurological involvement, DIC, hypotension, oliguria, ventilator requirement, leukocytosis, hyponatremia, acidosis, hyperkalemia, and jaundice were associated with mortality in malaria patients with AKI. The findings underscored the importance of heightened awareness and vigilance in managing patients with these conditions.
26 May 2026
Read appraisal →JMIR nursing
Health Care Professionals' Perspectives on the Use of a Wearable Device for Early Detection and Continuous Vital Signs Monitoring of Acute Respiratory Infections in Nursing Homes: Qualitative Study
BACKGROUND: The growing aging population and staff shortages are placing pressure on Dutch nursing homes (NHs). These challenges have led to an increased interest in digital health technologies. Among these are wearable devices that allow for remote continuous monitoring of vital signs. An example is the Healthdot (smartQare), a wearable electronic device that continuously monitors heart rate, respiratory rate, and physical activity. In the context of acute respiratory infections (ARIs) in NHs, where initial symptoms can go unnoticed, continuous monitoring may aid in early recognition, timely intervention, and reduce staff workloads. However, little is known about how health care professionals perceive the use of continuous vital signs monitoring devices, such as the Healthdot, for this cause in NHs. OBJECTIVE: This study aims to explore the perspectives of healthcare professionals on the use of the Healthdot for early detection and monitoring of ARIs in NHs, to inform potential future implementation. METHODS: Semistructured interviews were conducted with 20 physicians, nurses, and certified nursing assistants from 4 NHs and 1 acute geriatric community hospital located in a NH. Interview transcripts were thematically analyzed to identify themes regarding their perspectives on the use of the Healthdot for monitoring ARIs in this setting. RESULTS: Five main themes were identified that related to the appropriate use of the Healthdot for NH clients and health care professionals: alignment of Healthdot use and NH clients' treatment policies, balancing safety and freedom, impact of the Healthdot on work processes, supporting rather than replacing care, and possible use during pandemics and in the future. Additionally, several preconditions for the use of the Healthdot were identified, including its usability, a support base among care staff, adequate training and guidance, communication with NH clients and their relatives, and a clear policy regarding its use. CONCLUSIONS: Given the complexity of care in NHs, where clinical care is typically balanced against quality of life and a homelike environment, physicians generally expressed reserved attitudes toward the Healthdot, highlighting the need to consider multiple factors in its implementation. Care staff were generally positive about the device. Nevertheless, tailored assessment for each individual NH client remains essential, balancing treatment goals, safety, autonomy, and person-centered care. Additionally, clear communication and alignment between health care professionals in this setting are crucial, specifically regarding their expectations of the Healthdot's role in care processes. This study offers practical guidance that may inform future implementation efforts of continuous vital sign monitoring devices in NHs.
26 May 2026
Read appraisal →PloS one
Views, barriers, and facilitators of people living with human immunodeficiency virus and healthcare professionals regarding the use of a mobile health application to improve HIV self-care in Malaysia
AIM: The views, barriers, and facilitators of people living with HIV (PLWH) and healthcare professionals (HCPs), regarding the use of a mobile health application (m-HA) to improve HIV self-care were explored. SUBJECT AND METHODS: Seventeen PLWH, nine doctors and two nurses who owned a smartphone and understood English or Malay were recruited from the infectious disease clinic of a tertiary hospital in Malaysia. Semi-structured in-depth interviews were conducted face-to-face using a topic guide, audio-recorded and transcribed verbatim. Data was analysed using reflexive thematic analysis. Two researchers independently coded transcripts and met to resolve discrepancies and develop themes. Data collection continued until thematic saturation was achieved. RESULTS: Three themes emerged: (1) Perceived benefits and concerns regarding m-HA usage: participants perceived m-HA could improve knowledge, but expressed concerns regarding information overload. Participants viewed m-HA as a means to enhance access to hospital services like clinic visits, medication refills, communication with HCPs, and medical records documentation. However, concerns regarding misuse, data confidentiality and security remained. (2) Perceived motivators of m-HA: participants perceived that high utilitarian and hedonic motivators increase m-HA usage. (3) Perceived influences to use m-HA: participants believed PLWH would use m-HA if introduced by their peers or HCPs. CONCLUSION: These findings provided information for developing a patient-centred m-HA to improve HIV self-care in Malaysia.
24 May 2026
Read appraisal →Medicine
Efficacy of traditional Chinese medicine in treating severe pneumonia: A meta-analysis and systematic review
BACKGROUND: Severe pneumonia (SP) is a critical respiratory disease characterized by its severity and high mortality rate. Traditional Chinese medicine (TCM) has gradually been used as an adjunctive therapy in clinical treatment of SP, yet its efficacy and safety lack systematic evidence. This study aims to analyze, evaluate, and compare current research evidence on TCM adjunctive therapy for SP, providing a basis for clinical treatment of this condition. METHODS: A systematic search was conducted on both English and Chinese online databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP) to identify relevant papers published from inception to November 2023. High-quality randomized controlled tests (RCTs) were selected for analysis. Outcome measures related to SP were extracted from the literature. Statistical analysis was performed using RevMan 5.3 (Cochrane) software to assess heterogeneity among included studies, calculate mean differences, odds ratios, and their 95% confidence intervals, and detect publication bias. RESULTS: A total of 34 RCTs met the inclusion criteria. Comparative analysis revealed that integrating TCM with conventional treatment significantly improves the overall clinical effective rate(P < .05). Specifically, it markedly alleviates TCM symptoms (P < .05). Additionally, TCM adjunctive therapy reduces levels of inflammatory markers including white blood cells, C-reactive protein (P < .05), and decreases Clinical Pulmonary Infection Score and Acute Physiology and Chronic Health Evaluation II scores compared to conventional treatment alone (P < .05). Compared to conventional treatment alone, TCM adjunctive therapy also enhances arterial blood gas indices (PaO2) (P < .05) and pulmonary function (forced expiratory volume in 1 second) (P < .05). Complication rates and mortality are lower in the TCM adjunctive therapy group(P < .05). Moreover, TCM treatment significantly boosts immune function (cluster of differentiation 4+ T lymphocyte) (P < .05). CONCLUSION: Integrating TCM with conventional treatment shows advantages in the efficacy of SP treatment, clinical symptoms management, inflammatory markers, and severity grading. Compared to conventional treatment alone, TCM adjunctive therapy improves immune function, pulmonary function, complication rates. However, future research should focus on large-scale, high-quality RCTs to further validate the effectiveness and safety of TCM adjunctive therapy for SP.
24 May 2026
Read appraisal →Studies in health technology and informatics
Assessing AI-Based Decision Support in Early Sepsis and AKI Recognition
Sepsis and acute kidney injury (AKI) remain among the most critical conditions in acute care, associated with high morbidity and mortality. Early risk recognition is essential but often hampered by nonspecific symptoms. Recent studies have demonstrated that AI- and ML-based Clinical Decision Support Systems (CDSS) can enhance the early detection of sepsis and AKI and support clinical decision-making [1-3]. In May 2025, the University Hospital Augsburg (UKA) integrated an externally developed AI-based CDSS to provide real-time risk predictions for sepsis and AKI. This study evaluates the effectiveness of the system in routine clinical practice using retrospective data from periods before and after its implementation. Primary endpoints include diagnostic accuracy. The results will indicate whether the CDSS contributes to improved early risk recognition and enhanced patient safety in a real-world hospital environment.
24 May 2026
Read appraisal →Studies in health technology and informatics
Long Covid and Digital Health in Switzerland: Potentials and Limitations
Post-COVID-19 (or Long Covid) presents a complex and persistent health challenge affecting a growing number of individuals worldwide. Digital health interventions (DHIs) offer potential support for symptom monitoring, self-management, and information access. However, their availability, quality, and sustainability remain uncertain, particularly in smaller healthcare markets such as Switzerland. This study provides a descriptive assessment of ten representative DHIs for Long Covid available from Switzerland. Each tool was evaluated using a 19-item framework derived from validated instruments. Three independent reviewers tested all interventions on iOS and Android devices, with consensus ratings across five quality categories. Results showed strong usability (average 6.3/8) and practical usefulness (5/8), but consistent weaknesses in accessibility (3.7/8) and data protection (4.6/8). Total scores ranged from 14.7 to 26.3 out of 38. Several Swiss-based apps were discontinued during the study period, highlighting market fragility. Findings underscore the need for inclusive design, transparent data practices, and institutional support if DHIs are to complement Long Covid care sustainably.
24 May 2026
Read appraisal →PloS one
A qualitative study to inform the design and implementation of AI-driven diagnosis: Challenges, barriers, and clinical insights of physicians
INTRODUCTION: Acute febrile illnesses are significant clinical challenge in tropical regions due to overlapping symptomatology among infections such as dengue, scrub typhus, and leptospirosis. This diagnostic dilemma leads to delays in appropriate treatment and negatively impacted patient outcome due to limited diagnostic tool availability. Recent advancement in artificial intelligence (AI) application in healthcare help in developing diagnostic aiding tool in such clinical dilemma. AIMS: Study aimed to explore physicians' perspectives on diagnostic challenges of tropical Acute-febrile-illnesses and assess perceived utility of AI as a supportive tool in clinical decision-making. METHODS: A qualitative interview was conducted using validated semi-structured interview guide using literature and expert opinion and validated by IPR method. To understand the physicians perspective on management infectious diseases in critical care, interview guide administered among ten physicians with 10-30 years of experience across different centres of India. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed using ATLAS.ti software. RESULTS: Four major themes emerged: clinical experience and practice, diagnostic-challenges, diagnostic-parameters and decision-making, and AI integration in clinical-practice. However, no statistical test can be performed since study mainly focused to understand perception of physicians with respect to managing illness and hence prevalence cannot be determined. Diseases such as dengue, scrub typhus, and leptospirosis were reported as most prevalent, particularly during monsoon seasons. Key diagnostic challenges included overlapping symptoms, diagnostic delays, limited sensitivity/specificity of available tests, and cost constraints. Physicians primarily relied on clinical judgment and laboratory findings, despite the limitations. Most of the participants expressed positive attitudes toward the potential of AI as supportive tool, citing its ability to enhance diagnostic accuracy and streamline clinical workflow with proper validation. CONCLUSIONS: Growing in clinical dilemma AI has significant role in diagnosis of tropical fever with integration of the clinical data & physician perspective can successfully able to incorporate in clinical application.
23 May 2026
Read appraisal →BMJ paediatrics open
Enhancing respiratory virus surveillance among hospitalised children: a machine learning-based predictive model.
BACKGROUND: Viral respiratory tract infections (vRTIs) are a leading cause of paediatric hospitalisation and healthcare utilisation. Existing syndromic surveillance tools, including the WHO Severe Acute Respiratory Infection definition, demonstrate limited diagnostic accuracy in children whose symptom profiles vary widely. This study aimed to develop a machine learning (ML) model to predict microbiologically confirmed vRTIs in hospitalised children and to evaluate performance across age groups and viral pathogens. METHODS: We conducted a retrospective cross-sectional study of 2050 paediatric patients (<18 years) admitted with acute respiratory infections to two tertiary paediatric hospitals in Canada. Predictors included age, sex, hospital transfer status, chronic comorbidity status and 22 presenting symptoms. The primary outcome was microbiologically confirmed vRTI, determined by multiplex PCR or rapid antigen testing. Six ML algorithms were trained and the best-performing model, identified by area under the receiver operating characteristic curve (auROC), was tested on age subgroups, viral pathogens and sites. RESULTS: Among 2050 patients (median (IQR) age 2.4 (0.8-5.2) years), 1831 (89.3%) tested positive, most commonly for respiratory syncytial virus (RSV) (38.7%) and enterovirus/rhinovirus (32.8%). Logistic regression with L2 regularisation demonstrated the best performance (auROC, 0.754; 95% CI 0.697 to 0.808; sensitivity, 69.2%; specificity, 69.9%), with greatest performance among children <1 year (auROC, 0.763) and RSV cases (auROC, 0.727). CONCLUSIONS: An ML-based logistic regression model using admission data accurately predicted paediatric vRTIs, outperforming traditional syndromic surveillance definitions, especially among infants <1 year. By integrating ML models into hospital electronic medical records, healthcare systems can achieve enhanced respiratory virus surveillance, faster outbreak detection, greater diagnostic efficiency and improved pandemic preparedness.
23 May 2026
Read appraisal →JMIR infodemiology
Japanese-Language AI Agent System for Human Papillomavirus Vaccine Infoveillance and Public Communication: Development and Feasibility Evaluation
BACKGROUND: Human papillomavirus (HPV) vaccine hesitancy remains a significant public health challenge in Japan, where proactive vaccination recommendations were suspended between 2013 and 2021. The resulting information gap between medical institutions and vaccine-hesitant populations is exacerbated by misinformation on social media platforms. Traditional public health communication strategies cannot address individual queries while simultaneously monitoring population-level discourse. OBJECTIVE: This study aimed to develop and conduct a feasibility evaluation of a dual-purpose artificial intelligence agent system that delivers verified HPV vaccine information to the public through a conversational interface while generating infoveillance reports for medical institutions based on user interactions and social media discourse. METHODS: We implemented a system with 3 components: a vector database integrating 139,803 documents, including academic papers, Japanese government sources, news media, and social media posts; a retrieval-augmented generation chatbot using a ReAct agent architecture with iterative multitool orchestration across 5 specialized knowledge sources; and an automated report generation system with modules for news analysis, research synthesis, social media sentiment analysis, including stance classification and topic modeling, and user interaction pattern identification. System performance was assessed using both automated and manual evaluation protocols on a scale from 0 to 5. RESULTS: The entire system functioned as expected. For single-turn evaluation, the chatbot achieved mean scores of 4.83 (SD 0.67; 95% CI 4.71-4.93) for relevance, 4.89 (SD 0.53; 95% CI 4.79-4.97) for routing, 4.50 (SD 1.29; 95% CI 4.27-4.70) for reference quality, 4.90 (SD 0.62; 95% CI 4.78-4.99) for correctness, and 4.88 (SD 0.54; 95% CI 4.78-4.96) for professional identity, with an overall mean of 4.80. Multiturn evaluation yielded higher mean scores: 4.94 for context memory (SD 0.25; 95% CI 4.84-5.00) and an overall mean of 4.98, with topic centering and identity achieving 5.00. The report generation system achieved high scores across all sections: 4.83 for completeness (SD 0.37; 95% CI 4.73-4.94), 4.88 for correctness (SD 0.33; 95% CI 4.77-4.96), and 4.12 for helpfulness (SD 0.48; 95% CI 3.98-4.27). Reference validity achieved perfect scores (5.00) across all periods, with citation correctness averaging 4.21 (SD 0.58; 95% CI 3.96-4.46). CONCLUSIONS: This feasibility study demonstrated that an integrated artificial intelligence agent system can support both public HPV vaccine communication and social media infoveillance in a Japanese-language context. Prospective deployment with real users is needed to assess actual public health impact.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Safety and Immunogenicity of a Fourth Dose of Omicron BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18-55 Years Old
BACKGROUND: Emergence of severe acute respiratory syndrome coronavirus 2 sublineages warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS: In this phase 3 trial, adults 18‒55 years old who had previously received three 30 μg doses of BNT162b2 vaccine were randomized to receive a 60 or 30 μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60 μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron BA.1, BA.4, and BA.5 subvariants and ancestral strain. RESULTS: Among the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60 µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs], 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs, 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n = 30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5. CONCLUSIONS: Bivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to the original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains. CLINICAL TRIALS REGISTRATION: NCT04955626.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Evaluating Personal and Environmental Decolonization Strategies for Children With Skin and Soft Tissue Infection and Their Households - A Randomized Clinical Trial
BACKGROUND: Staphylococcus aureus colonization predisposes to skin and soft tissue infection (SSTI). Given the waning effectiveness of decolonization, we evaluated periodic-personal decolonization and household environmental decontamination to reduce SSTIs among households affected by S. aureus. METHODS: Households of children with community-associated S. aureus SSTI participated in an open-label randomized trial. After baseline decolonization, households were randomized 1:1:1 to a 3-month decolonization intervention: (1) periodic-personal (twice weekly chlorhexidine bathing and monthly intranasal mupirocin application); (2) environmental-hygiene (weekly household surface disinfection and enhanced laundry measures); or (3) integrated-approach of both periodic-personal and environmental-hygiene. Over 9 months, participants and household surfaces were sampled at 5 study visits to detect S. aureus; SSTI incidence was recorded. The primary outcome was household-level cumulative SSTI at 3 months, comparing the integrated-approach to the combined personal-periodic and environmental-hygiene groups. RESULTS: Between 2015 and 2021, 196 index patients and their household contacts (n = 623) were enrolled. Cumulative SSTI incidence did not differ between groups during the 3-month intervention. In index patients and household contacts with SSTI in the year prior to enrollment, SSTI incidence was lower among the integrated-approach at 6- and 9-months compared to the combined periodic-personal and environmental-hygiene groups. In multivariable analyses, prior year SSTI was associated with subsequent SSTI; intervention group was not significant. All interventions reduced methicillin-resistant S. aureus, but not methicillin-susceptible S. aureus, personal colonization over 9 months. CONCLUSIONS: While an integrated-approach of prolonged personal and environmental decolonization reduced SSTIs among participants with prior year SSTI, prior SSTI strongly predicted SSTI incidence longitudinally. Novel prevention strategies are needed.
22 May 2026
Read appraisal →BMJ open respiratory research
Symptom-based rehabilitation in people with post-COVID-19 condition (RELOAD study): a randomised controlled trial
RATIONALE: Post-COVID condition (PCC) is characterised by persistent symptoms that impair health-related quality of life (HRQoL); rehabilitation (REHAB) strategies remain scarce. OBJECTIVE: To investigate the effect of a symptom-based REHAB programme versus usual care on HRQoL in people with PCC. METHODS: In this single-blind randomised controlled trial, a total of 132 people with PCC were randomised to either a REHAB group or a control group, with 104 completing the trial. The REHAB group received a multimodal 3-week REHAB programme tailored to the participant's primary symptom-based group (fatigue, cognitive problems or somatic symptoms); the control group received usual care. The primary endpoint was the between-group difference in change in HRQoL, measured by the 12-item Short Form Health Survey (SF-12) physical component summary (PCS) score at 3 weeks post baseline (intervention period). Changes from baseline to a 3-month follow-up after the intervention period were also analysed as a secondary measure. Additional outcomes included mental HRQoL (SF-12 mental component summary (MCS)), depression symptoms (Patient Health Questionnaire 9 (PHQ-9)) and anxiety symptoms (Generalized Anxiety Disorder 7 (GAD-7)). RESULTS: Participants (mean age 47±12.3 years, 90.4% not hospitalised during acute SARS-CoV-2 infection, 69.2% female) in the REHAB group (n=47) showed a significantly greater improvement in PCS compared with the control group (n=57) (mean difference (Δ) 2.9 points, 95% CI 0.2 to 5.7, p=0.038) at 3 weeks post baseline. This difference remained significant at the 3-month follow-up (Δ 4.2 points, 95% CI 1.5 to 6.9, p=0.003). The REHAB group also showed significant improvements in mental HRQoL (MCS: Δ 5.7 points, 95% CI 2.0 to 9.4, p=0.003), as well as in depression symptoms (PHQ-9: Δ -2.7 points, 95% CI -4.2 to -1.2, p<0.001) and anxiety symptoms (GAD-7: Δ -2.4 points, 95% CI -3.7 to -1.1, p<0.001) at 3 weeks post baseline compared with the control group. At the 3-month follow-up, the reduction in depression symptoms remained significant, while no significant differences were observed for mental HRQoL or anxiety symptoms. CONCLUSION: A symptom-based rehabilitation programme significantly improved HRQoL in individuals with PCC after 3 weeks, with some benefits persisting at 3 months. TRIAL REGISTRATION NUMBER: NCT05172206.
22 May 2026
Read appraisal →PloS one
Computational models for the classification of antibody specificity using heavy chain features
BACKGROUND: Antibodies play a critical role in immune defense, with their antigen specificity primarily governed by the unique sequences of their heavy chains, rendering them invaluable tools in research and diagnostics. High-throughput sequencing technologies have facilitated comprehensive profiling of the immune repertoire, generating vast antibody sequence datasets that necessitate advanced analytical methods. METHODS: In this study, we utilized curated antibody sequences from NCBI databases to develop computational classification models for categorizing antibodies into predefined antigen classes. We extracted multifaceted features from the heavy chain sequences, encompassing physicochemical properties, structural composition, sequence order, and evolutionary information. These features were input into machine-learning classifiers to predict antigen specificity across five classes of antibodies: anti-dengue virus, anti-influenza virus, anti-tetanus bacillus, anti-SARS-CoV-2, and anti-Mycobacterium tuberculosis. RESULTS: Five tree-based machine-learning models were employed, with CatBoost achieving the highest accuracy of 0.7713. To further enhance predictive performance, we developed a stacking model leveraging multiple algorithms, resulting in an improved accuracy of 0.7803. Additionally, a Feature-Based Transformer deep-learning architecture was implemented, yielding an accuracy of 0.7399 and an F1-score of 0.6761. To elucidate the key determinants of antibody-antigen interactions, we applied the SHAP framework to assess feature importance. Among the top 30 contributing features, those representing sequence order and evolutionary information predominated, with amino acids such as cysteine (C), isoleucine (I), histidine (H), and phenylalanine (F) exhibiting notable SHAP values. Notably, cysteine (Cys) emerged as the most influential feature, underscoring its critical role in antibody structure and function. Specific antibodies contributed variably to these key features; for instance, the anti-tuberculosis antibody accounted for approximately 11% of a sequence order feature associated with alanine (A), while the anti-SARS-CoV-2 antibody contributed about 9.26% to a feature associated with isoleucine (I). CONCLUSIONS: Our study demonstrates the efficacy of machine-learning and deep-learning approaches in classifying antibodies into specific antigen categories, providing sequence-based insights into features associated with antibody specificity. These findings have significant implications for the mechanistic understanding, isolation, and development of potential therapeutic antibodies.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Respiratory Syncytial Virus Vaccination in Solid Organ Transplant Recipients: Interim Findings From a Phase 3 Trial of mRNA-1345
BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. METHODS: In this ongoing, open-label, phase 3 trial, adults ≥18 years with a history of liver, kidney, or lung transplant received 2 doses of mRNA-1345 RSV vaccine (50 µg) 56 days apart. Primary endpoints were tolerability, safety, and RSV-A/RSV-B neutralizing antibody (nAb) responses on Day 85; secondary endpoints included immunogenicity on Days 29 and 181. Cell-mediated immunity was an exploratory endpoint assessed in a subset of participants. RESULTS: 146/150 participants (median: age, 57 years; time since transplant, 4.7 years) received both doses. Reactogenicity was mild to moderate and transient. No vaccine-related discontinuations, deaths, adverse events of special interest (AESIs), or events of transplant rejection were reported within 28 days after any dose. One dose was immunogenic across all SOT types, with 4.9- and 3.4-fold increases in RSV-A/RSV-B nAb GMTs by Day 29, respectively. A second dose resulted in modest additional increases over baseline (RSV-A, 7.1-fold; RSV-B, 5.2-fold). Added benefit of the second dose was more apparent in participants with kidney and lung transplant, <2 years post-transplant, and on mycophenolate. Responses remained above baseline through Day 181. Polyfunctional CD4⁺ T-cell responses were robust and sustained; CD8⁺ responses were also observed. CONCLUSIONS: mRNA-1345 was well tolerated and immunogenic in SOT recipients. A single dose induced nAb responses across subgroups, with potential additional benefit from a second dose in specific groups. Durable antibody and cellular responses support mRNA-1345 as a preventive strategy for RSV in this vulnerable population. CLINICAL TRIALS REGISTRATION: NCT06067230.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Mycobacterium tuberculosis Transmission in Healthcare Settings: A Systematic Review of Frequency, Risk Factors, and Exposure Conditions
BACKGROUND: Uncertainty regarding factors that govern Mycobacterium tuberculosis transmission in healthcare settings leads to broad and variable exposure definitions and low-yield contact investigations. We systematically reviewed data on M. tuberculosis transmission in healthcare to inform risk stratification and exposure definitions. METHODS: We searched MEDLINE, Embase, CINAHL, and Cochrane databases from inception through December 2024 for studies describing M. tuberculosis transmission from adult patients to healthcare personnel (HCP) or patients. We tabulated data on transmission frequency, circumstances, and risk factors. RESULTS: Of 6695 studies screened, 86 met inclusion criteria, encompassing 1083 source patients, 35 698 exposed individuals, and 2517 secondary cases (7.1% overall transmission risk, 3.8% among studies published since the US Centers for Disease Control and Prevention last updated healthcare ventilation standards in 2005). Transmission was associated with prolonged contact between HCP and source patients (median duration 24 hours, interquartile range [IQR] 24-25 hours) and between patients in shared rooms (median duration 24 hours, IQR 12-24 hours), clinical care without N95 respirator (1232 transmissions/10 149 exposures that included data on face covering use, 12.1%), frequent direct care (185 transmissions/410 exposures, 45.1%), and lack of negative pressure ventilation (1906 transmissions/5670 exposures, 33.6%). Only 8/116 (6.9%) transmissions with documented exposure durations were associated with <8 hours of cumulative exposure and all in poorly ventilated spaces. CONCLUSIONS: Mycobacterium tuberculosis transmission in healthcare is uncommon, particularly in spaces that meet current healthcare ventilation standards. Risk factors for transmission include prolonged exposure, close contact, lack of respirators, and poor ventilation. Defining exposures as >8 hours without a respirator should identify most transmissions and could improve the efficiency of contact investigations.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial
BACKGROUND: No specific therapy is approved for human T-cell lymphotropic virus type 1 (HTLV-1) infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (PVL) in adults with HTLV-1 infection. METHODS: We conducted an open-label, randomized controlled phase 2 trial in Salvador, Brazil. Symptomatic adults with HTLV-1 infection were randomized 1:1 to DTG 50 mg once daily or vitamin C (VTC) 500 mg once daily for 48 weeks. We evaluated changes in gait performance (timed 10-meter walk test [T10MWT]). Key secondary endpoints included change in PVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intragroup and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations. RESULTS: Eighty-three participants (53 symptomatic) were randomized (DTG, n = 43; VTC, n = 40). At week 48, there was no between-group difference in T10MWT. However, DTG use significantly reduced PVL over 48 weeks compared with VTC (P < .001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower limb spasticity (P < .001), sensory function (light touch, P = .035; pinprick, P = .001), and median nocturia frequency (P = .012). Network analysis of cytokine expression showed a change in the DTG group from baseline to week 48, with loss of negative correlations and a more balanced pattern. DTG was well tolerated, with no unexpected safety signals. CONCLUSIONS: In this pilot randomized trial, DTG use was associated with significantly reduced PVL and improvement in neurofunctional and immunological characteristics of participants in exploratory analyses. These findings provide evidence supporting the use of integrase inhibitors for HTLV-1 infection. Clinical Trials Registration. Brazilian Clinical Trial Register (ReBEC), code RBR-5x7ccxp.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Cephalosporins Versus Non-cephalosporin Antibiotics for Perioperative Prophylaxis in Primary Arthroplasty: A Systematic Review and Meta-Analysis
BACKGROUND: The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. METHODS: We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. RESULTS: Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46-.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36-1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. CONCLUSIONS: Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Effects of Semaglutide on Cognitive Function in People With HIV: A Randomized, Controlled Trial
BACKGROUND: People with human immunodeficiency virus (HIV, PWH) are at higher risk for visceral adiposity, enhanced inflammation, and cognitive decline than controls who do not have HIV. We previously demonstrated that PWH with lipohypertrophy had a decrease in weight, visceral adipose tissue, and several inflammatory markers after receiving semaglutide, a glucagon-like peptide-1 receptor agonist. Our aim was to investigate the effect of semaglutide on cognitive function in PWH and the possible mediation of this effect by changes in adiposity or inflammation. METHODS: In this randomized, double-blind, placebo-controlled phase 2b clinical trial, PWH on antiretroviral therapy were randomized 1:1 to receive 32 weeks of subcutaneous semaglutide or placebo. The primary outcome was the change in cognitive function at 32 weeks. Secondary measures included changes in body composition and inflammatory markers. Causal mediation analysis assessed semaglutide's direct and indirect effects on Cognivue scores through changes in adiposity and inflammation. RESULTS: 108 participants were included (54 per arm); 65% were non-White, 40% were female, and median age was 53 years. Compared with placebo, PWH on semaglutide significantly increased visuospatial, naming/language, and delayed recall scores at 32 weeks (P = .01, .05, and .04, respectively). After adjusting for sex and absolute CD4 count, only visuospatial score remained statistically significant (P = .05). Semaglutide's total natural direct effect maintained a positive effect on the visuospatial score while accounting for potential changes in high-sensitivity C-reactive protein and soluble CD163 levels (P = .04). CONCLUSIONS: Semaglutide may have a beneficial impact on visuospatial cognitive function in PWH through its effect on inflammation. Clinical Trials Registration . NCT04019197.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetics of Dexamethasone in Tuberculous Meningitis
BACKGROUND: Dexamethasone is recommended as adjunctive therapy for tuberculous meningitis (TBM). Co-administration with rifampicin is expected to reduce dexamethasone exposure in TBM, an effect that may be more pronounced with the higher rifampicin doses currently being evaluated in clinical trials. METHODS: This pharmacokinetic study was nested in a randomized controlled trial comparing the safety of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, versus standard-dose rifampicin (10 mg/kg) for adults with HIV-associated TBM. All participants received adjunctive oral dexamethasone every 12 hours starting at a dose of 0.4 mg/kg/day. Dexamethasone concentrations were measured on intensively sampled plasma on day 3 after study enrollment and analysed using nonlinear mixed-effects modeling. RESULTS: In total, 261 dexamethasone concentrations from 43 participants were available for model development. Eight (18%) participants were on efavirenz-based ART and five (11%) were on a lopinavir/ritonavir-based regimen. The median duration of rifampicin therapy at the time of pharmacokinetic sampling was 4 days (range: 0-7). Dexamethasone pharmacokinetics was best described by a one-compartment disposition model with first-order absorption and elimination. Typical oral clearance (CL/F) was 131 L/h, reduced to 11.5 L/h with concomitant lopinavir/ritonavir. High-dose rifampicin had no significant additional effect on dexamethasone pharmacokinetic parameters compared with the standard-dose. CONCLUSIONS: In adults with HIV-associated TBM, there was high dexamethasone clearance, likely related to a drug-drug interaction with rifampicin. High-dose rifampicin had no additional effect on dexamethasone exposure.
22 May 2026
Read appraisal →Biochemistry
Antimycobacterial Peptides: From Natural Product Discovery to AI Guided Design
Mycobacterial pathogens remain major global health threats, exacerbated by both rapid acquisition of antibiotic resistance and the formidable drug diffusion barrier presented by the rigid mycomembrane. These challenges have renewed interest in antimycobacterial peptides (AMyPs), a diverse class of short amphiphilic sequences capable of rapidly killing both drug-sensitive and drug-resistant mycobacteria. Beyond their intrinsic potency, AMyPs can synergize with existing antibiotics and exhibit markedly slower resistance development relative to conventional small molecules. In this review, we synthesize recent advances spanning natural bioprospecting, mechanism-guided rational design, and chemical optimization strategies that have yielded increasingly potent and selective AMyP candidates. We further highlight the rapid emergence of artificial intelligence-driven discovery platforms, which leverage machine-learning models trained on curated, mycobacteria-specific data sets to predict and refine novel AMyPs with growing accuracy. Together, these technologic, biologic, and computational advances outline a rapidly expanding landscape for AMyP-based therapeutic development and establish a foundation for next-generation antimycobacterial drug design.
21 May 2026
Read appraisal →Scientific reports
Analysis, control, and forecasting the dynamics of SIRD models with saturated treatment and nonlinear incidence
This study addresses the challenge of managing complex epidemic dynamics exhibited by a novel Susceptible-Infected-Recovered-Deceased (SIRD) model. The introduced model incorporates a biologically and behaviorally mediated nonlinear incidence rate alongside a saturated treatment function, realistically capturing both physical transmission risks and the human behavioral responses during an outbreak. Our comprehensive analysis establishes the mathematical rigor of the system through positivity, boundedness, and a detailed investigation of equilibrium points and bifurcations (transcritical, saddle-node, and Hopf), which reveal the potential for complex, oscillatory, and chaotic epidemic patterns. To mitigate the disease burden, we apply Pontryagin's Maximum Principle to derive optimal time-dependent prevention and treatment control strategies. Furthermore, we introduce a highly efficient machine learning framework based on a Logistic-Map Reservoir Computer (LMRC) for accurate, real-time forecasting of these complex dynamics. Numerical simulations validate the theoretical findings and reveal the model's rich dynamical behaviors, including stable limit cycles and chaotic regimes driven by parameter variations. The integrated analytical, control, and machine learning approach provides a robust toolkit for public health policymakers, offering data-driven insights crucial for designing adaptive, cost-effective interventions that directly support the achievement of Sustainable Development Goal 3 (Good Health and Well-being).
21 May 2026
Read appraisal →BMJ open
Evaluation of a deep learning model applied to chest X-rays of patients with suspected pneumonia presenting to the emergency department designed to predict admission risk: a retrospective training and prospective non-intervention validation.
OBJECTIVES: To develop, train and test a deep learning model Image-based PROgnostication applied to Chest X Rays (IPRO-X) tool that predicts the inpatient (IP) admission risk in patients with suspected pneumonia presenting to the emergency department (ED). DESIGN: The study consists of a retrospective (training) and prospective non-interventional shadow deployment (validation) of a deep learning model. SETTING: Three-hospital tertiary care system with two EDs. PARTICIPANTS: Consecutive adult patients (18 years old or older) who presented to the ED from December 2022 to February 2023 with a chief clinical complaint potentially related to pneumonia were reviewed for eligibility (n=5567), with a final number of 3677 included in the validation study. PRIMARY AND SECONDARY OUTCOME MEASURES: IPRO-X was developed using standard two-dimensional convolutional neural network InceptionNet architecture and processes chest radiographs (CXRs) acquired at admission generating a continuous value from 0 (IP-negative) to 1 (IP-positive). We examined IPRO-X's ability to predict IP admission using accuracy, area under the curve (AUC), receiver operating characteristic, sensitivity, specificity, positive predictive value and negative predictive value. IPRO-X scores were compared against observed outcomes (admission and discharge) to determine clinical utility in an ED setting. Four thresholds were defined from the retrospective phase: Youden optimal, highest specificity and thresholds equivalent to 30-day mortality rates of Pneumonia Severity Index (PSI) Risk class IV and Confusion, Respiratory Rate, Blood Pressure and Age 65 or older Score (CRB-65) scores 1 and 2. Performance was also analysed per group of chief complaints. RESULTS: In the validation set, 3677 patients (1777 (48%) female, median age 56 years (min 18, max 99)) were included. IPRO-X predicted IP admissions with an AUC of 0.795, and in the pneumonia-specific chief complaints, AUC increased to 0.828, whereas in non-related pneumonia chief complaints, the AUC decreased to 0.755. IPRO-X score was significantly higher in admitted patients compared with discharged patients (p<0.001). The accuracy of IPRO-X when using the PSI-anchored threshold was 0.751 and with the CRB-anchored threshold was 0.729, with a specificity of 0.803 and 0.968, respectively. CONCLUSIONS: IPRO-X applied to CXR of patients with signs and symptoms commonly related to pneumonia in the ED can accurately predict IP admission.
21 May 2026
Read appraisal →Sexually transmitted infections
Complex role of digital health literacy in awareness and use of digital sexually transmitted and blood-borne infections testing: a structural equation modelling analysis of the 2022 GetCheckedOnline survey
BACKGROUND: Although digital health literacy (DHL) is recognised as a determinant of access to digital sexually transmitted and blood-borne infection (STBBI) testing, empirical evidence about its contribution to access disparities remains limited. We applied multidimensional DHL measures to examine inequities in awareness and use of GetCheckedOnline, British Columbia's (BC) publicly funded digital STBBI testing service. METHODS: We analysed data from GetCheckedOnline's 2022 community survey of English-speaking BC residents aged ≥16 years who were sexually active in the past year. Outcomes were awareness and use of GetCheckedOnline (yes/no). DHL was measured using latent factors from the eHealth Literacy Scale: Information Navigation, Resource Appraisal and Confidence in Use. Structural equation modelling (SEM) was used to estimate associations and mediation pathways between DHL, sociodemographic characteristics and service outcomes. Model fit was assessed using standard SEM indices. RESULTS: Among 1657 respondents (mean age 33 years, SD 11.77), Information Navigation was positively associated with awareness (β=0.162, p<0.001) and use (β=0.063, p=0.020) of GetCheckedOnline. Confidence in Use was positively associated with awareness (β=0.206, p=0.014) and use (β=0.115, p=0.020). In contrast, Resource Appraisal was negatively associated with awareness (β=-0.263, p=0.006) and use (β=-0.150, p=0.010). DHL factors mediated the effects of age, income, education and digital access on both outcomes. CONCLUSIONS: DHL operates as a multidimensional and socially patterned determinant of access to digital STBBI testing services. While information navigation and confidence in use facilitate access, higher resource appraisal may reduce use, potentially reflecting concerns about service fit, privacy or trust. Findings highlight the need for digital interventions that are not only accessible but also contextually relevant, trusted and responsive to the needs of diverse users.
20 May 2026
Read appraisal →Revista do Instituto de Medicina Tropical de Sao Paulo
Treatment of brucellosis in pregnant women: a systematic review and analysis of current gaps and future perspectives
Human brucellosis is a globally prevalent bacterial disease with significant implications during pregnancy due to obstetric complications. Despite the importance of early diagnosis and treatment, the lack of therapeutic consensus and robust evidence underscores the need for systematic evaluation to guide clinical practice. This study systematically reviewed the literature to identify and summarize available drug therapy options for brucellosis in pregnant women, focusing on efficacy, safety, and obstetric outcomes. The review followed PRISMA and Cochrane Handbook guidelines. Searches were conducted in MEDLINE, Embase, Cochrane Library, LILACS, and gray literature for references indexed up to September 15, 2025. Eligible studies reported therapeutic interventions in pregnant women with brucellosis. Risk of bias was assessed using the JBI Critical Appraisal tool, and data on participants, interventions, and outcomes were extracted. Of 737 records screened, six studies met the inclusion criteria, comprising retrospective and prospective reports published between 1991 and 2020, totaling 403 pregnant women. Therapeutic regimens varied, with sulfamethoxazole-trimethoprim (SMX-TMP) plus rifampicin being the most frequently used combination. Adverse obstetric outcomes associated with this regimen occurred in 16% (95%CI: 8%-30%) of cases. Overall, abortion occurred in 94 (23.3%) women, 20 preterm births were reported, and 10 newborns had low birth weight. Recurrence was observed in only 3% of cases. Heterogeneity in outcomes and definitions limited comparability. In conclusion, there is no standardized treatment for brucellosis during pregnancy. Adverse obstetric outcomes remain frequent, highlighting the need for controlled studies to establish safe and effective therapeutic protocols.
20 May 2026
Read appraisal →Revista do Instituto de Medicina Tropical de Sao Paulo
Molecular biomarkers associated with ATLL and HAM progression in HTLV-1 infection: a systematic review
Human T-lymphotropic virus type 1 (HTLV-1) infects approximately five to 10 million individuals worldwide, although only a minority develop severe outcomes such as adult T-cell leukemia/lymphoma (ATLL) or HTLV-1-associated myelopathy (HAM). Proviral load (PVL), while widely used, shows limited sensitivity and specificity, reinforcing the need for complementary biomarkers. Omics-based approaches have emerged as promising tools to improve risk prediction. We conducted a systematic review following PRISMA guidelines, searching PubMed, Web of Science, Virtual Health Library (BVS), and CAPES Periodicals databases for studies published between May 2020 and May 2025. Eligible studies included original observational designs investigating genomic, proteomic, and metabolic biomarkers associated with progression to ATLL or HAM. Methodological quality was assessed using tools from the National Heart, Lung, and Blood Institute (NHLBI). In total, 35 studies met the inclusion criteria, most conducted in Brazil, Japan, and Iran. A total of 67 biomarkers were identified: 37 genomic, 27 proteomic, and three metabolic with potential clinical applications in risk stratification, prognosis, and therapeutic monitoring of HTLV-1 infection. PVL remained the most frequently investigated marker but lacked predictive power in isolation. Additional candidates with strong potential included IFN-γ, CXCL10, Neopterin, AnxA1, and sTNFR2. This review highlights the potential of integrated multiparametric panels-combining PVL with omics-derived biomarkers-as a promising strategy to improve risk stratification, prognosis, and therapeutic monitoring in people living with HTLV-1 (PLHTLV-1). However, further longitudinal and clinically validated studies are needed to confirm their applicability and support their translation into early intervention strategies, particularly during the asymptomatic phase.
20 May 2026
Read appraisal →Journal of virology
Is the molecular microenvironment of the latent HIV reservoir predictable using deep learning approaches?
Although current antiretroviral therapy effectively suppresses viral replication in infected individuals, infections remain incurable. One of the main reasons for this is the uncertainty of the molecular microenvironment of the latent HIV reservoir. If this microenvironment can be precisely targeted, the effectiveness of current antiretroviral therapy can be leveraged. To better depict the potent microenvironments of the latent HIV reservoir, it is crucial to first understand the mechanisms that make some viruses transcriptionally active and others silent in the first place. It is currently feasible to predict gene activity from DNA sequence, coupled with epigenetics, using deep learning approaches. Substantial progress has been made in creating multidimensional data sets related to the HIV latent reservoir. The implementation of deep learning to mine potent attributes, enabling the characterization and prediction of the microenvironment of the latent HIV reservoir, is thus imperative. This minireview discusses potent features that can be integrated into deep learning methodologies to predict the likelihood of the potential microenvironment from different tiered levels of the latent HIV reservoir organization, and proposes the principal workflow to tackle this question using deep learning approaches.
20 May 2026
Read appraisal →Journal of the American Heart Association
Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial
BACKGROUND: COVID-19 and other respiratory viral infections can cause cardiovascular complications. SARS-CoV-2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID-19 and enrolled in the ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy. METHODS: We quantified SARS-CoV-2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine-Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death. RESULTS: In 93 patients, SARS-CoV-2 RNA and N-antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90-day death (hazard ratio [HR], 1.31 [95% CI, 1.17-1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24-1.47]). Viral RNA more effectively predicted survivorship than N-antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%-32.3%; P=0.048) after adjustment for age and sex of the relationship between viral RNA and the 90-day mortality rate. CONCLUSIONS: Elevated plasma SARS-CoV-2 RNA levels are associated with death in ACTIV-4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung-blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04505774.
20 May 2026
Read appraisal →Emerging microbes & infections
Clinical outcomes of carbapenem therapy in OXA-48-producing Enterobacterales infections: a French multicentre cohort, systematic review, and meta-analysis
OXA-48-producing Enterobacterales (OXA-48-PE) represent a growing global health threat. Most of OXA-48-PE remain categorized susceptible to carbapenems, which might encourage their use despite uncertain clinical efficacy. This study evaluated clinical outcomes of infections caused by OXA-48-PE treated with carbapenem compared with alternative active therapies. The analyses were performed at three levels: a descriptive analysis of the French cohort, a comparative descriptive analysis of all published studies, and a meta-analysis restricted to studies providing direct comparisons between carbapenem-based and alternative active regimens. Between September 2021 and March 2023, 59 patients with monomicrobial OXA-48-PE infections were included in a French multicenter retrospective cohort. In parallel, a systematic review was conducted to identify clinical studies published through 31 December 2024, reporting outcomes of OXA-48-PE infections. In the French cohort, the overall 30-day mortality was 49.1%. Clinical failure occurred in 57.1% of patients receiving meropenem monotherapy, including patients infected with isolates exhibiting meropenem MICs within the susceptible range. Across 12 clinical studies (817 patients), carbapenem therapy was associated with high and variable crude mortality (52%), whereas newer agents active against OXA-48-PE, particularly ceftazidime-avibactam, were associated with lower and more consistent crude mortality (30.7%). In the primary meta-analysis of 6 human comparative studies, carbapenem therapy was associated with an increased risk of clinical failure compared with alternative active regimens (OR = 2.02; 95% CI = 1.05-3.88). Despite apparent in vitro susceptibility, carbapenem therapy was consistently associated with unfavourable clinical outcomes in OXA-48-PE infections, supporting the prioritization of alternative active agents whenever available.
20 May 2026
Read appraisal →Human vaccines & immunotherapeutics
Coverage and determinants of childhood immunization in Somalia: A systematic review and meta-analysis
Childhood immunization is a cost-effective public health intervention, yet coverage remains suboptimal in Somalia. This systematic review and meta-analysis aimed to pool childhood immunization coverage and its determinants in Somalia. The electronic database search strategy yielded 11 eligible cross-sectional studies conducted between 2010 and 2025. Using Comprehensive Meta-Analysis Version 5 (Biostat, Englewood, NJ, USA), the pooled coverage for receiving at least one vaccine was 57.9%, while completion of the four basic vaccines was 16.1%, Full immunization coverage was 42.2%. Children born in health facilities were more likely to be immunized than home births (AOR = 2.10; 95% CI: 1.87-2.35). Unexpectedly, mothers with ≥4 ANC visits had lower odds of child immunization (AOR = 0.27; 95% CI: 0.24-0.30). Maternal education increased immunization likelihood (AOR = 1.14; 95% CI: 1.09-1.20). Children in rural areas were likely to be immunized than urban counterparts (AOR = 1.55; 95% CI: 1.49-1.61). These findings highlight the urgent need to strengthen integrated maternal and child health services.
19 May 2026
Read appraisal →Expert review of vaccines
Approaches to observational study designs and analytical options to evaluate the safety of multi-dose vaccines: a systematic review
INTRODUCTION: Observational studies require careful considerations when evaluating the safety of multidose vaccines. We reviewed design and analytical approaches in observational studies evaluating the safety of multidose vaccines in the post-licensure phase. METHODS: EMBASE, MEDLINE, Web of Science, and Scopus (2018-2022) were searched for hypothesis-testing studies evaluating the safety of multidose vaccines. Key features from frequently used designs were extracted. RESULTS: Among 123 eligible studies, cohort (46%) and self-controlled case series (SCCS)/self-controlled risk interval (SCRI) (40%) followed by case-control (12%) were the most common designs, and 15% of studies used multiple designs. Among cohort studies evaluating multiple doses, vaccination date (36%) and cohort entry with time-updated exposure status (32%) were frequent approaches used to define time zero. Twenty-eight percent of cohort studies did not report time zero; all but one evaluated COVID-19 vaccine effect on post-delivery and fertility-related outcomes. For SCCS/SCRI, 64% of studies accounted for event-dependent exposures, mainly by including pre-exposure periods (53%) and modified SCCS model (48%), while 20% employed multiple correction strategies. Among studies using multiple designs, 68% reached consistent conclusions. CONCLUSIONS: SCCS/SCRI and cohort designs dominate multidose vaccine safety studies. Clear reporting on time zero in pregnancy and fertility-related cohort studies, and on addressing event-dependent exposures in SCCS/SCRI studies is needed, along with guidance on interpreting results from multiple designs. Observational studies are important for assessing safety of vaccines especially for rare health outcomes that cannot be easily detected in randomized trials. Commonly used approaches include comparing these health outcomes between vaccinated and unvaccinated individuals or between different time points in relation to vaccination timing within individuals. However, both approaches have important design challenges. For example, comparison between vaccinated and unvaccinated individuals requires careful consideration of alignment of the time of starting to observe outcomes with the time when individuals become eligible and vaccination time for both comparison groups (time zero). Within-individual comparison requires that earlier occurrence of health outcomes does not influence whether someone receives later vaccine dose(s). These challenges become more complex to address when vaccines are given in multiple doses.In this review, we assessed how important design and analytical issues are handled and reported in published studies evaluating the safety of multidose vaccines and assessed agreement between different study designs when more than one is used.We found that 28% of studies comparing vaccinated and unvaccinated groups did not clearly report time alignment (time zero) mostly with studies on pregnancy and fertility outcomes. Similarly, about one-third of studies using within-individual comparison did not report checking and addressing the possibility that earlier outcomes could influence future vaccinations. When multiple designs were used, two-thirds of studies reached similar conclusions, although comparisons were mainly qualitative. Future work is needed to guide clear reporting of these issues to improve transparency in design and analysis and when comparing results across different designs.
19 May 2026
Read appraisal →Lupus science & medicine
Incidence of serious infections, herpes zoster and hepatitis B virus reactivation among patients with SLE: a cohort study using a health claims database in Japan
OBJECTIVES: To investigate the real-world incidence of serious infections (SI), herpes zoster (HZ) and hepatitis B virus (HBV) reactivation among patients with SLE. METHODS: This retrospective, non-interventional cohort study used an insurance claims database in Japan to calculate the incidence of SI requiring hospitalisation, HZ and HBV reactivation in patients with SLE from 1 April 2017 to 31 March 2021. As an exploratory analysis, HRs and 95% CIs were estimated for clinically relevant patient characteristics for SI and HZ, adjusting for age and sex. RESULTS: Among 10 865 patients with SLE (female: 83.1%, median age: 53.0 years), including those who had previously experienced each complication, the incidence rates (per 100 patient-years) for SI, HZ and HBV reactivation were 4.80 (95% CI 4.53 to 5.08), 0.52 (0.44 to 0.61) and 0.37 (0.30 to 0.45), respectively. For those who had no previous history of each complication, incidence rates were 3.67 (3.44 to 3.92), 0.48 (0.40 to 0.58) and 0.25 (0.20 to 0.32), respectively. Incidence rates in specific subgroups were as follows: history of each complication (SI: 37.93, HZ: 4.19, HBV reactivation: 72.01), history of SI (HZ: 1.51, HBV reactivation: 1.75) and glucocorticoid pulse therapy during follow-up (SI: 64.23, HZ: 3.10, HBV reactivation: 4.85). CONCLUSIONS: These results provide data on the occurrence of selected infections in SLE and may inform safety management.
18 May 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam compared with imipenem-cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial
BACKGROUND: Nacubactam (OP0595) is a newly developed diazabicyclooctane β-lactamase inhibitor used in combination with cefepime or aztreonam. We assessed the efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam versus imipenem-cilastatin in complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis. METHODS: The Integral-1 global, phase 3, multicentre, randomised, double-blind study recruited adults (aged ≥18 years) with cUTI or acute uncomplicated pyelonephritis at 79 sites in Bulgaria, China, Czech Republic, Estonia, Georgia, Japan, Latvia, Lithuania, and Slovakia. Patients were randomly assigned (2:1:1) to receive intravenous cefepime (2 g) plus nacubactam (1 g), aztreonam (2 g) plus nacubactam (1 g), or imipenem (1 g) plus cilastatin (1 g) every 8 h for 5-14 days. Randomisation was stratified by diagnosis and geographical region. The primary endpoint was the proportion of patients achieving composite clinical and microbiological success at test of cure in the microbiological modified intention-to-treat population-all patients who were randomly assigned, received any amount of the study drug, and had a baseline qualifying pathogen that was susceptible to imipenem and meropenem. The prespecified non-inferiority margin was more than 15 percentage points difference; the superiority margin was more than zero percentage points difference, for the lower bound of the two-sided 95% CI for imipenem-cilastatin. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT05887908. FINDINGS: Between May 22, 2023, and Nov 26, 2024, 614 patients were randomly assigned and 431 were included in the primary efficacy analysis (cefepime-nacubactam [n=214], aztreonam-nacubactam [n=112], or imipenem-cilastatin [n=105]); 228 patients (53%) were male and 203 (47%) were female. The primary endpoint was achieved by 176 (82%) of 214, 81 (72%) of 112, and 64 (61%) of 105 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. The percentage difference in the success rate versus imipenem-cilastatin was 21·3% (95% CI 10·9 to 32·0) for cefepime-nacubactam (non-inferior and superior), and 11·4% (-1·2 to 23·7) for aztreonam-nacubactam (non-inferior). Treatment-emergent adverse events were reported in 100 (33%) of 306, 45 (30%) of 152, and 65 (43%) of 150 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. No treatment-related deaths occurred. INTERPRETATION: Cefepime-nacubactam and aztreonam-nacubactam are potential treatment options for Gram-negative cUTI and acute uncomplicated pyelonephritis, including infections caused by antimicrobial-resistant strains. FUNDING: Meiji Seika Pharma and Japan Agency for Medical Research and Development.
18 May 2026
Read appraisal →The Journal of infectious diseases
Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial
BACKGROUND: Cerebral malaria (CM) is a common cause of febrile coma among African children. Despite treatment with highly efficacious intravenous artesunate, CM remains associated with high mortality and neurologic sequelae. In a mouse CM model, the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) demonstrated robust efficacy as a potential adjuvant therapy. Before testing DON in children with CM, we investigated tolerability in African adults, including individuals with malaria. METHODS: We conducted an open-label, prospective, dose-escalation, phase 1 clinical trial of single-dose intravenous DON in Blantyre, Malawi. Participants included healthy adults and adults with uncomplicated malaria, enrolled in dose-cohorts of 10 and administered DON at 0.1, 1.0, 5.0, or 10 mg/kg. We assessed adverse events (AEs) and plasma pharmacokinetics. RESULTS: Forty healthy adults and 38 adults with uncomplicated malaria received DON. Transient, asymptomatic creatinine elevation occurred 12 hours postinfusion in 18% of all participants. Nausea and vomiting were uncommon at 0.1 and 1.0 mg/kg but occurred more frequently at 5.0 and 10 mg/kg DON. All DON-related AEs resolved rapidly, without sequelae, and did not significantly differ between healthy and uncomplicated malaria participants. In healthy adults, maximum plasma concentrations increased proportional to dose, but adults with malaria had greater than dose-proportional increases. Terminal half-life ranged from 1.7 to 4.1 hours. CONCLUSIONS: DON was well tolerated in healthy adults and adults with uncomplicated malaria. Higher doses were associated with transient gastrointestinal AEs. Pharmacokinetics were minimally influenced by malaria disease. These results provide critical data to guide dosing strategies for adjunctive DON in children with CM. Clinical Trials Registration. NCT05478720.
18 May 2026
Read appraisal →Talanta
SERS technology helps bacterial inactivation in vivo: including detection, identification, and evaluation.
The problem of bacterial infection and antimicrobial resistance has become a major challenge threatening to human health. Detection, identification, and real-time evaluation of bacteria during the sterilization process are of great significance for interpreting the sterilization mechanism and ensuring the effectiveness of sterilization. With the advantages of high sensitivity, fast detection speed, and real-time monitoring, Surface-enhanced Raman Scattering (SERS) technology provides a revolutionary solution to in vivo bacterial detection, identification, and antibacterial effect evaluation through functional substrate optimization, microfluidic chip integration, and deep collaboration of machine learning algorithms. This review focuses on the prominent applications of SERS technology in chemical, biological, and physical sterilization processes. By analyzing the changes in bacterial SERS fingerprint patterns, precise detection and identification of sensitive/resistant bacteria have been achieved, deepening the interpretation of drug resistance mechanisms at the gene, cell, and biofilm levels. Meanwhile, SERS technology provides an ideal tool for monitoring and evaluating the biological sterilization process. In the process of physical sterilization, enhancing the substrate material not only helps to improve SERS signals, but also promotes bacterial inactivation. By monitoring real-time changes in bacterial metabolism, the sterilization process can be precisely regulated. This review summarizes the innovative application of SERS technology in accurately guiding the sterilization process in vivo, providing important support for optimizing antibacterial treatment strategies.
18 May 2026
Read appraisal →European journal of pediatrics
Prevalence of common respiratory viruses of infants with respiratory tract infections in European countries in the past decade: a systematic review and meta-analysis comparing between the pre-COVID-19, pandemic, and post-COVID-19 periods
UNLABELLED: The purpose of this study is. to determine the leading cause of respiratory tract infections over the decade; this review examined the proportions of airway viruses in infants with respiratory tract infections in Europe before, during, and after the COVID-19 pandemic. The protocol for this systematic review was registered in the PROSPERO database (CRD42024497097). Literature searches in PubMed, Embase, Scopus, and Web of Science (WoS) identified 20,453 studies reporting respiratory viral testing in Europe over the past decade (2012/13-2022/23). Eligible studies were English-language full-text or grey articles with low risk of bias and complete data, and reports that explicitly provided the number of positive airway virus cases (n, virus) and the total infant population (N). Risk of bias was assessed using the Hoy et al. scoring system. Pooled prevalence estimates (pooled proportion [95% CI]) were calculated for pre-, during-, and post-COVID-19 periods using proportional meta-analysis with the MetaProp package in R. Fifty studies before, ten studies during, and 18 studies after the COVID-19 pandemic were eligible for proportional meta-analyses of viral testing in infants. Before the pandemic, the predominant viruses in infants with respiratory infections were Respiratory Syncytial Virus (RSV) (0.48 [0.41-0.56]), Human rhinovirus (HRV) (0.24 [0.18-0.29]), and Influenza virus (IV) (0.08 [0.04-0.12]). Post-pandemic, the leading viruses were RSV (0.63 [0.51-0.75]), HRV (0.25 [0.11-0.40]), and IV (0.10 [0.00-0.20]) again. CONCLUSIONS: RSV and HRV remained the two most identified viruses in infants with respiratory infections, pre- and post-COVID-19 pandemic. Interestingly, both RSV and IV were suppressed during the pandemic. The trajectory dynamics of respiratory viruses were divergent, with resilient viruses (RSV, HRV, and IV) regaining dominance more rapidly than persistently suppressed viruses. WHAT IS KNOWN: • The COVID-19 pandemic induced an infection precautions policy, which reduced the spread of respiratory infectious diseases. • Respiratory Syncytial Virus (RSV) was estimated as one of the most common causes of respiratory infections in infants. Still, there are no reports summarising the geographical distributions of the various viral agents of infant respiratory diseases. WHAT IS NEW: • This meta-analysis shows that the prevalence of RSV and HRV infections in infants remains high in Europe following the COVID-19 pandemic and the associated precautionary policy. Furthermore, RSV proportionally experienced a marked reduction during COVID-19 pandemic (lockdown periods). However, the immunological debt may have led to a re-emergence in RSV positivity after the lockdown periods. • Our proportional meta-analysis indicates the heterogeneous post-pandemic recovery patterns of each respiratory virus commonly identified in infants, where HRV was shown to be resilient whilst RSV was rapidly rebound.
18 May 2026
Read appraisal →International journal of food microbiology
Machine learning-based modeling for monitoring and predicting the detection rate and severity of pathogenic microorganisms in seafood
Pathogenic microbial contamination in seafood presents persistent risks to food safety and public health. Conventional monitoring methods frequently lack adequate sensitivity and specificity, particularly under dynamic environmental conditions. To address these limitations, this study developed a machine learning (ML) framework utilizing microbial testing data from seafood samples collected in Yantai, China (2014-2024), with 2025 data reserved for external validation. The framework simultaneously predicts pathogen prevalence and severity levels. And, exploratory data analysis assessed variable distributions and statistical associations with detection rates. Time series analysis identified significant long-term trends and seasonal patterns, while spatial analysis revealed heterogeneity in contamination risk across administrative regions, particularly in coastal economic zones and major ports. Applying a dynamic threshold optimization strategy, detection rates were predicted using six ML algorithms: ROSE-LASSO, LightGBM, XGBoost, k-NN, CART, and SVM. LightGBM demonstrated optimal performance with 97.6% specificity and 99.9% positive predictive value (PPV) at an optimized threshold of 0.157. External validation confirmed its robustness, yielding 91.2% sensitivity, a 92.4% F1 score, and 93.6% PPV. For three-class severity classification, XGBoost achieved 93.7% overall accuracy and high sensitivity (80.0%) for high-risk samples, with an AUC of 0.989. By integrating spatiotemporal environmental features with adaptive thresholding, this framework provides a scalable approach for pathogen risk identification within coastal seafood supply chains, supporting early warning systems and evidence-based resource allocation.
17 May 2026
Read appraisal →Computer methods and programs in biomedicine
Prompt-to-policy: Leveraging large language models to guide deep reinforcement learning in public health emergencies
Rapid and effective decision-making is critical in public health emergencies, where resource allocation must balance multiple objectives under uncertain conditions. Traditional optimization methods often struggle with computational complexity and real-time, heterogeneous data. To address these challenges, we propose a hybrid intelligent agent combining an enhanced Double Deep Q-Network (D2QN-JDA) with large language models (LLMs). The D2QN-JDA improves learning stability and adaptability through joint state-action inputs, dynamic exploration rate, and adaptive reward normalization. The LLM component uses Retrieval-Augmented Generation (RAG) to integrate structured and unstructured data for real-time decision support. Experiments based on data from the Hong Kong COVID-19 outbreak show that the D2QN-JDA outperforms dynamic programming, greedy algorithms, genetic algorithms, and Q-learning, achieving reductions in cost. The LLM component also outperforms manual and regex methods in both single- and multi-point data extraction, enhancing accuracy, recall, F1 score, cost, and time. Our framework effectively addresses complex, multi-objective resource allocation in public health crises.
17 May 2026
Read appraisal →African journal of reproductive health
Evaluation of the effects of probiotic supplementation on the ecology and inflammatory factors of female vaginal flora: a systematic review and meta-analysis
This meta-analysis systematically evaluated the effects of probiotic supplementation on vaginal microbiota and inflammatory factors in women. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to January 2026 for randomized and controlled studies. Outcomes included vaginal pH, Nugent score, and inflammatory cytokines (IL-4, IL-6, IL-10, TNF-α). Fifteen studies were included. Compared with controls, probiotics did not significantly reduce IL-4, IL-6, IL-10, or TNFα levels, nor did they significantly improve Nugent score. However, probiotic supplementation significantly reduced vaginal pH (OR = 0.36, 95% CI: 0.15-0.89; P = 0.03), indicating improved maintenance of a weakly acidic vaginal environment. Sensitivity analyses showed generally stable results, although heterogeneity remained substantial for several outcomes. Overall, probiotics appear effective in modulating vaginal acid-base balance but show limited evidence for improving inflammatory cytokine profiles or restoring vaginal microbiota structure. Current data are insufficient to support routine probiotic use for optimizing vaginal microbiota and inflammatory status. Further high-quality, well-designed randomized controlled trials are required to clarify their clinical benefits. Cette méta-analyse a évalué de manière systématique les effets de la supplémentation en probiotiques sur le microbiote vaginal et les facteurs inflammatoires chez les femmes. Les bases de données PubMed, Embase, Web of Science, CNKI et Wanfang ont été consultées depuis leur création jusqu’en janvier 2026 afin d’identifier des études randomisées et contrôlées. Les critères de jugement comprenaient le pH vaginal, le score de Nugent et les cytokines inflammatoires (IL-4, IL-6, IL-10, TNF-α). Quinze études ont été incluses. Comparativement aux groupes témoins, les probiotiques n’ont pas réduit significativement les concentrations d’IL4, IL-6, IL-10 ou TNF-α, ni amélioré significativement le score de Nugent. En revanche, la supplémentation en probiotiques a significativement réduit le pH vaginal (OR = 0,36 ; IC à 95 % : 0,15–0,89 ; P = 0,03), indiquant un meilleur maintien d’un environnement vaginal faiblement acide. Les analyses de sensibilité ont montré des résultats globalement stables, bien qu’une hétérogénéité substantielle persiste pour plusieurs critères. Dans l’ensemble, les probiotiques semblent efficaces pour moduler l’équilibre acido-basique vaginal, mais les preuves restent limitées quant à leur capacité à améliorer les profils cytokiniques inflammatoires ou à restaurer la structure du microbiote vaginal. Les données actuelles sont insuffisantes pour recommander l’utilisation systématique des probiotiques dans l’optimisation du microbiote vaginal et du statut inflammatoire. Des essais contrôlés randomisés de haute qualité sont nécessaires pour confirmer leurs bénéfices cliniques.
16 May 2026
Read appraisal →The Journal of infectious diseases
Cytomegalovirus DNAemia in Hospitalized Adults With SARS-CoV-2 Infection Requiring Supplemental Oxygen: Virologic and Clinical Characteristics and Association With Outcomes
BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined. METHODS: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models. RESULTS: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death. CONCLUSIONS: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.
16 May 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
A meta-analysis of gut microbiome research in malnourished African populations: a natural language processing approach
Malnutrition still affects millions of children in Africa. Changes in the gut microbiome have been implicated in malnutrition, but there has been inconsistent nomenclature of microbes. This meta-analysis reviews the microbiome literature using natural language processing (NLP) methods. We searched PubMed for gut microbiome studies of undernourished children living in low- and middle-income countries (LMICs). The primary analysis focused on continental coverage and study characteristics of microbiome research in sub-Saharan Africa (ss-Africa). We also used an NLP tool for normalizing primary data from full-text publications in ss-Africa compared with other LMICs, and between diseased and healthy children. We identified 16 studies. Most studies were conducted in Malawi and characterized the faecal microbiome using 16S rRNA sequencing. For comparison, 18 studies conducted in Bangladesh, India, Pakistan and Peru were included. With this, we identified frequently reported microbes that were distinctly identified in ss-Africa and highlighted possible signatures of an undernourished faecal microbiome across the globe. The consistent associations between elevated Pseudomonadota levels and severe acute malnutrition provide new insights into host-microbiome interactions in African contexts. However, the overlap between taxa associated with healthy and stunting underscores the need for further research to better inform potential targeted interventions in Africa. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.
15 May 2026
Read appraisal →BMJ global health
Integrated mass drug administration for yaws eradication: evidence from a comparative observational study in Papua New Guinea and a systematic review with network meta-analysis
BACKGROUND: Yaws is a chronic infectious disease that disproportionately affects under-reached communities. In 2023, Papua New Guinea (PNG) reported 100 165 suspected yaws cases, accounting for 45% of cases reported worldwide. The WHO targets yaws eradication by 2030, primarily through mass drug administration (MDA) of azithromycin. This study evaluates the impact of an integrated MDA programme in PNG and reviews global evidence on optimal MDA strategies through a network meta-analysis (NMA). METHODS: A comparative observational study was undertaken analysing outpatient department (OPD) attendances between West New Britain province (WNB; intervention) and New Ireland province (NIP; comparator) from November 2023 to August 2024. The intervention in WNB involved a single-round, integrated four-drug MDA provided in December 2023, comprising azithromycin, ivermectin, diethylcarbamazine and albendazole. Temporal trends in OPD attendances were analysed using negative binomial regression. A Bayesian NMA of six studies identified through a systematic review compared the effectiveness of azithromycin-based regimens for yaws eradication. RESULTS: Between Q3 2023 and Q1 2024, yaws-related OPD attendances in WNB declined significantly, with a 41% (p<0.0001) reduction relative to the comparator province (NIP). This reduction was sustained for at least 6 months following MDA. Over the same period, a 33% decline in total skin-related outpatient attendances was observed. In the NMA, three rounds of azithromycin MDA were associated with lower odds of active yaws at follow-up than observation (OR 0.04, 95% CrI 0.005 to 0.24) and had the highest probability of being ranked most effective. Single-round azithromycin MDA was also associated with reduced odds of active yaws at follow-up (OR 0.15, 95% CrI 0.05 to 0.45). CONCLUSION: In a high-burden setting, a single round of integrated MDA was associated with substantial early reductions in yaws burden. Multi-round azithromycin strategies, particularly three-round regimens, were associated with larger and more sustained reductions in community prevalence. These findings inform considerations for yaws control efforts in settings with persistent transmission.
15 May 2026
Read appraisal →The New England journal of medicine
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
BACKGROUND: Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19. METHODS: In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2-negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory-confirmed positive reverse-transcriptase-polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory-confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo). RESULTS: The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19-related hospitalizations or deaths were reported. CONCLUSIONS: Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.).
15 May 2026
Read appraisal →JMIR medical informatics
Development Process of a Clinical Decision Support System for Empiric Antibiotic Therapies in Patients With Sepsis: Case Study
BACKGROUND: Antibiotic therapies are the main treatment for bacterial infections, but growing antibiotic resistance is a major global health threat, severely impacting patients with sepsis. Rapid selection of the most effective antibiotic therapy is critical for survival and for preventing further resistance. Physicians must consider numerous factors for proper empiric treatment selection. A clinical decision support system (CDSS) aims to support physicians in this process, facilitating rapid and targeted therapy. OBJECTIVE: The purpose of this work is to explore the extent to which the realization of a CDSS is possible based on the data available to us and to document insights gained during the development of a foundational model designed to assist physicians in determining empiric treatment options for patients with sepsis. In this regard, rather than aiming to develop a CDSS for clinical application, we highlight the importance of close interprofessional collaboration between scientists from various disciplines and analyze the effects of data quality and quantity on the performance of our statistical models. METHODS: Empirical scientists conducted interviews with medical practitioners to acquire the medical knowledge required to develop sound statistical models. We developed and applied 2-step cross-sectional, as well as time-series classification models, to carefully preprocessed data of patients with sepsis admitted to the intensive care unit of a German hospital. RESULTS: We identified several factors as crucial information for valid decisions on empiric therapy for treating patients with sepsis. These include the patients' core data, especially the infection focus. To prevent further resistance, individual risk factors such as travel history and professional background should be considered. The evaluation of a therapy's effectiveness is mainly based on the patient's general condition and blood values such as procalcitonin and interleukin 6. One key factor in the acceptance of a CDSS is the explainability of the results produced by the applied methods. Our models demonstrated mainly weak predictive ability for all considered empiric antibiotic therapies. However, they are not yet suitable for use in clinical practice, especially as they are based on prescribing habits rather than on optimal treatment decisions. CONCLUSIONS: This work highlights the importance of interprofessional collaboration between medical experts and model developers, ensuring that data quality and clinical relevance are central to the process. It emphasizes the urgent need for high-quality, comprehensive data to overcome challenges such as data discontinuity and improve model performance, particularly through enhanced digitization in health care. This feasibility study will facilitate future efforts to develop a CDSS for treating patients with sepsis and to translate it into clinical use.
15 May 2026
Read appraisal →Journal of clinical microbiology
Diagnostic performance of β-(1→3)-D-glucan, two Candida antigen, and five anti-Candida antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial
Invasive Candida infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-Candida-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-Candida [Serion-Mn]), and anti-Candida antibodies (Platelia-Candida-Ab-Plus, Serion-ELISA-Candida albicans-IgA/IgM/IgG, and Virclia-Candida albicans-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by Candida colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff >280 pg/mL), 46% (31.4-60.8) and 64% (35.1-87.2); Platelia-Mn (cutoff >50 pg/mL), 38% (24.0-52.6) and 64% (35.1-87.2); Serion-Mn (cutoff >0.7 U/mL), 38% (24.0-52.6) and 50% (23.0-77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-Candida antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.IMPORTANCEOur main findings based on our specific ICU cohort were as follows: (i) only Candida antigen levels, not anti-Candida antibody levels, were significantly elevated in ICI and candidemia. (ii) In patients without ICI, Candida colonization was not associated with altered antigen levels, but with elevated antibody levels. (iii) Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory, and cutoffs should be significantly adjusted. Potential optimal cutoff values are proposed by us. (iv) The evaluated antigen assays demonstrated overall comparable diagnostic performance in this study. (v) Anti-Candida antibody assays did not provide a meaningful diagnostic contribution. (vi) The combination of biomarkers offered no diagnostic advantage over the use of individual biomarkers, neither simultaneously nor sequentially. Our results suggest that the use of a single Candida antigen test with a cohort-adapted cutoff value may be sufficient. Furthermore, avoiding biomarker combinations could potentially reduce healthcare costs. The clinical implications of these findings should be interpreted with caution, given the limited data with associated large confidence intervals for candidemia and the cohort-specific nature of the study. Our results should therefore be confirmed in larger studies and additionally with other patient groups.
15 May 2026
Read appraisal →Journal of clinical microbiology
Prediction of KPC-producing Klebsiella pneumoniae by MALDI-TOF MS, ensemble learning, and spectral peak annotation
The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae represents a serious global health challenge. Rapid and accurate detection methods are essential to inform early and correct use of antimicrobial therapy to idealize patient outcomes and limit the spread of resistant isolates. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been evaluated for resistance detection, but its clinical application remains limited. In this study, MALDI-TOF MS was integrated with machine learning (ML) to improve detection of Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae isolates harboring KPC carbapenemase. Ensemble learning strategies were applied to 435 clinical isolates from different geographic locations (Spain, United States, South America, and Asia), with validation performed using external data sets. By constructing two peak matrices and applying four ML algorithms, as well as combinations of two and three in ensemble models, 92 different classifiers were tested. Ensemble combinations increased the specificity of classifiers to over 95%, while sensitivity reached 72%, being significantly higher than that of the MALDI Biotyper KPC module. Low sensitivity may be affected by technical variability during spectral acquisition. The first annotated MALDI-TOF MS spectrum for K. pneumoniae by in silico prediction of protein masses was developed to enable peak identification, including peaks potentially related to antimicrobial resistance. Overall, the results of this study show that combining MALDI-TOF MS with ensemble learning can enhance KPC detection performance.IMPORTANCERapid and accurate detection of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae informs early and correct use of antimicrobial therapy to idealize patient outcomes and limit the spread of antimicrobial resistance. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ensemble machine learning were employed to detect KPC-producing isolates, using diverse isolate collections, obtaining excellent specificity. An annotated K. pneumoniae MALDI-TOF MS profile is provided with peak annotation, providing a resource for peak analysis.
14 May 2026
Read appraisal →JAMA
Intrawound Tobramycin Plus Vancomycin to Prevent Surgical Site Infection in Tibial Fractures: The TOBRA Randomized Clinical Trial
IMPORTANCE: Previous research has suggested that intrawound vancomycin powder reduces deep surgical site infections among patients with periarticular tibial fractures at high risk of infection. It is unknown whether the addition of tobramycin powder further decreases infection rates. OBJECTIVE: To compare whether the combination of tobramycin plus vancomycin vs vancomycin alone delivered as intrawound powder at the time of definitive fixation reduces deep surgical site infections. DESIGN, SETTING, AND PARTICIPANTS: Open-label, assessor-masked, randomized clinical trial conducted at 39 US trauma centers. Eligible patients were adults with an operatively treated periarticular tibial fracture (either tibial plateau or pilon) who met 1 of 3 criteria for elevated infection risk. Enrollment occurred between June 18, 2021, and December 12, 2024 (final follow-up, July 15, 2025). INTERVENTIONS: Intrawound tobramycin (1.2 g) plus vancomycin (1.0 g) powder vs intrawound vancomycin (1.0 g) powder delivered at the time of definitive fixation. MAIN OUTCOMES AND MEASURES: The primary outcome was a deep surgical site infection requiring surgical management within 182 days of definitive fracture fixation. Secondary outcomes included deep surgical site infections with pathogens that were gram-negative only, deep surgical site infections with at least 1 pathogen that was gram-positive, deep surgical site infections with polymicrobial cultures, deep surgical site infections with negative culture results, and cellulitis or skin infections treated only with antibiotics. RESULTS: Among the 1660 participants randomized, 1528 (mean age, 47.0 [SD, 14.3] years; 603 female [39.5%]; 925 male [60.5%]) were included in the primary analysis. Deep surgical site infections occurred in 51 of 753 participants (182-day probability, 7.4%) in the tobramycin plus vancomycin group and 47 of 775 participants (182-day probability, 6.6%) in the vancomycin alone group (hazard ratio, 1.11; 95% bayesian credible interval, 0.75-1.66; posterior probability of superiority, 29.7%). The threshold required for superiority was not reached for any secondary outcome. CONCLUSIONS AND RELEVANCE: Among patients with operatively treated periarticular tibial fractures at high risk of infection, adding intrawound tobramycin powder to vancomycin powder at the time of definitive fixation did not reduce deep surgical site infections compared with vancomycin powder alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02227446.
14 May 2026
Read appraisal →European journal of heart failure
Effect of influenza vaccination in patients with decompensated heart failure: a systematic review and meta-analysis
AIMS: In patients with heart failure (HF) influenza vaccination has shown beneficial effects in preventing cardiac decompensations. However, no conclusive results have been achieved in the few studies that have evaluated the impact of vaccination during episodes of acute HF (AHF) decompensation. We conducted a systematic review and meta-analysis to determine the possible effects of influenza vaccination on all-cause mortality in patients diagnosed with AHF. METHODS: PubMed, Medline, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews databases were searched for longitudinal studies comparing patients with AHF vaccinated against influenza with unvaccinated patients. The primary outcome selected for meta-analysis was 1-year all-cause mortality, and secondary outcomes consisted of other outcomes reported in at least in two different studies. Statistical heterogeneity was determined by calculating the I² statistic. Individual adjusted results were pooled using a random effects model. Sensitivity analysis was run for the primary outcome by removing each individual study and then re-doing the meta-analysis. RESULTS: Up to 30 June 2025, five observational cohort studies examining the effect of influenza vaccination on 1-year all-cause mortality in AHF patients had been published. Statistical heterogeneity was low (I2 = 33.7%), meaning that between-study results were consistent. Pooled analysis of confounder-adjusted hazard ratio (HR) for all-cause mortality in vaccinated patients was 0.89 (95% CI 0.83-0.96) compared with unvaccinated patients. All sensitivity analyses rendered very similar results. In-hospital and 90-day mortality were reported in three and two studies and showed similar reductions in risk, with an adjusted odds ratio of 0.85, 95% CI 0.70-1.01, and adjusted HR of 0.86, 95% CI 0.76-0.96; respectively. Isolated data from single studies suggest no effect on hospitalization following discharge after the AHF episode. CONCLUSIONS: Influenza vaccination is associated with a lower short- and long-term all-cause mortality in patients with decompensated HF; however, as all the studies included in this meta-analysis were observational, these results could be subject to residual confounding and causality cannot be directly inferred from them.
14 May 2026
Read appraisal →Scientific reports
Federated learning with swarm intelligence for efficient and secure medical image analysis
Collaborative learning in healthcare faces challenges, including strict regulations and fragmented data. This research introduces a federated learning framework that employs swarm intelligence to augment communication and enhance the analysis of medical images. The method optimizes hyperparameters, selects features, and assigns aggregation weights to federated clients simultaneously by combining Particle Swarm Optimization (PSO) and the Firefly Algorithm (FA) with deep Convolutional Neural Networks (CNNs). The framework was tested on three medical datasets: COVID-19 chest X-rays (5,856 images), monkeypox skin images (569 images), and breast cancer mammograms (320 images). These datasets were shared among four fake healthcare institutions. It strives to strike a balance between privacy, communication costs, and classification accuracy. The results showed that the test was 96.71% accurate in detecting COVID-19, 96.06% accurate in classifying monkeypox, and 97.0% accurate in diagnosing breast cancer. The framework was able to handle noise and attacks from individuals who sought to disrupt it, which reduced communication rounds by 25-30%. A privacy-utility analysis revealed that there were acceptable trade-offs, with accuracy remaining above 94%. This study employs robust privacy measures and statistical validation. It also shows how to use medical AI in smaller healthcare settings without putting patients' privacy at risk.
14 May 2026
Read appraisal →Blood advances
Early mortality with bispecific antibody therapy in RRMM: an IMWG immunotherapy database real-world analysis
Recent therapeutic advances, including bispecific antibodies (bsAbs), have improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM). However, early mortality (EM) remains a significant challenge, even in the era of novel immunotherapies. We conducted a multicenter, retrospective analysis of real-world patients with RRMM treated with commercial bsAbs to evaluate the incidence and causes of EM. Between May 2022 and June 2025, a total of 441 patients were treated across 7 countries. EM, defined as death within 12 months of therapy initiation, occurred in 148 patients (34%), with a median time from bsAb initiation to death of 2.87 months (interquartile range, 1.38-6.85). The leading cause of EM was progressive disease (72%), followed by infection (13%); regardless of the cause of death, 82% had active disease at the time of death. Our findings highlight that despite encouraging efficacy, EM remains high among real-world bsAb recipients, emphasizing the need for improved disease control strategies and supportive care interventions.
13 May 2026
Read appraisal →Journal of computer-aided molecular design
Ensemble learning-guided discovery of anti-tuberculosis phytochemicals: computational prediction and mechanistic insights
Tuberculosis (TB) remains a major global health challenge driven by persistent Mycobacterium tuberculosis infection and increasing drug resistance. Phytochemicals represent a structurally diverse and underexplored chemical space for anti-TB drug discovery, yet systematic prioritization strategies integrating machine learning and structure-based validation are limited. A curated phenotypic anti-TB dataset of 425,180 compounds was used to train ensemble ExtraTrees models based on ECFP4 fingerprints and physicochemical descriptors. The models achieved strong predictive performance (ROC-AUC up to 0.983; MCC up to 0.871). SHAP analysis enabled mechanistic interpretation by identifying the key molecular descriptors and fingerprint features driving anti-TB activity predictions. The validated ensemble was applied to screen 4707 phytochemicals, yielding 3209 predicted actives, of which 778 satisfied applicability domain criteria. High-confidence candidates were subsequently evaluated by molecular docking against twelve structurally validated essential M. tuberculosis targets spanning cell wall biosynthesis, energy metabolism, nucleotide synthesis, and cofactor pathways. Docking analysis identified 486 phytochemicals with favorable predicted binding affinities, including 193 compounds exhibiting multi-target engagement. Several top-ranked candidates reproduced canonical interaction patterns of co-crystallized inhibitors, supporting mechanistic plausibility. This integrated chemoinformatics and structure-based framework enables robust prioritization of phytochemicals with biologically meaningful and multi-target antitubercular potential. The study provides a computationally grounded strategy for accelerating lead identification against drug-resistant TB.
13 May 2026
Read appraisal →Annals of medicine
Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis
BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.
13 May 2026
Read appraisal →Pediatric surgery international
Selective non-operative management of post-appendectomy abscesses in children: a comprehensive systematic review and pairwise meta-analysis
Post-appendectomy intra-abdominal abscess remains a common complication following pediatric appendicitis. Although drainage has traditionally been considered standard treatment, increasing evidence suggests selected patients may be successfully managed with antibiotics alone. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251075191). PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 20, 2025. Eligible studies included pediatric patients (0-18 years) with post-appendectomy abscess managed with antibiotic vs. invasive drainage. The primary outcome was failure of first-line treatment requiring escalation. Secondary outcomes included recurrence and length of hospital stay. Ten observational studies involving 363 pediatric patients were included (152 drainage, 211 conservative). Treatment success was 80.9% with drainage and 89.1% with antibiotics. Pooled analysis demonstrated no statistically significant difference in treatment success (RR 1.00; 95% CI 0.95-1.05) or recurrence (RR 0.99; 95% CI 0.57-1.74). Drainage was associated with longer hospital stays (MD 3.40 days; 95% CI 0.65-6.14; p = 0.02). Subgroup analyses demonstrated consistent findings. All included studies demonstrated a serious risk of bias due to confounding by indication. An antibiotics-first approach appears viable for clinically stable pediatric patients, achieving comparable outcomes with shorter hospitalization.
13 May 2026
Read appraisal →Lancet (London, England)
Impact of introducing RTS,S/AS01E malaria vaccine on mortality in young children in Ghana, Kenya, and Malawi: an observational evaluation of a cluster-randomised implementation programme
BACKGROUND: Malaria vaccines have been added to immunisation schedules in 25 sub-Saharan African countries, with the expectation that deaths in young children would be prevented. The introduction of the RTS,S/AS01E malaria vaccine (RTS,S) in Ghana, Kenya, and Malawi in 2019 was evaluated over 4 years to show the impact on mortality in young children and to monitor severe malaria admissions, vaccine uptake, and safety. Favourable evidence on safety and impact on severe malaria admissions during the first 2 years contributed to WHO's recommendations on malaria vaccines. Here, we report the primary analysis of the impact on mortality at 46 months. METHODS: Clusters of administrative units (districts in Ghana, subcounties in Kenya, and groups of immunisation clinics in Malawi), each with an estimated annual birth cohort of about 4000 children, were randomly assigned 1:1 to introduce the RTS,S malaria vaccine in 2019 (implementation areas), or to implement later (comparison areas). RTS,S was delivered in a four-dose schedule, at age 6, 7, 9, and 24 months in Ghana and Kenya, and at age 5, 6, 7, and 22 months in Malawi. Surveillance for post-neonatal mortality in children younger than 5 years was established throughout by a network of 26 000 local reporters who notified deaths in their community. The families were then visited at home by study staff to confirm details and complete a verbal autopsy. Surveillance for severe malaria and other conditions was strengthened in 18 sentinel hospitals serving part of the study area and maintained for 46 months. Uptake of RTS,S and other vaccines was monitored by the Expanded Programme on Immunisation in each country and independently through three household coverage surveys, at baseline, and at about 18 months and 30 months after introduction of RTS,S. The primary outcome of this impact evaluation was mortality due to any cause, except injury, in children eligible to receive three doses of RTS,S. Mortality rate ratios were estimated by comparing the ratio of deaths among vaccine-eligible age groups to deaths in non-eligible age groups between implementation and comparison areas. This evaluation is registered on ClinicalTrials.gov (NCT03806465) and is complete. FINDINGS: 158 clusters (66 in Ghana, 46 in Kenya, and 46 in Malawi) were selected and randomly assigned; 79 areas served as implementation areas and 79 as comparison areas. By the end of the 46-month evaluation period, 1 289 504 children had received the first dose of RTS,S, 1 158 850 had received the second dose, 1 068 039 had received a third dose, and 436 527 had received a fourth dose. Coverage assessed in 2022 was 82·8% (95% CI 80·7-84·9) for the first dose, 71·1% (68·8-73·5) for the third dose, and 39·9% (36·9-42·9) for the fourth dose. Excluding deaths due to injury, there were 5576 deaths in implementation areas versus 6152 in comparison areas in children eligible to have received the third dose of RTS,S, and 7534 versus 7044 deaths among non-eligible children. The mortality rate ratio was 0·87 (95% CI 0·77-0·97; p=0·016). INTERPRETATION: Introduction of the RTS,S malaria vaccine in routine immunisation programmes was associated with a significant reduction in mortality in young children, averting about one in eight deaths, in areas with moderate coverage of three doses of the vaccine and low uptake of the fourth dose. These results highlight the urgency to accelerate the deployment of malaria vaccines in areas of Africa where malaria continues to be a leading cause of child mortality. FUNDING: WHO; Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid. TRANSLATIONS: For the French translation of the abstract see Supplementary Materials section.
13 May 2026
Read appraisal →Journal of chemical information and modeling
HLABrew for Human Leukocyte Antigen Class I-Presented Epitope Recognition and Mimotope Discovery
Accurate identification of human leukocyte antigen (HLA) class I-presented epitopes is essential for developing personalized vaccines and immunotherapies. Here, we present HLABrew, a unified deep learning framework for HLA class I epitope prediction and allele-specific mimotope design. By integrating the Transformer, variational autoencoder, and dual cross-attention, HLABrew achieves state-of-the-art performance with hierarchical and allele-aware representations. HLABrew accurately deconvolves multiallelic immunopeptidomics data to recover allele-specific binding motifs and expand epitope coverage. Leveraging its generative capacity, HLABrew further designs mimotopes guided by learned peptide-HLA binding preferences, with the potential to enhance antigen presentation and provide candidates for downstream immunogenicity evaluation.
13 May 2026
Read appraisal →Expert review of vaccines
Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies
BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.
13 May 2026
Read appraisal →Vaccine
The immune response of the mRNA vaccine CS-2034 as a heterologous booster before and after breakthrough infection: A follow-up study.
BACKGROUND: The emergence of highly mutated SARS-CoV-2 variants challenges vaccine protection. Evaluating long-term immune protection from boosters is crucial. The experiment compares neutralizing antibody dynamics and ACE2-RBD binding inhibition induced by mRNA and inactivated vaccine boosters, and assesses the impact of breakthrough infections and age on immune responses. METHODS: This study is based on a previous randomized, double-blind, parallel controlled trial. Healthy participants aged ≥18 who had received ≥3 inactivated COVID-19 vaccine doses. Volunteers (32 aged 18-59 and 32 ≥ 60) were stratified by age and vaccine type (24 mRNA, 8 inactivated in each age group). Pregnant women, those with severe chronic diseases or a history of allergies are excluded. Neutralizing antibodies were measured via microneutralization assay, and ACE2-RBD binding inhibition by high-sensitivity electrochemiluminescence. The study assessed changes in antibody levels and ACE2-RBD binding inhibition pre- and post-infection across age groups to evaluate vaccine efficacy and durability. (Registed number: ChiCTR2200064575). RESULTS: The neutralizing antibody titers from mRNA vaccine showing stronger and more consistent responses against the original strain and variants like XBB and BA.5. After breakthrough infections, mRNA-vaccinated individuals show a significant and lasting boost in antibodies, while the increase in inactivated vaccine recipients is modest. By age, mRNA-vaccinated people over 60 experience a faster antibody decline post-vaccination, whereas the inactivated vaccine group sees an initial rise at three months before declining. For ACE2-RBD binding inhibition, mRNA vaccines maintain higher early-phase rates, while inactivated vaccines show a delayed rise at three months followed by decline. CONCLUSIONS: mRNA vaccines induce stronger neutralizing antibodies and broader immunity than inactivated vaccines. Breakthrough infections boost antibody levels more in mRNA recipients than in inactivated vaccine recipients. Antibody decline is faster with mRNA vaccines in people over 60, while inactivated vaccines show a modest but weaker antibody increase against variants in the elderly.
13 May 2026
Read appraisal →Journal of medical systems
Feasibility, Adherence, Acceptance and Usability of a Multimodal Telemonitoring for Pediatric Post-COVID Syndrome: A Bicentric Pilot Study
Existing healthcare infrastructure struggles to meet the complex care required for pediatric Post-COVID Syndrome (pPCS). Telemonitoring offers potential to enhance care access, reduce patient burden, and ensure continuity. This study introduces and evaluates a novel, multimodal telemonitoring concept for pPCS with high translational potential for broader pediatric chronic and post-infectious conditions. Telemonitoring included a patient app, digital sensors (spirometer, smartwatch), Patient Reported Outcome Measures, chat/video consultations (VC), and a medical telemonitoring platform. Patients aged 12-17 years with diagnosed PCS were recruited from two pPCS outpatient university clinics in Bielefeld and Munich, Germany. Monitoring lasted three months. Evaluation focused on feasibility, adherence, acceptance, and usability, using monitoring data, the System Usability Scale (SUS), Technology Usage Inventory (TUI), and a custom survey completed by patients and parents. 30 patients (mean age: 15y ± 1.9; 57% female (17/30); mean Baseline Bell-Score: 36.4) and 30 parents participated. Adherence was high, with an average of 3.4 (smartwatch) to 4.6 (spirometry) measurements/week. Questionnaire response rate was 86% (411/480) and 97% (58/60) of VCs were conducted. SUS scores indicated very high usability (patients: 81.25/100; parents: 75.42/100). TUI results showed low skepticism, and high interest. Telemonitoring supported symptom management independent of in-person visits, despite sensor connectivity issues. This is the first study to demonstrate successful integration of telemonitoring in pPCS, with high adherence and positive feedback from all stakeholders supporting its potential. Despite occasional technical challenges and resource needs, this concept shows promise for broader hybrid telemonitoring care implementation in PCS and other post-infectious syndromes. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), trial registration number: DRKS00029354. Registered 07 February 2023 - Retrospectively registered https://drks.de/search/en/trial/DRKS00029354/entails.
13 May 2026
Read appraisal →Vaccine
Factors affecting human papillomavirus vaccination: A review of individual, interpersonal, and structural factors affecting vaccine uptake among adolescents.
BACKGROUND: Human papillomavirus (HPV) related cancers, particularly cervical cancer, remain a major public health challenge in low- and lower-middle-income countries (LLMICs), which bear a disproportionate share of global HPV-attributable mortality. Despite the availability of safe and effective vaccines for nearly two decades, vaccination coverage remains low in LLMICs. Several barriers ranging from health misinformation to systemic delivery challenges have hindered efforts to scale up vaccination programs in these settings. OBJECTIVES: This systematic review aims to identify and synthesize the behavioral and structural factors influencing HPV vaccine uptake among adolescents in LLMICs. Guided by a multi-level behavioral health framework, findings were categorized across: individual, interpersonal, and structural domains. METHODS: A comprehensive search of seven databases identified 639 records, of which 34 empirical studies met inclusion criteria. Eligible studies focused on HPV vaccination uptake among adolescents in World Bank-defined LLMICs and were assessed for thematic relevance. Data extraction emphasized barriers and facilitators to uptake. RESULTS: Individual-level barriers included limited awareness, misconceptions about HPV and the vaccine, and fear of side effects. Interpersonal dynamics-particularly parental consent, gendered norms, and community endorsement-shaped adolescent vaccine decision-making. Structural barriers included vaccine stock-outs, weak delivery infrastructure, and limited reach among out-of-school youth. School-based delivery models, trusted healthcare workers, and community sensitization emerged as key facilitators. CONCLUSIONS: Improving HPV vaccine coverage in LLMICs requires coordinated, multi-level interventions that simultaneously address behavioral and structural determinants. Findings highlight the critical role of community engagement, flexible delivery models, and long-term sustainability planning to ensure effective implementation. These insights have direct implications for national immunization policy, health system strengthening, and achievement of global cervical cancer elimination targets in resource-limited settings. Tailoring implementation to the contextual realities of LLMICs will be essential to advancing equity in HPV-related cancer prevention.
13 May 2026
Read appraisal →Vaccine
Factors influencing rabies vaccines immunogenicity during post-exposure prophylaxis: a systematic literature search and meta-analysis
BACKGROUND: Rabies post-exposure prophylaxis (PEP) requires timely appropriate wound management and vaccination (including concomitant rabies immunoglobulin [RIG], depending on vaccination history and wound severity) to ensure rapid increases in rabies virus neutralizing antibody (RVNA) titers, a surrogate marker of protection. In this systematic review and meta-analysis, we assessed factors influencing the immunogenicity of rabies vaccines administered as PEP. METHODS: PubMed, Embase, and The Cochrane Library were systematically searched for randomized controlled trials published in English, French, Spanish, or Portuguese from January 1, 1983 to March 28, 2022 reporting the immunogenicity of rabies vaccines, specifically rabies human diploid cell vaccine (Imovax Rabies), purified Vero cell rabies vaccine (Verorab), and purified chick embryo cell rabies vaccine (RabAvert/Rabipur), as part of PEP in healthy individuals. Pooled RVNA geometric mean titers (GMTs) and seroconversion rates at Day 14 (D14) post-vaccination, determined by rapid fluorescent focus inhibition test, were estimated using random effects meta-analyses. RESULTS: We identified 1040 studies, of which 67 (9689 participants across 140 intervention groups) were included. The pooled RVNA GMT across all vaccines at D14 post-vaccination was 8.19 (95% CI: 6.73-9.98) and did not differ significantly by vaccine, administration route, or RIG use; however, there were significant interlaboratory differences. Meta-regression analysis, including titration year, demonstrated a negative association with log-transformed RVNA GMTs, equating to a 4.18% reduction (95% CI: -5.89 to -2.44) in log-transformed GMTs per year during the period assessed. Across all vaccines assessed, the pooled seroconversion rate by D14 post-vaccination was 98% (95% CI: 97-98; n = 7023; I2 = 64%) and was not impacted by vaccine, administration route, RIG use, test laboratory, or titration year. CONCLUSIONS: Although RVNA GMTs appear to have decreased by titration year, there was no clinically meaningful impact on immunogenicity, and the three licensed rabies vaccines assessed are expected to provide similar protection.
13 May 2026
Read appraisal →PloS one
Maternal body mass index and the risk of early-onset Group B Streptococcus disease in newborns: A systematic review and meta-analysis
BACKGROUND: Early-onset group B Streptococcus disease (EOGBS) remains a leading cause of neonatal morbidity and mortality. The incidence can be substantially reduced by intrapartum antibiotic prophylaxis in women with defined risk factors. However, the role of high prepregnancy body mass index (BMI) as a risk factor remains unclear. This systematic review and meta-analysis therefore aimed to evaluate the association between maternal BMI and the risk of EOGBS, as well as related proxy outcomes, including intrapartum vaginal GBS colonization and rectovaginal or urinary GBS colonization before term. METHODS: We systematically searched MEDLINE, Embase, and Cochrane CENTRAL on the 28th of January 2026, for studies examining the relationship between pregestational BMI and EOGBS or its proxy outcomes. Eligible studies included observational and interventional designs but not case reports and conference abstracts. Risk of bias was assessed using the QUIPS tool. Random-effects meta-regression and sensitivity analyses were performed. RESULTS: We identified 19 eligible observational studies reporting data from a total of 3,707,047 women, encompassing 277,887 cases. For the risk of EOGBS and its proxy outcomes, assuming a log-linear association, our meta-regression showed a 2.4% increase in the odds ratio (OR) per unit increase in BMI. This corresponds to an OR of 1.4 (95% CI 1.1-1.6) for a BMI of 35 and 1.7 (95% CI 1.3-2.3) for a BMI of 45, compared to a normal BMI of 22.3. One very large study on 1,971,346 live singleton births with 780 EOGBS cases, found a hazard ratio of 2.4 (95% CI 1.7-3.4) for a BMI of 35.0-39.9 compared to normal BMI (18.5-24.9). CONCLUSIONS: Although the overall association appears modest, incorporating BMI may improve prevention strategies for EOGBS .
13 May 2026
Read appraisal →Vaccine
Effect of time-of-day vaccination on the antibody response to mRNA and protein COVID-19 vaccine in adults
Time-of-day vaccination has been suggested as a feasible method to boost COVID-19 vaccine immunogenicity particularly in high-risk groups. However, several studies report inconsistent findings. We explored if time-of-day vaccination influences antibody responses to a fourth dose of mRNA (Moderna bivalent vaccine; mRNA-1273.214/mRNA-1273.222) or protein (Novavax; NVX-CoV-2373) COVID-19 vaccine as part of a randomised controlled trial (RCT) in Melbourne, Australia. Furthermore, we assessed if time-of-day vaccination effects differed by vaccine type or sex. At day 28 post-vaccination, antibody responses to all SARS-CoV-2 variants tested were higher for morning compared to afternoon vaccination in the Moderna group. Males in the Moderna group responded with higher antibodies to all SARS-CoV-2 variants tested after morning vaccination while responses in females were unaffected by time-of-day vaccination. Time-of-day vaccination had no effect on the response to Novavax, regardless of sex. Larger randomised trials are needed to confirm these findings to optimise vaccine timing strategies.
13 May 2026
Read appraisal →Vaccine
Effects of candidate vaccines against Zika virus infection: A systematic review of the clinical trials
INTRODUCTION: The 2015-2016 Zika virus (ZIKV) pandemic revealed a pathogenic potential, including Guillain-Barré syndrome and Congenital Zika Syndrome (CZS). Despite the decline in incidence, the potential for future circulation and the absence of specific antivirals underscore continued scientific interest in prophylactic vaccine development. OBJECTIVE: To synthesize evidence from clinical trials regarding the safety and preliminary immunogenicity of current ZIKV vaccine candidates. METHODS: This systematic review followed PRISMA guidelines (CRD420251056463). Searches were performed in MEDLINE, Embase, Web of Science, SciELO, and LILACS for clinical trials published between 2015 and 2025. Risk of bias was assessed using the Cochrane RoB 2 tool. RESULTS: Ten Phase 1 clinical trials were included, evaluating four platforms: inactivated virus (ZPIV, TAK-426, VLA1601), DNA (GLS-5700, VRC5283), mRNA (mRNA-1325, mRNA-1893), and viral vector (Ad26.ZIKV.001). All candidates demonstrated acceptable safety profiles, with predominantly mild-to-moderate and transient adverse events (e.g., injection site pain, fatigue, and headache); no vaccine-related serious adverse events were reported. Most platforms induced robust neutralizing antibody responses. Specifically, TAK-426 showed immune persistence for up to two years, while mRNA-1893 maintained responses for 13 months. The viral vector vaccine (Ad26.ZIKV.001) achieved 100% seroconversion with a single dose. Previous orthoflavivirus exposure did not significantly hinder vaccine-induced immunogenicity. Most studies presented a low risk of bias. CONCLUSIONS: ZIKV vaccine candidates across diverse technological platforms are safe and highly immunogenic. The evidence of long-term durability and the success of single-dose or mRNA regimens support the progression of the most promising candidates to Phase 2/3 trials.
12 May 2026
Read appraisal →Vaccine
Enhancing uptake of respiratory vaccinations in asthma and chronic obstructive pulmonary disease (COPD) patients: a systematic review.
INTRODUCTION: Despite influenza, pneumococcal and COVID vaccines being widely recommended for patients with chronic respiratory disease, vaccination rates in this cohort remain low. The aim of this systematic review is to identify interventions which are effective in increasing respiratory vaccination rates in adults with chronic obstructive pulmonary disease (COPD) or asthma. METHODS: The inclusion and exclusion criteria for the study can be found in the PROSPERO protocol (PROSPERO registration no: CRD42025588565). A search was run across four databases (MEDLINE, Embase, CENTRAL and ClinicalTrials.gov) in February 2025, which returned 2537 studies. Eleven studies were deemed to meet the study inclusion/exclusion criteria and these were narratively synthesised: four randomised clinical trials (RCTs), six longitudinal studies and one observational cohort study. Risk of bias was assessed using the Cochrane's Risk of Bias (RoB-V2) and ROBIN-I-V2 tools. Studies were categorised according to the COM-B model of behaviour change. RESULTS: All 11 studies consisted of COPD populations, with four studies also including asthma patients. Interventions focused on patient education, with/without involvement of a healthcare professional (HCP). Nine of the eleven studies showed a statistically significant improvement in influenza and/or pneumococcal vaccination rate with an intervention. No studies assessing COVID vaccine uptake in this population were suitable for inclusion. Most studies targeted patients' capability to get vaccinated through improving patients' and HCPs' knowledge. Fewer studies focused on social opportunity (e.g. support from other patients/HCPs) or automatic motivation (e.g. reminders). DISCUSSION: The published literature in this area is currently limited. Most studies are non-randomised and are at high-risk of bias, making meta-analysis not possible. Further research should assess the practicalities (physical opportunity) of vaccination, especially in low-income economies (where most respiratory patients reside) and standardising research methods to allow for future meta-analysis. OTHER: There is no funding for this review.
12 May 2026
Read appraisal →BMJ open respiratory research
Prevalence and determinants of drug-resistant pulmonary tuberculosis in the MENA region: a systematic review and meta-analysis
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a constraining challenge for tuberculosis (TB) control worldwide. The Middle East and North African (MENA) region represents a significant part of the global MDR-TB burden. AIM: To estimate the pooled prevalence of MDR-TB and its determinants in the MENA region. METHODS: We searched for studies published in English and French on the subject up to 31 January 2026 on Web of Science, PubMed, Scopus and Cochrane, without time restriction. Original studies reporting data on the prevalence of MDR-TB in individuals living in the MENA region were selected. The meta-analysis was done using the random effects model considering the heterogeneity among the included studies and I 2 statistic was used to assess the heterogeneity. RESULTS: A total of 1239 articles were identified and 25 studies from 6 countries were included in this review. The prevalence of MDR-TB in the MENA region ranged from 0% (95% CI 0% to 4.1%) to 17.1% (95% CI 10.6% to 25.4%). The pooled prevalence was 3.54% (95% CI 2.18% to 5.72%) with a high heterogeneity, I2 =95.6%; 95% CI 94.4% to 96.5%. Previous exposition to TB treatment, HIV infection, smoking and the presence of comorbidities were the most reported associated factors. CONCLUSION: This review underscores the persistence of MDR-TB in the MENA region, suggesting insufficiency in TB control. Multisectoral interventions integrating strong prevention measures, standardised treatment protocols and measures to enhance treatment adherence should be implemented.
12 May 2026
Read appraisal →Vaccine
Effect of neonatal BCG vaccination on oral herpes in early childhood: A nested study within a randomised controlled trial
BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine, primarily used against tuberculosis, has off-target (non-specific) immunomodulatory effects, including potential protection against recurrences of latent herpes simplex virus (HSV) infections. Recurrent episodes of HSV herpes labialis (oral 'cold sores') affect a substantial proportion of the population, including young children, and there is currently no effective preventive intervention. METHODS: This pilot study, nested within the MIS BAIR randomised controlled trial (RCT), explored whether neonatal BCG vaccination, compared with no BCG vaccination, reduces the incidence and recurrence of herpes labialis during the first five years of life. FINDINGS: Among the 563 children (44% of 1272 randomised) who completed the 5-year follow-up, children in the BCG group were less likely to develop herpes labialis, compared with the control group (5% vs 8%; 38% relative risk reduction, p = 0.1). Risk of recurrence was significantly lower in the BCG group (33% vs. 71%; 53% relative risk reduction, p = 0.02). BCG-vaccinated children also reported a later onset of symptoms and a reduced impact on fluid intake during episodes. INTERPRETATION: This exploratory study suggests a protective role for neonatal BCG against HSV in children. However, its limitations, including its sample size, incomplete follow up and lack of virological confirmation, mean further studies are needed to confirm these findings. FUNDING: National Health and Medical Research Council (NHMRC) of Australia and others, as detailed in the acknowledgements.
12 May 2026
Read appraisal →International health
Neglected tropical diseases in conflict-related humanitarian emergency settings: a systematic review of the literature
Neglected tropical diseases (NTDs) are a group of 21 conditions affecting an estimated 1 billion people worldwide, causing significant mortality and morbidity. WHO has targeted their control, elimination or eradication by 2030, while highlighting that conflict and humanitarian emergencies are risks to achieving this. A systematic review of peer-reviewed literature was undertaken, using terms related to conflict-related humanitarian emergencies (CRHE), based on the Armed Conflict Location & Event Data Project codebook terms for defining emergencies and terms including all WHO-defined NTDs. After a two-stage screening process, 26 papers were included. Common challenges for NTD programmes in CRHE were healthcare access, infrastructure, population movement and data quality. Multisectoral collaboration between actors in conflict-settings was offered as a learning for NTD programmes, along with community participation and decentralisation. Evidence gaps were identified in the knowledge base for certain NTDs and in high-quality evidence for interventions in CRHE. Collaboration is a key area for focused improvement for NTD programmes in CRHE. This should be across sectors and extend to research and analysis approaches, to ensure the most effective interventions are identified and implemented and that NTD road map targets can be achieved.
12 May 2026
Read appraisal →Immunologic research
An integrated AI-driven vaccine design process: a systematic review of workflows from generative design to translational prediction
Traditional vaccine development faced significant hurdles, including lengthy timelines and high costs, which hindered rapid responses to pathogens. Although the emergence of AI offered transformative potential, the necessity for a fully integrated workflow was often overlooked in studies focusing on individual tools. This review addressed a critical gap by synthesizing AI technologies across the vaccine design process, focusing on the integrated workflow from antigen discovery to clinical translation. A systematic framework was required to connect disparate tools and ensure seamless transitions. Consequently, this study provided a comprehensive roadmap for pandemic preparedness and vaccine discovery. A systematic analysis based on the PRISMA framework (2015-2024) was conducted, and 19 landmark articles were reviewed.It was demonstrated that the paradigm shift from predictive to generative AI offered unprecedented opportunities for developing novel antigens and adjuvants with superior immunogenicity. Synthesis of the literature revealed rapid progress toward sophisticated deep learning. Transformer models and Protein Language Models emerged as dominant for epitope prediction, while AlphaFold2 became the standard for structural modeling. The advent of generative AI for de novo antigen design represented the leading edge of the discipline. Additionally, AI-enhanced molecular dynamics and digital twin simulations accelerated clinical validation and manufacturing scalability. The "Integrated AI Workflow for Vaccine Design and Development" was emphasized as a comprehensive system and a prerequisite for sustainable innovation. Overall, this analysis served as a strategic roadmap for utilizing AI as a transformative framework for next-generation vaccine discovery and pandemic preparedness.
12 May 2026
Read appraisal →JMIR medical informatics
Cough Audio Recognition for Early Detection of Respiratory Diseases: Algorithm Development and Validation Study
BACKGROUND: Coughing is a common clinical symptom and a protective respiratory reflex closely associated with various respiratory system diseases. The acoustic characteristics of cough sounds are influenced by underlying pathological factors, with distinct acoustic signatures corresponding to different etiologies. Through rigorous analysis of these sounds, rapid identification and preliminary diagnosis of related conditions may be achieved. This approach holds great potential for broad application in mobile health and ubiquitous health platforms. OBJECTIVE: This study aimed to explore the application of acoustic analysis of cough sounds in the diagnosis of respiratory diseases to enhance the diagnostic efficiency of health care professionals. METHODS: In this study, we conducted extensive data collection, including voluntary cough audio recordings from patients diagnosed with respiratory diseases (eg, chronic obstructive pulmonary disease, lung cancer, COVID-19, and pneumonia) and from healthy participants. A total of 2610 audio samples were collected. We incorporated a channel attention mechanism (CAM) into the final convolutional block of each residual block in the ResNet18 neural network, thereby constructing the CAM-ResNet18 neural network model. The recorded cough audio samples were converted into spectrograms to form the input dataset for model training. The CAM-ResNet18 model was trained on the training set of this dataset, with iterative parameter adjustments until convergence was achieved. Finally, spectrograms from the test set were fed into the pretrained model for accurate classification of the cough-related conditions. RESULTS: Experimental results on the collected audio dataset demonstrate that the proposed CAM-ResNet18 model achieves an accuracy of 83.9% and an average F1-score of 82.52% in classifying 5 types of cough sounds. In comparison, the traditional ResNet18 model achieves an accuracy of 78.16% and an average F1-score of 78.29%, indicating a clear performance improvement with the integration of the CAM. CONCLUSIONS: The experimental results validate the effectiveness of the proposed method, highlighting its significant potential for application in clinical diagnosis.
12 May 2026
Read appraisal →Antiviral therapy
Factors associated with immunological non-response in HIV patients receiving antiretroviral therapy in Southeast Asia: A systematic review
ObjectiveThis systematic review summarizes factors associated with immunological non-response (INR) among people with HIV on antiretroviral therapy (ART) in Southeast Asia.MethodsWe conducted a systematic search of PubMed, ScienceDirect, DOAJ, and Lens.org for studies published between 2010 and 2025. Observational studies examining immunological outcomes following ART initiation and related factors were included. Study quality was assessed using the Newcastle-Ottawa Scale, and results were synthesized using a harvest plot.ResultTen eligible studies were included in the synthesis, comprising a total of 6,988 participants with substantial heterogeneity observed across studies. Factors associated with INR included age, sex, baseline CD4 cell count, HIV RNA levels, and co-infections. Among these factors, baseline CD4 cell count at the initiation of ART emerged as the most consistently associated determinant; lower baseline CD4 levels were linked to a higher risk of INR even with virological suppression.ConclusionThis review highlights baseline immunological status at ART initiation as a key predictor of immunological non-response in Southeast Asia. These findings underscore the critical importance of early HIV diagnosis and timely initiation of ART to prevent advanced immune damage and optimize immunological recovery.
12 May 2026
Read appraisal →European journal of pediatrics
Piperacillin-tazobactam versus cefepime monotherapy in pediatric patients with febrile neutropenia: a systematic review and meta-analysis
UNLABELLED: The purpose of this study is to evaluate whether piperacillin-tazobactam therapy, compared with cefepime monotherapy, results in significant difference in treatment success, mortality, and duration outcomes in pediatric patients with febrile neutropenia (FN). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched up to February 3. No starting limits for dates were used. We only included studies of pediatric patients with FN comparing piperacillin-tazobactam to cefepime monotherapy. Risk of bias was assessed using Cochrane RoB 2 tool. Meta-analysis was performed using random-effects model to calculate risk ratios (RR) and mean differences (MD). Five RCTs involving 470 episodes were included. The pooled analysis for treatment success showed no statistically significant difference between groups (RR = 1.02; 95% CI [0.89; 1.18]; P = 0.76) with low heterogeneity (I2 = 0.0%). No significant differences for mortality (RR = 2.09; 95% CI [0.62; 7.03]; P = 0.23; I2 = 0.0%). Duration of treatment was 0.9 day shorter for cefepime group (MD = 0.9 day; 95% CI [0.2; 1.6]; P < 0.1; I2 = 0%). CONCLUSION: No statistically significant difference was found in treatment success or mortality between the groups. Patients receiving cefepime had a treatment duration 0.9 days shorter than those receiving piperacillin-tazobactam, although this finding should be interpreted with caution. The available evidence remains limited. Further RCTs are needed to elucidate potential differences in treatment success, mortality, and duration between the drugs. REGISTRATION: PROSPERO (CRD420261296621). WHAT IS KNOWN: • Cefepime and piperacillin-tazobactam are widely utilized as empirical monotherapy for febrile neutropenia, but evidence regarding their comparative clinical efficacy and safety in children remains inconclusive. WHAT IS NEW: • This meta-analysis quantifies differences in treatment success, mortality and duration of treatment outcomes in pediatric patients with febrile neutropenia.
12 May 2026
Read appraisal →International health
Pneumonia in Ghana: prevalence, mortality and antimicrobial resistance-a systematic review and meta-analysis
Pneumonia is a major cause of morbidity and mortality in Ghana, especially among children <5 y of age and the elderly. However, comprehensive data on its prevalence and distribution remain limited. This systematic review addresses this gap by analysing the prevalence, regional variations, risk factors, antimicrobial resistance and mortality rates of pneumonia in Ghana. We searched PubMed, ScienceDirect, Web of Science and African Journals Online databases, including 21 studies with a total of 124 582 participants. A random-effects meta-analysis estimated pooled prevalence and subgroup differences based on age, region and participant type. Heterogeneity was assessed using the I2 test and meta-regression, with sensitivity analysis also conducted. Study quality was evaluated using standardized Joana Briggs Institute checklists for prevalence studies. The pooled prevalence of pneumonia in Ghana was 22.01%, with significant regional variations. The highest prevalence was observed in a study conducted in the Greater Accra and Northern regions (32.31%), while the lowest was in the Upper West (4.83%). The prevalence in children <5 y of age was 17.79%. Hospitalized patients had a higher prevalence (22.14%) than community children (21.49%). Streptococcus pneumoniae was the most common pathogen, with high resistance (>70%) to co-trimoxazole, gentamicin and tetracycline. Key risk factors included indoor air pollution and seasonal changes. The mortality rate for pneumonia was found to be 3.07%. This systematic review highlighted significant regional disparities, pathogen resistance patterns and environmental risk factors that shape the burden of pneumonia in Ghana, providing critical evidence for targeted public health strategies. The findings highlight avenues for future research, including environmental drivers of transmission, focusing on underreported regions and surveillance of antibiotic resistance of pathogens isolated from pneumonia patients.
11 May 2026
Read appraisal →International health
Global trends in travel-related antimicrobial resistance: a systematic review, 2020-2024
Antimicrobial resistance (AMR) is a growing global health threat, with international travel playing a key role in the spread of resistant bacteria. This systematic review examines trends in travel-associated AMR from 2020 to 2024. A search of PubMed, Scopus and Web of Science identified 10 studies involving 359 AMR isolates. Using the Newcastle-Ottawa scale, the study quality was assessed and findings were synthesised to identify patterns in prevalence, diversity and geographic spread. Results revealed a consistent rise in travel-associated AMR, particularly from regions such as Southeast Asia and Africa, which acted as major sources of diverse resistant pathogens. These include extended spectrum beta-lactamase-producing Escherichia coli, multidrug-resistant (MDR) Corynebacterium diphtheriae and colistin-resistant Enterobacterales. The number of MDR strains increased over time, making up 15.3% of cases by 2024. Healthcare exposure during travel emerged as a significant risk factor. Overall, the prevalence and diversity of AMR bacteria linked to travel have risen steadily, highlighting the urgent need for global cooperation. Enhanced surveillance, antimicrobial stewardship, infection control measures and international collaboration are essential to curb the spread of these dangerous pathogens.
11 May 2026
Read appraisal →International journal of health care quality assurance
Understanding trust in mandatory telemedicine use during COVID-19: a modified health belief model approach
PURPOSE: This study explores the determinants of trust in telemedicine when its use was mandated during the COVID-19 pandemic in South Korea. It extends the health belief model by incorporating two service related constructs: service quality and perceived cost. DESIGN/METHODOLOGY/APPROACH: An online survey was conducted with 288 individuals who were confirmed COVID-19 patients and required to use telemedicine services during isolation. Partial least squares structural equation modeling was applied to examine the relationships between health beliefs including perceived severity, perceived susceptibility and self-efficacy, service perceptions such as service quality and perceived cost, trust in telemedicine and behavioral intention to use telemedicine services. FINDINGS: The results showed that self-efficacy, service quality and perceived cost positively influenced trust in telemedicine. In contrast, perceived severity and perceived susceptibility did not have a meaningful impact. Trust was found to be a key factor in shaping patients' intention to continue using telemedicine services. Overall, the proposed model was supported, highlighting the importance of confidence and service related perceptions in building trust under mandatory usage conditions. ORIGINALITY/VALUE: This study provides empirical evidence on trust formation under mandatory telemedicine use, a scenario rarely explored in the literature. It demonstrates that trust is primarily driven by users' self-efficacy and service perceptions rather than by health risk perceptions, offering practical guidance for enhancing remote care engagement during policy enforced use conditions.
11 May 2026
Read appraisal →The Journal of dermatological treatment
Comparative efficacy and safety of oral azithromycin versus doxycycline in moderate-to-severe Acne vulgaris: a systematic review and meta-analysis
BACKGROUND: Acne vulgaris is a chronic inflammatory disease and is one of the leading causes of dermatological morbidities among young adults. Doxycycline is widely recommended as first-line therapy for moderate to severe acne; however, its use is limited. OBJECTIVE: To systematically compare the efficacy and safety of oral azithromycin pulse therapy versus doxycycline in patients with moderate to severe acne vulgaris. METHODS: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive literature search on different databases was performed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models based on heterogeneity. RESULTS: A total of 23 comparative studies comprising 2,769 patients were included. Pooled analysis demonstrated a statistically significant improvement in global acne severity favoring azithromycin (GAGS reduction: MD 1.81; 95% CI 1.28-2.34; I2 = 0%). Azithromycin achieved a significantly greater reduction in non-inflammatory lesion counts (MD -7.56; 95% CI -14.33 to -0.79). No significant differences were observed in inflammatory lesion reduction (MD 1.08; 95% CI -0.03 to 2.18). CONCLUSION: Oral azithromycin pulse therapy appears to have similar efficacy, better tolerability, and fewer side effects as compared to doxycycline.
11 May 2026
Read appraisal →Molecular pharmaceutics
mRNASyner: An Integrative Framework for Full-Length mRNA Sequence Optimization via Multimodule Synergistic Design
Messenger RNA (mRNA) technology holds great promise in biomedicine; however, its therapeutic efficacy relies heavily on translation efficiency and the in vivo stability of mRNA sequences, both of which are governed by dynamic interactions between the coding and noncoding regions. Existing optimization approaches typically focus on individual sequence components and lack the capacity for global, synergistic optimization. Moreover, their performance is often limited when processing long sequences or supporting iterative sequence refinement. To overcome these challenges, we propose a unified and interpretable in silico framework for full-length mRNA sequence design, integrating CDS optimization, UTR generation, and degradation modeling. In silico case studies based on respiratory syncytial virus (RSV) vaccine design demonstrated that mRNASyner achieved a favorable balance between translational accessibility and structural stability. mRNASyner thus enables the design of full-length mRNA sequences, supports long-sequence optimization, and offers a novel solution for the development of personalized mRNA therapeutics.
11 May 2026
Read appraisal →Transactions of the Royal Society of Tropical Medicine and Hygiene
Quality of life in Indian people affected by leprosy? A systematic review from the country with the highest burden of leprosy cases.
Quality of life (QoL) is important for people with leprosy since the disease can cause physical and psychological problems. These problems may result in stigma and social discrimination. India reported 107 851 new leprosy cases for the year 2023-24, accounting for 61.6% of new cases detected globally. This systematic review was conducted to assess the QoL among people affected by leprosy in India using existing literature. The Scopus, PubMed and Infolep databases were searched for articles for this systematic review and included only studies conducted in India. The critical appraisal tool of cross-sectional studies (AXIS) was used to assess the study quality and risk of bias. The search identified 253 articles. After screening titles and abstracts, 23 full-text articles were assessed for eligibility and 12 studies were included in the systematic review. The World Health Organization Quality of Life-Bref instrument was used to measure QoL. Of the 12 studies, the factors of disability (9 studies) and old age (8 studies) were highly associated with low levels of QoL. Five studies identified that low levels of QoL are associated with being female with the leprosy. Early identification and prevention of disabilities are important steps in improving the QoL. Increased investment is needed in leprosy programmatic activities and research to achieve the target of zero leprosy.
10 May 2026
Read appraisal →PloS one
Association between hemoglobin dynamic trajectories and 28-day mortality in elderly patients with sepsis: A retrospective cohort study using the MIMIC-IV database
BACKGROUND: Anemia is a common complication in sepsis and is associated with poor prognosis. However, there are few studies on the dynamic changes in hemoglobin (Hb) levels and their relationship with prognosis in elderly patients with sepsis. This study aims to retrospectively investigate the relationship between Hb trajectories and 28-day mortality in this population. METHODS: This retrospective observational study used data from 4,961 elderly patients with sepsis extracted from the MIMIC-IV database(2008-2019). Hb trajectories were identified using a Joint Latent Class Model (JLCM) for longitudinal pattern classification. Following validation of proportional hazards assumptions (Schoenfeld residual test), we assessed the prognostic relationship between Hb trajectories and 28-day mortality using multivariable Cox regression models and Kaplan-Meier survival curves. Sensitivity analyses included sex-stratified multivariable Cox regression, subgroup analysis, and E-value assessment. RESULTS: Hb trajectories were classified into three patterns: Class 1 with persistently low levels, Class 2 with medium levels and a gradual decline, and Class 3 with a rapid decline from higher levels. Using Class 2 as the reference, multivariable Cox regression showed that Class 1 (HR = 1.38, 95% CI = 1.18-1.62, p < 0.001) and Class 3 (HR = 1.21, 95% CI = 1.03-1.42, p = 0.020) were associated with higher 28-day mortality. Kaplan-Meier curves indicated the lowest survival probability in Class 1 and the highest in Class 2. Gender-specific analysis revealed consistent trajectory patterns between males and females, but higher Hb values in males. The predictive power of the rapid decline pattern for early mortality was stronger in males. CONCLUSION: The Hb trajectories in elderly sepsis patients are significantly associated with early mortality. Persistently low levels and rapid declines in Hb are indicators of poor prognosis.
10 May 2026
Read appraisal →Human vaccines & immunotherapeutics
Incidence of Bacille Calmette-Guérin associated lymphadenitis in healthy children: A systematic review and meta-analysis
Few systematic reviews or meta-analyses have addressed on the incidence of Bacille Calmette-Guérin (BCG) lymphadenitis in healthy children. A systematic literature search was independently conducted by two researchers using four English and Korean databases (PubMed, Scopus, KMbase, RISS). The risk of bias was assessed. A total of 52 peer-reviewed journal articles (about 1.8 million children) were included in meta-analyses. The incidence proportion of BCG lymphadenitis ranged from 0.0% to 25.6%. The pooled incidence proportion was 2.5% (95% CI, 1.6-3.6; I2 = 99%). Studies employing active (vs. passive) surveillance reported a significantly higher incidence proportion of lymphadenitis, as did randomized controlled trials (vs. prospective and retrospective cohort studies). Also, the incidence significantly differed according to study quality, publication period, and BCG strain. This study highlights substantial variability in the incidence of BCG lymphadenitis among diverse studies and underscores the influence of surveillance methods, study design, and vaccine strain on reported outcomes.
10 May 2026
Read appraisal →Annals of medicine
A comprehensive review of regulatory mechanisms of novel enterotoxin genes in Staphylococcus aureus from meat sources
BACKGROUND AND AIMS: Meat-borne Staphylococcus aureus (S. aureus) remains a leading global foodborne pathogen harbouring novel enterotoxin genes (NEGs) encoding superantigenic toxins with conditionally enhanced pathogenicity, representing a critical food safety hazard. This review characterizes NEG features, pathogenic mechanisms, multi-layered regulatory networks, and identifies key research challenges. METHODS: We systematically searched PubMed, Embase and the Web of Science Core Collection to synthesize molecular and multi-omics evidence (ChIP-seq, RNA-seq, CRISPR-Cas9) characterizing NEG classification, pathogenic mechanisms, multi-level regulatory networks (transcriptional, post-translational, environmental), and geographical distribution patterns in meat-derived S. aureus. RESULTS: NEGs comprise superantigenic and tissue-targeting subgroups mediating pathogenicity via cytotoxicity, intestinal microenvironment disruption, and immune evasion. Regulation involves a complex network of Agr/σB/SarA/Rot-mediated transcriptional control, phosphorylation/lactylation modifications and environmental sensing, exhibiting marked geographical divergence. Current limitations include technical resolution constraints, insufficient physiological model fidelity and incomplete regulatory crosstalk elucidation. CONCLUSIONS: Future research should prioritize transcription factor interaction mechanisms, growth-toxin correlation prediction models and multi-omics-based network decipherment. This review provides a foundational framework for NEG research to inform food safety risk assessment and targeted contamination control strategies.
10 May 2026
Read appraisal →Computer methods in biomechanics and biomedical engineering
Modified mutual information feature selection algorithm to predict COVID-19 using clinical data
The COVID-19 pandemic has profoundly impacted health, emphasizing the need for timely disease detection. Blood tests have become key diagnostic tools due to the virus's effects on blood composition. Accurate COVID-19 prediction through machine learning requires selecting relevant features, as irrelevant features can lower classification accuracy. This study proposes Modified Mutual Information (MMI) for feature selection, ranking features by relevance and using backtracking to find the optimal subset. Support Vector Machines (SVM) are then used for classification. Results show that MMI with SVM achieves 95% accuracy, outperforming other methods, and demonstrates strong generalizability on various benchmark datasets.
6 May 2026
Read appraisal →Journal of proteome research
NetMHCIIphosPan: A Machine Learning Tool for Predicting HLA Class II Antigen Presentation of Phosphorylated Peptides
Phosphorylated peptides presented by human leukocyte antigen (HLA) class II molecules play pivotal roles in immune regulation, yet their characterization and prediction remain challenging due to data noise and limited HLA coverage. Here, we introduce NetMHCIIphosPan, a prediction method for HLA-II antigen presentation of phosphorylated peptides, developed using mass spectrometry (MS)-based immunopeptidomics data sets. Employing a refined peptide identification workflow, we reanalyzed earlier HLA-II phospholigand data sets and trained predictive models, achieving superior performance compared to models trained on the original data. Binding motif analysis revealed that HLA-specific preferences for phospholigands closely aligned with those of unmodified ligands. Incorporating unmodified ligands into training further enhanced predictive accuracy, particularly for HLA-DP and HLA-DQ molecules. NetMHCIIphosPan outperformed existing tools, such as NetMHCIIpan-4.3 and MixMHC2pred-1.3, for prediction of HLA antigen presentation of phosphorylated peptides, demonstrating robustness and utility. This work establishes NetMHCIIphosPan as a state-of-the-art tool for understanding the HLA-II phospholigandome, with potential applications in immunotherapy and vaccine design.
4 May 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Bacterial quantitation in clinical infection: a systematic review
Pivotal clinical studies of new anti-infective drugs enrol patients with strictly defined clinical syndromes, with clinical and laboratory endpoints used to define treatment success. Assessing bacterial killing in the host by serial quantitation has potential as a more efficient pharmacometric approach to assess antibiotic efficacy. We conducted a systematic review of the use of bacterial quantitation in clinical infection. The main syndromes studied in the 222 included articles were bacteraemia, chronic respiratory disease, diarrhoea, pneumonia and sexually transmitted infections. Most reports (135 articles, 61%) quantified bacterial load in different specimen types using quantitative polymerase chain reaction (qPCR). For bacteraemias, bacterial DNA load measured in whole blood by qPCR at clinical presentation was typically 2-3 log10 copies ml-1, usually substantially higher than the estimates from quantitative culture. Higher bacterial loads were associated with increased mortality in 28 of 35 studies. Faster bacterial clearance was correlated with appropriate antibiotic therapy and improved outcome in the majority of studies. Most studies sampled too infrequently for accurate characterization of bacterial clearance rates. The rate of bacterial clearance from blood or other compartments is an informative pharmacodynamic endpoint in the assessment of antibacterial therapeutic effects, but standardized approaches to assessment are needed based on optimal study design. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.
3 May 2026
Read appraisal →PloS one
Auditing the impact of social media's policy shift on anti-vaccine discourse: A large language model-driven empirical study
The sudden termination of X's (formerly Twitter) misinformation policy on November 23, 2022, provides an opportunity to assess the effects of lifting content moderation restrictions on vaccine-related discourse. This study examines changes in the prevalence, thematic composition, and engagement of anti-vaccine discourse following X's policy shift, analyzing tweets from a seven-day period before and after the policy termination (November 16-30, 2022), excluding the announcement date itself from regression analyses. Using GPT-4o for stance classification, thematic categorization, and stance consistency assessment, with validation through external benchmarks and cross-annotator agreement, we find that anti-vaccine tweets increased significantly post-policy (OR = 1.60, 95% CI: 1.50-1.72), particularly via retweets, suggesting content amplification. Sensitivity analyses excluding highly retweeted content revealed that the policy change was also associated with increased creation of new anti-vaccine content. Thematically, health concerns over vaccination became more prominent, while conspiracy-related and anti-mandate narratives declined in relative prevalence. Stance consistency in quote tweets increased, indicating reinforced ideological alignment in anti-vaccine discourse. These results suggest that content moderation policies may constrain both the volume and amplification of anti-vaccine content, with policy removal associated with rapid shifts in discourse patterns.
3 May 2026
Read appraisal →PLoS computational biology
MsgaBpred: A B-cell epitope predictor integrating AlphaFold3-predicted structures with multi-scale GCNs and pre-trained language model ESM-C
Accurate prediction of B-cell epitopes plays a key role in facilitating advancements in vaccines, therapeutics, and diagnostics. In contrast to labor-intensive experimental approaches, computational strategies provide a more economical and efficient means of identifying potential epitopes. Existing methods are often limited by their reliance on experimentally resolved protein structures or by the use of lower-accuracy predicted structures. Sequence-based approaches, while fast, largely fail to capture the 3D spatial context essential for conformational epitopes. With the breakthroughs achieved by AlphaFold3 in predicting protein structures, we present MsgaBpred, the model to apply AlphaFold3-derived structures to B-cell epitope identification. Given only a protein sequence, our model employs a multi-scale graph convolutional network and additive attention to capture complex structural dependencies without relying on experimentally determined structures. The multi-scale design allows for effective modeling of both local and global contexts by aggregating information across different neighborhood ranges. Additionally, we leverage ESM-C, a more expressive protein language model than ESM-2, to enhance feature representation for B-cell epitope prediction. Extensive evaluations across multiple benchmark datasets demonstrate that MsgaBpred achieves competitive and robust performance; notably, it yields a statistically significant improvement in AUC compared to existing state-of-the-art methods. Moreover, the modular and scalable architecture of MsgaBpred holds promise for broader applications, including the structural analysis of other biomolecular entities such as nucleic acids and carbohydrates.
3 May 2026
Read appraisal →PloS one
Clinical manifestations of bed bug bites: A systematic review of case reports
IMPORTANCE: Clinical characterization of bed bug (Cimex spp.) bite manifestations remains limited. OBJECTIVE: This systematic review synthesizes case reports to describe dermatological, systemic, and psychological outcomes of bed bug bites. EVIDENCE REVIEW: Following PRISMA guidelines, multiple databases, including Pubmed and Scopus, were searched using terms such as "bed bug," "Cimex lectularius," "Cimex hemipterus," "case report," and "case series." Extracted data included demographics, species, lesion type, anatomical distribution, and clinical manifestations. Quantitative and qualitative analyses were conducted. RESULTS: Eighty-four patients were included: 76 with C. lectularius (90.5%) and, 8 with C. hemipterus (9.5%). Sex distribution was balanced (47.6% females, 52.4% males), and mean ages were similar (females 37.5 ± 22.1, males 42.3 ± 21.27 years; p = 0.332). Extremities were commonly affected, arms were reported in 71.4% of cases, legs in 59.5% and trunk in 34.5%. Psychological symptoms were registered in a handful of case reports (Anxiety 9.5%, Stress 9.5%, Hopelessness 9.5%). Systemic symptoms, generally associated with anemia, were reported in cases related to severe infestations in neglected patients. Some differences in systemic and local signs and symptoms were detected depending on age group. CONCLUSIONS: Bed bug bites predominantly affect exposed extremities, although with variable dermatologic patterns that can be confused with other arthropod bites. Psychological manifestations were reported in a small subset of cases, while systemic complications were rare.
3 May 2026
Read appraisal →Journal of medical Internet research
Rapid Deployment of Telemedicine in HIV Care: Mixed Methods Study of Providers' Attitudes and Perceptions
BACKGROUND: The COVID-19 pandemic prompted an abrupt transition to telemedicine for HIV care, necessitating the exploration of provider attitudes and experiences to understand its ongoing viability and impact. OBJECTIVE: This study aimed to assess providers' attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic at 2 time points and at 2 clinical sites. METHODS: We conducted a convergent mixed methods study to evaluate and explore providers' attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic, applying the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and the updated Consolidated Framework for Implementation Research. This study assessed HIV providers via surveys at 2 time points, capturing responses on the acceptability, appropriateness, feasibility, and maintenance of telemedicine. Semistructured key informant interviews were conducted on a random selection of 10 participants to explore perceived experiences with telemedicine. RESULTS: Among emailed providers, 43 of 83 (51.8%) and 27 of 82 (32.9%) responded to survey 1 and survey 2, respectively. The first survey recorded telemedicine usage at 75%, which decreased to 58% by the second survey. Overall, the majority of respondents agreed with statements that assessed telemedicine as appropriate, acceptable, and feasible. There were overall few statistical differences in responses between sites, although more providers at the community site indicated at least some potential value in telemedicine when compared to providers at the university hospital (100% agree or strongly agree vs 82.3%; P=.04) in survey 1. In survey 1, providers with more than 10 years of experience were less likely to report telemedicine helped them see more patients (31.6% agree or strongly agree vs 70.6% for providers with ≤10 y of experience; P=.008). Fewer experienced providers felt they could talk about private issues with their patients during telemedicine (57.9% of more experienced vs 88.3% of less experienced providers; P=.03). Key informant interviews provided qualitative insights into telemedicine integration, revealing mixed sentiments; providers appreciated the flexibility and accessibility that telemedicine offered but preferred in-person visits for their thoroughness, especially for physical examinations and laboratory tests. Despite initial barriers such as technical challenges and patient preferences for in-person visits, telemedicine was deemed feasible for maintaining communication and care quality. Providers highlighted the need for better technological support and ongoing training to optimize telemedicine usage. CONCLUSIONS: Our study underscores telemedicine as a sustainable adjunct to traditional HIV care, emphasizing the importance of addressing technological and training barriers to enhance its efficacy.
3 May 2026
Read appraisal →ChemMedChem
A Novel Triose Phosphate Isomerase Inhibitor With Dual Trypanosomicidal Activity was Identified Using Artificial Intelligence-Based Virtual Screening
Chagas disease and leishmaniasis are neglected protozoan diseases recognized by the World Health Organization as major public health problems. These diseases affect millions of people worldwide, yet effective treatments remain unavailable. Triosephosphate isomerase (TIM), a glycolytic enzyme that exhibits high catalytic efficiency for the isomerization of glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate exclusively in its dimeric form, was subjected to virtual screening. Using a deep neural network for structure-based drug design that predicts binding affinity between small molecules and proteins of known structure, 12.5 million commercially available compounds were screened. From this, 82 compounds were selected for in vitro evaluation. Six compounds inhibited TIM from Trypanosoma cruzi, three of which exhibited anti-T. cruzi activity. Eight compounds demonstrated activity against the parasites T. cruzi and Leishmania infantum. Two compounds showed similar potency against both parasites: 3-(1-acetyl-5-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-6-methyl-2H-pyran-2-one (IC50 = 16 ± 3 μM) and 3-[(4-bromophenyl)sulfanyl]-1-(3-nitrophenyl)propan-1-one (IC50 = 12 ± 1 μM). These compounds exhibit favorable selectivity and toxicological profiles, as well as in vivo activity, indicating their potential for future drug development.
2 May 2026
Read appraisal →Lancet (London, England)
Clinical and bacteriological effectiveness of three different short-course antibiotic regimens and single-dose fosfomycin for uncomplicated lower urinary tract infections in women (SCOUT): a pragmatic, multicentre, open-label, randomised clinical trial
BACKGROUND: Most guidelines recommend nitrofurantoin, fosfomycin, and sometimes pivmecillinam for uncomplicated urinary tract infections (UTIs), but direct comparisons between these antibiotics are needed. This study evaluated the effectiveness and safety of a single dose of fosfomycin compared with two doses of fosfomycin and short-course regimens of nitrofurantoin and pivmecillinam in women with UTI symptoms. METHODS: This phase 4, pragmatic, multicentre, parallel-group, open-label, randomised clinical trial was conducted in Spanish primary care centres from 2022 to 2024. Women aged 18 years or older with at least one UTI-specific symptom (dysuria, urinary urgency, urinary frequency, or suprapubic tenderness) and a positive urine dipstick test for either nitrites or leukocyte esterase were randomly assigned (1:1:1:1) to one of four treatments: a single 3 g dose of fosfomycin, two 3 g doses of fosfomycin, nitrofurantoin (100 mg three times per day for 5 days), or pivmecillinam (400 mg three times per day for 3 days). Doctors and patients were not masked to group assignment. The primary outcome was the proportion of patients with clinical resolution (defined as the disappearance of all infection symptoms) at day 7. This trial is registered with ClinicalTrials.gov (NCT04959331) and EudraCT (2021-001332-26) and is completed. FINDINGS: Of the 804 patients assessed for eligibility between April 4, 2022 and Nov 14, 2024, 768 patients were randomly allocated (191 to the single-dose fosfomycin group, 194 to the two-dose fosfomycin group, 190 to the nitrofurantoin group, and 193 to the pivmecillinam group). Patients had a median age of 48 years (IQR 34-63). Race and ethnicity data were not collected. Among the 720 women with available data included in the primary analysis, single-dose fosfomycin had the lowest proportion of clinical resolution (109 [59%] of 185 patients), while nitrofurantoin had the highest (128 [74%] of 172 patients; difference 15·5 percentage points [95% CI 5·9 to 25·1] vs single-dose fosfomycin; p=0·0168), followed by pivmecillinam (127 [70%] of 182; difference 10·9 percentage points [1·1 to 20·6]; p=0·2352) and the two-dose fosfomycin group (122 [67%] of 181; difference 8·5 percentage points [-1·4 to 18·3]; p=0·6935). Adverse events occurred in 38 (19·9% [95% CI 14·9 to 26·1) of 191 patients who received single-dose fosfomycin, 51 (26·3% [20·6 to 32·9]) of 194 who received two-dose fosfomycin, 51 (26·8% [21·0 to 33·6]) of 190 who received nitrofurantoin, and 41 (21·2% [16·1 to 27·5]) of 193 who received pivmecillinam. Most adverse events were mild and self-limiting, primarily gastrointestinal. Four serious adverse events occurred, of which one was related to the study treatment (one case of pyelonephritis in the pivmecillinam group). INTERPRETATION: Nitrofurantoin was the most effective treatment and single-dose fosfomycin the least effective treatment for UTIs. Adverse events were mild. The role of fosfomycin as a first-line antibiotic for uncomplicated UTI should be re-evaluated. FUNDING: Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund.
2 May 2026
Read appraisal →Lancet (London, England)
Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial
BACKGROUND: Malaria remains a major cause of mortality globally, especially among young children in sub-Saharan Africa. The long-acting monoclonal antibody L9LS has shown high efficacy in preventing malaria in children aged 6-10 years exposed to seasonal transmission but remains untested in perennial transmission settings and younger children. We assessed the safety, tolerability, and efficacy of L9LS in infants and children in a high perennial malaria transmission setting. METHODS: This double-blind, two-part, randomised, placebo-controlled, phase 2 trial was done in Siaya county in western Kenya. In parts 1a and 1b, we tested the safety and tolerability of L9LS using an age de-escalation and dose escalation approach and randomly assigned (3:1) cohorts of healthy children (three cohorts aged 5-10 years, three cohorts aged 5-59 months, and two cohorts aged 5-71 months) to L9LS at doses of 5, 10, 20, 30, or 40 mg/kg subcutaneously or to placebo (normal saline). In part 2, healthy children aged 5-59 months were randomly assigned (1:1:1) by use of centralised computer-generated lists to receive two doses of L9LS at 10-20 mg/kg at baseline and month 6, one dose of L9LS at baseline and placebo at month 6, or placebo at both timepoints. Children were followed up for 12 months with monthly clinic visits and blood smear collections. Primary safety outcomes were incidence and severity of local and systemic solicited adverse events within 7 days of dosing and serious adverse events throughout follow-up. The primary efficacy endpoint was Plasmodium falciparum infection detected by blood smear over 12 months. Primary analyses were done in the modified intention-to-treat population, consisting of all randomly assigned participants who received the study intervention. This trial is registered with ClinicalTrials.gov (NCT05400655) and is complete. FINDINGS: In parts 1a and 1b, 96 children were enrolled and randomly assigned between Oct 1, 2022, and Jan 16, 2024; 72 participants were assigned to L9LS and 24 were assigned to placebo. In part 2, 324 children aged 5-59 months were enrolled and randomly assigned between Jan 26 and June 2, 2023; 108 children were assigned to one-dose L9LS, 106 to two-dose L9LS, and 110 to placebo. Across all study parts, grade 3 or worse treatment-related adverse events occurred after four (1%) of 384 L9LS injections and two (1%) of 338 placebo injections; these events all resolved by study end. The proportion of solicited and unsolicited adverse events was similar across all L9LS dose groups. There were no serious adverse events related to the trial. In part 2, 70 (66%) of 106 children in the two-dose L9LS group had at least one P falciparum infection during the 12-month follow-up versus 91 (83%) of 110 children in the placebo group (protective efficacy 42·7%, 95% CI 22·5-57·7; p=0·0003). INTERPRETATION: L9LS was protective against malaria in young children in western Kenya without evident safety concerns over 6-12 months. A higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial P falciparum transmission. FUNDING: Gates Foundation.
2 May 2026
Read appraisal →The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B
Chronic hepatitis B remains a major global health challenge despite the advances in antiviral therapy. Although hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure, liver-related complications, particularly hepatocellular carcinoma, may still occur after viral clearance. This residual risk reflects the lasting impact of host and liver factors rather than ongoing viral activity. Conventional prediction models have attempted to stratify the residual risk after a functional cure but remain limited in their ability to guide individualized management. Recent advances in machine learning have enabled more precise risk stratification by capturing complex host-driven determinants of the long-term outcomes. These approaches support a shift from uniform surveillance toward risk-adaptive monitoring strategies. Nevertheless, post-cure management is emerging as a new clinical priority as more patients achieve a functional cure. Therefore, a functional cure should be viewed not as the end of the disease, but as the beginning of a phase requiring personalized risk assessment and surveillance.
28 Apr 2026
Read appraisal →Journal of ethnopharmacology
Salvia plebeia R.Br.: A comprehensive review of its ethnopharmacology, phytochemistry, pharmacological activities, quality control, and current applications.
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R.Br. (Lamiaceae), the dried aerial parts, has been traditionally used across China and East/South Asia to treat sore throat, bronchitis, nephritis edema, abscesses, mastitis, hemorrhoids, and bleeding disorders, consistent with traditional indications of heat-clearing, detoxifying, cooling blood, and promoting diuresis. AIM OF THE REVIEW: This study provides a systematic overview of the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and current applications of S. plebeia, while highlighting current research gaps and future perspectives. MATERIALS AND METHODS: A comprehensive literature search was conducted using multiple scientific databases, including Web of Science, PubMed, Elsevier, ACS, CNKI, and Google Scholar, covering publications from database inception to October 2025. Relevant information on the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and applications of S. plebeia was systematically collected, screened, and synthesized according to predefined inclusion/exclusion criteria. RESULTS: To date, 325 constituents have been identified, dominated by flavonoids, phenolic acids, terpenoids, volatile oils, sterols, lignans, and others. Extracts and purified compounds show tradition-relevant anti-inflammatory, antiviral, immunoregulatory, and antioxidant activities, while other reported effects (hepatoprotective, hypolipidemic, cardiovascular-protective, sedative/anticonvulsant, anticancer, and anti-photoaging) are presented as exploratory findings. Quality evaluation evolved from UV and HPLC to UPLC-MS fingerprinting using flavonoids and sesquiterpenes as markers. In practical applications, S. plebeia has been used in medicinal preparations for the management of pharyngitis, bronchitis, nephritis, dermatitis, and anorectal inflammation. In food sector, it has been developed into functional products, including health teas, chewable or effervescent tablets, composite beverages, and co-fermented vinegars. CONCLUSION: Although S. plebeia shows broad pharmacological potential, current investigations remain constrained by incomplete chemical space coverage, limited pharmacokinetic and toxicological characterization, and insufficient well-designed clinical evidence. Future research should focus on comprehensive constituent profiling, mechanism-oriented validation aligned with traditional indications, standardized quality markers/fingerprints, and rigorous PK-toxicology-clinical translation, to promote safe, effective, and evidence-based utilization of S. plebeia in medicine and functional food development.
27 Apr 2026
Read appraisal →Science advances
Repertoire-scale antibody structural prediction informs therapeutic design
We present AF3-TurboAb, a scalable framework that makes a repertoire-scale antibody-antigen complex structural decoding routine for antibody engineering. By eliminating preprocessing bottlenecks, AF3-TurboAb enables end-to-end complex modeling in 0.5 minutes per seed on a single GPU while preserving near-experimental interface fidelity, as validated on ~1000 posttraining Protein Data Bank (PDB) benchmarks and 12 experimentally determined cryo-electron microscopy nanobody-antigen structures. Applying this capability to 275,371 immunization-derived antigen-specific nanobodies produced 28,013 high-confidence complex predictions, substantially expanding the structural landscape of antibody recognition. The resulting atlas reveals hundreds of previously unmapped epitopes, extensive coverage of solvent-exposed surfaces, and recurrent affinity hotspots enriched in aromatic and charged residues. Despite wide sequence diversity, we observe structural convergence at shared epitopes and consistent physicochemical and geometric features that complement and extend existing PDB entries. We demonstrate translational utility by (i) designing durable (escape-proof), multiepitope neutralizers against highly evolved viruses, (ii) identifying cross-species and glycoform-specific binders to a cancer checkpoint, and (iii) enabling near-real-time in silico binder triage. The models and metadata will be shared for community use, establishing repertoire-scale structural decoding as a practical design modality that transforms the scale and speed of structure-guided antibody engineering.
27 Apr 2026
Read appraisal →The New England journal of medicine
Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients
BACKGROUND: Nirmatrelvir-ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir-ritonavir in persons who have been vaccinated, infected naturally, or both is unclear. METHODS: In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)-ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization. RESULTS: From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir-ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir-ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir-ritonavir. Serious adverse events with nirmatrelvir-ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial. CONCLUSIONS: In two open-label trials, nirmatrelvir-ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection. (Funded by the National Institute for Health and Care Research, and others; PANORAMIC ISRCTN number, 2021-005748-31; CanTreatCOVID ClinicalTrials.gov number, NCT05614349.).
25 Apr 2026
Read appraisal →Cell reports. Medicine
A metabolite-augmented FIB-4 machine learning panel achieves superior liver fibrosis staging in chronic liver disease
Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.
25 Apr 2026
Read appraisal →Renal failure
Explainable machine learning using urinary metabolomics to predict pediatric sepsis-associated acute kidney injury: a two-center prospective observational study
Sepsis-induced acute kidney injury (S-AKI) is a common and serious complication in critically ill children with a poor prognosis, and its early and accurate prediction remains challenging due to the lack of reliable biomarkers. Urinary small-molecule metabolomics offers a promising approach to capture the dynamic metabolic changes during the progression of S-AKI. In this two-center prospective observational study, we enrolled 360 children from both centers. Urine samples were collected within 24h after hospitalized children diagnosed with sepsis, stored at -80 °C, and analyzed using gas chromatography-mass spectrometry (GC-MS). Based on urinary metabolic fingerprints (U-MF), we developed and validated a machine learning model for early prediction of S-AKI. The Shapley Additive Explanations (SHAP) algorithm was applied to visually explain the optimal model. A panel of 10 metabolites was selected as common discriminative features. Among the 4 machine learning models evaluated, the support vector machine (SVM) demonstrated the best performance in both the discovery cohort (AUC 0.94, 95% CI: 0.91-0.98) and the external validation cohort (AUC 0.89, 95% CI: 0.82-0.96), enabling early prediction of S-AKI within 24 h. Furthermore, the U-MF panel was integrated into an open-access online platform to facilitate clinical translation. Our findings suggest that U-MF combined with machine learning holds promise as a robust and noninvasive approach with potential utility for early prediction of S-AKI in pediatric patients.
24 Apr 2026
Read appraisal →PloS one
Hepatitis C distribution across diverse population groups in the Eastern Mediterranean Region: An umbrella review
BACKGROUND: Hepatitis C virus (HCV) remains a major public health challenge in the Eastern Mediterranean Region (EMR), with prevalence varying across population groups. This umbrella review summarizes the distribution of HCV infection across diverse populations in the region. METHODS: We conducted an umbrella review of systematic reviews with meta-analyses reporting HCV prevalence in the EMR. PubMed, Web of Science, Scopus, Iranian databases, including Magiran and the Scientific Information Database (SID), were searched. Google Scholar was additionally screened to ensure comprehensive coverage. Pooled estimates were extracted across four population groups: apparently healthy individuals; those with clinical or healthcare-associated exposure risk; patients co-infected with hepatitis viruses or other liver-related diseases; and key populations at increased risk (groups disproportionately affected due to their behaviors and higher vulnerability). For time-period analyses, meta-analyses were grouped into two intervals (before 2015 vs. 2015 and after) based on the median year of data collection of primary studies. Pooled prevalence was calculated using a random-effects model in STATA version 17. RESULTS: A total of 55 meta-analyses were included. The pooled HCV prevalence was 31.0% (95% CI: 27.0-38.0) among key populations, and also 31.0% (95% CI: 12.0-49.0) among patients co-infected with other hepatitis viruses or liver-related diseases. Those with clinical or healthcare-associated exposure risk showed a prevalence of 28.0% (95% CI: 23.0-32.0), whereas the apparently healthy population had the lowest prevalence at 2.0% (95% CI: 1.0-2.0). Subgroup analysis indicated a decline in prevalence among clinically exposed populations after 2015, from 29% to 10%, coinciding with the direct-acting antivirals (DAAs) and strengthened infection-control practices. The highest prevalence was observed among key populations in Libya, healthcare-exposed populations in Morocco, and apparently healthy individuals in Egypt. CONCLUSION: Variation in HCV prevalence across populations in the EMR highlights the need for population-specific strategies to support progress toward World Health Organization elimination targets.
24 Apr 2026
Read appraisal →Journal of Korean medical science
Association Between Changes in Socioeconomic Status Before and After Human Immunodeficiency Virus Infection Diagnosis and Mortality Rates in Korea
BACKGROUND: This study investigated changes in medical insurance status as a surrogate marker of socioeconomic status after human immunodeficiency virus (HIV) infection, and their association with mortality among people living with HIV in Korea. METHODS: This study included 13,112 individuals newly diagnosed with HIV between 2004 and 2018, identified from the claims data of the National Health Insurance System-National Health Information Database. Participants' medical insurance status was categorized into National Health Insurance (NHI) and medical aid (MA). Using the Cox proportional hazards model, the association between mortality and changes in medical insurance status before and after HIV infection diagnosis was assessed using hazard ratios (HRs) and confidence intervals (CIs). RESULTS: The insurance coverage rates before HIV diagnosis were 95.1% and 4.9% for NHI and MA recipients, respectively. After diagnosis, the insurance coverage rates were 13.4% and 86.6% for MA and NHI recipients, respectively, demonstrating a threefold increase in the proportion of MA recipients. The conversion rate from NHI to MA was highest in the 35-44 and 45-54-year age groups at HIV infection diagnosis (32.9% and 29.4%, respectively). Compared with NHI recipients, the HR was significantly higher among individuals that transitioned from NHI to MA (HR, 1.66; 95% CI, 1.39-1.97) and individuals that remained on MA (HR, 1.74; 95% CI, 1.40-2.18), suggesting a higher mortality rate in these groups. CONCLUSION: In Korea, where highly active antiretroviral therapy is essentially free of charge, a significant association was observed between a decline in medical insurance status following HIV diagnosis and increased mortality.
23 Apr 2026
Read appraisal →mSystems
Short-chain fatty acid-producing microbes differentiate non-infectious and infectious neutropenic fever in leukemia.
UNLABELLED: Neutropenic fever (NF) is often the first sign of infection in patients with hematologic malignancies, but its cause is frequently unknown, leading to broad-spectrum antibiotic use without confirmed infections. Although research links gut microbiome disruptions to treatment-related infections, it typically examines NF as the outcome, leaving a gap in understanding how the microbiome and metabolic factors distinguish infectious from non-infectious cases. Stool samples from acute myeloid leukemia patients were analyzed to characterize gut microbiome composition and fecal metabolites at baseline and at fever onset. Machine learning models, network analyses, and functional profiling were used to differentiate infectious NF vs non-infectious NF at baseline and at fever onset. The baseline model (area under the receiver operating characteristic [AUROC] = 0.769) identified higher levels of Akkermansia, Enterobacter, Escherichia-Shigella, and Flavonifractor as predictors of infectious NF, while Collinsella, Lachnospiraceae, Coprococcus, and acetic acid were linked to non-infectious cases. At fever onset, Enterococcus was enriched in infectious NF, whereas Gemella, Butyrate, Lachnospiraceae, Ruminococcaceae, and Eisenbergiella abundances favored non-infectious NF outcomes (AUROC = 0.752). Network analyses also revealed greater functional diversity and microbiome-metabolome connectivity in non-infectious cases at fever onset. This study suggests that gut microbiota and metabolites may serve as biomarkers for distinguishing infectious from non-infectious neutropenic fever, warranting further validation in larger cohorts. IMPORTANCE: Our study tackles the challenge of managing neutropenic fever (NF) in immunocompromised patients whose numbers have increased due to various immunodeficiencies and treatments that suppress immune function. Fever is often the only sign of a serious infection in these patients, yet there are neither clear patterns linking risk factors to infection nor biomarkers reliable for ruling out non-infectious causes. As a result, febrile patients are typically empirically treated for major pathogens, even in the absence of confirmed infections, which propagates antimicrobial resistance and gut dysbiosis. Our research utilizes gut microbiome and targeted metabolomic profiling from two cohorts of patients with acute myeloid leukemia undergoing chemotherapy and employs a machine learning framework to distinguish between infectious and non-infectious NFs at baseline and upon fever onset.
23 Apr 2026
Read appraisal →PloS one
Prevalence of antimicrobial resistance in Tanzania: A systematic review and meta-analysis
Antimicrobial resistance (AMR) threatens global health, and understanding resistance patterns aids in effective treatment and promotes responsible antimicrobial use. Despite the urgency of resistant pathogens, systematic reviews focusing specifically on Tanzania are limited, and while several studies report resistance patterns for individual pathogens, a consolidated analysis of overall prevalence is needed to inform policymaking and public health interventions. Therefore, this review and meta-analysis assessed the prevalence of antimicrobial resistance among clinically relevant pathogens in Tanzania, providing a comprehensive overview to support surveillance, infection control, and stewardship efforts. A total of 1865 studies identified from Google Scholar (1600), PubMed (13), and Science Direct (252) underwent screening and full article review. Finally, 28 studies were included. A subgroup analysis was performed to evaluate the resistance patterns within antibiotic classes for specific pathogens. Descriptive statistics were used to describe the characteristics of the studies, while the prevalence of antimicrobial resistance was estimated through Meta-analysis. Inconsistency and heterogeneity between studies were quantified by the I2 index. Among the included studies, most isolates (25.0%) were obtained from urine samples. Of these studies, 75% were cross-sectional studies and 92.9% were conducted in hospital settings. The analysis revealed high resistance to penicillin, particularly amoxicillin-clavulanic and ampicillin, with Klebsiella pneumoniae (0.96 [0.83-0.99]), Acinetobacter baumannii (0.94 [0.67-0.99]) and Escherichia coli (0.90 [0.81-0.95]). Similarly, erythromycin resistance was most prevalent in Campylobacter spp. (0.85 [0.80-0.89]). Ciprofloxacin resistance was highest in Acinetobacter baumannii (0.54 [0.33-0.73]), whereas amikacin resistance was highest in Proteus spp. (0.86 [0.35-0.99]). Ceftriaxone resistance was particularly high in Acinetobacter baumannii (0.91 [0.70-0.98]) and Pseudomonas aeruginosa (0.85 [0.74-0.92]). Meropenem resistance was lowest among Escherichia coli (0.04 [0.01-0.10]) and Klebsiella spp. (0.07 [0.03-0.15]), while the pooled resistance across ESKAPE-E pathogens was (0.11[0.06-0.19]). Imipenem and clindamycin each had an overall pooled resistance of (0.06[0.02-0.14]) against both Escherichia coli and Klebsiella pneumoniae. The findings highlight widespread resistance among bacterial pathogens, ESKAPE-E, particularly in the Access and Watch groups of antibiotics. The variability in resistance patterns underscores the need for the Ministry of Health to re-evaluate empirical treatment protocols (STG/NEMLIT) to ensure effective treatment regimens, strengthen antimicrobial stewardship, enhance surveillance systems, and promote rational antibiotic use.
23 Apr 2026
Read appraisal →The Analyst
Third-generation nanopore sequencing: advancing real-time pathogen detection and antimicrobial resistance surveillance in food safety applications
Foodborne diseases impact 600 million people annually, causing 420 000 deaths and over $110 billion in economic losses. Conventional pathogen detection methods take 3-7 days and lack sensitivity for low-abundance pathogens and antimicrobial resistance (AMR) genes. This review evaluates nanopore sequencing's potential in food microbiology, analyzing real-time pathogen detection, AMR surveillance, and performance versus traditional methods. A systematic review of 80 studies (2015-2025) revealed nanopore sequencing reduces detection time to <24 hours with 95-98% species identification accuracy and >90% AMR gene sensitivity, at $50-200 per sample versus $300-800 for traditional whole-genome sequencing. It enables multiplex pathogen detection, viable but non-culturable organism identification, and real-time AMR profiling. However, challenges include error rates of 8-15% in homopolymeric regions and the need for bioinformatics expertise. Addressing challenges, including error rates of 8-15% in homopolymeric regions and the need for bioinformatics expertise, requires strategic mitigation approaches. Despite limitations, advances in base-calling and workflows make nanopore sequencing a transformative tool for next-generation food safety surveillance.
23 Apr 2026
Read appraisal →Infectious diseases of poverty
Progress and challenges in development of minimum essential dataset for disease surveillance through a One Health lens: a scoping review
BACKGROUND: Minimum essential dataset (MED) enables One Health surveillance by facilitating cross-sectoral data sharing. Yet, existing MED research represents insufficient integration of the One Health concept, and its progress in disease surveillance remains unclear. This study aims to evaluate the current progress and gaps in MED research in disease surveillance through a One Health lens. METHODS: This scoping review systematically searched Embase, PubMed, Scopus, and Web of Science from the inception of databases to November 30th, 2024 to identify studies published in English. Studies were independently screened by two reviewers for inclusion based on their relevance to the development of MEDs for disease surveillance. The progress and challenges were synthesized based on data extracted from eligible studies. RESULTS: This review includes 28 eligible studies for analysis, all of which focused on infectious diseases. MED development is predominantly concentrated on the human health interface (89.3%), whereas animal and environmental interfaces are comparatively limited (≤ 10.7%). The One Health concept has been adopted in 16 of the eligible studies; however, there is still insufficient interdisciplinary and cross-sectoral collaboration (57.1%). Meanwhile, numerous methods have been employed in the development of MEDs, with qualitative approaches being the most prevalent (42.9%), while data-driven approaches remain scarce. The absence of a standardized approach is recognized as a primary barrier. Thus, we propose a pathway and operational tool to detail the specific steps, which could facilitate future research on MED. CONCLUSION: This review highlights critical gaps in MED development at the human-animal-environment interface, and proposes a pathway and operational tool to inform future development of MED, including scope identification, establishment, modification and improvement. This study promotes the improvement of disease surveillance system and provides insights to enhance future preparedness for reducing the global public health burden.
23 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Lung transplant in people with cystic fibrosis and nontuberculous mycobacteria infection
RATIONALE: Cystic fibrosis (CF) is an inherited multi-organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease. OBJECTIVES: To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026. ELIGIBILITY CRITERIA: We considered non-randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx. OUTCOMES: Our critical outcomes were mortality, disseminated NTM infection post-LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review. RISK OF BIAS: We assessed the risk of bias in three studies using ROBINS-I and in one study using the Joanna Briggs Institute checklist for case series. SYNTHESIS METHODS: We could only report results narratively. We used GRADE to assess the certainty of the evidence. INCLUDED STUDIES: We included four single-centre retrospective studies (388 adults). Sample sizes ranged from nine to 177 participants. Mycobacteria abscessus was the most common NTM species identified, and all studies reported infection with other pathogens. All studies compared pwCF and NTM infection to pwCF without NTM infection, all undergoing LTx. Each study reported mortality and disseminated NTM infection post-LTx; two studies recorded CLAD. No study reported quality of life, specific lung function measures (although one study commented briefly on lung function in general), hospitalisations for pulmonary exacerbations, or nutritional parameters. SYNTHESIS OF RESULTS: We analysed all NTM infections together for practical reasons and were not able to undertake a planned subgroup analysis by subspecies, but acknowledge that the prognosis and clinical trajectory of pwCF infected with different NTM may not be similar. We downgraded the certainty of the evidence due to non-randomised study design and serious risk of bias across all studies. We assessed all identified evidence as of very low certainty, such that lung transplant may have little to no effect on any of the outcomes listed below, but the evidence is very uncertain. Mortality Two studies (18 participants with NTM) reported similar survival data between NTM-positive LTx recipients and matched controls without NTM. Another study (9 participants) reported that two of five participants NTM-positive at LTx died within a few months post-LTx, whilst one of four NTM-negative participants died three years post-LTx due to chronic rejection. One study (177 participants) found that pwCF who had positive NTM cultures pre-LTx had a longer median survival duration than those who had negative cultures. This study additionally reported on survival of participants with post-LTx NTM infection, finding that the five participants who had post-LTx NTM disease had a longer mean survival duration than the 141 participants without post-LTx NTM disease. Disseminated NTM infection post-LTx In the largest study, of the 18 pwCF with NTM at the time of LTx, seven had at least one positive NTM culture, and four developed NTM disease post-LTx. Conversely, 79 of the 89 pwCF without NTM remained so post-LTx; 10 participants recorded a positive NTM culture, but none developed NTM disease. For the 39 participants without a baseline NTM culture, three participants recorded positive NTM cultures post-LTx, and one developed NTM disease. Of the remaining small studies, one reported that NTM was isolated in four of 13 participants at LTx and in three of these post-LTx. A second study reported that one out of five pwCF had NTM infection post-LTx (all were positive at LTx). The third study reported that five out of nine participants had NTM disease at LTx, and two of these five remained NTM-positive post-LTx. CLAD Two studies assessed CLAD. One study reported that none of the five NTM-positive LTx recipients developed CLAD, stating that the risk of CLAD appeared to be similar between the NTM and the comparator group. The second study stated that three out of nine LTx recipients with NTM disease developed chronic rejection or graft dysfunction. AUTHORS' CONCLUSIONS: There are no randomised trials to guide clinicians and patients or their families when making decisions regarding LTx in pwCF with NTM. The available data come from observational studies and registry data, often with few people with NTM reported. It has not been possible to pool the available data in meta-analysis, and we are very uncertain of the effect of NTM on pwCF undergoing LTx on the risk of developing NTM disease post-LTx, survival after LTx, and the development of CLAD. The studies were small and at times contradictory. In the era of highly effective modulator treatments, as some centres do not offer LTx to people with a history of NTM, there is an urgent need for more data to guide decision-making. FUNDING: This review is part of a suite of reviews on NTM funded jointly by the CF Foundation and the CF Trust. REGISTRATION: Protocol registration (2024): www.crd.york.ac.uk/PROSPERO/view/562682.
23 Apr 2026
Read appraisal →Journal of rehabilitation medicine
Effect of inspiratory muscle training on inspiratory muscle strength in adults with post-COVID-19 condition and inspiratory muscle weakness: a randomized controlled trial
OBJECTIVE: Evaluate the effect of inspiratory muscle training in adults with post-COVID-19 condition (PCC) and inspiratory muscle weakness. DESIGN: Randomized controlled trial. SUBJECTS/PATIENTS: Adults with PCC and inspiratory muscle weakness. METHODS: Participants were randomized to inspiratory muscle training twice daily plus individualized exercise twice weekly or exercise alone, with weekly follow-ups over 8 weeks. PRIMARY OUTCOME: inspiratory muscle strength (Maximal Inspiratory Pressure). SECONDARY OUTCOMES: expiratory muscle strength (Maximal Expiratory Pressure); functional capacity (Six‑Minute Walk Test; One‑Minute Sit‑to‑Stand); lung function (spirometry); dyspnoea (mMRC); respiratory symptoms (chest tightness, impaired deep breathing, breathing‑related pain); cough frequency (CAAT cough item); fatigue (Fatigue Severity Scale); physical activity (Frändin-Grimby Activity Scale); activity limitations (Patient‑Specific Functional Scale); and health-related quality of life (EQ‑5D‑5L). Intention-to-treat analyses used imputed missing data. Estimated sample size: 90. RESULTS: Forty-four participants were included (median age 47; 82% women; n = 22/group). Between‑group differences favoured the intervention for inspiratory muscle strength (mean difference: 18%; 95% CI: 5-30; OR for clinically meaningful improvement: 7.08, 95% CI: 1.31-38.32) and cough frequency. No other between-group differences were observed. CONCLUSION: Inspiratory muscle training may improve inspiratory muscle strength and reduce cough frequency, but limited sample size and underrepresentation of the most severely affected warrant cautious interpretation.
23 Apr 2026
Read appraisal →Veterinaria italiana
A One Health systematic review and meta-analysis of Coxiella burnetii prevalence in humans, animals, and vectors in Algeria
Coxiella burnetii, the causative agent of Q fever, is a globally distributed zoonotic pathogen affecting humans, domestic animals, and arthropod vectors. In Algeria, fragmented data suggest widespread circulation, yet no comprehensive quantitative assessment exists. This study aimed to systematically review and meta-analyse the prevalence of C. burnetii in humans, animals, and vectors in Algeria, using a One Health perspective. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted up to January 2026. Studies reporting serological or molecular detection of C. burnetii in Algeria were included. Random-effects meta-analysis was performed to estimate pooled prevalence, with subgroup analyses by host species, region, and diagnostic method. A total of 35 studies were included, encompassing 8,372 samples and 80 prevalence observations. Pooled prevalence was highest in camels (73.7%; 95% CI: 66.5-79.8%), followed by small ruminants (15.8%; 95% CI: 10.6-22.9%) and cattle (11.8%; 95% CI: 7.2-18.8%). Ticks showed a pooled prevalence of 10.0% (95% CI: 3.2-27.1%), while human infection had a pooled prevalence of 3.7% (95% CI: 0.9-13.9%). The south-eastern region exhibited the highest prevalence, and serological methods generally reported higher rates than molecular methods. High heterogeneity (I² > 75%) was observed across studies. Coxiella burnetii is widely circulating among humans, domestic animals, camels, and ticks in Algeria, with notable variation between hosts and regions. Camels and small ruminants act as major reservoirs, while humans remain at risk, particularly those in close contact with livestock. Integrated One Health surveillance and targeted control strategies are urgently needed to reduce the burden of Q fever.
22 Apr 2026
Read appraisal →European journal of pediatrics
Different doses of vitamin A supplementation as adjuvant treatment for pneumonia in children: a network meta-analysis of randomized controlled trials
UNLABELLED: While previous meta-analyses have established a link between vitamin A supplementation and outcomes in children with pneumonia, the efficacy and safety of different dosing regimens remain unclear. Existing evidence is predominantly based on single-dose trials, creating a critical knowledge gap. We systematically searched PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and VIP databases from their inception to December 2025. Study searches were independently carried out in December 2025 by two reviewers. Two researchers used the Cochrane risk of bias tool to independently assess the quality of the included studies. Data analysis was conducted through the "netmeta" package in R software (version 4.3.3). Twenty-five trials involving 3116 patients were included. Network meta-analysis revealed that medium-dose vitamin A supplementation was most effective in reducing the duration of fever and cough. Low-to-medium doses were consistently associated with better clinical outcomes than high-dose regimens. However, evidence regarding safety outcomes remained limited and inconclusive. CONCLUSION: Low-to-medium dose vitamin A supplementation appears superior to high-dose regimens for alleviating clinical symptoms in children with pneumonia. However, the evidence is limited by high heterogeneity, indirect comparisons between dose groups, and poor reporting of adverse events. Future trials should prioritize direct dose-comparisons and rigorous safety monitoring to refine dosing guidelines. WHAT IS KNOWN: • Pneumonia poses a significant threat to the health and lives of children. Vitamin A supplementation plays an adjuvant role in the treatment of pneumonia in children. • There are currently divergent conclusions in the research regarding the optimal dosage of vitamin A, particularly with regard to the safety of high-dose supplementation and the effectiveness of low-dose supplementation. WHAT IS NEW: • This study revealed that medium-to-low-dose vitamin A supplementation appears to be more effective than high-dose therapy in alleviating the primary symptoms of childhood pneumonia. • This study also suggests that children in developed regions have higher baseline serum retinol levels, which may diminish the marginal benefits of high-dose supplementation and may even predispose them to its immunosuppressive effects.
22 Apr 2026
Read appraisal →Journal of medical Internet research
Facility-Level Associations Between Use of a Digital Health Platform for Voluntary Counseling and Testing and HIV Testing Outcomes in the Urban Primary Health Care Centers of Guangzhou, China: Cross-Sectional Study
BACKGROUND: WellTest, a digital health platform designed to facilitate HIV voluntary counseling and testing (VCT) services, has been widely implemented in Guangzhou, China. However, the extent of its use by primary health care centers (PHCs) and the facility-level associations between WellTest use and HIV testing outcomes remain unclear. OBJECTIVE: This study aimed to assess the use of WellTest at the facility level across PHCs in urban Guangzhou, China, and to explore the associations between WellTest use and HIV testing outcomes. METHODS: We obtained data on VCT services visits from the National HIV/AIDS Prevention and Control Information System and the WellTest platform between January 1 and December 31, 2022. Two facility-level HIV testing outcomes, the HIV testing volume and HIV positivity rate, were calculated for each PHC. A structured questionnaire collected data on the PHCs' characteristics. Multilevel negative binomial regression and zero-inflated gamma models were used to examine associations between WellTest use and 2 HIV testing outcomes at the facility level. RESULTS: A total of 81 PHCs across 5 urban districts in Guangzhou were included. WellTest was used for 7997 active consultations and 7969 HIV tests that resulted in 157 newly diagnosed HIV cases, for an overall positivity rate of 2.0%, during 2022. The median share of clients booking via WellTest was 71% (IQR 34%-98%), and 81% (66/81) of PHCs offered online slots on all service days without mandates. PHCs that actively confirmed appointments had significantly lower HIV testing volumes compared with those that took no actions after clients scheduled appointments (incidence rate ratio 0.75, 95% CI 0.58-0.97; P=.03) but exhibited higher HIV positivity rates (β=.39, 95% CI 0.02-0.76; P=.04). Additionally, PHCs where ≥50% of clients used WellTest to schedule appointments showed higher HIV positivity rates than those with lower uptake (β=1.11; 95% CI 0.82-1.40; P<.001). CONCLUSIONS: WellTest showed substantial use among VCT clients and providers in urban Guangzhou PHCs, with greater use of digital appointments and counselor follow-up linked to increased HIV positivity rates. Strategies to optimize institutional adoption may help address stigma-related barriers, strengthen engagement in HIV testing, and support HIV case finding in primary health care settings.
20 Apr 2026
Read appraisal →Journal of gastrointestinal cancer
Effect of Probiotics on the Clinical Outcome and Inflammatory Response in Gastric Cancer Surgery: A Double Blinded Randomized Control Trial
BACKGROUND AND AIM: Gut dysbiosis contributes to postoperative complications and worsens the inflammatory and immune dysfunction in gastric cancer (GC) patients. Probiotics may mitigate these effects by modulating gut microbiota. This study aimed to evaluate the effect of probiotics on the length of hospital stay, other post-operative clinical outcomes, nutritional status, inflammatory and immune markers in patients undergoing gastrectomy for gastric cancer. METHODS: This was a single-centred, prospective, double blinded, placebo-controlled trial. Participants were patients who underwent open gastrectomy for gastric cancer. Participants were randomized to receive probiotics or placebo for 10 days starting on postoperative day (POD) 1. Blood samples were collected preoperatively and POD 10 to assess haemoglobin, total counts, albumin, IL6, TNFα, and IgA. Clinical outcomes including time to first flatus, first passage of stools, oral diet resumption and length of hospital stay (LOHS). Postoperative complications were monitored for 30 days and classified using the Clavien-Dindo system. RESULTS: Of 42 participants (22 probiotic, 20 placebo), baseline characteristics were comparable. The probiotic group had a significantly shorter median LOHS (9 vs. 12 days, p<0.05), earlier time to first passage of flatus (2.6 vs. 4.3 days, p<0.05), earlier time to first passage of stools (3.6 vs. 5.7 days, p<0.05), and oral diet resumption (3.6 vs. 5.7 days, p<0.05). No significant differences were observed in inflammatory markers (TLC, IL-6, TNF-α), immune markers (IgA), nutritional status (albumin, haemoglobin), or postoperative complications (p>0.05). CONCLUSION: Postoperative probiotic supplementation reduced LOHS and improved gastrointestinal recovery in GC patients undergoing gastrectomy, but did not significantly affect inflammatory, immune, or nutritional markers.
20 Apr 2026
Read appraisal →Medicine
Trends and determinants of tuberculosis incidence in Turkey: A secondary data analysis
Tuberculosis remains a major public health concern, with incidence rates influenced by social determinants of health. Although tuberculosis incidence in Turkey has declined markedly in recent decades, the factors associated with this decline have not been comprehensively evaluated at the country-level. This study aimed to examine trends in tuberculosis incidence in Turkey from 1982 to 2021 and to identify determinants of tuberculosis incidence rates between 2000 and 2021, considering variables categorized under composite development, economic indicators, population, and health services. A longitudinal ecological study was conducted using secondary data to examine trends and determinants of tuberculosis incidence in Turkey. Univariate and multivariable linear regression were employed to evaluate the associations between tuberculosis incidence rates and 10 selected variables. Tuberculosis incidence in Turkey declined substantially over the 40-year period analyzed, with an overall decrease of 86.6% and sharper reductions observed in certain intervals. In multivariable linear regression, only the Human Development Index remained independently associated with tuberculosis incidence (β = -1.041, P < .001), indicating that higher Human Development Index values were associated with lower tuberculosis incidence rates in Turkey. These findings indicate that tuberculosis incidence in Turkey has declined alongside changes in human development, as reflected by the composite Human Development Index.
20 Apr 2026
Read appraisal →PloS one
Comparison of OneChoice AI-based clinical decision support recommendations with infectious disease specialists and non-specialists for bacteremia treatment in Lima, Peru
Bacteremia is a major contributor to global morbidity and mortality, particularly in low- and middle-income countries where diagnostic delays and empirical antimicrobial misuse exacerbate resistance. This study assessed the accuracy of OneChoice®, an artificial intelligence (AI)-based Clinical Decision Support System (CDSS), in guiding antimicrobial therapy for bloodstream infections (BSIs) in Lima, Peru. A cross-sectional, observational design was used, comparing therapeutic recommendations generated by OneChoice®-based on molecular (FilmArray®) and phenotypic (MALDI-TOF MS, VITEK2) data-with the clinical decisions of 94 physicians (35 infectious disease [ID] specialists and 59 non-specialists) across 366 survey-based evaluations of bacteremia cases. Concordance between CDSS and physician decisions was analyzed using Cohen's Kappa and logistic regression. The overall concordance rate was 96.1% when considering any suggested treatment, and 74.6% for the top recommendation, with a substantial agreement (κ = 0.70). ID specialists showed significantly higher concordance (κ = 0.78) than non-ID physicians (κ = 0.61), and specialization was the strongest predictor of agreement (OR = 2.26, p = 0.001). Escherichia coli cases had the highest concordance, while Pseudomonas aeruginosa showed the lowest. The CDSS reduced inappropriate antibiotic use, particularly unnecessary carbapenem prescriptions. These findings support the utility of AI-CDSS tools in enhancing antimicrobial stewardship and standardizing care, especially in resource-limited healthcare settings.
20 Apr 2026
Read appraisal →PloS one
Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)
BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,. METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery. RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret. CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.
20 Apr 2026
Read appraisal →Gut microbes
Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture
Patients with Clostridioides difficile infection have high colonic levels of primary bile acids, which are potent germinators of Clostridioides difficile. Several studies have suggested that re-establishing a normal bile acid composition is a key factor in fecal microbiota transplantation (FMT) for recurrent C. difficile infection, yet former studies supporting this lacked controls. In a subgroup from a randomized controlled trial, we compared the bile acid composition in patients with recurrent C. difficile infection treated with either FMT, a bacterial mixture, or vancomycin. The fecal bile acid content was analyzed several times before and after treatments. Furthermore, we used 16S rDNA gene sequencing to analyze the presence of some bacterial species involved in bile acid metabolism. Stool donors served as healthy controls. We observed a higher proportion of primary bile acids in patients with recurrent C. difficile infection than in donors, yet a donor-like dominance of secondary bile acids was observed after successful treatment in all groups. The shift seemed to occur earliest in the FMT group, followed by the vancomycin group, and the latest in the bacterial mixture group. In approximately half of the participants, the rise in secondary bile acids was timely associated with the detection of bile acid-transforming bacteria that were absent before treatment. Our findings indicate that FMT re-establishes the bile acid composition faster than vancomycin, reducing the time of susceptibility to recurrences of C. difficile infection. Hence, bacterial mixtures developed as an alternative to donor stool for treating recurrent C. difficile infection might benefit from including bile acid-metabolizing bacteria.
19 Apr 2026
Read appraisal →PloS one
Hybrid feature-selection and diversity-guided stacking framework for interpretable ensemble learning: Application to COVID-19 mortality prediction
BACKGROUND: Reliable predictive modeling in high-dimensional biomedical data requires a balance between accuracy, interpretability, and computational efficiency. However, existing ensemble methods often overlook model diversity or rely on ad hoc feature-selection approaches, which limit generalizability. This study introduces a hybrid feature-selection and diversity-guided stacking framework designed to improve robustness and scalability across clinical and other data-intensive domains. METHODS: The proposed framework integrates a hybrid feature-selection pipeline-combining Variance Inflation Factor (VIF), Analysis of Variance (ANOVA), Sequential Backward Elimination (SBE), and Lasso regression-to reduce multicollinearity and overfitting. It also employs a diversity-aware stacking strategy that constructs sub-model sets based on pairwise diversity measures (Disagreement, Yule's Q, and Cohen's Kappa) and non-pairwise metrics (Entropy and Kohavi-Wolpert). Sixteen base classifiers and five meta-learners were trained using repeated 10-fold cross-validation. The framework was evaluated using data from 4,778 hospitalized COVID-19 patients with 116 clinical and laboratory attributes, preprocessed using robust scaling and ROSE-based class balancing. RESULTS: The optimal configuration, which stacked Random Forest and XGBoost models using a Neural Network meta-learner, achieved 91.4% accuracy (95% CI: 89.8-92.8), AUC = 0.955, F1 = 0.801, and MCC = 0.746, outperforming the best individual model (AdaBoost, 90.2%). Training time (~450 s) and per-case inference time (<0.2 s) demonstrated computational feasibility. Feature-importance analysis and SHAP-based interpretation confirmed clinical relevance and interpretability. CONCLUSIONS: The hybrid feature-selection and diversity-guided stacking framework improves predictive accuracy and interpretability while maintaining computational efficiency. Although validated using COVID-19 mortality data, the approach is broadly applicable to biomedical, environmental, and engineering prediction tasks that require interpretable and scalable ensemble learning.
19 Apr 2026
Read appraisal →Inflammation research : official journal of the European Histamine Research Society ... [et al.]
The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.
BACKGROUND: Sepsis and septic shock are major causes of mortality in critically ill patients. They are linked to widespread metabolic and immune dysregulation, including alterations in calcium and phosphate homeostasis. The calcium-sensing receptor (CaSR) not only plays a role in mineral balance, but also modulates key immune pathways and may contribute to the pathogenesis of sepsis. METHODS: A systematic literature review was conducted according to PRISMA 2020 guidelines. Four databases (PubMed, EMBASE, Cochrane Library, and Google Scholar) were searched for studies published since 1990. To be eligible for inclusion, articles had to be original research, reviews, or clinical trials involving adult models (mammalian or human). Full-text availability was required. Risk of bias was assessed for all studies included. RESULTS: Sixty-six articles met the inclusion criteria: 49 original studies and 17 reviews. No randomized controlled trials or meta-analyses were identified. Most studies relied on in vitro or in vivo models. CaSR was consistently reported to be upregulated or activated following exposure to bacterial and inflammatory stimuli in immune cells, including monocytes and lymphocytes. CaSR activation promotes proinflammatory cytokine release, notably IL-1β via the NOD like receptor family 3 (NLRP3) inflammasome although results in intestinal epithelial models remain inconsistent. In non-septic models, CaSR activation was associated with tissue and organ injury, including renal and cardiac damage, as well as vasoplegia related to endothelial dysfunction. Preclinical models of pneumonia and endotoxemia suggest that CaSR antagonists may effectively mitigate inflammation and organ injury. CONCLUSION: This systematic review identifies the CaSR as an amplifier of the host inflammatory response across both septic and non-septic preclinical models The lack of robust clinical data underscores the need for translational studies assessing CaSR expression or activity in patients with sepsis or septic shock, alongside in vivo validation of CaSR inhibition as a therapeutic strategy.
19 Apr 2026
Read appraisal →JMIR human factors
Interactive, Personalized Patient Decision Aid for COVID-19 Vaccination in Canada: User-Centered Design Approach
BACKGROUND: The COVID-19 pandemic highlighted the need for practical digital health tools to support informed decision-making amid rapidly evolving evidence and widespread misinformation. OBJECTIVE: We iteratively developed and refined VaxDA-C19, a bilingual (English and French) web-based patient decision aid designed to support informed decision-making in Canada about COVID-19 vaccination. VaxDA-C19 integrates interactive and personalized features aimed to enhance vaccine confidence, reduce cognitive overload, and respond to diverse informational needs. METHODS: VaxDA-C19 was developed using an iterative, user-centered design approach. Throughout the development process, we involved a citizen panel, health care professionals, user experience designers, and scientific experts to guide refinements. We also conducted usability testing sessions with adults in Canada, using semistructured interviews, comparative testing, and think-aloud protocols with thematic analysis. We ultimately conducted 4 design cycles in total with adults in Canada (users) and expert reviewers (experts). Cycle 1 involved 9 people (9 users), cycle 2 involved 22 people (22 users), cycle 3 involved 9 people (3 users and 6 experts), and cycle 4 involved 9 people (9 experts). RESULTS: In cycle 1, user feedback guided design decisions about how to present quantitative information and technical vaccine descriptions more simply. In cycle 2, while most users (9/11, 82%) favored in-depth explanations of vaccine development, a few raised concerns about content that could be perceived as politically charged. Cycle 3 identified usability improvements, including more explicit navigation controls, simplified medical terminology, and optimized interactive components (avatars and sliders). Expert reviews in cycle 4 refined linguistic consistency, mobile responsiveness, content transparency, and scientific accuracy, emphasizing explicit instructional guidance and bilingual accessibility. CONCLUSIONS: Our iterative process produced a personalized, bilingual digital decision aid to support evidence-informed, values-congruent decisions about COVID-19 vaccination. A randomized controlled trial will further evaluate VaxDA-C19's impact on vaccination intentions, knowledge retention, emotional responses, decisional conflict, and decisional regret. If it proves effective, the patient decision aid may also be used as a platform to support other vaccine decisions, namely, influenza, measles, shingles, pertussis, and potentially other emerging infectious diseases.
18 Apr 2026
Read appraisal →Emerging microbes & infections
Optimizing machine learning-based diagnosis of neurosyphilis in HIV-negative patients: a multicenter, real-world comparison of international diagnostic criteria
Neurosyphilis continues to rise globally, yet diagnosis remains challenging, often requiring multidisciplinary expertise and multiple CSF assays that are difficult to access in resource-limited settings. We developed and compared machine-learning (ML) models tailored to six international diagnostic guidelines and built a free, web-based tool for guideline-adapted decision support. We assembled 1,648 suspected neurosyphilis cases from four centers, using Guangzhou as the training cohort and Beijing, Xiamen (China) and Seattle (USA) as external validation cohorts. Five algorithms (Random Forest, AdaBoost, SVC, NuSVC, XGBoost) were trained with randomized search and three-fold cross-validation; performance was assessed by AUC, PRAUC, calibration, decision-curve net benefit, Brier score, and SHAP for model explainability. Across models and guidelines, neurological symptoms, CSF protein, and CSF white blood cell count consistently ranked as the strongest predictors. All models achieved excellent discrimination (AUC and PRAUC >0.90) with good calibration, reliability, and positive clinical utility, though performance varied modestly by guideline. These findings indicate that the optimal ML approach depends on the diagnostic definition applied. Our freely available online tool operationalizes these models to provide clinicians worldwide with context-adapted support aligned to local criteria.
18 Apr 2026
Read appraisal →Nanoscale
Bifunctional PVDF/MXene membranes with high piezoelectric sensitivity and near infrared photothermal antibacterial efficacy toward wearable human activity monitoring
In the realm of wearable health monitoring, establishing a reliable interface that ensures both high-fidelity sensing and long-term biological safety remains a critical challenge, particularly due to the risk of bacterial infection caused by sweat accumulation at the device-skin contact. Herein, we address this issue by developing a scenario-driven, bifunctional PVDF/MXene nanofibrous membrane that integrates robust piezoelectric performance with on-demand photothermal antibacterial capability. In this design, MXene nanosheets function simultaneously as nucleating agents to boost the electroactive β-phase content of PVDF from 80.3% to 93.3% and as efficient near-infrared (NIR) photothermal agents. The optimized membrane exhibits a superior piezoelectric sensitivity of 0.502 V/N, enabling the precise detection of diverse human activities ranging from subtle pulse waveforms to vigorous jumping motions, and motion-triggered Morse code communication. Crucially, addressing the hygiene concerns of reusable wearables, the membrane achieves rapid, non-contact sterilization during off-wear intervals. Under safe NIR irradiation (0.3 W cm-2), the surface temperature rises to ∼60 °C within 60 s, achieving an antibacterial efficacy of >99% against S. aureus and E. coli. Combined with excellent in vitro cytocompatibility, this work provides a "one-structure, dual-function" solution for constructing hygienic, high-performance electronic skins.
17 Apr 2026
Read appraisal →PloS one
upsML: A high-accuracy machine learning classifier for predicting Plasmodium falciparum var gene upstream groups
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the hypervariable var gene family, is central to malaria pathogenesis, influencing both disease severity and immune evasion. Classifying var genes into upstream groups (upsA, upsB, upsC, upsE) is important for understanding parasite biology and clinical outcomes, but remains challenging, especially with partial sequences, such as the DBLα tag or RNA-Seq assemblies. We developed upsML, a machine-learning-based classifier trained on 2,530 curated var genes, to accurately assign upstream groups based on sequence features from different partial gene regions. We compared seven methods, including support vector machines, random forests, XGBoost, and HMMER models. Several models in upsML achieve accuracies of 83% for DBLα-tag sequences and 92% for full-length PfEMP1 sequences, thereby significantly outperforming existing tools. Additionally, we developed a model to distinguish internal from subtelomeric var genes, which we applied to a global collection of P. falciparum genomes, revealing a higher frequency of internal var genes in Asia. upsML is available at https://github.com/sii-scRNA-Seq/upsML, providing a robust and efficient resource for large-scale var gene analysis. It can classify var genes from 20 genomes in under one second.
17 Apr 2026
Read appraisal →JMIR formative research
A Survey of Primary Care Clinician Experiences With Electronic Health Record-Based Clinical Decision Support to Improve HIV Pre-Exposure Prophylaxis Prescribing
A survey of primary care clinicians suggests that a clinical decision support tool to support sexual risk assessment and prescribing of HIV pre-exposure prophylaxis was appropriate and useful for identifying at-risk patients, but uptake was hindered by workflow and usability barriers, which underscores the importance of postimplementation clinician feedback to improve the use of clinical decision support tools.
17 Apr 2026
Read appraisal →BMJ open respiratory research
Personalised management of community-acquired pneumonia and the role of Clinical Decision Support Software
Community-acquired pneumonia (CAP) is one of the most common causes of hospital admission and is associated with significant morbidity and mortality. National and international guidelines are available to guide the management of CAP, including antibiotic prescribing. However, these guidelines are often not adhered to and there is significant overprescribing of broad-spectrum antibiotics, contributing to the growing pandemic of antimicrobial resistance. Clinical Decision Support Software (CDSS) are electronic tools that use individual patient data to generate patient specific assessments or recommendations, that can then be acted on by the patient or clinical decision maker. This article reviews the evidence surrounding the initial management of CAP in hospital and considers the potential of CDSS to support CAP management.
17 Apr 2026
Read appraisal →Computers in biology and medicine
A systematic review and benchmarking of modern metagenomic tools for taxonomic classification
Advancements in metagenomics have been driven by the continuous development of bioinformatic tools, particularly taxonomic classification software, which are central to the accurate characterization of microbial communities. However, establishing direct comparisons between these tools remains challenging due to variations in evaluation metrics, reference databases, and input data types. In this study, we present a systematic review of recently developed metagenomic taxonomic classification tools. Of the 31 identified tools, nine satisfied all functional and methodological criteria for the benchmark analysis. We evaluated their accuracy and computational performance using a standardized dataset derived from the NCBI RefSeq database. Our analysis revealed that most of these tools are domain-specific, each excelling in particular areas. Tools like TAMA, CAMITAX and PhyloFlash achieved higher accuracy for prokaryotic organisms, while ViWrap and PhaBOX achieved higher accuracy for viral classifications. SqueezeMeta achieved high F1 scores across most domains, though its assembly-based architecture limits effectiveness on highly diverse samples. MegaPath-Nano was least affected by increased mutation rates. The execution time varied widely among the tools, with domain-specific and machine learning-based tools generally being faster, while tools like BASTA had longer runtimes and lower accuracy. This review synthesizes performance results for current tools, providing an overview of their strengths and computational methodologies.
17 Apr 2026
Read appraisal →Water research
Representation of urban and rural contexts in the application of wastewater surveillance for antimicrobial resistance: A systematic review.
Wastewater surveillance (WWS) can reveal community health trends through targeted monitoring of sewage. Given concerns regarding the global dissemination of drug-resistant infections, there is growing integration of antimicrobial resistance (AMR) in WWS infrastructure. However, most WWS has focused on highly urbanized sewersheds in resource-rich areas, which may exacerbate disparities in disease burdens and clinical datasets. This work presents both a systematic and scoping review of current published WWS efforts targeting antimicrobial resistance (AMR), with the aim to quantify and compare applied monitoring efforts capturing rural vs. urban areas and lower-income vs. higher-income countries. Of the 2,873 deduplicated manuscripts identified through a systematic search of four databases, 454 examined untreated domestic sewage and were characterized via a brief scoping review. Of these, 48 articles included an explicit focus on monitoring for population health surveillance, and were subject to methodological data extraction and risk of bias assessment. Sampling trends observed in the scoping and systematic review were similar. Only 13-19 % of scoping review sampling sites were classified as rural, and 44 % were located within lower- or middle-income countries (LMICs). Few articles examined AMR within unsewered communities. While analytical methods were similar across income brackets, rural monitoring efforts were more reliant on culture-based techniques than urban efforts. Monitoring in rural sites and LMICs were typically part of multi-site campaigns and featured less longitudinal sampling. Overall, methodological inconsistencies rendered a meta-analysis infeasible. The combined lack of research in rural and low-income areas indicates that key at-risk communities for circulation of AMR are an oversight.
17 Apr 2026
Read appraisal →BMJ open
Trends and characteristics of syphilis incidence in Japan: a nationwide claims-based analysis of working-age populations and their dependents, 2016-2023
OBJECTIVES: To examine trends and demographic characteristics of syphilis incidence in Japan using a large nationwide claims database with family linkage, with particular focus on differences by sex, age, HIV status and family relationships. DESIGN: Retrospective cohort study. SETTING: JMDC claims database (JMDC Inc, Tokyo, Japan), a nationwide administrative claims database in Japan, using data from 2016 to 2023. PARTICIPANTS: Individuals aged 16-59 years enrolled in the JMDC database, including employees of medium-to-large companies and their dependents (n=12.5 million). OUTCOME MEASURES: Syphilis cases were defined by International Classification of Diseases, 10th Revision (ICD-10) codes (A50-A53) with concurrent treatment with relevant antibiotics. We determined syphilis incidence rates per 100 000 person-years, stratified by sex, age, HIV status and family relationships. We also investigated within-couple concordance patterns and reinfection rates. RESULTS: Among 16.4 million individuals, 9357 syphilis infections were identified among 8881 individuals. Incidence increased markedly during the pandemic, reaching 48.2 (men) and 12.9 (women) per 100 000 person-years in 2023. Men showed consistently high incidence in their 20s-50s, whereas female incidence peaked in the 10s-20s. Among 2 294 184 married couples, dependent women (ie, housewives) showed comparably high incidence to age-matched men (10-20 per 100 000 person-years). In 1286 couples with at least one syphilis case, 12.4% of wives in their 20s were also diagnosed, compared with 2%-3% in older groups. In 20s couples, the proportion of syphilis among wives only and husbands only was similar. Subgroup analysis revealed notably high incidence among unmarried female dependent youths (2022: 66.7 per 100 000 person-years). Individuals living with HIV had substantially elevated incidence (3000-15 000 per 100 000 person-years) and reinfection rates. CONCLUSIONS: Using a large claims database with family linkage, we found that while male syphilis incidence remained dominant, high rates were also observed among dependent women and youths. These findings suggest that syphilis risk may extend beyond traditionally recognised high-risk populations and emphasise the need for targeted screening and preventive strategies in broader demographic groups.
17 Apr 2026
Read appraisal →Stem cell reports
Cellular immunotherapy for COVID-19-induced acute respiratory distress syndrome: Results of the CIRCA-19 phase 1 safety and phase 2 randomized controlled trials
The ability of immunomodulatory mesenchymal stromal cells (MSCs) to improve COVID-19-associated acute respiratory distress syndrome (ARDS) in clinical trials is uncertain. We assessed whether freshly cultured umbilical cord (UC)-derived MSCs improved outcomes in patients with severe COVID-19 ARDS. We enrolled 37 patients with severe COVID-19 ARDS: 15 in the phase 1 dose escalation and open label extension studies (NCT04400032), and 22 patients in the phase 2b randomized clinical trial (NCT04865107). Delivery of up to 270 × 106 MSCs in three divided daily doses was well tolerated and resulted in qualitative improvement in all clinical outcomes. Furthermore, MSCs resulted in resolution of lymphopenia, consistent with an important immunomodulatory effect, with significant improvement in patient reported quality-of-life measures (SF-36) at 6 months pointing to possible durable clinical effects. These findings suggest a potential benefit of freshly cultured, UC-MSCs in severe COVID-19 ARDS, associated with biological evidence of favorable immunomodulatory activity.
17 Apr 2026
Read appraisal →Emerging microbes & infections
Cross-protection against highly pathogenic avian influenza H5N1 virus from seasonal influenza vaccines: a systematic review and meta-analysis of ferret studies
The recent surge in spillover events of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b to humans and mammals in North America has raised urgent pandemic concerns. Human H5N1 vaccines are unavailable in most countries. We synthesized data from ferret challenge trials to evaluate whether widely available seasonal influenza vaccines confer cross-protection against lethal H5N1 infection. We systematically searched PubMed, Embase, and Web of Science for ferret studies of lethal H5N1 challenge published up to 5 July 2025 (PROSPERO #CRD42024520346). Random-effects meta-analyses were conducted to compare vaccine efficacy (VE) of seasonal influenza vaccines and H5N1 vaccines against H5N1-related mortality. Seroprotection was defined as a neutralizing antibody titre of ≥1:40. We identified 35 studies (157 trials). Seasonal influenza vaccines without N1 did not confer significant cross-protection (five trials; VE 14.8%, 95% CI -3.6 to 30.0). In contrast, VE was 73% for N1-containing seasonal influenza vaccines (19 trials; 95% CI 54-84) and 77% for H5N1 vaccines overall (133 trials; 95% CI 72-82) (p = 0.52). The VE of N1-containing seasonal influenza vaccines was modestly lower than that of H5N1 vaccines with seroprotection (88%; 66 trials; 95% CI 84-91; p = 0.009), but comparable to H5N1 vaccines that did not achieve seroprotection (63%; 67 trials; 95% CI 52-71; p = 0.29). The VE of seasonal influenza vaccines against H5N1 was robust across sensitivity analyses, with no evidence of publication bias (p = 0.99). Seasonal influenza vaccines significantly reduce H5N1-associated mortality in ferret trials, suggesting the cross-protection potential of currently available vaccines. Human studies are warranted.
16 Apr 2026
Read appraisal →The New England journal of medicine
Selective Decontamination of the Digestive Tract during Ventilation in the ICU
BACKGROUND: Whether selective decontamination of the digestive tract (SDD) reduces mortality among patients undergoing mechanical ventilation and whether it adversely affects microbial ecology in the intensive care unit (ICU) remain unclear. In an earlier analysis of data from Australia, SDD did not result in a lower incidence of in-hospital death than standard care, but data from the full international trial are needed. METHODS: We randomly assigned ICUs in Australia and Canada to use SDD or to continue standard care for two 12-month periods in patients undergoing mechanical ventilation. Patients in the SDD group received specific oral and gastric antimicrobial interventions for the duration of ventilation and an intravenous antibiotic agent for the first 4 days after enrollment. All other patients in the ICU were included in an observational ecologic assessment. Previously reported data from Australia are now combined with data from Canada. The primary outcome was in-hospital death from any cause at 90 days. The secondary clinical outcomes, assessed at 90 days, were death in the ICU and the number of days alive and free of mechanical ventilation, ICU admission, and hospitalization. Microbiologic secondary outcomes included new positive cultures for bloodstream infections and antibiotic-resistant organisms. For the ecologic assessment, the microbiologic outcomes were tested for noninferiority (noninferiority margin, 2 percentage points). RESULTS: In this trial involving 20,000 patients in 26 ICUs, 9289 patients were enrolled in the randomized trial and 10,711 were included in the ecologic assessment. At 90 days, 1175 of 4215 patients (27.9%) in the SDD group and 1494 of 5065 (29.5%) in the standard-care group had died before hospital discharge (odds ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P = 0.27). New bloodstream infections occurred in 4.9% of the patients in the SDD group and in 6.8% of those in the standard-care group (adjusted mean difference, -1.30 percentage points; 95% CI, -2.55 to -0.05); antibiotic-resistant organisms were cultured in 16.8% and 26.8%, respectively (adjusted mean difference, -9.60 percentage points; 95% CI, -12.40 to -6.80). In the ecologic assessment, noninferiority of SDD was not confirmed for the development of new antibiotic-resistant organisms. Adverse events considered to be related to SDD or standard care were reported in 12 patients (0.3%) in the SDD group and in no patients in the standard-care group. Serious adverse events occurred in 47 patients (1.1%) and 59 patients (1.2%), respectively. CONCLUSIONS: Among critically ill patients undergoing mechanical ventilation, SDD did not result in a lower incidence of in-hospital death than standard care. (Funded by the National Health and Medical Research Council of Australia and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02389036.).
16 Apr 2026
Read appraisal →Global health action
Impact of climate change on pediatric health outcomes
Climate change has become one of the most critical health issues globally in the twenty-first century with children bearing the disproportionate burden of the burden since they are more vulnerable than adults because of their physiological, behavioral, and developmental capacities. It is a systematic review that rates the evidence of the relationship between climatic exposures such as heat, air-pollution, and extreme weather events and pediatric health outcomes. The number of peer-reviewed studies involved was 23 published in 2000-2025, which represented different geographic areas and study designs and assessed acute and chronic health outcomes. The Newcastle-Ottawa Scale and the ROBINS-I tool were used to evaluate the methodological quality, and the majority of the studies had low to moderate risks of bias. The narrative synthesis shows that there are always links between air pollutants especially PM2.5, NO2 and O3 and respiratory morbidity, prevalence of asthma and hospitalization of children. Amplified temperatures as well as heat waves were associated with increased cases of heat illness, dehydration, and febrile state in infants and young children. There were elevated cases of diarrheal and vector-related infections, especially in low-resource settings, which were linked to extreme weather events especially floods. Although the overall results were similar, significant differences in the regions and methods were found, and low-income countries show little evidence. In addition, exposures as analyzed in most studies were usually considered individually, which may have underestimated the cumulative or compound climate risks. Main findings: This review shows that rising temperatures, air pollutants, and extreme weather events are consistently linked with higher rates of respiratory illness, heat-related illness, and infectious diseases among children.Added knowledge: The synthesis brings together two decades of evidence showing that children across multiple continents experience similar health vulnerabilities when exposed to climate-related environmental conditions.Global health impact for policy and action: The findings highlight an urgent need for stronger climate-responsive child health policies and early warning systems to protect children from worsening environmental threats worldwide.
16 Apr 2026
Read appraisal →ChemMedChem
Structure- and Ligand-Based Discovery of Novel 3-Chymotrypsin-Like Protease Nonpeptidomimetic Hits
The SARS-CoV-2 3-chymotrypsin-like (3CLpro) protease is a key target for the development of COVID-19 therapeutics. While ensitrelvir and nirmatrelvir are approved drugs for treatment, the continuous research and development for new antiviral drugs is necessary to combat the emergence of variants and other related viruses. This study employed structure- and ligand-based computer-assisted approaches to identify new 3CLpro nonpeptidomimetic inhibitors. Using data from COVID Moonshot, NCATS, and the literature, computational methods such as shape-based, ensemble docking, and machine learning (ML) techniques were developed, achieving robust validation metrics: AUC = 87%, EF = 7, BEDROC = 60% for shape-based; AUC = 87%, EF = 7.03, BEDROC = 62% for ensemble docking, and ACC = 81%, MCC = 62% for ML models, combing Random forest + ECFP4 fingerprint. These models were utilized in virtual screening (VS) campaigns using the H3D and ChemBridge libraries, from which six promising hits with IC50 values ≤80 µM were identified, including LabMol-499 with an IC50 of 13.71 µM and a Ki of 21.74 µM. Moreover, we found that LabMol-499 acts as a noncompetitive, reversible inhibitor of 3CLpro. These findings provide a foundation for hit-to-lead optimization of new nonpeptidomimetic 3CLpro inhibitors.
15 Apr 2026
Read appraisal →European journal of pediatrics
Clinical response and risk factors of fecal microbiota transplantation in children: a systematic review and meta-analysis
UNLABELLED: The objective of this study is to investigate the clinical response and incidence of adverse events (AEs) following fecal microbiota transplantation (FMT) in children, across various diseases, populations, and treatment protocols. A systematic search was conducted across eight major Chinese and English databases, identifying 47 studies up to August 28, 2025, for inclusion. Study quality was assessed using the Quality Assessment with Diverse Studies (QuADS) tool. Single-arm rates were pooled via meta-analysis employing the Freeman-Tukey double arcsine transformation, followed by extensive subgroup comparisons to identify influencing factors. FMT demonstrated efficacy in pediatric recurrent Clostridium difficile infection (rCDI), inflammatory bowel disease (IBD), and autism spectrum disorder (ASD), although a higher incidence of AEs was observed in children with IBD. Subgroup analyses revealed that the use of donor feces from relatives or friends was associated with a higher clinical response rate in rCDI. The presence of comorbidities such as IBD diminished the response rate in rCDI patients. Younger age in rCDI and IBD patients showed a trend towards higher clinical response rates, though this did not reach statistical significance. No statistically or clinically significant differences were found in other subgroup comparisons. Meta-regression suggested IBD to be a risk factor for FMT-related AEs. CONCLUSION: This study innovatively delineates the efficacy-safety profile of pediatric FMT and outlines a pathway for optimizing individualized treatment regimens, providing crucial evidence-based guidance for clinical practice. TRIAL REGISTRATION: This study has been registered on the PROSPERO database (CRD42024614196). WHAT IS KNOWN: • Fecal Microbiota Transplantation (FMT) demonstrates preliminary therapeutic potential in several pediatric diseases. • Existing evidence remains fragmented, with limited systematic data on factors modifying efficacy and safety in children. WHAT IS NEW: • The study revealed FMT's high efficacy across rCDI, IBD, and ASD, and identified IBD as a risk factor for elevated FMT-related adverse events in pediatric patients. • Notably, related/friend donors improved rCDI response rates, while comorbidities like IBD reduced rCDI treatment efficacy.
15 Apr 2026
Read appraisal →Current pain and headache reports
Stellate Ganglion Block in the Treatment of Long COVID: A Systematic Review
OBJECTIVES: This review evaluates stellate ganglion block as a treatment for long COVID, seeking to evaluate the treatment's efficacy by various symptoms and the limitations of the current literature. STUDY DESIGN: Systematic Review. SETTING: Ambulatory or Outpatient Setting. METHODS, SUBJECTS: A systematic review of the current literature regarding use of stellate ganglion block in patients with long COVID was conducted. 2 databases were searched on August 28th, 2025. Search terms were "long COVID" and "stellate ganglion block", yielding 45 results. Studies examining patient outcomes after stellate ganglion block were included. Case reports, case series, basic science studies and previous reviews were excluded. Seven studies met inclusion criteria. RESULTS: Patients received a single stellate ganglion block in some studies and multiple stellate ganglion blocks in others. All studies reported symptomatic improvement without control groups. Response rates ranged from 55.8% to 100%. The most robust improvements (> 80% patients reporting relief) were seen in cough, dyspnea, headache, joint pain, pain interference/intensity, pins/needles, subjective relief. CONCLUSION: Stellate ganglion block is a promising treatment that appears to generate substantive benefit for many of the symptoms seen in long COVID. However, the current literature has small, uncontrolled studies with heterogenous study designs and follow-up periods. Standardized research with larger sample sizes, control groups, and longer-term follow up is necessary to elucidate the degree of benefit. IRB approval and clinical trial registration not required.
15 Apr 2026
Read appraisal →Nature communications
A group 1 hemagglutinin stem vaccine elicits broad humoral responses against influenza in phase 1/2a study
Vaccines targeting the conserved stem region of influenza hemagglutinin (HA) may induce broad immunity and reduce reliance on strain-matched seasonal formulations. This Phase 1/2a study evaluates safety and immunogenicity of a universal influenza vaccine component comprising a soluble trimeric stabilized group 1 HA-stem protein (INFLUENZA G1 mHA). Healthy adults aged 18-to-45 received one or two doses at 45 µg or 135 µg, with or without Al(OH)₃. Primary endpoints were safety and reactogenicity. All regimens were well-tolerated with no vaccine-related serious adverse events. Secondary and exploratory endpoints included binding, neutralizing, and ADCC responses compared to a matched quadrivalent seasonal influenza vaccine cohort. A single dose induced robust binding antibody responses to H5 HA and homologous stem HA, with 6.5-16.4-fold increases at Day 29 versus baseline, exceeding responses elicited by the seasonal influenza vaccine. Additionally, we demonstrate broader binding to a panel of group 1 HAs, with responses maintained for at least one year. Neutralizing antibody and ADCC responses at Day 29 showed 7.9-15-fold and 4.9-8.6-fold increases, respectively. Importantly, serum from vaccinated participants protect mice against lethal heterologous H5N1 challenge. This study provides proof of concept that the HA stem vaccine elicits broad and durable influenza A group 1-directed immunity. This trial is registered with ClinicalTrials.gov (NCT05901636).
15 Apr 2026
Read appraisal →PloS one
Use of administrative data for evaluating trends in medically-attended Lyme disease, Manitoba, Canada, 2010-2021
While Lyme disease (LD) is the most common tick-borne disease reported to public health surveillance in North America and is increasingly recognized as a public health threat in Canada, it's incidence may be underreported. Our study aims to estimate medically-attended LD incidence in Manitoba, Canada, using administrative health data. We identified medically-attended LD cases in Manitoba from 2010 - 2021 in a claims database (Manitoba Population Research Data Repository), which contains the health records of >95% of the residents of Manitoba, using diagnostic codes, antibiotic dispensations, and laboratory results. The incidence of claims-based LD cases ranged from 8.4 to 28.5 per 100,000 population per year, 5.1 to 11.0 times higher than the incidence of surveillance-reported LD cases. The incidence of claims-based LD cases was particularly higher than the incidence of surveillance-reported LD cases in females and health regions with a low surveillance-reported incidence. Our study suggests that medically attended LD is more common than reported in surveillance. Further study is required to identify barriers to reporting. Interventions are needed to reduce the substantial burden of LD in Manitoba.
15 Apr 2026
Read appraisal →Journal of medical Internet research
Digital Monitoring of Pre-Exposure Prophylaxis Users Through Electronic Patient-Reported Outcome Measures and Electronic Patient-Reported Experience Measures: Multicenter Prospective Study on Feasibility, Safety, and Predictive Modeling of Digital Engagement
BACKGROUND: Digital health tools integrating electronic patient-reported outcome and experience measures (ePROMs/ePREMs) enable longitudinal monitoring of health-related quality of life (HRQoL), psychological well-being, and treatment satisfaction in pre-exposure prophylaxis (PrEP) users. However, determinants of sustained engagement with digital follow-up platforms remain insufficiently characterized. OBJECTIVE: To describe the feasibility of the Naveta-Phemium digital platform for longitudinal monitoring of safety, HRQoL, and treatment satisfaction among PrEP users, and to develop and internally validate a machine learning framework to characterize and predict engagement with digital follow-up. METHODS: A prospective observational study was conducted using the Naveta digital follow-up platform. HIV-negative adults at high risk of HIV infection received tenofovir disoproxil fumarate (245 mg) plus emtricitabine (200 mg). Clinical safety, HRQoL, and satisfaction were assessed using laboratory parameters and validated ePROMs/ePREMs (Hospital Anxiety and Depression Scale, Patient-Reported Outcome Measurement Information System Profile-29, Treatment Satisfaction Questionnaire for Medication, and Person-Centered Coordinated Care Experience Questionnaire). Engagement was defined at the questionnaire level and analyzed using the ALGOPROMIA-Classification framework with repeated stratified cross-validation. Model explainability was assessed using permutation-based Shapley Additive Explanations. RESULTS: A total of 81 participants contributed repeated questionnaire-level observations (mean PrEP duration 689 d). PrEP was well tolerated, with no moderate or severe adverse events; mild transient symptoms were mainly gastrointestinal (31/45, 68.9%) and neurological (26/45, 57.8%). Renal function remained stable (creatinine: 0.86 [SD 0.13] mg/dL; estimated glomerular filtration rate: P=.498). Psychological well-being and HRQoL remained stable (Hospital Anxiety and Depression Scale<7; Patient-Reported Outcome Measurement Information System Profile-29 near population norms). Treatment satisfaction was consistently high (Treatment Satisfaction Questionnaire for Medication≈85-87), and satisfaction with the NAVETA telemedicine model remained stable (8/10). Engagement showed clear sociodemographic and behavioral gradients. Ensemble-based machine learning models achieved good discrimination in predicting engagement (area under the curve≈0.82) across ≈12,300 questionnaire-level observations. Random forest was retained for robustness and consistency. Shapley Additive Explanations analysis highlighted lifestyle-related variables as the most influential predictors, with heterogeneous individual-level effects. CONCLUSIONS: Naveta enabled feasible telemedicine-based PrEP follow-up with preserved HRQoL, high satisfaction, and stable safety. Combining longitudinal ePROMs/ePREMs with explainable machine learning allowed detailed characterization of digital engagement, supporting digitally supported PrEP care optimization and informing future comparative and cost-effectiveness studies.
15 Apr 2026
Read appraisal →PloS one
Virologic suppression among HIV-positive pregnant and lactating women receiving antiretroviral therapy in Africa: A systematic review and meta-analysis
BACKGROUND: The elimination of mother-to-child transmission of human immunodeficiency virus (HIV) is a key global public health priority. In Africa, virologic failure among people living with HIV continues to pose a significant public health challenge, affecting both individual well-being and community health. Maintaining viral load suppression is crucial to prevent vertical transmission of HIV and to minimize maternal morbidity and mortality. To stop the vertical transmission of HIV and lower the risk of maternal morbidity and mortality, it is important to achieve viral load suppression. Although many African countries have adopted the global 95-95-95 targets, comprehensive data on virologic suppression among pregnant and lactating mothers across the continent remains limited. The objective of this systematic review and meta-analysis was to determine the pooled estimate of virologic suppression and to examine the factors associated with it among HIV-positive pregnant and lactating women on antiretroviral therapy in Africa. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251186121). We carried out a thorough systematic review by examining PubMed, ScienceDirect, Hinari, and Google Scholar for relevant studies. Data from the studies were retrieved using an Excel sheet and analyzed with STATA version 17. The Joanna Briggs Institute appraisal tool was used to evaluate the methodological quality of studies. A random-effects model with restricted maximum likelihood (REML) was applied to determine the pooled prevalence of virologic suppression (viral load threshold ≤1000 copies/ml) among pregnant and lactating mothers in Africa. A funnel plot and the Egger's test were used to investigate publication bias. Statistical heterogeneity was assessed using the I2 statistic and Cochrane's Q test. RESULTS: A total of 55 eligible studies, comprising 304,883 participants, were included in the quantitative meta-analysis. Accordingly, the overall prevalence of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was 80.86% (95% CI: 77.63%, 84.09%, I2 = 99.84%). In contrast, the pooled estimate for achieving an undetectable viral load was substantially lower, at 60.92% (95% CI: 52.46%, 69.39%; I2 = 99.91%). Virologic suppression was significantly associated with women's age (15-24 years) (AOR = 0.49; 95% CI: 0.32-0.77), disclosure of HIV status to a partner (AOR = 1.66; 95% CI: 1.31-2.11), first-line antiretroviral therapy regimen (AOR = 6.53; 95% CI: 1.93-22.06), and good antiretroviral drug adherence (AOR = 3.61; 95% CI: 1.18-11.02). In addition, other socio-demographic variables, higher educational level, being married/cohabitant, urban residency, healthcare utilization (time of ANC booking, time of ART initiation, duration of ART), fear of stigma, distance to health facility, shortage of health professionals, ART drug stock-out, and lack of HIV care commodities were significantly associated with virologic suppression among HIV-positive pregnant and lactating women in Africa. CONCLUSION: The pooled estimate of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was approximately 81%, below the global target of 95% virological suppression. This emphasizes the necessity of targeted strategies for younger HIV-positive women, disclosing HIV status, initiating first-line antiretroviral regimens, and promoting antiretroviral treatment adherence. Upgrading health care systems to enable regular viral load monitoring, as well as addressing socio-demographic and antiretroviral therapy-related variables, are vital steps towards attaining and sustaining VS in these groups of population, ultimately assisting in achieving elimination of MTCT of HIV.
14 Apr 2026
Read appraisal →Biomacromolecules
Highly Flexible, Adhesive, Antimicrobial, and Self-Powered Hydrogel Strain Sensor for Human Motion Monitoring
Piezoelectric hydrogel sensors are a recent innovation that combines the flexibility of hydrogels with the self-powering of piezoelectric materials. Here, we present a self-powered hydrogel strain sensor by incorporating piezoelectric Na0.5Bi0.5TiO3 nanoparticles into a dual-network hydrogel composed of poly(vinyl alcohol), acrylamide, and 2-acrylamido-2-methyl-1-propanesulfonic acid. The hydrogel exhibits excellent mechanical properties, achieving a tensile strength of 1.28 MPa, an elongation at break of 1127%, and strong tissue adhesion (55.97 kPa on porcine skin). The sensor delivers a maximum output voltage of 237.4 mV, a sensitivity of 17.99 mV under small compressive strain, and a broad tensile strain detection range of 30 to 400%. It reliably monitors both subtle physiological activities (facial expression, swallowing, pulse) and large joint movements. Moreover, it exhibits notable antibacterial performance via ultrasound-driven piezocatalysis, reducing bacterial viability to below 1.5%. This tough, adhesive, and antibacterial piezoelectric hydrogel sensor holds significant promise for wearable electronics and human-machine interfaces.
14 Apr 2026
Read appraisal →Journal of chemical information and modeling
Multiscale-Aware Graph Embedding Approach Uncovers LC-61, a Potent Anti-Leishmania infantum Compound
Visceral leishmaniasis caused by Leishmania infantum remains a lethal disease with few therapeutic options, necessitating innovative computational methods and approaches to accelerate drug discovery. Here, we present a graph neural network (GNN) framework incorporating well-established multiscale mechanisms to improve the identification of novel antileishmanial compounds. Across two classificatory antileishmanial data sets, our GNNs demonstrated significant improvements in predictive performance, with area under the receiver operating characteristic curve (AUC) increases of 2.2-29.2% on the imbalanced data set (activity cutoff: 1 μM) and 3.4-22.5% on the balanced data set (activity cutoff: 10 μM) compared to default GNNs. Subsequently, the framework was applied to screen a library of approximately 1.3 million compounds, pinpointing LC-61 as a potent antileishmanial agent with nanomolar activity against intracellular L. infantum (IC50 = 0.076 μM) and minimal cytotoxicity to macrophages (THP-1 CC50 = 157 μM). A comprehensive in vitro ADME profiling revealed that LC-61 combines high solubility at both acidic and physiological pH (>28 μg/mL), balanced lipophilicity (eLogD = 4.07), and favorable passive permeability (PAMPA = 4.86 × 10-6 cm/s), while exhibiting lower microsomal stability. Overall, our GNN framework effectively accelerated the discovery of LC-61, a novel and biologically validated hit suitable for hit-to-lead optimization.
14 Apr 2026
Read appraisal →Medicine
Comparative evaluation of human T lymphocytes in HIV patients treated with lamivudine + zidovudine combined with nevirapine versus efavirenz
This study aimed to explore the efficacy of lamivudine + zidovudine plus nevirapine and efavirenz in the treatment hf human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). A total of 100 patients with HIV/AIDS admitted to our hospital from June 2021 to September 2024 were selected and randomly assigned into nevirapine and efavirenz groups (n = 50 per group). The nevirapine group was treated with lamidudine plus zidovudine combined with nevirapine, and the efavirenz group was treated with lamidudine plus zidovudine plus efavirenz. The primary outcomes measured were the changes of lymphocyte count and adverse effects after 3 months of treatment. There was no statistical difference in baseline information between the 2 groups. After treatment, CD3 + and CD4 + levels were higher in the nevirapine group than in the efavirenz group (P <.05, 95% CI: 45.2-98.7 for CD3 + and 32.8-76.4 for CD4+), and CD8 + levels were lower in the nevirapine group than in the efavirenz group (P <.05); the overall incidence of adverse effects in the nevavirapine group was significantly lower than that in the efavirenz group (P <.05). In HIV/AIDS patients, treatment with lamivudine + zidovudine combined with nevirapine resulted in significantly improved CD4 + T cell counts, enhanced immune function, and fewer adverse reactions compared to treatment with lamivudine + zidovudine plus efavirenz, suggesting superior clinical value of the nevirapine-containing regimen.
12 Apr 2026
Read appraisal →Medicine
Association of blood urea nitrogen to serum albumin ratio with mortality in ICU patients with sepsis-induced coagulopathy: A Retrospective Cohort Study from MIMIC-IV database
The blood urea nitrogen to serum albumin ratio (BAR) has shown promise as a prognostic marker in sepsis, yet its specific role in sepsis-induced coagulopathy (SIC) remains unclear. We aimed to clarify whether BAR informs mortality risk in critically ill intensive care unit (ICU) patients with SIC. Using the Medical Information Mart for Intensive Care IV database, we identified consecutive ICU patients admitted between 2008 and 2022 who fulfilled Sepsis-3 criteria and had an SIC score ≥4. BAR was calculated from the 1st available laboratory values. Multivariable Cox regression and restricted cubic splines were used to estimate mortality associations after adjustment for demographics, comorbidities, interventions, severity scores (Sequential Organ Failure Assessment, Simplified Acute Physiology Score II), and laboratory parameters. The primary end-point was 30-day mortality; 90- and 365-day mortality were secondary. Among 4244 patients, higher admission BAR independently predicted increased mortality at 30, 90, and 365 days. Each 10-unit rise in BAR conferred a 30% higher hazard of death within 30 days (unadjusted hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.25-1.35; P < .001). After full adjustment, the association persisted (HR 1.18, 95% CI 1.12-1.24; P < .001). Similar patterns were seen for longer-term outcomes. A clear dose-response relationship was observed across BAR tertiles; patients in the highest tertile (BAR ≥ 10 mg/g) had markedly higher mortality risk (adjusted HR 1.69, 95% CI 1.43-2.00; P < .001) than those in the lowest. Nonlinear analysis revealed a curvilinear BAR-mortality relationship, and subgroup analyses showed consistent findings, with significant effect modification by age. In critically ill patients with SIC, an elevated admission BAR independently predicts short- and long-term mortality and may aid risk stratification and early intervention planning.
12 Apr 2026
Read appraisal →Medicine
Prognostic factors for mortality in age-stratified elderly sepsis patients: A retrospective cohort study based on the MIMIC-IV database
Sepsis represents a major cause of death among elderly patients; however, prognostic factors specific to different age strata within this population remain insufficiently characterized. This retrospective cohort study aimed to identify early predictors of mortality in elderly sepsis patients using the MIMIC-IV database. We included 13,461 sepsis patients aged ≥60 years, stratified into younger-old (60-74 years; n = 7618) and older-old (75-90 years; n = 5843) groups. Propensity score matching was applied to balance baseline characteristics, yielding 4657 matched patients per group. Multivariable logistic regression, receiver operating characteristic analysis, and Kaplan-Meier survival curves were employed to assess clinical and biochemical markers for 28-day mortality and to identify age-specific prognostic indicators. These findings underscore the importance of age-stratified prognostic models to guide targeted clinical interventions and potentially improve outcomes in elderly patients with sepsis. Lactate dehydrogenase (LDH) and the PaO2/FiO2 ratio emerged as key mortality predictors in the younger-old group, whereas urea nitrogen and hypoalbuminemia were predominant in the older-old group. Urine output served as a common predictor across both strata, with oliguria associated with a 2.5-fold increase in mortality risk among older patients. While a combination of predictors enhanced prognostic accuracy in younger-old patients, this was not observed in the older-old group, suggesting a greater influence of frailty and comorbidities in advanced age.
12 Apr 2026
Read appraisal →Vaccine
Adenovirus type 5 vector-based COVID-19 vaccine does not increase the likelihood of HIV infection
BACKGROUND: There is a concern about the potential increased risk of acquiring HIV infection after vaccination with adenovirus type 5 (Ad5) vector-based vaccines. We aimed to investigate whether Ad5-nCoV increases the risk of HIV infection. METHODS: Between September 2020 and March 2021, a Phase 3 clinical trial was executed to evaluate the efficacy of Ad5-nCoV. This trial, employing a double-blind, randomized, and placebo-controlled design, enrolled 44,247 participants from 66 clinical sites spanning Argentina, Chile, Mexico, Russia, and Pakistan. Participants were allocated randomly in a 1:1 ratio to receive either Ad5-nCoV or a placebo, and their HIV-negative status was assessed by self-report and confirmed by HIV testing on a baseline blood sample at the end of the study. Consequently, individuals initially administered a placebo received one dose of Ad5-nCoV, while those initially given Ad5-nCoV finally received two doses, with an interval of approximately 6-10 months between administrations. The trial design and primary outcomes have been previously reported. This analysis involves a comprehensive assessment of the associations between pre-existing Ad5 neutralizing antibodies, HIV prevalence and incidence before and after vaccination while accounting for demographic variables. RESULTS: A total of 43,780 participants who had valid HIV baseline testing results were included in this study. Prior to vaccination, there was no discernible difference in HIV prevalence between the placebo group (0·39% of 21,877 participants) and the Ad5-nCoV group (0·38% of 21,893 participants). This similarity persisted when the data were stratified by country, gender, age, and race. Paired analyses assessing HIV incidence were conducted on participants who tested negative for HIV before vaccination, with data collected over a 6-month period post-vaccination. The results revealed notable similarity in HIV incidence across all groups: 0·29% for Group A (Ad5-nCoV group), 0·21% for Group B (Placebo group), 0·27% for group A + D (Ad5-nCoV group and 1 × Placebo+1 × Ad5-nCoV group), 0·1% for Group C (2 × Ad5-nCoV group), and 0·25% for Group A + C + D (participants who received at least one dose of Ad5-nCoV). Testing approximately 100 randomly chosen participants in each country revealed a similar distribution of pre-existing Ad5 neutralizing antibodies (Nab), with the ratio above a titer of 200 ranged from 65·42% to 67·71%. Notably, the heightened presence of pre-existing Ad5 Nab did not result in an increased risk of HIV infection. CONCLUSION: The Ad5-nCoV did not increase the short-term risk of HIV infection in this large and diverse sample of the general population, regardless of the presence of pre-existing Ad5 Nab providing valuable insights into the safety of Ad5 vector-based vaccines. CLINICALTRIALS: gov, NCT04526990.
12 Apr 2026
Read appraisal →PloS one
Integrative bioinformatics and machine learning identify shared molecular mechanisms and diagnostic biomarkers between Helicobacter pylori infection and atrial fibrillation
BACKGROUND: Helicobacter pylori (H. pylori) infection and atrial fibrillation(AF) are major global health concerns. Emerging evidence has suggested a potentially chronic inflammation-mediated link between them, but the shared genetic mechanisms remain unclear. METHODS: We analyzed multidataset gene expression profiles from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment, and machine learning were employed to identify common genes, pathways, and diagnostic biomarkers. Protein-protein interaction (PPI) networks, drug-gene analysis, and molecular docking were used to identify hub genes and potential therapeutics. RESULTS: We identified 73 common differentially expressed genes (DEGs) between H. pylori infection and AF, which were predominantly enriched in immune-related processes including leukocyte activation, neutrophil migration, and myeloid cell-mediated immunity. Machine learning identified 15 and 23 key feature genes for H. pylori and AF, respectively, with S100A8 emerging as a shared diagnostic biomarker. Ten hub genes including TYROBP, ITGB2, and SPI1, were identified from the PPI network. Drug repositioning analysis suggested retinoic acid, indirubin, and ropivacaine as candidate therapeutics targeting these key hub genes. CONCLUSION: Our integrative analysis highlights the central role of immune-inflammatory pathways in linking H. pylori infection to AF. We propose S100A8 and other identified hub genes as potential biomarkers and therapeutic targets. The predicted candidate therapeutics, particularly retinoic acid, may offer novel avenues for intervention, warranting further experimental validation.
12 Apr 2026
Read appraisal →BMJ paediatrics open
Which healthcare services did children and adolescents use before presentation at specialised outpatient clinics for post-COVID-19 condition? Descriptive findings from the Post-COVID Kids Bavaria study.
OBJECTIVE: Measuring the utilisation of healthcare services in children and adolescents with symptoms suggesting post-COVID-19 condition (PCC) until their presentation at specialised outpatient clinics (SOC). METHODS: 117 patients (aged 4-17 years) with symptoms suggesting PCC were recruited for study participation in SOCs of the comprehensive care network 'Post-COVID Kids Bavaria' for children and adolescents with PCC in Bavaria, Germany. Information on healthcare utilisation from their initial SARS-CoV-2 infection until presentation at an SOC was collected via telephone interviews with parents. RESULTS: Participants had a median of 6.5 physician contacts (Q1-Q3: 3.8-11.5), mainly in person (99.1%, n=116) and rarely used telemedicine (21.4%, n=25). Contacts were mainly with paediatricians (72.6%, n=85), followed by general practitioners (46.2%, n=50). Non-pharmacological measures were used by 56 participants (47.9 %), with therapies by Heilpraktiker and osteopaths being used most commonly (30.8%, n=36). 76 participants (65.0%) were prescribed medications, and 71 (60.7%) used non-prescribed medications or supplements. CONCLUSIONS: Children and adolescents with PCC symptoms frequently consult healthcare services, often self-initiated measures provided by Heilpraktiker and osteopaths, until their presentation at an SOC. This may be due to unclear care pathways. Paediatricians and general practitioners are key providers, making their expertise and strong connections with SOCs essential for early diagnosis and appropriate treatment.
12 Apr 2026
Read appraisal →BMJ paediatrics open
Systematic review of the evidence of cardiac dysfunction and intravenous fluid use among children with severe acute malnutrition and severe dehydration
BACKGROUND: A sizeable proportion of cholera attributed mortality occurs among children with severe acute malnutrition (SAM). International guidelines severely limit the use of intravenous fluids among children with SAM and cholera due to their perceived vulnerability to fluid overload. We reviewed the cardiac function evidence and studies of intravenous fluid use among children with SAM. METHODS: Two systematic reviews of Chinese, English, French and Spanish language papers published after the last Global Task Force for Cholera Control recommendations on the treatment of children with cholera and SAM (2017) were conducted. The first included studies of cardiac function among children presenting to hospital with SAM. The second included studies of intravenous fluid use among children with dehydrating diarrhoea and SAM. RESULTS: Among eight echocardiographic studies of cardiac function in children with SAM at presentation to hospital, all found left ventricular mass to be decreased but none found systolic function to be impaired. Seven of the eight studies assessing diastolic function found some degree of mild-to-moderate impairment. Two echocardiographic studies monitored responsiveness to intravenous fluid resuscitation and found no evidence of fluid overload. Finally, four studies gave intravenous fluids to children with SAM and either shock or dehydration. Collectively, these studies included 251 children with SAM given intravenous fluid. No cases of fluid overload were observed. CONCLUSION: No evidence to support decreased systolic function among children with SAM and no documented cases of fluid overload during intravenous rehydration of these children were identified. These data call into question guidelines that severely restrict intravenous fluids among children with SAM and highly dehydrating conditions such as cholera.
12 Apr 2026
Read appraisal →Global public health
Seroprevalence of hepatitis C virus among refugees, asylum seekers, and internally displaced populations within Africa: A systematic review and meta-analysis
Hepatitis C virus (HCV), an often overlooked public health concern, is highly prevalent among marginalized groups. Refugees, asylum seekers, and internally displaced people (RASIDP) constitute an underserved population in healthcare. Given that displacement rates are increasing and that HCV is endemic to many African countries, we aimed to determine the prevalence of HCV among RASIDP communities in Africa. Studies investigating HCV prevalence within RASIDP communities across Africa were identified via the following database searches: Ovid MEDLINE, EMBASE, Web of Science, APA PsycINFO, and the WHO Africa Index Medicus. Seroprevalence estimates were meta-analysed using a random-effects model, with data stratified by participant region, age, and gender. Across 9 studies, we estimated a pooled HCV seroprevalence of 3.63% (95% CI: 0.54, 9.16) among RASIDP in Africa. Seroprevalence varied by region of origin and age, with those from Northern Africa and those aged > 40 years having the highest seroprevalence, at 10.03% (95% CI:9.03, 11.13) and 5.70% (95% CI: 0.81, 14.21), respectively. RASIDP communities represent a marginalised and vulnerable population that often faces significant barriers to accessing healthcare. Our findings show that HCV seroprevalence within these communities varies by region and age, thus suggesting a need for targeted screening approaches.
12 Apr 2026
Read appraisal →Vaccine
Increasing HPV vaccine uptake using a "start at 9" strategy: A pilot program
BACKGROUND: Human papillomavirus (HPV) vaccine completion rates by 13 years remain suboptimal. Earlier HPV vaccination may result in improved timely completion rates. We aim to describe the impact of recommending HPV vaccine at 9 years of age on vaccine completion rates. METHODS: We implemented a multi-level program (including policy development, provider and office personnel education, electronic health record changes, and use of vaccine promotional items) to facilitate routine HPV vaccine recommendation at 9 years at 2 pediatric practices. Monthly chart reviews were performed 6 months before through 18 months after program implementation. Outcome measures included rates of HPV vaccination and documentation of HPV vaccine during the visit. Quarterly data (age, HPV vaccination status, gender, race, ethnicity, insurance, and primary care provider type) were obtained from the electronic health records of 9-12-year-olds served by the practice from baseline through 18 months after program implementation. RESULTS: Following program implementation, the median percentage of HPV vaccine uptake among 9-10-year-olds increased from 8% to 41% at the urban practice and from 3% to 23% at the suburban practice. Similarly, HPV vaccine completion rates among 9-12 year olds increased from 9% to 14%, p < 0.001 and from 6% to 16%, p < 0.001, respectively. Documentation of provider vaccine recommendation strongly correlated with HPV vaccination. CONCLUSION: Implementation of a multi-level program to routinely recommend the HPV vaccine at 9 years of age is feasible and effective in increasing in HPV vaccine completion by 13 years of age.
12 Apr 2026
Read appraisal →PloS one
Predicted meta-omics: A potential solution to multi-omics data scarcity in microbiome studies
Imbalances in the gut microbiome have been linked to conditions such as inflammatory bowel disease, diabetes, and cancer. While metagenomics and amplicon sequencing are commonly used to study the microbiome, they do not capture all layers of microbial functions. Other meta-omics data can provide more insights, but these are more costly and laborious to procure. The growing availability of paired meta-omics data offers an opportunity to develop machine learning models that can infer connections between metagenomics data and other forms of meta-omics data, enabling the prediction of these other forms of meta-omics data from metagenomics. We evaluated several machine learning models for predicting meta-omics features from various meta-omics inputs. Simpler architectures such as elastic net regression and random forests generated reliable predictions of transcript and metabolite abundances, with correlations of up to 0.77 and 0.74, respectively, but predicting protein profiles was more challenging. We also identified a core set of well-predicted features for each meta-omics output type, and showed that multi-output regression neural networks performed similarly when trained using fewer output features. Lastly, our experiments demonstrated that predicted features can be used for the downstream task of inflammatory bowel disease classification, with performance comparable to that of experimental data.
11 Apr 2026
Read appraisal →Vaccine
Impact of pharmacy-based interventions on vaccination coverage among vulnerable and underserved populations: a systematic review and meta-analysis
BACKGROUND: Vaccination coverage remains suboptimal among vulnerable and underserved adult populations. We investigated the effectiveness of pharmacy-based interventions in improving vaccine uptake in high-risk groups and the most effective strategies. METHODS: A systematic search (PubMed/MEDLINE, Embase, Scopus; 26 July 2025) identified experimental and observational studies evaluating pharmacy-led vaccination interventions targeting adults ≥65 years or individuals aged 18-64 years with chronic conditions or limited healthcare access. The primary outcome was vaccination coverage. Odds ratios (ORs) were pooled using fixed- and random-effects models. Sensitivity analyses were conducted by intervention type and setting. Risk of bias was assessed using ROBINS-I, RoB 2, and NOS tools. RESULTS: A total of 35 studies were included, encompassing over 1.3 million participants. In pre-post comparisons, pharmacy-based interventions nearly doubled vaccination uptake (random-effects OR = 1.88; 95% CI: 1.68-2.12). In case-control analyses, individuals exposed to pharmacist interventions were almost five times more likely to be vaccinated (random-effects OR = 4.87; 95% CI: 2.23-10.64). Multicomponent strategies and direct vaccine administration by pharmacists produced the most consistent improvements. CONCLUSIONS: Pharmacist-led vaccination interventions significantly increase vaccine uptake among vulnerable adults. The most effective approaches involved pharmacists included eligibility assessment, counselling, administration, and documentation, integrated within routine care workflows.
11 Apr 2026
Read appraisal →PloS one
Inconsistent condom use and its associated factors among female sex workers in African countries: Systematic review and meta-analysis
BACKGROUND: Inconsistent condom use represents the most proximal behavioral risk factor for acquisition and transmission of sexually transmitted infections, including human immunodeficiency virus. However, certain situations hinder female sex workers from practicing consistent condom use. This study aimed to assess the pooled estimate of inconsistent condom use among female sex workers and identify factors associated with it. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 reporting checklist. Electronic databases (PubMed, Cochrane Library, Epistemonikos, Hinari, and Science Direct), Google Scholar, and other university repositories were searched until March 20, 2024, based on the eligibility criteria. Three independent reviewers screened the titles, abstracts, and full texts. Two independent reviewers extracted the data. The Joanna Briggs Institute quality appraisal checklist was used. The Higgin's I² test was used to quantify heterogeneity. Pooled analysis was conducted using a random-effects model. Sensitivity and subgroup analyses were done. Publication bias was assessed using Egger's regression test and funnel plot. The pooled prevalence and statistical association were declared at a p-value < 0.05 with the 95% CI. RESULTS: A total of 24 studies involving 23,496 female sex workers with a median age of 27.3 years were included. The overall pooled prevalence of inconsistent condom use among FSW in Africa was estimated at 46.73% (95% CI: 37.60, 55.86), I² = 99.59%, and p = 0.00. Condom availability (AOR = 0.68; 95% CI: 0.50, 0.92), depression (AOR = 1.51; 95% CI: 1.00, 2.30), no education (AOR = 1.87; 95% CI: 1.19, 2.93), two or more nonpaying clients (AOR = 2.90; 95% CI: 1.51, 5.54), having >9 current client number (AOR = 0.46; 95% CI: 0.29, 0.74), violence (AOR = 1.74; 95% CI: 1.33, 2.27), and police harassment (AOR = 2.28; 95% CI: 1.03, 5.05) were significant factors. CONCLUSION AND RECOMMENDATION: Inconsistent condom use was high in Africa. Factors including availability of condoms, depression, and education, having two or more nonpaying clients, client numbers, violence, and police harassment were significant factors. Strategies like improving peer education, providing mental health support, empowering women, and improving female sex workers educational status, ensuring condom availability, and strengthening supply for easily accessible condoms can decrease inconsistent condom use and protect FSWs from STI including HIV.
11 Apr 2026
Read appraisal →PloS one
Risk factors for spontaneous abortion following hepatitis E vaccination during and shortly before pregnancy: Further analysis from a cluster-randomized trial
BACKGROUND: A recent randomized trial of Hepatitis E Vaccine (HEV239) found an elevated risk of spontaneous abortion (SAB) in women given HEV239 during or within ninety days before pregnancy. Here we present additional analyses to better understand this risk. METHODS: We investigated whether maternal risk profiles of SAB or gestational age at SAB differed between women receiving HEV239 versus control Hepatitis B vaccine (HBV). We also assessed whether HEV239-vaccinated women who experienced SABs had distinct short-term adverse reactions compared to HEV239-vaccinated women who had live births, exploring potential inflammatory mechanisms. Finally, we assessed maternal exposure to HEV239 in narrowly defined pre-last menstrual period (LMP) windows to more precisely demarcate pre-LMP at which HEV-239 vaccination was associated with an elevated risk of SAB. Chi-square tests and Mann-Whitney U tests were performed for bivariate comparisons. Poisson models were used for multivariable analyses. FINDINGS: Baseline maternal risk factors for SAB (age, body mass index, parity, and histories of SAB, hypertension, or diabetes) were similar between the SABs in HEV239 and HBV groups. Median gestational age at SAB was comparable (10.5 weeks [IQR 10-13] for HEV239 vs. 11 weeks [IQR 9-12.2] for HBV, p = 0.783). No increased short-term adverse events (pain: 9% vs. 9%; fever: 2% vs. 1%) were observed among HEV239 recipients who experienced SABs compared to those who did not. An elevated risk of SAB was observed in HEV239 recipients vaccinated 31-60 days pre-LMP (Relative Risk 4.3 [95% CI 1.3-19.3], p = 0.026). INTERPRETATION: Our analyses did not uncover associations pointing to a biological mechanism underlying the original observation of an increased SAB rate connected to HEV239 vaccination shortly before or during pregnancy. Targeted studies such as placental examinations and genetic testing are needed to investigate potential mechanisms.
11 Apr 2026
Read appraisal →Cell host & microbe
VIBRANT: A phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis
Bacterial vaginosis (BV) is characterized by high microbial diversity. High recurrence rates following antibiotics may stem from poor recolonization by protective Lactobacillus species. This phase 1 randomized trial in the United States and South Africa evaluated two vaginally delivered live biotherapeutic products (LBPs) containing multiple Lactobacillus crispatus strains. After metronidazole treatment for BV, participants received either a placebo or 3 or 7 days of active LBPs. LBP strains were detected by metagenomics in 66.1% (47/71) of participants in the active arms in the first 5 weeks. Among those, nearly half (49%, 23/47) remained colonized at 12 weeks despite the short initial treatment course. Participants were most often colonized by one of three component strains, with no geographic differences in strain colonization observed. LBPs were safe, acceptable, and well tolerated, with no serious adverse events (AEs) reported. These results provide a foundation for the development of transformational interventions aimed at optimizing the vaginal microbiome.
11 Apr 2026
Read appraisal →Cell host & microbe
Vaginal microbiota impacts of a Lactobacillus crispatus live biotherapeutic and predictors of colonization in randomized controlled trial
Bacterial vaginosis (BV) affects >25% of women worldwide and often recurs after standard-of-care metronidazole (MTZ) treatment. LACTIN-V, a live biotherapeutic product (LBP) containing Lactobacillus crispatus strain CTV-05, significantly reduced recurrent BV in a phase 2b clinical trial, but efficacy was incomplete. Here, we characterize microbiota and immune effects using multi-omics and define correlates of treatment success. By week 12, an L. crispatus-dominant microbiota was achieved in 30% of LBP recipients compared with 9% of placebo recipients (benefit ratio: 3.31; p < 0.005). This is primarily due to CTV-05, but native L. crispatus strains are also present and increase over time. Inflammatory cytokines decrease in both arms after MTZ but return to baseline in placebo recipients. Successful L. crispatus colonization is associated with pre-MTZ microbiota, baseline inflammatory profiles, post-MTZ bacterial load, and clinical and behavioral variables. These findings elucidate LBP microbiota effects and identify predictors of treatment success, informing improved intervention strategies to advance women's health.
11 Apr 2026
Read appraisal →PloS one
An interpretable deep learning framework for predictive modeling of postoperative infections in ICU patients
A significant proportion of intensive care unit (ICU) patients undergo surgical procedures, and some may develop postoperative infections. Accurately predicting postoperative infection risk and identifying key contributing factors is crucial for improving postoperative management and understanding infection mechanisms. However, this task is challenging due to the complex interplay of multiple risk factors. While machine learning models can model these intricate associations to predict postoperative infection risk, their lack of interpretability - failing to uncover each factor's impact-hinders their adoption in clinical settings. To address this difficulty, we introduced an interpretable deep neural network (DNN) model that integrates a permutation feature importance test (PermFIT). PermFIT rigorously evaluates the impact of each feature on postoperative infection risk through a rigorous statistical inference. By using only the identified important features as inputs, the DNN's predictive performance can be further enhanced. We conducted an extensive study using electronic health records (EHRs) from the Medical Information Mart for Intensive Care (MIMIC-III), a large-scale ICU EHR database. Under the PermFIT framework, our DNN model effectively identifies significant factors associated with postoperative infections while delivering the most accurate postoperative infection risk predictions. These findings highlight the clinical utility of our proposed DNN framework in managing postoperative care for ICU surgical patients, ultimately improving their health outcomes.
10 Apr 2026
Read appraisal →Microbiology spectrum
PneumoWiki: a pan-genome-based database for the pathogen Streptococcus pneumoniae
UNLABELLED: The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that exhibits more than 100 different capsular serotypes and considerable genomic variability. S. pneumoniae is also an important model organism for basic and biomedical research, with a number of strains with different characteristics being used. To address this, we have created the manually curated pan-genome database PneumoWiki (https://pneumowiki.med.uni-greifswald.de) that integrates genomic data of 43 S. pneumoniae strains with various aspects of functional annotation. All data relating to a specific gene and gene product are compiled on a Gene page. In addition to the gene and protein sequences and annotation from NCBI RefSeq, this includes, for example, data on gene expression, protein function, and localization. The information is supplemented with links to the data sources as well as to other databases and relevant literature. The basic concept of PneumoWiki is the interlinked presentation of pan-genome-based and strain-specific information. Therefore, register tabs with strain names at the top of the Gene pages allow switching between orthologous genes and the corresponding pan-genome page. The pan-genome gene pages contain a summary with functional information and the occurrence of the gene, an ortholog table for the 43 S. pneumoniae strains, a multiple-strain genome viewer as well as a protein sequence alignment. PneumoWiki was developed as a user-friendly tool and is available free of charge. The data collected in PneumoWiki are accessible via various download options. Overall, PneumoWiki is a resource for the research community that supports the analysis and interpretation of experimental data and, in particular, enables the integration of the knowledge available for different S. pneumoniae strains. IMPORTANCE: Databases that integrate and curate the large amounts of genomic data and functional information available for well-studied organisms play an increasingly important role in many areas of life sciences, including infection research. Streptococcus pneumoniae is a major human pathogen associated with high morbidity and mortality rates. The species exhibits high variability in its genome sequence, and a number of strains with different characteristics are used in pneumococcal research. We created the wiki-type database PneumoWiki to provide researchers with curated, up-to-date information on a range of pneumococcal genomes, focusing on the individual genes and encoded proteins and their functional annotation. The key feature of PneumoWiki is the pan-genome approach, which allows combining information of individual strains, thereby supporting the analysis of experimental data and comparisons between studies using different strains. In this way, the database becomes a valuable research tool that can contribute to a better understanding of pneumococcal physiology.
10 Apr 2026
Read appraisal →Journal of medicinal chemistry
Rational Design of Broad-Spectrum Non-Nucleoside Reverse Transcriptase Inhibitors via Pharmacophore-Oriented Generative Artificial Intelligence
Guided by the pharmacophore-oriented molecular generation platform PhoreGen, we employed rilpivirine (RPV) as a lead compound to generate 300 structurally diverse analogs that preserve key pharmacophoric features. Subsequent drug-likeness evaluation, molecular docking score, and synthetic feasibility led to the identification of compound No.102 (A19), which displayed potent inhibition activity against WT HIV-1 (EC50 = 3.15 nM) and low cytotoxicity (CC50 > 335 μM). Subsequent structure-activity relationship optimization identified A24, which demonstrated robust activity against clinically relevant drug-resistant HIV-1 mutants (EC50 = 2.07-28.8 nM). Notably, compared to RPV, A24 exhibited significantly reduced cytotoxicity (CC50 = 82.3 μM vs. 3.98 μM) and enhanced potency against the Y188L (EC50 = 28.8 nM vs. 79.4 nM) and F227L + V106A (EC50 = 19.0 nM vs. 81.6 nM) mutants. Pharmacokinetic evaluations revealed that A24 exhibited attenuated CYP enzyme inhibition (IC50 ≥ 1.88 μM), reduced hERG-related toxicity (IC50 = 2.633 μM), and improved metabolic stability (human t1/2 = 39.1 min). Collectively, these favorable properties position A24 as a promising NNRTI for further development.
10 Apr 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Prevalence of respiratory viruses in stable and acute asthma: a systematic review and meta-analysis
BACKGROUND: Respiratory viruses, frequently detected in asthma, are associated with worse outcomes. This meta-analysis systematically quantifies the prevalence of respiratory viruses in stable and acute asthma, across children and adults, and explores factors associated with increased viral burden through meta-regression. METHODS: This prospectively registered meta-analysis (PROSPERO-CRD42023375108) included studies employing molecular techniques to assess respiratory virus prevalence in asthma. Three databases were searched in August 2024. Risk of bias and certainty of evidence were assessed. We performed random-effects meta-analysis of proportions. RESULTS: We included 111 eligible studies. Moderate-certainty evidence indicated a pooled prevalence of any respiratory virus of 33.9% (95% confidence interval 24.8-43.7%) in children and 23.0% (12.9-35.0%) in adults with stable asthma. In acute asthma, prevalence increased to 58.8% (52.5-65.0%) in children and 49.9% (41.2-58.5%) in adults (moderate certainty). Rhinovirus was the most frequently identified virus, especially in acute asthma (45.0% in children versus 21.2% in adults). Respiratory syncytial virus and bocavirus were more common in younger children, while coronavirus and influenza were more frequently detected in adults; respiratory syncytial virus peaked in older adults too. A higher prevalence of influenza virus B and adenovirus in children, and of influenza virus A and parainfluenza 2 in adults with severe versus non-severe acute asthma suggests a potential association with more severe acute attacks. CONCLUSION: Respiratory viruses are common in both stable and acute asthma. This suggests that the diagnostic value of a positive viral test during acute episodes may be limited and could benefit from complementary biomarkers to improve interpretation.
10 Apr 2026
Read appraisal →Sexual health
Resilience of STI service delivery in community-based organizations during the 2024 armed conflict: insights from Lebanon.
This study explores the potential impact of war on STI services in Lebanon. Programmatic STI service data from Lebanon were analyzed, alongside a targeted review of the literature on conflict-affected settings, using public health databases covering the period 2014-2024. Evidence-based STI service packages for conflict settings remain limited. Drawing insights from the COVID-19 crisis, periods of emergencies are associated with an elevated risk of STI surges among key populations. Programmatic data from the conflict further demonstrated this increased risk, reflected in reductions in prevention and early detection activities compared with pre- and post-conflict periods. Self-care and outreach service packages could be critical in these contexts. Community-based organizations (CBOs) should adapt STI services to the wartime environment and evaluate the effectiveness of these interventions post-conflict. CBOs are encouraged to prioritize the implementation of self-care modalities for STI prevention and early detection, expand the availability of telehealth services, and deploy mobile clinics to maximize service continuity. This editorial analyzes STI service delivery within the specific context of the Lebanese war.
9 Apr 2026
Read appraisal →The New England journal of medicine
Immunogenicity and Safety of vYF, a Yellow Fever Vaccine - A Phase 2 Trial
BACKGROUND: A next-generation, live-attenuated yellow fever vaccine, vYF, was developed in Vero cells to improve vaccine supply and availability. The safety of and immune response to vYF as compared with those of the licensed yellow fever vaccine, YF-VAX, are unclear. METHODS: In this year 1 interim analysis of a phase 2, observer-blinded, randomized, active-controlled trial, we randomly assigned healthy adults 18 to 60 years of age in a 2:1 ratio to receive vYF or YF-VAX as a single vaccine injection on day 1. Neutralizing antibody titers were measured on day 29, month 6, and year 1. The primary analysis focused on the per-protocol population, which included participants with no history of yellow fever infection or vaccination and with no protocol deviations. Noninferiority would be shown if the lower limit of the two-sided 95% confidence interval of the between-group difference in the percentage of participants with seroconversion was greater than -5 percentage points on day 29. RESULTS: A total of 568 participants were enrolled: 382 in the vYF group and 186 in the YF-VAX group; 329 and 156 participants, respectively, were included in the per-protocol population for the noninferiority analysis. Seroconversion by day 29 occurred in 99.7% of participants receiving vYF and 99.4% of those receiving YF-VAX (difference, 0.3 percentage points; 95% confidence interval, -1.2 to 3.2, which met the criterion for noninferiority). Neutralizing antibody geometric mean titers were similar in the two vaccine groups, peaking on day 29 (in the vYF group, 1:2654 among participants with no history of yellow fever infection or vaccination and 1:1312 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:3147 and 1:1079, respectively), then decreasing through 1 year after vaccination (in the vYF group, 1:401 among participants with no history of yellow fever infection or vaccination and 1:490 among participants with a history of yellow fever infection or vaccination; in the YF-VAX group, 1:548 and 1:646, respectively). No major safety concerns were identified. The safety profiles were similar in the two vaccine groups: solicited adverse events were reported by 208 of 367 participants (56.7%) in the vYF group and 113 of 185 participants (61.1%) in the YF-VAX group, and unsolicited adverse events were reported by 99 of 379 participants (26.1%) and 39 of 186 participants (21.0%), respectively. CONCLUSIONS: In this trial, vYF had immunogenicity and safety profiles similar to those of YF-VAX. (Funded by Sanofi; ClinicalTrials.gov number, NCT04942210.).
9 Apr 2026
Read appraisal →Sexual health
E-screening for sexually transmissible infections and blood-borne viruses in New South Wales, Australia: a cost analysis.
BACKGROUND: MyCheck is an e-testing pathway, first implemented at Sydney Sexual Health Centre, which enhances access to STI/HIV testing via telehealth and off-site sample collection; thus, reducing clinic visits. This study evaluates MyCheck's direct and indirect costs versus standard in-person screening (Xpress). METHODS: A 12-month bottom-up cost analysis from a societal perspective compared MyCheck and Xpress. Direct medical (health system), direct non-medical (patient travel) and indirect non-medical (productivity) costs were calculated using retrospective Sydney Sexual Health Centre data. Costs included pathology, staff time, overheads, consumables, patient travel and forgone productivity. Statewide scale-up costs were estimated, with sensitivity analyses adjusting for inflation, minimum wage and an increase in the proportion of MyCheck users with productivity loss. RESULTS: From January to July 2023, Sydney Sexual Health Centre conducted 2548 screening episodes (45% MyCheck, 55% Xpress), with MyCheck attracting more men who have sex with men/transgender and gender diverse patients. MyCheck's shorter appointments (median 5 min vs Xpress's 15 min) led to lower staff costs (A$5 vs A$16). MyCheck had higher overall health system cost (A$127/patient) compared with Xpress (A$91/patient), mostly due to pathology costs. However, considering patient travel cost and productivity loss for Xpress, MyCheck's societal cost (A$137) was lower than Xpress (A$146), yielding A$104,260 annual savings. Statewide scale-up provides significant societal savings (A$419,077/year). CONCLUSION: This analysis of MyCheck's direct and indirect costs compared with traditional in-person screening demonstrates significant societal savings, despite higher direct pathology costs. It underscores the importance of a broader societal perspective in cost analyses. Lowering private pathology costs could further enhance MyCheck's cost-effectiveness. MyCheck, an innovative e-screening pathway, reduces barriers for STI/blood-borne virus screening by improving patient convenience and reduced opportunity costs. Despite higher direct pathology costs, its societal cost savings support statewide scale-up for improved screening accessibility.
9 Apr 2026
Read appraisal →Microbiology spectrum
Evaluation of contezolid's cerebrospinal fluid concentration and safety in tuberculous meningitis patients
Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) with high mortality. This study evaluated the cerebrospinal fluid (CSF) concentration and safety of the novel oxazolidinone contezolid compared to linezolid in TBM patients. In this randomized prospective study, 10 TBM patients received either a linezolid-containing (n = 5) or contezolid-containing (n = 5) anti-TB regimen. CSF and blood concentrations were measured at 2 and 6 h post-dose. Peak (2 h) and trough (6 h) concentrations, area under the concentration-time curve (AUC), and safety were assessed. Contezolid CSF concentrations exceeded the Mycobacterium tuberculosis (Mtb) MIC (0.5 μg/mL) at 2 h (median: 1.0806 μg/mL, range: 0.9295-1.3165 μg/mL) but declined by 6 h (median: 0.7920 μg/mL, range: 0.1867-1.0194 μg/mL). Linezolid CSF concentrations were significantly higher than contezolid at both 2 h (median: 3.251 μg/mL, range: 1.9545-4.9636 μg/mL; P = 0.008) and 6 h (median: 1.623 μg/mL, range: 0.941-1.765 μg/mL; P = 0.016), remaining above MIC in all samples at 6 h. The mean CSF AUC for contezolid (4.637 μg·h/mL, 95% CI: 3.599-5.675) was significantly lower than that for linezolid (12.537 μg·h/mL, 95% CI: 7.8797-17.277; P = 0.008). Blood concentrations were higher than CSF for both drugs at all time points. No serious drug-related adverse events occurred. Contezolid effectively penetrates the blood-CSF barrier in TBM patients, achieving CSF concentrations above the MIC for Mtb. Although its CSF exposure was significantly lower than linezolid, its demonstrated penetration and safety profile suggest contezolid warrants further investigation as a potential treatment option for drug-resistant TBM.IMPORTANCETuberculous meningitis (TBM) is the deadliest form of tuberculosis, especially difficult-to-treat drug-resistant TBM. Finding new, effective, and safe medicines is critical. This study provides evidence in TBM patients that a newer antibiotic, contezolid, successfully reaches the infection site in cerebrospinal fluid (CSF) at levels expected to kill Mycobacterium tuberculosis. While linezolid achieved higher levels in CSF, contezolid still reached concentrations predicted to be effective and caused no serious side effects in our study. This is important because contezolid might offer a safer alternative to linezolid, which can have significant long-term toxicity. These promising results suggest contezolid could become a valuable new weapon against refractory drug-resistant TBM, potentially saving lives where current options are limited or too toxic.
9 Apr 2026
Read appraisal →Journal of clinical microbiology
Etiologies of community-acquired febrile illness identified by TaqMan Array Card qPCR on blood samples: a systematic review and meta-analysis
UNLABELLED: Community-acquired febrile illness presents a significant diagnostic challenge. The TaqMan Array Card (TAC) enables simultaneous detection of many bacterial, viral, parasitic, and fungal pathogens. This systematic review aimed to characterize the etiologies of community-acquired fever diagnosed by TAC directly on blood specimens. A systematic search of PubMed, Scopus, Embase, and Web of Science (from inception to January 2026 in English) identified studies using TAC to detect pathogens directly in human blood to identify the etiology of community-acquired febrile illness. Eligible studies were appraised using a modified Joanna Briggs Institute (JBI) checklist. Pooled proportions and meta-analyses were conducted using a random-effects model. A total of 16 studies comprising 8,937 participants from 12 African and Asian countries met inclusion criteria. TAC detected at least 1 pathogen in 0.43 (95% CI [0.32; 0.54]), with high between-study heterogeneity (I² = 99%). Parasitic infections were most common (56%), nearly all due to Plasmodium spp., followed by bacterial (26%), viral (22%), and fungal (0.5%) etiologies. Plasmodium spp., Rickettsia spp., dengue virus, Lassa fever virus, Streptococcus pneumoniae, Orientia tsutsugamushi, Mycobacterium tuberculosis complex, and Salmonella spp. were the most frequently identified pathogens. Culture-negative bacteria accounted for 56% of bacterial detections. Positivity with more than 1 organism occurred in 6% of cases. TAC showed strong concordance with blood culture for culturable organisms (positive agreement: 73%, 95%CI [0.53; 0.89]; negative: 98%, 95%CI [0.95; 1.00]). TAC provides culture-independent pathogen detection and reveals overlooked causes of febrile illness, such as culture-negative bacteria. Its application may improve clinical diagnosis and surveillance programs. IMPORTANCE: Accurate identification of the causes of community-acquired febrile illness is essential for guiding clinical decision-making, surveillance programs, and public health response. This systematic review and meta-analysis synthesizes data from more than 8,937 patients across Africa and Asia tested with blood-based TaqMan Array Card (TAC) assays. TAC enabled broad, culture-independent detection of bacterial, viral, parasitic, and fungal pathogens-revealing both expected causes, such as Plasmodium spp. and dengue virus, and neglected culture-negative bacteria including Orientia tsutsugamushi, Coxiella burnetii, and Rickettsia spp. By uncovering these underrecognized etiologies, TAC provides valuable pathogen-level data to strengthen fever surveillance, inform outbreak detection, and refine regional disease prioritization frameworks. These findings highlight the potential of high-throughput molecular diagnostics to enhance infectious disease control, particularly in resource-limited settings.
9 Apr 2026
Read appraisal →Journal of clinical microbiology
Identification of Aspergillus at section and species levels by artificial intelligence-based microscopic morphology image recognition
Rapid and accurate identification of Aspergillus species in clinical microbiology laboratories is crucial for aspergillosis diagnosis and antifungal therapy. However, traditional methods still face challenges in distinguishing phylogenetically related species due to their morphological similarities. This study presents FungalNet, a deep learning model integrating ResNet-50 architecture with Focal Loss algorithm, specifically designed to enhance feature extraction for Aspergillus identification. A total of 12,000 high-resolution images were obtained from lactophenol cotton blue-stained slide preparations under a 100× oil immersion objective, among which 311 images were excluded through a novel quality control approach combining fivefold cross-validation and expert manual review. The performance of four deep learning models (FungalNet and three established models) for identifying Aspergillus species and sections was evaluated using the remaining 11,689 qualified images. FungalNet demonstrated superior classification performance, achieving overall accuracies of 98.45% and 97.85% at the section and species levels, respectively. These results indicate that FungalNet shows significant promise for rapid and accurate identification of Aspergillus species. With further optimization and multicenter validation, this tool could potentially be integrated into routine diagnostic workflows to enhance the efficiency and reliability of fungal identification in clinical settings.IMPORTANCEThis study integrates microscopic morphology identification with deep learning to address the challenge of accurate Aspergillus species identification. Twelve clinically isolated Aspergillus species belonging to eight different sections were included. From touch-tape slide preparations with lactophenol cotton blue staining under a 100× oil immersion objective, 11,689 qualified images were collected and analyzed using FungalNet (our proposed model) along with three established models (GoogLeNet, ResNet-50, and Xception). The results showed that FungalNet demonstrated superior performance in Aspergillus identification, achieving the highest classification accuracy at both section (98.45%) and species (97.85%) levels. Given its rapid turnaround time and cost-effectiveness, this AI-based image analysis approach shows promising potential for the rapid and accurate identification of Aspergillus species in clinical microbiology laboratories.
9 Apr 2026
Read appraisal →Journal of medical Internet research
Social Media Intervention Based on the Information-Motivation-Behavioral Skills Model Promotes HIV Testing and Reduces High-Risk Behaviors Among Men Who Have Sex With Men in Resource-Limited Settings in China: Randomized Controlled Trial
BACKGROUND: Social media intervention may enhance HIV prevention among men who have sex with men, but the effect of this intervention in resource-limited settings remains unclear. OBJECTIVE: This randomized controlled trial evaluated whether a social media intervention grounded in the information-motivation-behavioral skills (IMB) model could be beneficial for HIV prevention among men who have sex with men in resource-limited settings. METHODS: Participants were recruited in Nanning, China, between April 2023 and April 2024. Eligible participants were randomly assigned to either the social media intervention group or the routine HIV prevention services control group. Participants in the intervention group received a 3-month social media intervention, which included completing video-based tasks. Baseline surveys were conducted, followed by follow-up surveys every 3 months, for a total of 2 follow-ups. Outcomes included HIV testing uptake, high-risk behavior, AIDS-related knowledge, safe sex self-efficacy, and attitude. RESULTS: A total of 180 eligible men who have sex with men were enrolled (90 per group). Follow-up rates were 97.8% (88/90) and 95.5% (86/90) for the intervention and control groups, respectively. At the follow-ups, the intervention group demonstrated significantly higher uptake of HIV testing, a lower proportion of participants reporting high-risk sexual behaviors, and higher condom use self-efficacy compared to the control group (all P<.05). After controlling for sociodemographic variables, generalized estimating equations analysis revealed that the intervention group had significantly higher odds of HIV testing (risk ratio [RR] 1.739, 95% CI 1.110-2.730), HIV self-testing (RR 2.306, 95% CI 1.593-3.340), and consistent condom use (RR 2.457, 95% CI 1.636-3.690) than the control group. Cochran-Armitage trend tests within the intervention group revealed that with increasing intervention duration, both HIV testing and HIV self-testing significantly increased, while high-risk sexual behaviors significantly decreased (all P<.05). CONCLUSIONS: The social media intervention guided by the IMB model demonstrated a positive effect on expanding HIV testing coverage, reducing high-risk behavior, enhancing AIDS-related knowledge, and improving safer sex self-efficacy among men who have sex with men in resource-limited settings. These findings provide valuable guidance for future HIV prevention and control efforts targeting this population.
8 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Antibiotic treatment for low back pain, radicular pain, or both.
RATIONALE: Low back pain is the leading cause of disability worldwide. Research has associated Modic changes (signal changes in the vertebral endplate on magnetic resonance imaging (MRI)) with low back pain. Some hypothesise that Modic type 1 changes (oedema) may have an infective cause, and that antibiotics could serve as targeted treatment. OBJECTIVES: To assess the benefits and harms of antibiotic therapy, compared with placebo or another treatment, in people with low back pain, radicular pain, or both. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registries up to 26 August 2025, with no restrictions related to language or date of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that assessed antibiotics versus placebo (primary comparison) or other treatments. We assessed the evidence separately for four populations of adults with low back pain, radicular pain, or both: those with 1) Modic type 1 changes and evidence of disc herniation, 2) other Modic changes and evidence of disc herniation, 3) any Modic changes but no evidence of disc herniation, and 4) evidence of disc herniation without any Modic changes. OUTCOMES: Critical outcomes were pain intensity and disability or function up to 12 to 14 weeks, and the number of participants with any adverse events and serious adverse events at the end of the trial period. RISK OF BIAS: Two review authors independently evaluated the risk of bias using the Cochrane risk of bias tool RoB 1. SYNTHESIS METHODS: Two review authors independently screened studies and extracted data. We synthesised results for each outcome using random-effects meta-analysis. Where this was not possible due to the nature of the data, we reported the results descriptively. We used GRADE to assess the certainty of evidence. The primary comparison was antibiotics versus placebo in people with low back pain, radicular pain, or both, and Modic type 1 changes with evidence of disc herniation (population 1) up to 12 to 14 weeks. INCLUDED STUDIES: We included three trials, conducted in Denmark, Belgium, and Norway, with a total of 402 participants (mean ages ranged from 44.7 years to 51.0 years). Two trials recruited people with chronic (> 6 months) moderate-to-severe low back pain (with or without radicular pain), Modic changes, and disc herniation. One trial included people with Modic type 1 changes only (population 1) and compared oral amoxicillin-clavulanate 500 mg/125 mg to placebo (for both treatments, 1 or 2 tablets 3 times daily for 100 days). The second trial included people with either Modic type 1 changes (population 1) or Modic type 2 changes (population 2) and compared oral amoxicillin 750 mg to placebo (for both treatments, 3 times daily for 100 days). Follow-up was 12 months in both trials. The third trial recruited people with lumbar radicular pain (with or without low back pain) and disc herniation. Modic changes was not an inclusion criterion (population 4). This trial evaluated minocycline 100 mg versus amitriptyline 25 mg versus placebo and followed participants for 14 days (treatment duration). There were no trials with population 3. SYNTHESIS OF RESULTS: All three trials were at low risk of selection, performance, and detection bias. We rated one trial at high risk of attrition bias and unclear risk of reporting and other bias. The overall certainty of evidence is low to very low, primarily due to imprecision and indirectness. In people with low back pain, Modic type 1 changes, and disc herniation, the antibiotic oral amoxicillin (with or without clavulanate) may improve pain slightly and may result in a small to moderate improvement in disability at 12 to 14 weeks compared with placebo (low-certainty evidence, downgraded for imprecision and indirectness). At this time point, the mean back pain score was 50.6/100 (where a lower score indicates less pain) in the amoxicillin group versus 59/100 in the placebo group (mean difference (MD) -8.42 points, 95% CI -16.18 to -0.67; I² = 35%; 2 trials, 255 participants), and the mean disability score was 45.2/100 (where a lower score indicates less disability) in the amoxicillin group versus 55.7/100 in the placebo group (MD -10.52 points, 95% CI -15.94 to -5.09; I² = 0%; 2 trials, 255 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting adverse events (very low-certainty evidence, downgraded for imprecision, inconsistency, and indirectness). Adverse events were reported in 76 of every 100 people taking amoxicillin compared with 49 of every 100 people taking placebo (risk ratio (RR) 1.79, 95% CI 0.54 to 5.94; I² = 96%; 2 trials, 262 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting serious adverse events (very low-certainty evidence, downgraded for imprecision and indirectness). Serious adverse events were reported in three of every 100 people taking amoxicillin (with or without clavulanate) compared with two of every 100 people taking placebo (RR 1.43, 95% CI 0.11 to 18.35; I² = 45%; 2 trials, 262 participants). We are unsure of the effects of amoxicillin compared to placebo in people with low back pain, Modic type 2 change, and disc herniation. Similarly, we are unsure of the effects of minocycline compared to placebo or amitriptyline in people with low back pain, disc herniation, and no Modic changes. AUTHORS' CONCLUSIONS: In people with low back pain, Modic type 1 changes, and evidence of disc herniation, the antibiotic amoxicillin (with or without clavulanate) may provide slight to small benefits in reducing back pain and small to moderate benefits in improving disability compared to placebo at 12 to 14 weeks. The evidence on the risk of adverse events, including serious adverse events, with amoxicillin (with or without clavulanate) is very uncertain. Further research is likely to change our confidence in the estimates. FUNDING: This review had no dedicated funding. REGISTRATION: Protocol (2021): DOI 10.1002/14651858.CD014221.
8 Apr 2026
Read appraisal →PloS one
Clinical impact of broad- versus narrow-spectrum empiric therapy in acute cholangitis: A Japanese claims database study
The clinical benefit of broad-spectrum empiric therapy in patients with acute cholangitis is unclear. We aimed to evaluate the impact of broad-spectrum and narrow-spectrum empiric therapies on patient outcomes using a Japanese claims database. The study included patients who were diagnosed with acute cholangitis between April 2014 and August 2022, aged 18-99 years, received antibiotics, had blood cultures collected, and underwent biliary drainage. Patients who received empiric therapy with carbapenems, piperacillin/tazobactam, or fourth-generation cephalosporins were included in the broad-spectrum group, whereas others were included in the narrow-spectrum group. Of the 4,755 eligible patients, 3,377 were categorized into the narrow-spectrum group and 1,378 into the broad-spectrum group. In the multivariate logistic regression analysis, older age, higher Charlson Comorbidity Index, the presence of sepsis, and intensive care unit admission were associated with increased 30-day in-hospital mortality, whereas the receipt of broad-spectrum empiric therapy was not (adjusted odds ratio, 1.37 [95% confidence interval {CI}, 0.84-2.23]). In the propensity score matching analysis, there was also no association between the receipt of broad-spectrum empiric therapy and 30-day in-hospital mortality (odds ratio, 1.43 [95% CI, 0.82-2.50]). Furthermore, in the propensity score-matched cohort, the broad-spectrum group had longer duration of intravenous antibiotic therapy (median interquartile range [IQR]: 8 [6 -11] day vs. 9 [7 -13] day; difference 1 day [95% CI, 0.31-1.69 day]) and length of hospital stay (median [IQR]: 13 [9 -20] day vs. 16 [11 -25] day; difference 3 day [95% CI, 1.87-4.13 day]), compared with the narrow-spectrum group. In this large-scale study using a Japanese claims database, broad-spectrum empiric therapy was not associated with improved clinical outcomes, compared with narrow-spectrum empiric therapy. Therefore, the necessity of broad-spectrum empiric therapy may be limited in clinical practice, and narrow-spectrum empiric therapy may represent an effective treatment strategy for acute cholangitis.
5 Apr 2026
Read appraisal →Vaccine
Applied immunoinformatics in modern vaccine design: a comprehensive review of available computational tools
The rapid evolution of computational biology has transformed vaccine design from a largely empirical process into a rational, data-driven discipline. At the center of this transformation lies immunoinformatics, which integrates immunology, molecular biology, and data science to accelerate the identification, evaluation, and optimization of vaccine candidates. By enabling the systematic transition from genomic data to viable immunotherapeutic candidates, these approaches offer an unprecedented capacity to shorten development timelines, reduce costs, and broaden population coverage compared to traditional trial-and-error vaccine pipelines. This review provides a state-of-the-art overview of the currently available immunoinformatic tool that underpins modern vaccine design. From identification of conserved and functionally essential pathogen targets, advances in structural prediction, epitope mapping, safety assessment, and systems-level analyses of host-pathogen interactions, immunoinformatics allows researchers to design vaccines with enhanced success rate. Special emphasis is placed on the shift from purely predictive models toward generative frameworks, where artificial intelligence and deep learning now support not only the evaluation, but also the rational engineering of optimized vaccine candidates. For this review, we systematically examined more than 250 computational tools and algorithms spanning every stage of the vaccine discovery pipeline. From this extensive survey, we distilled and discussed the approaches that currently demonstrate the highest performance and practical usability, thereby providing researchers with a curated overview of some the most reliable resources available.
5 Apr 2026
Read appraisal →Nanoscale
A machine learning-assisted Ag-TiO2 SERS platform for intraoperative osteomyelitis diagnosis
Osteomyelitis is a progressive bone infection with high disability and recurrence rates. However, current diagnostic approaches, including bacterial culture, imaging, and serological assays, suffer from poor sensitivity, low specificity, and delayed turnaround, making intraoperative evaluation particularly challenging. Here, we present an Ag-TiO2-based surface-enhanced Raman scattering (SERS) platform for rapid, label-free detection of osteomyelitis using minimal volumes of wound saline irrigation fluid (WSIF). Benefiting from the synergistic interplay between electromagnetic field amplification and enhanced interfacial charge-transfer interactions, the Ag-TiO2 substrate provides ultrasensitive detection with high spectral reproducibility, enabling reliable identification of subtle biochemical changes in complex clinical samples. Quantitative analysis indicates that strengthened charge-transfer processes significantly enhance molecular Raman responses, while plasmonic electromagnetic effects remain essential for overall signal amplification. Distinct Raman fingerprints of infected, non-infected, and recovered patients were successfully classified using artificial intelligence (AI) models, revealing metabolic alterations in amino acids, purines, proteins, and lipids associated with bacterial infections and immune response. This integration of SERS with AI not only elucidates the mechanistic basis of spectral enhancement but also demonstrates clinical feasibility for intraoperative osteomyelitis diagnosis, offering a promising strategy to improve surgical precision and reduce recurrence risk.
5 Apr 2026
Read appraisal →BMJ paediatrics open
Oxygen therapy for children with an oxygen saturation of 90-93% in Malawi: the NoGoLO2 pilot randomised controlled trial
OBJECTIVE: Oxygen is a cornerstone treatment for pneumonia with hypoxaemia. WHO guidelines recommend oxygen therapy for children with a peripheral arterial haemoglobin oxygen saturation (SpO2) <90%. Children in low- and middle-income countries with an SpO2 of 90-93% are at increased risk of mortality and may benefit from oxygen therapy. We aimed to determine the feasibility of a randomised controlled trial comparing standard of care (no oxygen), low-flow nasal cannula (LFNC) and high-flow nasal cannula (HFNC) among children with pneumonia and an SpO2 of 90-93%. DESIGN: Pilot, open-label, three-armed randomised control trial (NCT06176664). SETTING: Salima District Hospital, Malawi. PATIENTS: Children 1-59 months old with WHO-defined pneumonia and an SpO2 of 90-93%. INTERVENTIONS: Standard care (no oxygen), LFNC or HFNC. MAIN OUTCOME MEASURES: The primary outcome was feasibility defined as an average of ≤2 protocol deviations per participant. Secondary outcomes included consent refusal, participant attrition and treatment failure within 14 days. Treatment failure was defined as an SpO2 <90% for standard care participants or <94% in the LFNC and HFNC arms despite maximum therapy as described, any new severe respiratory distress (grunting, very severe chest indrawing) or any new WHO-defined emergency sign. RESULTS: Of the 29 eligible patients, 21 (72%) were enrolled and randomised. There was an average of 0.8 (16/21) deviations per participant. Seven (43.8%) protocol violations were related to study intervention protocols and nine (56.3%) to medication availability and routine care. No participants withdrew from the study. Three of 21 participants (14.3%) had treatment failure. All participants were successfully followed to obtain the 14-day outcome. CONCLUSIONS: A three-armed, open-label randomised control trial is feasible to compare standard of care, LFNC and HFNC oxygen for children with pneumonia and an SpO2 of 90-93% in Malawi. TRIAL REGISTRATION NUMBER: NCT06176664.
4 Apr 2026
Read appraisal →Regional anesthesia and pain medicine
Deciphering risk factors for severe postherpetic neuralgia in patients with herpes zoster: an interpretable machine learning approach
INTRODUCTION: Postherpetic neuralgia (PHN) is a common complication of herpes zoster (HZ). This study aimed to use a large real-world electronic medical records database to determine the optimal machine learning model for predicting the progression to severe PHN and to identify the associated risk factors. METHODS: We analyzed the electronic medical records of 23,326 patients diagnosed with HZ from January 2010 to June 2020. PHN was defined as pain persisting for ≥90 days post-HZ, based on diagnostic and prescription codes. Five machine learning algorithms were compared with select the optimal predictive model and a subsequent risk factor analysis was conducted. RESULTS: Of the 23,326 patients reviewed, 8,878 met the eligibility criteria for the HZ cohort. Among these, 801 patients (9.0%) progressed to severe PHN. Among the various machine learning approaches, XGBoost-an approach that combines multiple decision trees to improve predictive accuracy-performed the best in predicting outcomes (F1 score, 0.351; accuracy, 0.900; area under the receiver operating characteristic curve, 0.787). Using this model, we revealed eight major risk factors: older age, female sex, history of shingles and cancer, use of immunosuppressants and antidepressants, intensive initial pain, and the neutrophil-to-lymphocyte ratio. When patients were categorized into low-risk and high-risk groups based on the predictive model, PHN was seven times more likely to occur in the high-risk group (p<0.001). CONCLUSIONS: Leveraging machine learning analysis, this study identifies an optimal model for predicting severe PHN and highlights key associated risk factors. This model will enable the establishment of more proactive treatments for high-risk patients, potentially mitigating the progression to severe PHN.
4 Apr 2026
Read appraisal →N Engl J Med
Adenoviral Inciting Antigen and Somatic Hypermutation in VITT
BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare prothrombotic complication that occurs after adenoviral vector-based vaccination against coronavirus disease 2019; in rare cases, it can also occur after natural adenovirus infection. VITT is mediated by platelet-activating antibodies against the highly cationic protein platelet factor 4 (PF4). The underlying inciting antigen trigger and immunopathogenesis remain unknown. METHODS: We used antibody proteomics to determine the amino acid sequences of anti-PF4 antibodies from 21 patients with VITT and sequenced the genes encoding the immunoglobulin light-chain hypervariable region from 100 patients with VITT. To identify an adenoviral trigger, we used the antigen-binding fingerprints of anti-PF4 and anti-adenovirus protein antibodies to identify a shared serum clonotype and subsequently used adenovirus protein peptides and recombinant anti-PF4 VITT antibodies to map the mimicking linear epitope. RESULTS: Genomic and proteomic profiling of VITT antibodies revealed a shared immunoglobulin light-chain allele, IGLV3-21*02 or *03, harboring a critical somatic hypermutation, K31E. Only antibodies purified against adenoviral core protein VII (pVII) contained anti-PF4 species matching the VITT fingerprint; antibodies against intact virions or other adenoviral proteins did not. Cross-reactive IgGs were mapped to a basic linear epitope on pVII. A pathogenic anti-PF4 VITT antibody, back-mutated to germline (K31), lost its prothrombotic activity in vitro and in vivo and preferentially bound pVII, a finding that directly supported the role of the hypermutation in the antigenic shift from adenovirus pVII to PF4. CONCLUSIONS: The results of our study indicate that VITT occurs when, in persons with immunoglobulin light-chain allele IGLV3-21*02 or *03, a specific somatic hypermutation develops that affects antibodies that recognize a specific epitope on the adenoviral core protein pVII, which results in misdirection of antibody targeting toward PF4. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00025738; EU Post-Authorization Study Register number, EUPAS45098.).
1 Feb 2026
Read appraisal →Clin Dermatol
Gonorrhea.
Neisseria gonorrhoeae, a Gram-negative intracellular pathogen, causes gonorrhea. Although usually sexually transmissible, it can be acquired by direct inoculation. Untreated gonococcal infections have deleterious impacts, including adverse pregnancy outcomes, ectopic pregnancy, infertility, and even blindness. Extended-spectrum cephalosporins remain the mainstay of therapy, and gonococcal culture is essential to determine susceptibility to these agents. Antimicrobial resistance is a global public health concern, and a few new agents are in the pipeline. Gonorrhea control programs rely on health education, access to diagnostic testing (where possible), effective therapy, and partner notification. Introducing inexpensive, sensitive, and specific point-of-care tests will aid antimicrobial stewardship efforts in countries using the syndromic management approach. Targeted vaccination of higher-risk populations with cross-protective outer membrane vesicle-based meningococcal B vaccines might reduce N. gonorrhoeae transmission in the future. Doxycycline postexposure prophylaxis may further reduce gonococcal incidence in the short term; however, its long-term impact on the human resistome/microbiome remains unknown.
1 Jan 2026
Read appraisal →Clin Dermatol
Chancroid.
Chancroid, caused by Haemophilus ducreyi, is a sexually transmitted genital ulcerative condition associated with inguinal bubo formation. The relative prevalence of chancroid has dramatically declined based on surveillance findings in those few endemic settings where the appropriate diagnostic tools exist; however, laboratory-based diagnostics are lacking to assist clinical management and support etiological surveillance in most parts of the world. Recent yaws surveys within the Western Pacific region indicate that H ducreyi has re-emerged as a frequent cause of chronic skin ulceration. Although there have been no antimicrobial susceptibility studies for three decades, it is assumed that a cure remains possible with extended-spectrum cephalosporins, macrolides, or fluoroquinolones. HIV-1-infected patients require careful followups due to reports of treatment failure with single-dose regimens. Buboes may need additional treatment with either aspiration or excision and drainage.
1 Jan 2026
Read appraisal →Cell
Generation of antigen-specific paired-chain antibodies using large language models.
The traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody sequences in a target-agnostic manner. In this work, we present MAGE (monoclonal antibody generator), a sequence-based protein language model (PLM) fine-tuned for the task of generating paired human variable heavy- and light-chain antibody sequences against targets of interest. We show that MAGE can generate novel and diverse antibody sequences with experimentally validated binding specificity against SARS-CoV-2, an emerging avian influenza H5N1, and respiratory syncytial virus A (RSV-A). MAGE represents a first-in-class model capable of designing human antibodies against multiple targets with no starting template.
1 Dec 2025
Read appraisal →Blood Rev
Advances in the critical care management for patients with hematological malignancies
Hematological malignancies (HMs) are increasingly associated with life-threatening complications requiring intensive care unit (ICU) management. Recent advancements in therapies, diagnostics, and critical care protocols have improved outcomes for these patients, yet significant challenges persist. This manuscript explores the evolving landscape of critical care in hematology, emphasizing the unique complications, management strategies, and future directions in the field. Patients with HMs are particularly vulnerable to infections, sepsis, organ dysfunction, and treatment-related toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and coagulopathies. Innovations in the management of acute respiratory failure, septic shock, and invasive fungal infections have contributed to better survival rates, yet outcomes remain suboptimal for certain high-risk groups. Furthermore, new therapies, including CAR-T cells, bispecific antibodies, and immune checkpoint inhibitors, present both opportunities and challenges in the ICU setting due to their potential toxicities. Emerging trends emphasize the importance of early ICU admission, multidisciplinary collaboration, and precision medicine in improving patient care. The integration of biomarker-driven strategies, advanced diagnostics, and artificial intelligence holds promise for optimizing therapeutic interventions and enhancing antimicrobial stewardship. Additionally, patient-centered approaches, including time-limited trials and goal-oriented discussions, aim to balance aggressive care with quality-of-life considerations. This review underscores the need for continued research to address disparities in access to care, improve long-term outcomes, and develop standardized protocols for managing critically ill hematology patients. By advancing the integration of oncology and critical care, clinicians can better navigate the complexities of modern therapies and provide holistic, evidence-based care that aligns with patient values and priorities.
1 Nov 2025
Read appraisal →Intensive Care Med
Invasive candidiasis in intensive care medicine: shaping the future of diagnosis and therapy
BACKGROUND: Invasive candidiasis (IC) remains one of the most challenging infections in critical care, contributing significantly to morbidity, prolonged organ support, and mortality among intensive care unit (ICU) patients. The clinical landscape of IC is evolving, with increasing recognition of Candida non-albicans species and other yeasts formerly classified as Candida spp., alongside emerging multidrug resistance and growing complexity in host immune profiles. OBJECTIVES: This contemporary, multidisciplinary narrative review-authored by intensivists, infectious diseases specialists, clinical microbiologists, and pharmacologists-aims to provide ICU clinicians with practical, up-to-date insights into the diagnosis and management of IC. To maintain clinical focus, the review excludes non-IC fungal infections and non-ICU patient populations. METHODS: Relevant literature and expert consensus were critically reviewed to summarize current diagnostic and therapeutic approaches for IC in critically ill patients. Emphasis was placed on pragmatic clinical application, diagnostic limitations, antifungal stewardship, and personalized therapeutic decision-making. RESULTS: Despite the availability of novel antifungal agents with improved pharmacokinetic properties, treatment success in IC depends equally on timely and accurate diagnosis and individualized, context-aware therapy. Blood cultures continue to demonstrate limited sensitivity (~40%). Non-culture assays, including β-D-glucan and molecular diagnostics, provide faster detection and high negative predictive value but suffer from low positive predictive value and inconsistent adoption in clinical practice. The absence of validated host-derived biomarkers further limits risk stratification, antifungal discontinuation decisions, and personalized care. CONCLUSIONS: Emerging antifungal agents, stewardship strategies, and multidisciplinary care models are essential to improve clinical outcomes and reduce antifungal resistance. This review underscores the need for integrated, team-based diagnostic and therapeutic approaches to close persistent gaps in IC management, ultimately promoting more effective, timely, and individualized care for critically ill patients with Candida spp.
1 Nov 2025
Read appraisal →Cell
A generative deep learning approach to de novo antibiotic design
The antimicrobial resistance crisis necessitates structurally distinct antibiotics. While deep learning approaches can identify antibacterial compounds from existing libraries, structural novelty remains limited. Here, we developed a generative artificial intelligence framework for designing de novo antibiotics through two approaches: a fragment-based method to comprehensively screen >107 chemical fragments in silico against Neisseria gonorrhoeae or Staphylococcus aureus, subsequently expanding promising fragments, and an unconstrained de novo compound generation, each using genetic algorithms and variational autoencoders. Of 24 synthesized compounds, seven demonstrated selective antibacterial activity. Two lead compounds exhibited bactericidal efficacy against multidrug-resistant isolates with distinct mechanisms of action and reduced bacterial burden in vivo in mouse models of N. gonorrhoeae vaginal infection and methicillin-resistant S. aureus skin infection. We further validated structural analogs for both compound classes as antibacterial. Our approach enables the generative deep-learning-guided design of de novo antibiotics, providing a platform for mapping uncharted regions of chemical space.
1 Oct 2025
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