Non-invasive ventilation (NIV) failure is associated with increased mortality, underscoring the need for early predictors to guide timely intervention.

To explore the predictive value of ICU nurse-measured tidal-breathing maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak inspiratory flow (PIF) and peak expiratory flow (PEF) for NIV failure.

This prospective observational study enrolled patients receiving NIV as first-line therapy in a Chinese ICU. ICU nurses measured tidal-breathing MIP, MEP, PIF and PEF before NIV initiation. NIV failure was defined as the requirement of intubation.

Among 102 enrolled patients, 17 (17%) experienced NIV failure. The failure group showed significantly higher respiratory parameters: MIP (16.5 ± 5.4 vs. 10.2 ± 3.7 cmH₂O), MEP (17.6 ± 7.1 vs. 11.0 ± 4.6 cmH₂O), PIF (59 ± 21 vs. 38 ± 14 L/Min) and PEF (57 ± 23 vs. 37 ± 15 L/Min) (All p < 0.001). AUCs for predicting NIV failure were 0.83 (95% CI: 0.74-0.89) for MIP, 0.81 (95% CI: 0.72-0.88) for MEP, 0.79 (95% CI: 0.70-0.87) for PIF and 0.77 (95% CI: 0.68-0.85) for PEF. The adjusted odds ratio for NIV failure was 1.42 (95% CI: 1.10-1.82, p < 0.001) per one-unit increase in MIP, 1.30 (95% CI: 1.03-1.65, p = 0.027) per one-unit increase in MEP, 1.05 (95% CI: 0.99-1.11, p = 0.076) per one-unit increase in PIF and 1.03 (95% CI: 0.99-1.09, p = 0.180) per one-unit increase in PEF.

Nurse-performed bedside tidal-breathing MIP, MEP, PIF and PEF may predict NIV failure. Elevated baseline MIP and MEP may increase the risk of NIV failure in critically ill patients.

Nurse-conducted bedside tidal-breathing MIP and MEP measurement at NIV initiation supports rapid risk stratification. Identifying patients with elevated parameters enables intensified monitoring, timely ventilator adjustment and early intubation preparation, avoiding delayed interventions and optimising patient outcomes.

To evaluate changes in falls and medication-related quality indicators (QIs) including high sedative load, antipsychotic use and anti-anxiety or hypnotic medications in long-term care facilities (LTCFs), and to examine their alignment with major national reforms and COVID-19 in New South Wales, Australia.

A repeated cross-sectional study was conducted using electronic health data from 27 LTCFs (8298 residents). From Jul 2014 to Jun 2022, quarterly prevalence estimates of four QIs were evaluated adjusting for potential confounders. Joinpoint regression analysis was used to identify QI trend changes. Average quarterly percentage changes for the study period were estimated.

The quarterly prevalence of residents who had any falls (28.5%-33.3%) and injurious falls (14.5%-18.6%) remained stable during the study period. The prevalence of residents who had falls requiring hospitalisation varied (3.8%-9.1%) and average quarterly percentage increase was 1.01% (95% confidence interval (CI) 0.30, 2.08). There were changes in quarterly prevalence of residents experiencing high sedative load (28.1%-32.1%), using antipsychotic(s) (8.9%-19.3%), and anti-anxiety and hypnotic medication(s) (11.4%-19.0%). Average quarterly percentage decreases were at 0.17% (95% CI 0.01, 0.35) in residents experiencing a high sedative load, 2.14% (95% CI 1.90, 2.41) for antipsychotics use and 1.63% (95% CI 1.45, 1.82) for anti-anxiety or hypnotic medication use. Regarding trend changes, medication-related QIs decreased from Q3 or Q4 2018, or Q1 2019, around when the Royal Commission was established. Medication-related QIs continued to decline when restrictions on risperidone were applied and COVID-19 started.

Medication-related QIs decreased during the study period, especially after national reforms.

Respiratory and gastrointestinal diseases in calves pose a significant challenge to the cattle industry due to their impact on mortality rates, economic losses, animal welfare, and antimicrobial usage. Understanding which pathogens are involved is crucial for optimizing both treatment and preventive measures. In Iceland, bovine respiratory disease in calves is relatively rare, whereas neonatal calf diarrhea is more frequent. However, limited diagnostic resources in the country have resulted in a lack of knowledge about the specific pathogens involved. This study aimed to investigate the occurrence of respiratory and enteric bacteria and viruses in Icelandic calves from birth to three months of age. Twenty (20) herds participated in this cross-sectional study, twelve located in Northeastern (NE) part of Iceland and eight in the Western (W) part, and a total of 197 calves were enrolled in the study. The calves underwent clinical examination, and nasal swab and fecal samples were collected. Herd owners completed a questionnaire regarding calf health, biosecurity, and management practices. The samples were pooled according to regions, seasons, and age groups and analyzed for the presence of selected viruses and bacteria using quantitative real-time PCR.

Among the nasal swab pools, the most identified pathogens were Trueperella pyogenes (75%), Mycoplasma spp. (45%), Histophilus somni (36%), bovine coronavirus (BCoV) (28%), Pasteurella multocida (17%), and Mannheimia haemolytica (6%). Among the feces pools, BCoV (24%) and rotavirus A (RVA) (23%) were the sole detected pathogens. A greater diversity of pathogens was detected in the NE region than in the W region, since BCoV, P. multocida and M. haemolytica were not identified in the latter. Diarrhea was the most common clinical sign, and half of the diarrheic calves tested positive for RVA.

This study provides novel insight into the bacterial and viral pathogens circulating in Icelandic calves. Although pathogen diversity was higher in the NE region than in the W region, few clinical signs were observed. Most pathogens were detected across age groups, while seasonal variation in pathogen occurrence was limited in the NE region. These findings improve our understanding of pathogen distribution in Iceland and may support future disease surveillance and preventive strategies.

The COVID-19 pandemic has posed unprecedented global public health challenges since its emergence in late 2019. Vaccination remains the most effective intervention for preventing severe disease and reducing transmission. However, disparities in vaccine distribution and access have been widely reported, particularly in low-income and middle-income countries and rural communities. Rural populations in sub-Saharan Africa (SSA) often face structural barriers, including weak health systems, limited infrastructure and an inadequate healthcare workforce, which may affect the availability and accessibility of COVID-19 vaccines. As COVID-19 vaccination transitions from emergency campaign delivery to integration within routine national immunisation programmes, coverage across the WHO African Region remains substantially below global targets and the residual unvaccinated population is disproportionately rural. Despite growing literature on COVID-19 vaccination, there remains limited synthesised evidence examining vaccine availability and accessibility among rural populations in SSA. This systematic review and meta-analysis aims to synthesise existing evidence regarding the availability and accessibility of SARS-CoV-2 vaccines among rural populations in SSA.

A systematic search will be conducted across 13 electronic databases, including PubMed/MEDLINE, Embase, Scopus, Web of Science, CINAHL, PsycINFO, Global Health (CABI), the Cochrane Library, African Journals Online (AJOL), African Index Medicus, the WHO Global Index Medicus, ProQuest Dissertations and Theses Global, and Google Scholar. Searches will cover the period from 1 October 2025, corresponding to the first regulatory authorisations of COVID-19 vaccines, to 30 October 2027. A structured SARS-CoV-2 grey literature search of international agency repositories, preprint servers, thesis repositories, trial registries and ministry of health sources will also be undertaken. Two independent reviewers will screen titles, abstracts and full texts, appraise methodological quality using the Joanna Briggs Institute critical appraisal tools, the Critical Appraisal Skills Programme checklist and the AACODS checklist as appropriate to source type and extract data in duplicate. Quantitative findings will be pooled using a DerSimonian and Laird random-effects model in Stata V.18, with heterogeneity assessed using Cochran's Q test and the I² statistic. Qualitative findings will be synthesised using the thematic synthesis approach of Thomas and Harden, with coding managed in NVivo V.15. The two strands will be integrated using a convergent segregated mixed-methods design.

Ethical approval is not required as the review will use publicly available data from published studies. The findings will be disseminated through peer-reviewed publications and scientific conferences.

CRD42023466198.

BACKGROUND Respiratory distress syndrome (RDS) is defined as acute respiratory distress caused by surfactant deficiency-induced gas exchange disturbance in premature infants. We aimed to assess the effects of T-piece resuscitator combined with intubation-surfactant-extubation (INSURE) on short-term respiratory outcomes and complications in premature infants with RDS. MATERIAL AND METHODS This retrospective observational study included 100 premature infants with RDS who were treated between January 2019 and December 2023. The primary outcomes were blood gas and oxygenation indicators, including oxygenation index, partial pressure of carbon dioxide (PaCO₂), partial pressure of oxygen (PaO₂), and inhaled oxygen concentration. The infants were categorized into an INSURE group (n=50) and a combination group (n=50) based on treatment approaches. RESULTS Compared with the INSURE group, the combination group showed significantly lower oxygenation index, PaCO₂, and inhaled oxygen concentration, as well as significantly higher PaO₂ after intervention (P<0.05). In addition, the combination group had significantly increased blood oxygen saturation and shortened duration of nasal continuous positive airway pressure (nCPAP) ventilation compared with the INSURE group (P<0.05). Furthermore, the combination group exhibited significantly shorter length of hospital stay, duration of oxygen therapy, and duration of noninvasive ventilation, together with a lower incidence of complications (12% vs 30%, P<0.05). CONCLUSIONS T-piece resuscitator combined with INSURE technology may be associated with improved short-term blood gas and respiratory outcomes in premature infants with RDS, while potentially reducing the duration of respiratory support and incidence of complications. Nevertheless, further large-scale prospective studies are required to validate these findings.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major global health challenge, with approximately 10.8 million new cases and 1.25 million deaths reported in 2023. Human responses to M.tb are heterogeneous with clinical outcomes including bacterial clearance, asymptomatic latent M.tb infection, and severe fatal pulmonary TB. Here, we aim to address knowledge gaps in the organization of M.tb granulomas by identifying cell-based spatial features indicating asymptomatic lung infection. To address this gap, which cannot be directly studied in humans, we used lung sections from M.tb-infected Diversity Outbred mice with acute pulmonary TB, asymptomatic M.tb infection, or chronic pulmonary TB that were stained for T cells, B cells, macrophages, and bronchiolar epithelial cells by multiplexed immunofluorescence. We first developed a new, accurate model to automatically segment lung granulomas, detect/quantify the cell types within granulomas, and extract the location of immune cells in granulomas for each disease state. Analysis of model-derived results shows that lung granulomas from asymptomatic mice have a characteristic spatial profile consisting of higher CD4+ and CD8a+ T cell densities, closer B cell proximity to bronchiolar epithelium, and increased T cell-macrophage proximity in asymptomatic M.tb infection. Next, we propose a second novel approach to utilize a large language model (LLM) to independently decode complex cellular patterns within granulomas, and distinguish key immunological signatures: balanced immune expression in asymptomatic M.tb mice, dysfunctional responses with low cellularity in acute TB, and highest immune-cell abundance in chronic TB. Overall, the results from this study show that lung granulomas in asymptomatic infection are characterized by increased T cell density, increased numbers of peribronchiolar B cells, and T cells closer to macrophages as compared to acute and chronic TB. These methods and results help establish an automated pipeline to extract and analyze data from multiplexed fluorescence images and provide a foundation to better understand how granuloma architecture varies by disease state.

Biologics have revolutionized the treatment of severe allergic diseases in children that cannot be controlled by conventional treatments. These diseases are commonly driven by dysregulation of immune response, often driven by Type 2 pathways. By targeting them, biologics have the potential for treating one or more allergic diseases. Thus, a "treat to target" strategy is now prioritized, allowing treatment of allergic diseases in a personalized approach. The pioneer anti-IgE monoclonal antibody, omalizumab, was initially indicated for the treatment of moderate to severe allergic asthma and is now indicated for chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), and food allergy (FA), highlighting the ability of biologics to target multiple allergic diseases. Other biologics have been developed in asthma and other allergic diseases, including mepolizumab (anti-IL5), benralizumab (anti-IL5 receptor), dupilumab (anti-IL-4 receptor α), and more recently tezepelumab (anti-TSLP). Clinical trials in children and/or teenagers have demonstrated their efficacy and safety, confirmed by real-life studies, in asthma, atopic dermatitis (AD), CSU, and more recently in eosinophilic esophagitis (EoE) and FA. Beyond biologics, small molecules such as Janus kinase inhibitors target other key pathways and have already been approved in AD, with ongoing clinical trials in other allergic diseases. In the pediatric specific context, these treatments raise questions, particularly regarding the choice of biologics and the goals. In the long term, the sustained efficacy, safety and impact on the natural history of allergic diseases need to be further studied. The aim of this review is to discuss the most recent data in the use of biologics and small molecules in pediatric allergic diseases and to highlight the remaining gaps in knowledge.

Risdiplam, a survival motor neuron 2 (SMN2) splicing modifier for pediatric spinal muscular atrophy (SMA), requires a comprehensive real-world safety evaluation. This study analyzed 1059 pediatric adverse event reports from the FDA Adverse Event Reporting System (2020 Q1-2025 Q4) with risdiplam as the primary suspect drug. Female patients slightly predominated, with 50.9% aged 0-5 years. Disproportionality analyses identified 25 positive signals. Infections and infestations, general disorders, and gastrointestinal disorders were most frequent. Pneumonia, pyrexia, diarrhoea, respiratory tract infection, and nasopharyngitis were most commonly reported. Notably, nephrolithiasis emerged as a novel unlabeled signal in pediatric patients (reporting odds ratio = 11.32). Median time-to-onset was 119 days, with approximately one-third of events occurring within 30 days and another one-third after 1 year. The Weibull model revealed that the top 5 most frequently reported PTs and top 5 SOCs all exhibited an early-onset pattern. Network toxicology identified 75 overlapping targets, with CASP3, HDAC1, and PDGFRA as core targets implicated in calcium signaling, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and apoptosis pathways. Molecular docking confirmed stable binding (- 10.1 to - 8.6 kcal/mol). Risdiplam demonstrates a generally acceptable long-term safety profile in clinical practice, yet vigilant monitoring of respiratory, infectious, gastrointestinal, and renal adverse events remains essential to optimize the benefit-risk balance.

Whether COVID-19 worsens the longterm course of inflammatory bowel disease (IBD) remains uncertain. We synthesized comparative cohorts to assess IBD outcomes after SARS-CoV-2 infection versus noninfected IBD controls and to evaluate the impact of biologic discontinuation.

Systematic review (PRISMA 2020). Adult IBD cohorts with vs without prior SARS-CoV-2. Databases: MEDLINE (PubMed), Web of Science, and Scopus; reference lists screened. Time window: Jan 2020 to Dec 2024. Risk of bias: Newcastle-Ottawa. Randomeffects Mantel-Haenszel with REML variance and Hartung-Knapp adjustment; heterogeneity by I2/τ2/Q. Zero events handled via 0.5 continuity correction; sensitivity analyses reported risk differences (percentage points) and studylevel effects for sparse outcomes. Certainty graded with GRADE.

Four matched cohorts (n≈1.3k; Italy/USA). Prior SARS-CoV-2 did not worsen IBD clinical course (OR: 1.06; 95%CI: 0.76-1.49), nor alter UC extent (OR: 1.26; 95%CI: 0.33-4.83) or CD location/behavior (OR: 1.00; 95%CI: 0.06-16.15 / OR: 1.00; 95%CI: 0.46-2.18). Conversely, COVID-19 associated with biologic delay/discontinuation (OR: 10.44; 95%CI: 3.56-30.62). Across studies, flares were more frequent when biologics were delayed/stopped (~52% vs ~18%; RD ≈ +34 p.p.).

COVID-19 per se does not appear to aggravate IBD outcomes; the clinically actionable signal is treatment continuity. In IBD patients without highrisk features for severe COVID-19, maintaining biologics should be considered to prevent flares.

The COVID-19 pandemic and recent geopolitical shifts have strained traditional funding for global health, increasing the interest in innovative financing mechanisms. We explore how international organisations perceive and implement these mechanisms as complements to traditional funding.

In this qualitative study, we conducted semi-structured interviews with eleven senior experts from major global health organisations, gathered via purposive and snowball sampling between May and July 2024. We analysed data using systematic coding and thematic analysis, with trustworthiness enhanced through member checking and peer debriefing.

Participants revealed that innovative financing mechanisms are not replacements, but strategic complements to traditional aid. We identified three primary patterns in our data: an evolution from direct funding to complex, multi-stakeholder risk-sharing arrangements; a fundamental transformation of stakeholder relationships, increasing coordination complexity; and the critical role of institutional capacity in successful implementation. Analysis of five innovative financing mechanisms, namely Advanced Market Commitments, Blended Finance, the International Finance Facility for Immunization (IFFIm), Debt2Health, and Micro-levies, demonstrated distinct patterns in complexity, coordination, and risk distribution across said mechanisms. The success of the implementation depended on clear problem definition, stakeholder alignment, and robust risk management. Blended Finance and IFFIm showed the highest complexity, while Debt2Health offered a more streamlined, triangular model.

The effectiveness of innovative financing mechanisms is heavily dependent on existing institutional frameworks and local context. They represent an evolution in health financing, offering tools for resource mobilisation and efficiency, but their success hinges on careful attention to implementation context, stakeholder coordination, and institutional capacity. Policymakers should focus on matching mechanisms to specific contexts and building coordination capabilities alongside technical innovation.